Compression Open Flow Measurement and Use

Abstract

This invention compresses open-flow assays and uses, relating to methods, devices, and systems that enable bio / chemical sensing (including but not limited to immunoassays, nucleic acid assays, electrolyte analyses, etc.) to be faster, more sensitive, require fewer steps, are easier to perform, require less sample volume, and require less or no professional assistance and / or are less expensive than many current sensing methods and devices. This invention also allows testing to be performed via smartphone.

Description

[0001] Cross-references

[0002] This application is a divisional application of Chinese national phase application No. 201880020574.1, filed on February 7, 2018. This application claims the benefit of U.S. Provisional Patent Application No. 62 / 456,065, filed February 7, 2017; U.S. Provisional Patent Application No. 62 / 456,504, filed February 8, 2017; U.S. Provisional Patent Application No. 62 / 459,972, filed February 16, 2017; and U.S. Provisional Patent Application No. 62 / 460,062, filed February 16, 2017, each of which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] This invention relates to the fields of biological / chemical sampling, sensing, measurement, and application. Background Technology

[0004] In biological and chemical assays (e.g., diagnostic tests), there is often a need for rapid and simple measurement of the volume of a sample or a portion of a sample, modification of its shape, and / or detection of an analyte, particularly with high sample homogeneity, which typically results in high assay accuracy. This invention provides apparatus and methods for achieving these objectives. Summary of the Invention

[0005] The following brief overview is not intended to include all features and aspects of the invention. The present invention relates to methods, apparatus, and systems that enable bio / chemical sensing (including but not limited to immunoassays, nucleic acid assays, electrolyte analyses, etc.) to be faster, more sensitive, require fewer steps, be easier to perform, require less sample volume, require less or no professional assistance, and / or be less expensive than many current sensing methods and devices. Attached Figure Description

[0006] Those skilled in the art will understand that the accompanying drawings described below are for illustrative purposes only. The drawings are not intended to limit the scope of the invention in any way. The drawings may not be drawn to scale. In graphs showing experimental data points, the lines connecting the data points are only for guiding observation and have no other meaning.

[0007] Figure 1This is an illustration of a CROF (Compression-Regulated Open Flow) embodiment. Figure (a) shows a first plate and a second plate, wherein the first plate has a spacer. Figure (b) illustrates sample deposition on the first plate (shown), the second plate (not shown), or both (not shown) in an open configuration. Figure (c) illustrates (i) using two plates to disperse the sample (the sample flows between the plates) and reduce the sample thickness, and (ii) using spacers and plates to regulate the sample thickness in a closed configuration. The inner surface of each plate has one or more binding sites and / or storage sites (not shown).

[0008] Figure 2 Plates with binding sites or storage sites are shown. Figure (a) shows a plate with binding sites. Figure (b) shows a plate with reagent storage sites. Figure (c) shows a first plate with binding sites and a second plate with reagent storage sites. Figure (d) shows a plate with multiple sites (binding sites and / or storage sites).

[0009] Figure 3 This is a flowchart and schematic diagram of a method for reducing incubation time by reducing sample thickness. Figure (a) shows a first plate having at least one binding site on a substrate surface. Figure (b) shows a second plate (which may have different dimensions than the first plate). Figure (c) shows the deposition of a sample (containing the target binding entity) onto a substrate surface (shown) or a cover plate (not shown), or both (not shown). Figure (d) shows moving the first and second plates so that they face each other, and reducing the sample thickness by decreasing the spacing of the internal space between the plates. The sample with reduced thickness is incubated. The reduced sample thickness accelerates the incubation time. Some embodiments of this method use spacers to adjust the spacing, which are not shown in the figures.

[0010] Figure 4 The diagram illustrates how reducing binding or mixing time can be achieved by using two plates, spacers, and compression (shown in cross-section) to reduce sample thickness. Figure (a) shows the time required to reduce the binding of a substance in the sample to a binding site on a solid surface (X - (volume to surface)). Figure (b) shows the time required to reduce the binding of a substance (e.g., a reagent) stored on one plate surface to a binding site on another surface (X - (surface to surface)). Figure (c) shows the time required to reduce the time required to add a reagent stored on the plate surface to a sample sandwiched between the plate and another plate (X - (surface to volume)).

[0011] Figure 5This illustrates how to avoid or reduce localized bending in a flexible sheet. Figure (a) shows that, given a set of samples and compression conditions, if the spacing distance is too large for the flexible sheet (the second sheet, such as a plastic film), assuming the first sheet is rigid, the sheet exhibits localized sagging (i.e., inward bending) between two adjacent spacers in a closed configuration. Samples between the sheets are not removed. Figure (b) illustrates how to reduce or virtually avoid localized bending (sagging) in the flexible sheet of Figure (a) by using an appropriate spacing distance and appropriate compression force. Samples between the sheets are not removed.

[0012] Figure 6 The diagram illustrates the diminishing effect of large dust particles on plate spacing (sample thickness) adjustment. Figure (a) shows that when using two rigid plates, dust thicker than the height of the spacer disrupts the intended plate spacing adjustment (and thus the intended sample thickness adjustment). No sample is extracted between the plates. Figure (b) shows that using appropriate flexible plates and a suitable spacing distance, the effect of dust is isolated to a small area around the dust, while in other areas, the plate spacing (and therefore the sample thickness) is adjusted by the spacer rather than the dust. This diagram features a rigid first plate, a flexible second plate, and the spacer initially fixed to the first plate. Figure (c) illustrates that using appropriate flexible plates and a suitable spacing distance, the effect of dust is isolated to a small area around the dust, while in other areas, the plate spacing (and therefore the sample thickness) is adjusted by the spacer rather than the dust. This diagram features a rigid first plate, a flexible second plate, and the spacer initially fixed to the second plate.

[0013] Figure 7 The effects of reducing surface flatness variations in plates by using appropriate spacer arrangements and flexible plates are illustrated. Figure (a) shows that surface flatness variations can be quite large compared to the desired sample thickness, leading to errors in sample thickness determination. In this illustration, only one plate has a large flatness variation (in reality, two plates can have large flatness variations). Samples are not extracted between the plates. Figure (b) shows the surface flatness variation distance of the plates, i.e., the distance from a local maximum to an adjacent local minimum of surface height. Figure (c) shows how small surface flatness variations can be achieved by making one or two plates flexible and using appropriate spacer distances and appropriate compressive forces to correct for the original surface flatness variations of the plates in an open configuration when the configuration is closed. Samples are not extracted between the plates. Figure (d) shows how sample thickness variations are made smaller than the initial surface flatness variations of the plates by using a flexible second plate and appropriate spacer distances. The flexible plate follows the contour of the rigid plate. Samples are not extracted between the plates.

[0014] Figure 8Spacers on the plate. (a) Photograph top view of a 46μm × 46μm column spacer with a column spacing of 54μm, and (b) Photograph top view of a 10μm × 70μm column spacer with a column spacing of 10μm; (c) Photograph of a 30μm × 40μm column spacer with a spacer height of 2μm, and (d) Photograph foreground of a 30μm × 40μm column spacer with a spacer height of 30μm.

[0015] Figure 9 Illustrations of certain aspects of exemplary apparatus and methods for collecting exhaled gas condensate (EBC) using SiEBCA (Single Drop EBC Collector / Analyzer).

[0016] Figure 10 A diagram of a SiEBCA with "open spacers" and "closed spacers", where the open spacers are pillars (columns) and the closed spacers are annular spacers (d) and four-cell grid spacers (e).

[0017] Figure 11 Surface wetting properties of untreated and treated (better wetting than untreated) surfaces of the collection plate.

[0018] Detailed description of exemplary embodiments

[0019] The following detailed description illustrates some embodiments of the invention by way of example, not limitation. Section headings and any subtitles used herein are for organizational purposes only and should not be construed as limiting the subject matter in any way. The content under section headings and / or subtitles is not limited to the section headings and / or subtitles, but applies to the entire description of the invention.

[0020] References to any publication are for information prior to the filing date and should not be construed as an admission that this claim is not entitled to a prior invention prior to such publication. Furthermore, the provided publication date may differ from the actual publication date (which may require separate verification).

[0021] Compressed Regulation Open Flow (CROF)

[0022] In an assay, manipulation of the sample or reagent can lead to improvements in the assay. Manipulation includes, but is not limited to, manipulating the geometry and position of the sample and / or reagent, mixing or combining the sample and reagent, and the contact area between the reagent / sample and the plate.

[0023] Many embodiments of the present invention use a method called “Compression-Regulated Open Flow (CROF)” and a device for performing CROF to manipulate the geometry, position, contact area, and mixing of samples and / or reagents.

[0024] The term “compressed open flow (COF)” refers to a method of altering the shape of a flowable sample deposited on a plate by: (i) placing another plate on top of at least a portion of the sample, and (ii) then compressing the sample between the two plates by pushing the two plates toward each other; wherein the compression reduces the thickness of at least a portion of the sample and causes the sample to flow into the open space between the plates.

[0025] The terms “compression-regulated open flow” or “CROF” (or “self-calibrated compression-regulated open flow” or “SCOF” or “SCCOF”) refer to a specific type of COF in which the final thickness of part or all of the compressed sample is “regulated” by spacers placed between two plates.

[0026] The term "final thickness of part or all of the sample is adjusted by the spacer" in CROF means that during CROF, once a specific sample thickness is reached, the relative movement of the two plates and therefore the change in sample thickness ceases, where the specific thickness is determined by the spacer.

[0027] like Figure 1 As shown, one embodiment of the CROF method includes:

[0028] (a) Obtain a flowable sample;

[0029] (b) Obtain a first plate and a second plate that can be moved relative to each other to different configurations, wherein each plate has a substantially flat sample contact surface, wherein one or both of the plates include spacers and the spacers have a predetermined height, and the spacers are on the respective sample contact surfaces;

[0030] (c) When the plates are configured in an open configuration, a sample is deposited on one or both of the plates; wherein the open configuration is such that the two plates are partially or completely separated and the spacing between the plates is not adjusted by spacers; and

[0031] (d) After (c), the sample is spread by bringing the plate into a closed structure, wherein the plates are facing each other, the spacer and the relevant volume of the sample are between the plates, the thickness of the relevant volume of the sample is adjusted by the plates and the spacer, wherein the relevant volume is at least a portion of the total volume of the sample, and wherein the sample flows laterally between the two plates during sample spreading.

[0032] Unless otherwise stated, the term "plate" refers to a plate used in the CROF process, whose solid has a surface that can be used with another plate to compress a sample placed between the two plates, thereby reducing the thickness of the sample.

[0033] The term "plate" or "pair of plates" refers to two plates in the CROF process.

[0034] The terms "first plate" or "second plate" refer to the plate used in the CROF process.

[0035] The term "boards facing each other" refers to a pair of boards that are at least partially facing each other.

[0036] Unless otherwise stated, the term "spacer" or "stop" refers to a mechanical object that limits the minimum distance between two plates when placed between them, a limitation achieved when the two plates are compressed together. That is, during compression, the spacer stops the relative movement of the two plates to prevent the plate spacing from becoming less than a preset (i.e., predetermined) value. There are two types of spacers: "open spacers" and "closed spacers."

[0037] The term "open spacer" refers to a spacer having a shape that allows liquid to flow around and through its entire perimeter. For example, a column is an open spacer.

[0038] The term "closed spacer" refers to a spacer with a shape in which liquid cannot flow around the entire periphery of the spacer and cannot flow through the spacer. For example, an annular spacer is a closed spacer for liquid inside a ring, wherein the liquid inside the annular spacer is kept inside the ring and cannot reach the outside (outer periphery).

[0039] The terms "spacer with a predetermined height" and "spacer with a predetermined spacing distance" mean that the values ​​of the spacer height and spacing distance are known prior to the CROF process. If the values ​​of the spacer height and spacing distance are unknown prior to the CROF process, then the values ​​of the spacer height and spacing distance are not predetermined. For example, in the case where beads are sprayed onto a plate as spacers, where the beads land at random locations on the plate, the distance between the spacers is not predetermined. Another example of not predetermined spacing distance is when the spacers move during the CROF process.

[0040] In the CROF process, the term "spacer fixed to its corresponding plate" means that the spacer is attached to the plate at a certain position and remains attached to that position during CROF (i.e., the spacer's position on the corresponding plate does not change). An example of "spacer fixed to its corresponding plate" is that the spacer is made integrally from a single piece of material of the plate, and the spacer's position relative to the plate surface does not change during CROF. An example of "spacer not fixed to its corresponding plate" is that the spacer is bonded to the plate with adhesive, but during the use of the plate, during CROF, the adhesive fails to hold the spacer in its original position on the plate surface, and the spacer moves away from its original position on the plate surface.

[0041] The term "spacer integrally fixed to the plate" means that the spacer and the plate behave like a single object, wherein the spacer does not move or separate from its original position on the plate during use.

[0042] In the CROF process, the term "open construction" for two plates refers to a construction in which the two plates are either partially or completely separated, and the spacing between the plates is not adjusted by spacers.

[0043] In the CROF process, the term "closed configuration" for two plates refers to a configuration in which the plates face each other, the spacer and the relevant volume of the sample are between the plates, the thickness of the relevant volume of the sample is adjusted by the plates and the spacer, and the relevant volume is at least a portion of the total volume of the sample.

[0044] In the CROF process, the term "sample thickness adjusted by plate and spacer" means that, given the plate, sample, spacer, and plate compression method, the thickness of at least one port of the sample under the closed configuration of the plate can be predetermined based on the properties of the spacer and plate.

[0045] In CROF apparatus, the term "inner surface" or "sample surface" of a plate refers to the surface of the plate that contacts the sample, while the other surface of the plate (that does not contact the sample) is called the "outer surface".

[0046] The term "X-plate" in CROF devices refers to a plate containing space on the sample surface of the plate, wherein spacers have a predetermined spacing distance and spacer height, and wherein at least one of the spacers is located within the sample contact area.

[0047] The term "CROF apparatus" refers to an apparatus for performing the CROF process. The term "CROFed" refers to the use of the CROF process. For example, the term "sample is CROFed" means that the sample is placed in a CROF apparatus, the CROF process is performed, and the sample is held in the final CROF configuration unless otherwise specified.

[0048] The term "CROF plate" refers to two plates used for the CROF process.

[0049] The term "surface smoothness" or "surface smoothness variation" for a flat surface refers to the average deviation of a flat surface from a perfectly flat plane over a short distance of approximately or less than a few micrometers. Surface smoothness is different from surface flatness variation. A flat surface can have good surface flatness, but poor surface smoothness.

[0050] The term "surface flatness" or "surface flatness variation" for a flat surface refers to the average deviation of a flat surface from an ideal flat plane over a long distance of approximately or greater than 10 μm. Surface flatness variation is different from surface smoothness. A flat surface can have good surface smoothness, but poor surface flatness (i.e., large surface flatness variation).

[0051] The term "relative surface flatness" for plates or samples refers to the ratio of the change in plate surface flatness to the final sample thickness.

[0052] Unless otherwise stated, the term "final sample thickness" in the CROF process refers to the sample thickness under the closed configuration of the plate in the CORF process.

[0053] The term "compression method" in CROF refers to the method of transforming two plates from an open structure to a closed structure.

[0054] The term "region of interest" or "region of concern" in board terminology refers to the area of ​​the board that is relevant to the function performed by the board.

[0055] The term "at most" means "equal to or less than". For example, the spacer height is at most 1 μm, which means that the spacer height is equal to or less than 1 μm.

[0056] The term "sample region" refers to the area of ​​the sample that is approximately parallel to the space between the plates and perpendicular to the sample thickness.

[0057] The term "sample thickness" refers to the sample size in a direction perpendicular to the surfaces of the plates facing each other (e.g., the spacing between the plates).

[0058] The term "plate spacing" refers to the distance between the inner surfaces of two plates.

[0059] In CROF, the term "deviation of final sample thickness" refers to the difference between the predetermined spacer height (determined by the manufacture of the spacer) and the average final sample thickness, where the average final sample thickness is averaged over a given area (e.g., the average of 25 different points (4 mm apart) in a 1.6 cm × 1.6 cm area).

[0060] In the CROF process, the term "uniformity of the measured final sample thickness" refers to the standard deviation (e.g., the standard deviation relative to the mean) of the final sample thickness measured over a given sample area.

[0061] In the CROF process, the terms “relevant volume of sample” and “relevant area of ​​sample” refer to the volume and area of ​​a portion or all of the sample deposited on the plate during the CROF process, respectively, which are associated with the functions performed by the appropriate methods or apparatus, including but not limited to reducing the binding time of analytes or entities, detecting analytes, quantifying volume, quantifying concentration, mixing reagents, or controlling concentration (analytes, entities, or reagents).

[0062] The terms “some embodiments”, “in some embodiments”, “in some embodiments”, “embodiment”, “one embodiment”, “another embodiment”, “certain embodiments”, “many embodiments”, etc., used in this invention refer to embodiments that apply to the entire disclosure (i.e., the entire invention), unless otherwise specifically stated.

[0063] Unless otherwise specified, the terms "height" or "thickness" for objects in the CROF process refer to the dimension of the object in a direction perpendicular to the surface of the plate. For example, spacer height is the dimension of the spacer in a direction perpendicular to the surface of the plate, and spacer height and spacer thickness mean the same thing.

[0064] Unless otherwise specified, the term "area" in the CROF process refers to an area of ​​an object that is parallel to the surface of the plate. For example, a gap area is a gap area that is parallel to the surface of the plate.

[0065] Unless otherwise specified, the term "lateral" or "transversely" in the CROF process refers to a direction parallel to the surface of the board.

[0066] Unless otherwise specified, the term "width" in the CROF process refers to the lateral dimension of the spacer.

[0067] The term "spacers inside the sample" refers to spacers that are surrounded by the sample (e.g., columnar spacers inside the sample).

[0068] In the CROF process, the term "critical bend span" for a plate refers to the span (i.e., distance) between two supports at which, for a given flexible plate, sample, and compressive force, the plate bends equal to the allowable bend. For example, for a given flexible plate, sample, and compressive force, if the allowable bend is 50 nm and the critical bend span is 40 μm, then the bend of the plate between two adjacent spacers 40 μm apart will be 50 nm, and if the two adjacent spacers are less than 40 μm apart, the bend will be less than 50 nm.

[0069] The term "flowable" for a sample refers to an increase in lateral dimensions as the sample thickness decreases. For example, fecal samples are considered flowable.

[0070] In some embodiments of the invention, the sample does not flow under the CROF process to benefit from the process, provided that the sample thickness can be reduced under the CROF process. For example, in order to stain tissue by placing dye on the surface of a CROF plate, the CROF process can reduce the tissue thickness and thus accelerate the saturation incubation time for dye staining.

[0071] The terms “CROF card (or card)”, “COF card”, “QMAX card”, “Q card”, “CROF device”, “COF device”, “QMAX device”, “CROF plate”, “COF plate”, and “QMAX plate” are interchangeable, except that in some embodiments, the COF card does not include a spacer; and these terms refer to a device comprising a first plate and a second plate, the first plate and the second plate being movable relative to each other into different configurations (including open configurations and closed configurations), and the device comprising a spacer comprising adjusting the spacing between the plates (except in some embodiments of COF). The term “X plate” refers to one of the two plates in a CROF card to which the spacer is fixed. Further description of the COF card, CROF card, and X plate is described in Provisional Application Serial No. 62 / 456065, filed February 7, 2017, the entire contents of which are incorporated herein by reference for all purposes.

[0072] Examples of the present invention

[0073] I. Forming a uniform thin fluid layer by imprecise pressure pressing.

[0074] The term "inaccurate pressing pressure" was not further elaborated upon; a definition of inaccurate pressing pressure was then added.

[0075] As used herein, in the context of force (e.g., "imprecise pressure"), the term "imprecise" refers to force.

[0076] (a) It has a quantity that is not precisely known or precisely predicted when the force is applied;

[0077] (b) Having a magnitude in the range of 1N to 20N and / or a pressure in the range of 0.1psi to 280psi;

[0078] (b) The magnitude changes with each subsequent application of the force;

[0079] The inaccuracy (i.e. variation) of the force in (d), (a), and (c) is at least 20% of the total force actually applied.

[0080] Imprecise force can be applied by the hand, for example, by pinching an object together between the thumb and forefinger, or by pinching an object together between the thumb and forefinger and rubbing it together.

[0081] A. Inaccurate force, specified as IGS^4 / hE

[0082] A1. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising:

[0083] The first plate, the second plate, and the spacer, wherein:

[0084] i. The plates can be moved relative to each other to different configurations;

[0085] ii. One or both plates are flexible;

[0086] iii. Each plate includes an inner surface having a sample contact area for contacting the fluid sample;

[0087] iv. Each plate contains a force zone on its respective outer surface, which is used to apply an imprecise pressure that forces the plates together;

[0088] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0089] vi. The spacer has a predetermined substantially uniform height of 200 micrometers or less and a predetermined fixed spacing distance;

[0090] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below; and

[0091] viii. At least one of the spacers is located inside the sample contact area;

[0092] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0093] Another type of construction is a closed structure, which is constructed after the sample is deposited in an open structure and the plates are forced into a closed structure by applying imprecise pressure to the force zone; and in the closed structure: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is regulated by the plates and spacers.

[0094] A2. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps:

[0095] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0096] i. The plates can be moved relative to each other to different configurations;

[0097] ii. One or both plates are flexible;

[0098] iii. Each plate includes an inner surface having a sample contact area for contacting the fluid sample;

[0099] iv. Each plate contains a force zone on its respective outer surface, which is used to apply an imprecise pressure that forces the plates together;

[0100] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0101] vi. The spacer has a predetermined substantially uniform height of 200 micrometers or less and a predetermined fixed spacing distance;

[0102] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below; and

[0103] viii. At least one of the spacers is located inside the sample contact area;

[0104] (b) Obtain a fluid sample;

[0105] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0106] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surfaces of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0107] Place the two boards together; and

[0108] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacers; and wherein the reduced thickness of the sample reduces the time required for mixing the reagent at the storage site with the sample,

[0109] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0110] B. Manual pressing, specifying spacer hardness - contact area product B1. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising:

[0111] The first plate, the second plate, and the spacer, wherein:

[0112] i. The plates can be moved relative to each other to form different configurations;

[0113] ii. One or both plates are flexible;

[0114] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0115] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0116] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0117] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0118] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; and

[0119] viii. At least one of the spacers is located inside the sample contact area;

[0120] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0121] Another of the aforementioned configurations is a closed configuration configured after the sample is deposited in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and adjusted by the plates and the spacer; and

[0122] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0123] B2. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps:

[0124] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0125] i. The plates can be moved relative to each other to form different configurations;

[0126] ii. One or both plates are flexible;

[0127] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0128] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0129] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0130] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0131] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; and

[0132] viii. At least one of the spacers is located inside the sample contact area;

[0133] (b) Obtain a fluid sample;

[0134] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0135] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0136] Place the two boards together; and

[0137] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacers; and wherein the reduced thickness of the sample reduces the time required for mixing the reagent at the storage site with the sample,

[0138] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0139] C. Manual pressing, specifying IDS / hE & spacer hardness - contact area product C1. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising:

[0140] The first plate, the second plate, and the spacer, wherein:

[0141] i. The plates can be moved relative to each other to form different configurations;

[0142] ii. One or both plates are flexible;

[0143] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0144] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0145] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0146] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0147] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; and

[0148] viii. At least one of the spacers is located inside the sample contact area;

[0149] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0150] Another of the aforementioned configurations is a closed configuration configured after the sample is deposited in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer;

[0151] The force used to press the two plates into a closed structure is imprecise and is provided by hand.

[0152] C2. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps:

[0153] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0154] i. The plates can be moved relative to each other to form different configurations;

[0155] ii. One or both plates are flexible;

[0156] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0157] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0158] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0159] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0160] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; and

[0161] viii. At least one of the spacers is located inside the sample contact area;

[0162] (b) Obtain a fluid sample;

[0163] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0164] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0165] Place the two boards together; and

[0166] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacers; and wherein the reduced thickness of the sample reduces the time required for mixing the reagent at the storage site with the sample,

[0167] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0168] D. Manual pressing, specifying column spacers and IDS / W ratio. D1. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising:

[0169] The first plate, the second plate, and the spacer, wherein:

[0170] i. The plates can be moved relative to each other to form different configurations;

[0171] ii. One or both plates are flexible;

[0172] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0173] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0174] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0175] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0176] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater;

[0177] viii. At least one of the spacers is located inside the sample contact area; and

[0178] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0179] Another of the aforementioned configurations is a closed configuration configured after the sample is deposited in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer;

[0180] The force used to press the two plates into a closed structure is imprecise and is provided by hand.

[0181] D2. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps:

[0182] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0183] i. The plates can be moved relative to each other to form different configurations;

[0184] ii. One or both plates are flexible;

[0185] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0186] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0187] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0188] vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers;

[0189] vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater;

[0190] viii. At least one of the spacers is located inside the sample contact area; and

[0191] (b) Obtain a fluid sample;

[0192] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0193] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0194] Place the two boards together; and

[0195] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample produces substantially uniform pressure, and the pressing causes at least a portion of the sample to spread laterally between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample reduces the time for mixing the reagent with the sample at the storage site, and wherein the force pressing the two plates into the closed configuration is an imprecise pressure provided by hand. EQ(V-1) volume determination, specifying IGS^4 / hE

[0196] E1. An apparatus for determining the volume of a relevant sample by pressing with an imprecise force provided by a human hand, comprising:

[0197] The first plate, the second plate, the spacer, and the area determination device, wherein:

[0198] i. The plates can be moved relative to each other to form different configurations;

[0199] ii. One or both plates are flexible;

[0200] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured;

[0201] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0202] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0203] vi. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance;

[0204] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below;

[0205] viii. At least one of the spacers is located inside the sample contact area; and

[0206] ix. The region determination device is constructed to determine the lateral region of the relevant volume;

[0207] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0208] Another of the aforementioned configurations is a closed configuration configured after the sample is deposited in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer;

[0209] The relevant volume of the sample is a portion or the entire volume of the uniform thickness layer, and its value is determined by the uniform thickness and a defined lateral region; and

[0210] The force used to press the two plates into a closed structure is imprecise and is provided by hand.

[0211] The apparatus of any of the foregoing embodiments, wherein the region determination device is a camera.

[0212] + The region determining device includes a region within the sample contact area of ​​the plate, wherein the region is smaller than 1 / 100, 1 / 20, 1 / 10, 1 / 6, 1 / 5, 1 / 4, 1 / 3, 1 / 2, 2 / 3 of the sample contact area, or within a range between any two values.

[0213] + The region determination device includes a region in the sample contact area of ​​the camera and plate, wherein the region is in contact with the sample. E2. A method for forming a thin fluid sample layer with a uniform predetermined thickness by pressing with imprecise pressure, comprising the steps of:

[0214] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0215] i. The plates can be moved relative to each other to form different configurations;

[0216] ii. One or both plates are flexible;

[0217] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured;

[0218] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0219] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0220] vi. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance;

[0221] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below;

[0222] viii. At least one of the spacers is located inside the sample contact area; and

[0223] ix. The region determination device is constructed to determine the lateral region of the relevant volume;

[0224] (b) Obtain a fluid sample;

[0225] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0226] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0227] Place the two boards together; and

[0228] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacers; and wherein the reduced thickness of the sample reduces the time required for mixing the reagent at the storage site with the sample,

[0229] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0230] FQ(V-1) volume determination, specifying IGS^4 / hE

[0231] F1. An apparatus for determining the volume of a relevant sample by pressing with an imprecise force provided by a human hand, comprising:

[0232] The first plate, the second plate, the spacer, and the area determination device, wherein:

[0233] i. The plates can be moved relative to each other to form different configurations;

[0234] ii. One or both plates are flexible;

[0235] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured;

[0236] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0237] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0238] vi. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance;

[0239] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below;

[0240] viii. At least one of the spacers is located inside the sample contact area; and

[0241] ix. The region determination device is constructed to determine the lateral region of the relevant volume;

[0242] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0243] Another of the aforementioned configurations is a closed configuration configured after the sample is deposited in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer;

[0244] The relevant volume of the sample is a portion or the entire volume of the uniform thickness layer, and its value is determined by the uniform thickness and a defined lateral region; and

[0245] The force used to press the two plates into a closed structure is imprecise and is provided by hand.

[0246] F2. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps:

[0247] (a) Obtain the first plate, the second plate, and the spacer, wherein:

[0248] i. The plates can be moved relative to each other to form different configurations;

[0249] ii. One or both plates are flexible;

[0250] iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured;

[0251] iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0252] v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0253] vi. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance;

[0254] vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below;

[0255] viii. At least one of the spacers is located inside the sample contact area; and

[0256] ix. The region determination device is constructed to determine the lateral region of the relevant volume;

[0257] (b) Obtain a fluid sample;

[0258] (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0259] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises:

[0260] Place the two boards together; and

[0261] At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacers; and wherein the reduced thickness of the sample reduces the time required for mixing the reagent at the storage site with the sample,

[0262] The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

[0263] 1. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a flat top.

[0264] 2. The apparatus or method of any of the foregoing embodiments, wherein the apparatus is further configured to have a sample thickness with thickness and uniformity substantially the same after the pressure is removed as when the force is applied.

[0265] 3. The apparatus or method of any of the foregoing embodiments, wherein the imprecise force is provided by hand.

[0266] 4. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is substantially constant.

[0267] 5. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is substantially periodic in the region of uniform sample thickness.

[0268] 6. The apparatus or method of any of the foregoing embodiments, wherein the product of the fill factor and the Young's modulus of the spacer is 2 MPa or greater.

[0269] 7. The apparatus or method of any of the foregoing embodiments, wherein the force is applied directly or indirectly by hand.

[0270] 8. The apparatus or method of any of the foregoing embodiments, wherein the applied force is in the range of 5N to 20N.

[0271] 9. The apparatus or method of any of the foregoing embodiments, wherein the thickness variation of the highly uniform layer is less than 15%, 10%, or 5% of the average thickness.

[0272] 10. The apparatus or method of any of the foregoing embodiments, wherein the imprecise force is applied by clamping the apparatus between the thumb and forefinger.

[0273] 11. The apparatus or method of any of the foregoing embodiments, wherein the predetermined sample thickness is greater than the height of the spacer.

[0274] 12. The apparatus or method of any of the foregoing embodiments, wherein the apparatus retains itself in a closed configuration after the pressure is removed.

[0275] 13. The apparatus or method of any of the foregoing embodiments, wherein the region of the uniform thickness sample layer is larger than the region of applied pressure.

[0276] 14. The apparatus or method of any of the foregoing embodiments, wherein the spacer does not significantly deform during the application of pressure.

[0277] 15. The apparatus or method of any of the foregoing embodiments, wherein the pressure is not predetermined and is not measured.

[0278] 16. The apparatus of any of the foregoing embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0279] 17. The apparatus of any of the foregoing embodiments, wherein the analyte comprises leukocytes, erythrocytes and platelets.

[0280] 18. The apparatus of any of the foregoing embodiments, wherein the analyte is stained.

[0281] 19. The method or apparatus of any of the foregoing embodiments, wherein the spacing distance (SD) is equal to or less than about 120 μm (micrometers).

[0282] 20. The method or apparatus of any of the foregoing embodiments, wherein the spacing distance (SD) is equal to or less than about 100 μm (micrometers).

[0283] 21. The method or apparatus of any of the foregoing embodiments, wherein the fourth power of the spacing distance (ISD) is divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below.

[0284] 22. The method or apparatus of any of the foregoing embodiments, wherein the fourth power of the spacing distance (ISD) is divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 5μm 3 / GPa or below.

[0285] 23. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape, a substantially flat top surface, a predetermined substantially uniform height and a predetermined constant spacing distance, the spacing distance being at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 2 MPa, wherein the fill factor is the ratio of the spacer contact area to the total plate area, and wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (-).

[0286] 24. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape, a substantially flat top surface, a predetermined substantially uniform height, and a predetermined constant spacing distance, the spacing distance being at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 2 MPa, wherein the fill factor is the ratio of the spacer contact area to the total plate area, and wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (1), wherein the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below.

[0287] 25. The apparatus of any of the foregoing embodiments, wherein the ratio of the spacing distance of the spacers to the average width of the spacers is 2 or greater, and the fill factor of the spacers multiplied by the Young's modulus of the spacers is 2 MPa or greater.

[0288] 26. The method or apparatus of any of the foregoing embodiments, wherein the analyte is an analyte for detecting proteins, peptides, nucleic acids, synthetic compounds and inorganic compounds.

[0289] 27. The method or apparatus of any of the foregoing embodiments, wherein the sample is a biological sample selected from amniotic fluid, aqueous humor, vitreous fluid, blood (e.g., whole blood, graded blood, plasma, or serum), breast milk, cerebrospinal fluid (CSF), earwax, chyle, chyme, endolymph, perilymph, feces, respiration, gastric acid, gastric juice, lymph, mucus (including nasal drainage and sputum), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheumatic fluid, saliva, exhaled condensate, sebum, semen, sputum, sweat, synovial fluid, tears, vomit, and urine.

[0290] 28. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape and the ratio of the width to the height of the column is equal to or greater than 1.

[0291] 29. The method of any of the foregoing embodiments, wherein the sample deposited on one or two plates has an unknown volume.

[0292] 30. The method or apparatus of any of the foregoing embodiments, wherein the sample is used to detect, purify and quantify compounds or biomolecules associated with certain disease stages.

[0293] 31. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with infectious and parasitic diseases, injuries, cardiovascular diseases, cancer, mental disorders, neuropsychiatric disorders, lung diseases, kidney diseases, and other organic diseases.

[0294] 32. The method or apparatus of any of the foregoing embodiments, wherein the sample involves the detection, purification and quantification of microorganisms.

[0295] 33. The method or apparatus of any of the foregoing embodiments, wherein the sample involves viruses, fungi, and bacteria from the environment (e.g., water, soil, or biological samples).

[0296] 34. The method or apparatus of any of the foregoing embodiments, wherein the sample involves the detection and quantification of compounds or biological samples (e.g., toxic waste, anthrax) that pose a threat to food safety or national security.

[0297] 35. The method or apparatus of any of the foregoing embodiments, wherein the sample is correlated with the quantification of vital parameters in medical or physiological monitoring.

[0298] 36. The method or apparatus of any of the foregoing embodiments, wherein the sample is related to glucose, blood, oxygen level, or total blood cell count.

[0299] 37. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with the detection and quantification of specific DNA or RNA from a biological sample.

[0300] 38. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with the sequencing and comparison of genetic sequences of DNA in chromosomes and mitochondria for genomic analysis.

[0301] 39. The method or apparatus of any of the foregoing embodiments, wherein the sample relates to, for example, detecting reaction products during drug synthesis or purification.

[0302] 40. The method or apparatus of any of the foregoing embodiments, wherein the sample is cells, tissue, body fluid, or feces.

[0303] 41. The method or apparatus of any of the foregoing embodiments, wherein the sample is a sample for detecting proteins, peptides, nucleic acids, synthetic compounds, or inorganic compounds.

[0304] 42. The method or apparatus of any of the foregoing embodiments, wherein the sample is a sample in the fields of human, veterinary, agricultural, food, environmental and pharmaceutical testing.

[0305] 43. The method or apparatus of any of the foregoing embodiments, wherein the sample is a biological sample selected from the group consisting of: blood, serum, plasma, nasal swab, nasopharyngeal washings, saliva, urine, gastric juice, cerebrospinal fluid, tears, feces, mucus, sweat, earwax, oil, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, interstitial fluid derived from tumor tissue, eye discharge, cerebrospinal fluid, throat swab, respiration, hair, nails, skin, biopsy, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid, sputum, pus, microbiota, meconium, breast milk, exhaled condensate, nasopharyngeal washings, throat swabs, fecal samples, hair, nails, earwax, respiration, connective tissue, muscle tissue, nerve tissue, epithelial tissue, cartilage, cancer samples, or bone.

[0306] 44. The apparatus or method of any of the foregoing embodiments, wherein the spacer of the layer of uniform thickness has a fill factor of at least 1%, wherein the fill factor is the ratio of the spacer region in contact with the layer of uniform thickness to the total plate region in contact with the layer of uniform thickness.

[0307] Column spacer flat top

[0308] In some embodiments of the invention, the spacer is a post having a flat top and feet fixed to a plate, wherein the flat top has a smoothness with small surface variations, and the variations are less than 5, 10 nm, 20 nm, 30 nm, 50 nm, 100 nm, 200 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, 800 nm, 1000 nm, or in any range between two values. Preferably, the smoothness of the flat post top is a surface variation of 50 nm or less.

[0309] Furthermore, the surface variation is relative to the spacer height, and the ratio of the column top surface variation to the spacer height is less than 0.5%, 1%, 3%, 5%, 7%, 10%, 15%, 20%, 30%, 40%, or within any two values. Preferred column top smoothness has a ratio of column top surface variation to spacer height of less than 2%, 5%, or 10%.

[0310] Column spacer sidewall corner

[0311] In some embodiments of the invention, the spacer is a column with sidewall angles. In some embodiments, the sidewall angle is less than 5 degrees (measured from the surface normal), 10 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 70 degrees, or within any two values. In a preferred embodiment, the sidewall angle is less than 5 degrees, 10 degrees, or 20 degrees.

[0312] A uniform thin fluid layer is formed by imprecise pressure pressing.

[0313] In some embodiments of the invention, a uniform thin fluid sample layer is formed by using a pressing force with imprecise force. The term "imprecise pressing force" is not further elaborated here; a definition of imprecise pressing force is then added. As used herein, in the context of force (e.g., "imprecise pressure"), the term "imprecise" refers to force.

[0314] (a) It has a quantity that is not precisely known or precisely predicted when the force is applied; (b) It has a value of 0.01 kg / cm 2 (square centimeters) to 100 kg / cm² 2 The pressure within the range, (c) the magnitude varies with each subsequent application of the force; and (d) the inaccuracy (i.e. variation) of the force in (a) and (c) is at least 20% of the total force actually applied.

[0315] Imprecise force can be applied by the hand, for example, by pinching an object together between the thumb and forefinger, or by pinching an object together between the thumb and forefinger and rubbing it together.

[0316] In some embodiments, the imprecise force applied by hand is 0.01 kg / cm. 2 0.1kg / cm 2 0.5kg / cm 2 1kg / cm 2 2kg / cm 2 kg / cm 2 5kg / cm 2 10kg / cm 2 20kg / cm 2 30kg / cm 2 40kg / cm 2 50kg / cm 2 60kg / cm 2 100kg / cm 2 150kg / cm 2 200kg / cm 2 , or the range between any two values; and 0.1 kg / cm 2 Up to 0.5 kg / cm 2 0.5kg / cm 2 Up to 1kg / cm 2 1kg / cm 2 Up to 5kg / cm 2 5kg / cm 2 Up to 10kg / cm 2The preferred range of pressure (pressure).

[0317] Spacer fill factor.

[0318] The term "spacer fill factor" or "fill factor" refers to the ratio of the spacer contact area to the total plate area. In a closed configuration, the spacer contact area refers to the area where the top surface of the spacer contacts the inner surface of the plate. The total plate area refers to the total area of ​​the inner surface of the plate that the spacer contacts with its flat top. Since there are two plates and each spacer has two contact surfaces, with each contact surface contacting one plate, the fill factor is the minimum fill factor.

[0319] For example, if the spacer is a column with a flat top (10 μm × 10 μm), a nearly uniform cross-section, and a height of 2 μm, and the spacer is periodic with a period of 100 μm, then the fill factor of the spacer is 1%. If, in the above example, the foot of the column spacer is a 15 μm × 15 μm square, then the fill factor is still 1% by definition.

[0320] IDS^4 / hE

[0321] A1. An apparatus for forming a thin fluid sample layer with a uniform predetermined thickness by pressing, comprising:

[0322] The first plate, the second plate, and the spacer, wherein:

[0323] ix. The plates can be moved relative to each other to form different configurations;

[0324] x. One or both plates are flexible;

[0325] xi. Each plate includes an inner surface having a sample contact area for contacting the fluid sample;

[0326] xii. Each plate includes a force region on its respective outer surface, which is used to apply a pressure that forces the plates together;

[0327] xiii. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0328] xiv. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined fixed spacing distance;

[0329] xv. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below; and

[0330] xvi. At least one of the spacers is located inside the sample contact area;

[0331] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0332] Another type of construction is a closed structure, which is constructed after the sample is deposited in an open structure and the plates are forced into a closed structure by applying pressure to the force zone; and in the closed structure: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is regulated by the plates and spacers.

[0333] A2. A method for forming a thin fluid sample layer with a uniform predetermined thickness by pressing, comprising the following steps:

[0334] (e) Obtaining the apparatus of Example A1;

[0335] (f) Depositing a fluid sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which two plates are partially or completely separated and the spacing between the plates is not adjusted by spacers;

[0336] (g) After (b), the two plates are forced into a closed configuration, wherein at least a portion of the sample is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and adjusted by the plates and spacers.

[0337] A3. An apparatus for analyzing fluid samples, comprising:

[0338] The first plate, the second plate, and the spacer, wherein:

[0339] i. The plates can be moved relative to each other to form different configurations;

[0340] ii. One or both plates are flexible;

[0341] iii. Each plate has a sample contact area on its respective inner surface for contacting the fluid sample.

[0342] iv. One or two plates include spacers, and the spacers are fixed to the inner surface of the respective plates;

[0343] v. The spacers have a predetermined substantially uniform height of 200 micrometers or less, and the spacing is predetermined;

[0344] vi. The Young's modulus of the spacer multiplied by the spacer's fill factor must be at least 2 MPa; and

[0345] vii. At least one of the spacers is located inside the sample contact area; and

[0346] One of the structures is an open structure, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both plates; and

[0347] Another of the configurations is a closed configuration, which is configured after the sample has been deposited in an open configuration; and in the closed configuration: at least a portion of the sample is compressed by two plates into a layer of very uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and is adjusted by the plates and spacers.

[0348] A4. A method for forming a thin fluid sample layer with a uniform predetermined thickness by pressing, comprising the following steps:

[0349] (a) The apparatus for obtaining Example A3;

[0350] (b) Depositing a fluid sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by spacers;

[0351] (c) After (b), the two plates are forced into a closed configuration, wherein at least a portion of the sample is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and adjusted by the plates and spacers.

[0352] A5. An apparatus for analyzing fluid samples, comprising:

[0353] The first board and the second board, of which:

[0354] i. The plates can be moved relative to each other to form different configurations;

[0355] ii. One or both plates are flexible;

[0356] iii. Each plate has a sample contact area on its respective surface for contacting a sample containing the analyte;

[0357] iv. One or both plates include spacers permanently fixed to the plates in the sample contact area, wherein the spacers have a substantially uniform predetermined height and a fixed predetermined spacing distance, the spacing distance being at least about 2 times larger than the size of the analyte and at most 200 μm, and wherein at least one of the spacers is located inside the sample contact area.

[0358] One of the structures is an open structure, in which: the two plates are separate, the spacing between the plates is not adjustable by spacers, and the sample is deposited on one or both plates; and

[0359] Another configuration is a closed configuration configured after sample deposition in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by two plates into a layer of very uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and adjusted by the plates and spacers.

[0360] A6. A method for forming a thin fluid sample layer with a uniform predetermined thickness by pressing, comprising the following steps:

[0361] (a) The apparatus for obtaining Example A5;

[0362] (b) Depositing a fluid sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by spacers;

[0363] (c) After (b), the two plates are forced into a closed configuration, wherein at least a portion of the sample is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and adjusted by the plates and spacers.

[0364] A7. An apparatus for forming a thin fluid sample layer with a uniform predetermined thickness by pressing, comprising:

[0365] The first plate, the second plate, and the spacer, wherein:

[0366] ix. The plates can be moved relative to each other to form different configurations;

[0367] x. One or both plates are flexible;

[0368] xi. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample;

[0369] xii. Each plate contains a region on its respective outer surface for applying forces that force the plates together;

[0370] xiii. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates;

[0371] xiv. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined fixed spacing distance equal to or less than 200 micrometers;

[0372] xv. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; and

[0373] xvi. At least one of the spacers is located inside the sample contact area;

[0374] One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates;

[0375] Another configuration is a closed configuration arranged after sample deposition in the open configuration; and in the closed configuration: at least a portion of the sample is compressed by two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area between the two plates and is adjusted by the plates and spacers. A8. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the steps of:

[0376] (a) The apparatus for obtaining Example A7;

[0377] (b) Obtain a fluid sample;

[0378] (e) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer;

[0379] (d) After (c), the two plates are forced into a closed configuration, wherein at least a portion of the sample is compressed by the two plates into a layer of substantially uniform thickness, wherein the uniform thickness of the layer is defined by the sample contact surface of the plates and adjusted by the plates and spacers.

[0380] In any of the foregoing embodiments of the apparatus or method, the spacer is in the shape of a column having feet fixed to one of the plates and a flat top surface for contacting the other plate.

[0381] In any of the foregoing embodiments of the apparatus or method, the spacer is in the shape of a column having a foot fixed to one of the plates for contacting the flat top surface of the other plate, and a substantially uniform cross-section.

[0382] In any of the foregoing embodiments of the apparatus or method, the spacer is in the shape of a column having a foot fixed to one of the plates and a flat top surface for contacting the other plate, wherein the variation of the flat top surface of the column is less than 10 nm.

[0383] In any of the foregoing embodiments of the apparatus or method, the spacer is in the shape of a column having a foot fixed to one of the plates and a flat top surface for contacting the other plate, wherein the variation of the flat top surface of the column is less than 50 nm.

[0384] In any of the foregoing embodiments of the apparatus or method, the spacer is in the shape of a column having a foot fixed to one of the plates and a flat top surface for contacting the other plate, wherein the variation of the flat top surface of the column is less than 50 nm.

[0385] In any of the preceding embodiments of the apparatus or method, the spacer is in the shape of a column having a foot fixed to one of the plates and a flat top surface for contacting the other plate, wherein the variation of the flat top surface of the column is less than 10 nm, 20 nm, 30 nm, 100 nm, 200 nm, or within any two of the values.

[0386] In any of the apparatuses or methods described in the foregoing embodiments, the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 2 MPa.

[0387] The apparatus or method of any of the foregoing embodiments, wherein the sample comprises an analyte, and a predetermined constant interval distance is at least about twice the size of the analyte, and at most 200 μm.

[0388] The apparatus or method of any of the foregoing embodiments, wherein the sample comprises an analyte, the predetermined constant spacing distance is at least about twice the size of the analyte and at most 200 μm, and the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 2 MPa.

[0389] As in any of the foregoing embodiments of the apparatus or method, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below.

[0390] As in any of the foregoing embodiments of the apparatus or method, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 1×10 6 μm 3 / GPa or below.

[0391] As in any of the foregoing embodiments of the apparatus or method, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 5 μm 3 / GPa or below.

[0392] As in any of the foregoing embodiments of the apparatus or method, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 2 MPa, and the fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD)4 / (hE)) is 1x10 5 μm 3 / GPa or below.

[0393] As in any of the foregoing embodiments of the apparatus or method, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 2 MPa, and the fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 1×10 4 μm 3 / GPa or below.

[0394] In any of the apparatuses or methods described in the foregoing embodiments, the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 20 MPa.

[0395] In any of the foregoing embodiments of the apparatus or method, the ratio of the spacing distance to the average width of the spacer is 2 or greater.

[0396] In any of the foregoing embodiments of the apparatus or method, the ratio of the spacing distance to the average width of the spacer is 2 or greater, and the Young's modulus of the spacer multiplied by the fill factor of the spacer is at least 2 MPa.

[0397] In any of the apparatuses or methods described in the foregoing embodiments, the spacing distance is at least about twice the size of the analyte, and at most 200 μm.

[0398] In any of the apparatuses or methods described in the foregoing embodiments, the ratio of the spacing distance to the width of the spacer is 1.5 or greater.

[0399] In any of the apparatuses or methods described in the foregoing embodiments, the ratio of the width to the height of the spacer is 1 or greater.

[0400] In any of the apparatuses or methods described in the foregoing embodiments, the ratio of the width to the height of the spacer is 1.5 or greater.

[0401] In any of the apparatuses or methods described in the foregoing embodiments, the ratio of the width to the height of the spacer is 2 or greater.

[0402] In any of the apparatuses or methods described in the preceding embodiments, the ratio of the width to the height of the spacer is greater than 2, 3, 5, 10, 20, 30, or 50, or within the range of any two values.

[0403] The method of any of the foregoing embodiments, wherein the force that compresses the two plates into a closed configuration is an imprecise pressure.

[0404] In any of the preceding embodiments, the force used to press the two plates into a closed configuration is an imprecise pressure provided by human hand.

[0405] The method of any of the foregoing embodiments, wherein forcing two plates to compress at least a portion of the sample into a layer having a substantially uniform thickness comprises conformally pressing a region of at least one of the plates in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on the plates at least a portion of the sample generates substantially uniform pressure, and the pressing causes at least a portion of the sample to spread laterally between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample reduces the time required to mix the reagent at the storage site with the sample.

[0406] The method of any of the foregoing embodiments, wherein the pressure is an imprecise force, the imprecise force having a magnitude that is (a) unknown and unpredictable when the force is applied, or (b) cannot be known and cannot be predicted within an accuracy equal to or better than 20% of the average pressure applied.

[0407] The method of any of the foregoing embodiments, wherein the pressure is an imprecise force, the imprecise force having a magnitude that is (a) unknown and unpredictable when the force is applied, or (b) cannot be known and cannot be predicted within an accuracy equal to or better than 30% of the average pressure applied.

[0408] The method of any of the foregoing embodiments, wherein the pressure is an imprecise force having a magnitude that is (a) unknown and unpredictable, or (b) unknowable and unpredictable within 30% of the accuracy of the applied average pressure; and wherein the layer of very uniform thickness has a uniform thickness variation of 20% or less.

[0409] The method of any of the foregoing embodiments, wherein the pressure is an imprecise force, the imprecise force having a quantity that cannot be determined when the force is applied within a range equal to or better than 30%, 40%, 50%, 70%, 100%, 200%, 300%, 500%, 1000%, 2000%, or any two of those values.

[0410] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 10 μm to 200 μm.

[0411] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 20 μm to 100 μm.

[0412] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 25 μm to 180 μm.

[0413] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 200 μm to 260 μm.

[0414] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is equal to or less than 250 μm, 225 μm, 200 μm, 175 μm, 150 μm, 125 μm, 100 μm, 75 μm, 50 μm, 25 μm, 10 μm, 5 μm, 1 μm, or within any two values.

[0415] The apparatus or method described in any of the foregoing methods, wherein the viscosity of the sample is in the range of 0.1 to 4 (mPa s).

[0416] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 200 μm to 260 μm.

[0417] The apparatus or method of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 20 μm to 200 μm and the Young's modulus is in the range of 0.1 to 5 GPa.

[0418] 45. The method of any of the preceding claims, wherein the sample deposition in step (b) is a deposition directly from the object to the plate without the use of any transfer equipment.

[0419] 46. ​​The method of any of the preceding claims, wherein the amount of sample deposited on the plate during the deposition in step (b) is unknown.

[0420] 47. The method of any of the preceding claims, wherein the method further comprises an analytical step (e) of analyzing the sample.

[0421] 48. The method of any of the preceding claims, wherein the analysis step (e) comprises calculating the volume of the relevant sample volume by measuring a lateral region of the relevant sample volume and calculating the volume from the lateral region and the height of a predetermined spacer.

[0422] 49. The method of any of the preceding claims, wherein the analytical step (e) comprises measurement:

[0423] i. Imaging, selected from photoluminescence, electroluminescence, and electrochemiluminescence.

[0424] iii. Surface Raman scattering,

[0425] iv. Resistive reactance selected from resistors, capacitors, and inductors, or

[0426] Any combination of vi-iv.

[0427] 50. The method of any of the preceding claims, wherein the analysis step (e) comprises reading, image analysis, or counting analysis, or a combination thereof.

[0428] 51. The method of any of the preceding claims, wherein the sample comprises one or more analytes, and one or two plate sample contact surfaces comprise one or more binding sites, each binding site binding and immobilizing a respective analyte.

[0429] 52. The method of any of the preceding claims, wherein one or both plate sample contact surfaces contain one or more storage sites, each storage site storing one or more reagents, wherein the reagents dissolve and diffuse in the sample during or after step (c).

[0430] 53. The method of any of the preceding claims, wherein one or both plate sample contact surfaces contain one or more amplification sites, each amplification site being capable of amplifying a signal from the analyte or a label of the analyte when the analyte or label is within 500 nm of the amplification site.

[0431] 54. The method of any of the preceding claims, wherein:

[0432] i. One or two plate sample contact surfaces contain one or more binding sites, each binding site binding and immobilizing its respective analyte; or

[0433] ii. One or two plate sample contact surfaces contain one or more storage sites, each storage site storing one or more reagents; wherein the reagents dissolve and diffuse into the sample during or after step (c), and wherein the sample contains one or more analytes; or

[0434] iii. One or more amplification sites, each amplification site being capable of amplifying a signal from the analyte or the tag when the analyte or tag is 500 nm away from the amplification site;

[0435] iv. any combination of i to iii.

[0436] 55. The apparatus or method of any of the foregoing embodiments, wherein the liquid sample is a biological sample selected from amniotic fluid, aqueous humor, vitreous fluid, blood (e.g., whole blood, graded blood, plasma, or serum), breast milk, cerebrospinal fluid (CSF), earwax, chyle, chyme, endolymph, perilymph, feces, respiration, gastric acid, gastric juice, lymph, mucus (including nasal drainage and sputum), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheumatic fluid, saliva, exhaled condensate, sebum, semen, sputum, sweat, synovial fluid, tears, vomit, and urine.

[0437] 56. The apparatus or method of any of the foregoing embodiments, wherein the uniform thickness layer in the closed structure is less than 150 μm.

[0438] 57. The method of any of the preceding claims, wherein pressurization is provided by a pressurizing liquid, a pressurizing gas, or a conformal material.

[0439] 58. The method of any of the preceding claims, wherein the analysis comprises counting cells in a layer of uniform thickness.

[0440] 59. The method of any of the preceding claims, wherein the analysis is performed in a layer of uniform thickness.

[0441] 60. The apparatus or method of any of the foregoing embodiments, wherein the determination is a binding determination or a biochemical determination.

[0442] 61. The method of any of the preceding claims, wherein the deposited sample has a total volume of less than 0.5 μL.

[0443] 62. The method of any of the preceding claims, wherein multiple droplets of sample are deposited on one or two plates.

[0444] 63. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 1 μm to 120 μm.

[0445] 64. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 120 μm to 50 μm.

[0446] 65. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 120 μm to 200 μm.

[0447] 66. The apparatus of any of the preceding claims, wherein the thickness of the flexible plate is in the range of 20 μm to 250 μm and the Young's modulus is in the range of 0.1 to 5 GPa.

[0448] 67. The apparatus of any of the preceding claims, wherein for the flexible plate, the thickness of the flexible plate multiplied by the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm.

[0449] 68. The apparatus of any of the preceding claims, wherein the uniform thickness of the sample layer is at least 1 mm. 2 The horizontal area is uniform.

[0450] 69. The apparatus of any of the preceding claims, wherein the uniform thickness sample layer is at least 3 mm. 2 The horizontal area is uniform.

[0451] 70. The apparatus of any of the preceding claims, wherein the uniform thickness of the sample layer is at least 5 mm. 2 The horizontal area is uniform.

[0452] 71. The apparatus of any of the preceding claims, wherein the uniform thickness of the sample layer is at least 10 mm. 2The horizontal area is uniform.

[0453] 72. The apparatus of any of the preceding claims, wherein the uniform thickness of the sample layer is at least 20 mm. 2 The horizontal area is uniform.

[0454] 73. The apparatus of any of the preceding claims, wherein the uniform thickness of the sample layer is 20 mm. 2 Up to 100mm 2 The horizontal area within the range is uniform.

[0455] 74. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 5% or better.

[0456] 75. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 10% or better.

[0457] 76. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 20% or better.

[0458] 77. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 30% or better.

[0459] 78. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 40% or better.

[0460] 79. The apparatus of any of the preceding apparatus claims, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 50% or better.

[0461] 80. The device of any of the preceding device claims, wherein the spacer is a column having a cross-sectional shape selected from a circle, polygon, annular, square, rectangular, oval, elliptical or any combination thereof.

[0462] 81. The device of any of the preceding device claims, wherein the spacer has a columnar shape, a substantially flat-topped surface, and a substantially uniform cross-section, wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1.

[0463] 82. The apparatus of any of the preceding apparatus claims, wherein the interval is periodic.

[0464] 83. The device of any of the preceding device claims, wherein the spacer has a fill factor of 1% or higher, wherein the fill factor is the ratio of the spacer contact area to the total plate area.

[0465] 84. The apparatus of any of the preceding claims, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 20 MPa, wherein the fill factor is the ratio of the spacer contact area to the total plate area.

[0466] 85. The apparatus of any of the preceding claims, wherein the distance between the two plates in the closed configuration is less than 200 μm.

[0467] 86. The apparatus of any of the preceding claims, wherein the spacing between the two plates in the closed configuration is a value selected between 1.8 μm and 3.5 μm.

[0468] 87. The apparatus of any of the preceding claims, wherein the spacing is fixed on the plate by means of a direct impression plate or an injection-molded plate.

[0469] 88. The device of any of the preceding device claims, wherein the material of the plate and the spacer is selected from polystyrene, PMMA, PC, COC, COP or another plastic.

[0470] 89. The device of any of the preceding device claims, wherein the spacer has a columnar shape and the sidewall corners of the spacer have a circular shape with a radius of curvature of at least 1 μm.

[0471] 90. The device according to any of the preceding device claims, wherein the spacer has a diameter of at least 1000 mm. 2 The density.

[0472] 91. The apparatus of any of the preceding device claims, wherein at least one of the plates is transparent.

[0473] 92. The apparatus of any of the preceding apparatus claims, wherein the mold for manufacturing the spacer is manufactured by a mold containing features, the features being manufactured by (a) direct reactive ion etching or ion beam etching or (b) by repeated or multiple reactive ion etching or ion beam etching features.

[0474] 93. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is in the range of 1% to 5%.

[0475] In any of the foregoing embodiments of the apparatus or method, the surface variation is relative to the spacer height, and the ratio of the column top surface variation to the spacer height is less than 0.5%, 1%, 3%, 5%, 7%, 10%, 15%, 20%, 30%, 40%, or within any two values. Preferably, the column top smoothness has a ratio of column top surface variation to spacer height of less than 2%, 5%, or 10%.

[0476] 94. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is in the range of 1% to 5%.

[0477] 95. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is in the range of 5% to 10%.

[0478] 96. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is in the range of 10% to 20%.

[0479] 97. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is in the range of 20% to 30%.

[0480] 98. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is 5%, 10%, 20%, 30%, 40%, 50%, or within any two values.

[0481] 99. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor is 50%, 60%, 70%, 80%, or within a range of any two values.

[0482] 100. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 2 MPa to 10 MPa.

[0483] 101. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 10 MPa to 20 MPa.

[0484] 102. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 20 MPa to 40 MPa.

[0485] 103. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 40 MPa to 80 MPa.

[0486] 104. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 80 MPa to 120 MPa.

[0487] 105. The apparatus or method of any of the foregoing embodiments, wherein the spacer is configured such that the fill factor multiplied by the Young's modulus of the spacer is in the range of 120 MPa to 150 MPa.

[0488] 106. The apparatus or method of any of the foregoing embodiments, wherein the apparatus further comprises a drying agent coated on one or two plates.

[0489] 107. The apparatus or method of any of the foregoing embodiments, wherein the apparatus further comprises dry binding sites having predetermined regions on one or two plates, wherein the dry binding sites bind and immobilize analytes in the sample.

[0490] 108. The apparatus or method of any of the foregoing embodiments, wherein the apparatus further comprises a releasable desiccant and a release time control material on one or two plates, the release time control material delaying the time at which the releasable desiccant is released into the sample.

[0491] 109. The apparatus of any of the foregoing embodiments, wherein the release time control material delays the time at which the drying reagent begins to be released into the sample by at least 3 seconds.

[0492] 110. The apparatus of any of the foregoing embodiments, wherein the reagent comprises an anticoagulant and / or a staining reagent.

[0493] 111. The apparatus of any of the foregoing embodiments, wherein the reagent comprises a cell lysis reagent.

[0494] 112. The apparatus or method of any of the foregoing embodiments, wherein the apparatus further comprises one or more dry binding sites and / or one or more reagent sites on one or two plates.

[0495] 113. The apparatus of any of the foregoing embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0496] 114. The apparatus of any of the foregoing embodiments, wherein the analyte comprises leukocytes, erythrocytes and platelets.

[0497] 115. The apparatus of any of the foregoing embodiments, wherein the analyte is stained.

[0498] 116. The apparatus or method of any of the foregoing embodiments, wherein the spacer of the layer of uniform thickness has a fill factor of at least 1%, wherein the fill factor is the ratio of the spacer region in contact with the layer of uniform thickness to the total plate region in contact with the layer of uniform thickness.

[0499] 117. The apparatus or method of any of the foregoing embodiments, wherein for the spacer of the uniform thickness layer, the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 10 MPa, wherein the fill factor is the ratio of the spacer region in contact with the uniform thickness layer to the total plate region in contact with the uniform thickness layer.

[0500] 118. The apparatus or method of any of the foregoing embodiments, wherein for the flexible plate, the thickness of the flexible plate multiplied by the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm.

[0501] 119. The apparatus or method of any of the foregoing embodiments, wherein for the flexible plate, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) of the flexible plate, ISD 4 / (hE) equals or is less than 10 6 μm 3 / GPa,

[0502] 120. The apparatus or method of any of the foregoing embodiments, wherein one or both plates include position marks located on or inside the surface of the plates, the position marks providing information about the position of the plates.

[0503] 121. In any of the foregoing embodiments of the apparatus or method, one or both plates include scale markings on or inside the surface of the plates, the scale markings providing information on the lateral dimensions of the sample and / or the structure of the plates.

[0504] 122. The apparatus or method of any of the foregoing embodiments, wherein one or both plates include imaging marks located on or inside the surface of the plates, the imaging marks assisting in imaging the sample.

[0505] 123. The apparatus or method of any of the foregoing embodiments, wherein the spacer serves as a position marker, a scale marker, an imaging marker, or any combination thereof.

[0506] 124. The apparatus or method of any of the foregoing embodiments, wherein the average thickness of the uniform thickness layer is approximately equal to the minimum size of the analyte in the sample.

[0507] 125. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 7 μm to 50 μm.

[0508] 126. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 50 μm to 120 μm.

[0509] 127. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 120 μm to 200 μm (micrometers).

[0510] 128. The apparatus or method of any of the foregoing embodiments, wherein the interval distance is substantially periodic.

[0511] 129. The apparatus or method of any of the foregoing embodiments, wherein the spacer is a column having a cross-sectional shape selected from a circle, polygon, annulus, square, rectangle, oval, ellipse or any combination thereof.

[0512] 130. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a columnar shape and a substantially flat-topped surface, wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1.

[0513] 131. The apparatus or method of any of the foregoing embodiments, wherein each spacer has a ratio of the spacer's lateral dimension to its height of at least 1.

[0514] 132. The apparatus or method of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is less than or substantially equal to the minimum dimension of the analyte in the sample.

[0515] 133. The apparatus or method of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is in the range of 0.5 μm to 100 μm.

[0516] 134. The apparatus or method of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is in the range of 0.5 μm to 10 μm.

[0517] 135. The apparatus or method of any of the foregoing embodiments, wherein the sample is blood.

[0518] 136. The apparatus or method of any of the foregoing embodiments, wherein the sample is whole blood that has not been diluted with liquid.

[0519] 137. The apparatus or method of any of the foregoing embodiments, wherein the sample is a biological sample selected from amniotic fluid, aqueous humor, vitreous fluid, blood (e.g., whole blood, graded blood, plasma, or serum), breast milk, cerebrospinal fluid (CSF), earwax, chyle, chyme, endolymph, perilymph, feces, respiration, gastric acid, gastric juice, lymph, mucus (including nasal drainage and sputum), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheumatic fluid, saliva, exhaled condensate, sebum, sebum, sputum, sweat, synovial fluid, tears, vomit, and urine.

[0520] 138. The apparatus or method of any of the foregoing embodiments, wherein the sample is a biological sample, an environmental sample, a chemical sample, or a clinical sample.

[0521] 139. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a columnar shape and the sidewall corners of the spacer have a circular shape with a radius of curvature of at least 1 μm.

[0522] 140. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a thickness of at least 100 mm. 2 The density.

[0523] 141. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a diameter of at least 1000 mm. 2 The density.

[0524] 142. The apparatus or method of any of the foregoing embodiments, wherein at least one of the plates is transparent.

[0525] 143. The apparatus or method of any of the foregoing embodiments, wherein at least one of the plates is made of a flexible polymer.

[0526] 144. The apparatus or method of any of the foregoing embodiments, wherein for pressure on the compression plate, the spacer is incompressible and / or independently, only one of the plates is flexible.

[0527] 145. The apparatus of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 10 μm to 200 μm.

[0528] 146. The apparatus or method as described in any of the foregoing embodiments, wherein the variation is less than 30%.

[0529] 147. The apparatus or method as described in any of the foregoing embodiments, wherein the variation is less than 10%.

[0530] 148. The apparatus or method as described in any of the foregoing embodiments, wherein the variation is less than 5%.

[0531] 149. The apparatus or method of any of the foregoing embodiments, wherein the first plate and the second plate are connected and configured to change from an open configuration to a closed configuration by means of a folding plate.

[0532] 150. The apparatus or method of any of the foregoing embodiments, wherein the first plate and the second plate are connected by a hinge and configured to change from an open configuration to a closed configuration by folding the plates along the hinge.

[0533] 151. The apparatus or method of any of the foregoing embodiments, wherein the first plate and the second plate are connected to the plate by a hinge, the hinge being a separate material and configured to change from an open configuration to a closed configuration by folding the plate along the hinge.

[0534] 152. The apparatus or method of any of the foregoing embodiments, wherein the first plate and the second plate are made of a single sheet material and are configured to change from an open configuration to a closed configuration by folding the plate.

[0535] 153. The apparatus or method of any of the foregoing embodiments, wherein the uniform thickness of the sample layer is at least 1 mm. 2 The horizontal area is uniform.

[0536] 154. The apparatus or method of any of the foregoing embodiments, wherein the apparatus is configured to analyze a sample in 60 seconds or less.

[0537] 155. The apparatus or method of any of the foregoing embodiments, wherein, in a closed configuration, the final sample thickness device is configured to analyze the sample in 60 seconds or less.

[0538] 156. The apparatus or method of any of the foregoing embodiments, wherein, in a closed configuration, the final sample thickness device is configured to analyze the sample in 10 seconds or less.

[0539] 157. The apparatus or method of any of the foregoing embodiments, wherein the dry binding site comprises a trapping agent.

[0540] 158. The apparatus or method of any of the foregoing embodiments, wherein the stem binding site comprises an antibody or nucleic acid.

[0541] 159. The apparatus or method of any of the foregoing embodiments, wherein the releasable drying agent is a labeled agent.

[0542] 160. The apparatus or method of any of the foregoing embodiments, wherein the releasable drying reagent is a fluorescently labeled reagent.

[0543] 161. The apparatus or method of any of the foregoing embodiments, wherein the releasable drying reagent is a fluorescently labeled antibody.

[0544] 162. The apparatus or method of any of the foregoing embodiments, wherein the releasable drying agent is a cell staining agent.

[0545] 163. The apparatus or method of any of the foregoing embodiments, wherein the releasable drying agent is a cell lysis agent.

[0546] 164. The apparatus or method of any of the foregoing embodiments, wherein the detector is a photodetector for detecting optical signals.

[0547] 165. The apparatus or method of any of the foregoing embodiments, wherein the detector is an electrical detector for detecting electrical signals.

[0548] 166. The apparatus of any of the foregoing embodiments, wherein the spacing is fixed on the plate by a direct imprint plate or an injection-molded plate.

[0549] 167. The apparatus of any of the foregoing embodiments, wherein the materials of the plates and spacers are selected from polystyrene, PMMA, PC, COC, COP or another plastic.

[0550] 168. A system for rapidly analyzing samples using a mobile phone, comprising:

[0551] (a) The apparatus as described in any of the foregoing embodiments;

[0552] (b) A mobile communication device comprising:

[0553] i. One or more cameras used to detect and / or image a sample;

[0554] ii. Electronic devices, signal processors, hardware, and software for receiving and / or processing detected signals and / or images of samples and for remote communication; and

[0555] (c) A light source from a mobile communication device or an external source;

[0556] In any of the foregoing embodiments, the detector of the apparatus or method is provided by a mobile communication device and detects the analyte in the sample in a closed configuration.

[0557] 169. A system as described in any of the foregoing system embodiments, wherein one of the plates has binding sites for the analyte, wherein at least a portion of a uniform sample thickness layer is above the binding sites and is substantially smaller than the average lateral linear dimension of the binding sites.

[0558] 170. The system of any of the foregoing system embodiments further comprises:

[0559] (d) Housing configured to hold the sample and to be installed on the mobile communication device.

[0560] 171. The system of any of the foregoing system embodiments, wherein the housing includes optics for facilitating imaging and / or signal processing of the sample by the mobile communication device, and a base configured to hold the optics on the mobile communication device.

[0561] 172. The system of any of the foregoing system embodiments, wherein the elements of the optical devices in the housing are movable relative to the housing.

[0562] 173. The system of any of the foregoing system embodiments, wherein the mobile communication device is configured to transmit test results to medical professionals, medical institutions or insurance companies.

[0563] 174. The system of any of the foregoing system embodiments, wherein the mobile communication device is further configured to transmit information about the test and the subject to medical professionals, medical institutions or insurance companies.

[0564] 175. The system of any of the foregoing system embodiments, wherein the mobile communication device is further configured to transmit test information to a cloud network, and the cloud network processes the information to improve the test results.

[0565] 176. The system of any of the foregoing system embodiments, wherein the mobile communication device is further configured to transmit information of the test and the subject to a cloud network, the cloud network processing the information to improve the test results, and the improved test results being sent back to the subject.

[0566] 177. A system as described in any of the foregoing system embodiments, wherein the mobile communication device is configured to receive prescriptions, diagnoses, or advice from a medical professional.

[0567] 178. The system of any of the foregoing system embodiments, wherein the mobile communication device is configured with hardware and software to:

[0568] (a) Capture an image of the sample;

[0569] (b) Analyze the test and control positions in the images; and

[0570] (c) The values ​​obtained from the analysis of the test location are compared with the thresholds that characterize the rapid diagnostic test.

[0571] 179. The system of any of the foregoing system embodiments, wherein at least one of the plates includes a storage site for storing the assay reagent.

[0572] 180. In any of the foregoing system embodiments, at least one camera reads signals from the device.

[0573] 181. The system of any of the foregoing system embodiments, wherein the mobile communication device communicates with a remote location via WiFi or a cellular network.

[0574] 182. The system of any of the foregoing system embodiments, wherein the mobile communication device is a mobile phone.

[0575] 183. A method for rapidly analyzing analytes in a sample using a mobile phone, comprising:

[0576] (a) Depositing a sample onto the apparatus of any of the foregoing system embodiments;

[0577] (b) to determine the analytes in the sample deposited on the device to produce results; and

[0578] (c) Transmit the results from the mobile communication device to a location remote from the mobile communication device.

[0579] 184. The method of any of the foregoing embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0580] 185. The method of any of the foregoing embodiments, wherein the analyte comprises leukocytes, erythrocytes and platelets.

[0581] 186. The method of any of the foregoing embodiments, wherein the determination includes performing a white blood cell differential assay.

[0582] 187. The method of any of the foregoing embodiments, wherein the method comprises:

[0583] Analyze results at remote locations to provide analytical results; and

[0584] The analysis results are transmitted from a remote location to a mobile communication device.

[0585] 188. The method of any of the foregoing embodiments, wherein the analysis is performed by a medical professional at a remote location.

[0586] 189. The method of any of the foregoing embodiments, wherein the mobile communication device receives a prescription, diagnosis, or advice from a medical professional at a remote location.

[0587] 190. The method of any of the foregoing embodiments, wherein the sample is a body fluid.

[0588] 191. The method of any of the foregoing embodiments, wherein the body fluid is blood, saliva, or urine.

[0589] 192. The method of any of the foregoing embodiments, wherein the sample is whole blood that has not been diluted with liquid.

[0590] 193. The method of any of the foregoing embodiments, wherein the analytical step comprises detecting an analyte in the sample.

[0591] 194. The method of any of the foregoing embodiments, wherein the analyte is a biomarker.

[0592] 195. The method of any of the foregoing embodiments, wherein the analyte is a protein, nucleic acid, cell, or metabolite.

[0593] 196. The method of any of the foregoing embodiments, wherein the method comprises counting the number of red blood cells.

[0594] 197. The method of any of the foregoing embodiments, wherein the method includes counting the number of white blood cells.

[0595] 198. The method of any of the foregoing embodiments, wherein the method comprises staining cells in a sample and counting the number of neutrophils, lymphocytes, monocytes, eosinophils and basophils.

[0596] 199. The method of any of the foregoing embodiments, wherein the determination performed in step (b) is a binding assay or a biochemical assay.

[0597] 200. A method for analyzing a sample, comprising:

[0598] An apparatus for obtaining any of the foregoing embodiments of the apparatus;

[0599] Deposit the sample onto one or two plates of the device;

[0600] Placing the plate in a closed structure and applying an external force to at least a portion of the plate; and

[0601] Analyze layers of uniform thickness when the plate is in a closed structure.

[0602] 201. The apparatus or method of any of the foregoing embodiments, wherein the first plate further includes a first predetermined measurement site and a second predetermined measurement site on its surface, wherein when the plate is in a closed position, the distance between the edges of the measurement sites is significantly greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the predetermined measurement sites, and wherein the sample has one or more analytes capable of diffusing in the sample.

[0603] 202. The apparatus or method of any of the foregoing embodiments, wherein the first plate has at least three analyte measurement sites on its surface, and when the plate is in a closed position, the distance between the edges of any two adjacent measurement sites is much greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes that are capable of diffusing in the sample.

[0604] 203. The apparatus or method of any of the foregoing embodiments, wherein the first plate has at least two adjacent analyte measurement sites (not separated by a certain distance) on its surface, the distance being substantially greater than the thickness of the uniform thickness layer when the plate is in the closed position, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes capable of diffusing in the sample.

[0605] 204. The apparatus or method of any of the foregoing embodiments, wherein the analyte determination region is located between a pair of electrodes.

[0606] 205. The apparatus or method of any of the foregoing embodiments, wherein the measurement area is defined by a patch of drying reagent.

[0607] 206. The apparatus or method of any of the foregoing embodiments, wherein the measurement region is bound to and immobilizes the analyte.

[0608] 207. The apparatus or method of any of the foregoing embodiments, wherein the measurement area is defined by a binding reagent patch that, upon contact with the sample, dissolves into the sample, diffuses into the sample, and binds to the analyte.

[0609] 208. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 14 μm to 200 μm.

[0610] 209. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is in the range of 7 μm to 20 μm.

[0611] 210. The apparatus or method of any of the foregoing embodiments, wherein the spacer is a column having a cross-sectional shape selected from a circle, polygon, annulus, square, rectangle, oval, ellipse or any combination thereof.

[0612] 211. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a columnar shape and a substantially flat-topped surface, wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1.

[0613] 212. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a columnar shape and the sidewall corners of the spacer have a circular shape with a radius of curvature of at least 1 μm.

[0614] 213. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a diameter of at least 1000 mm. 2 The density.

[0615] 214. The apparatus or method of any of the foregoing embodiments, wherein at least one of the plates is transparent.

[0616] 215. The apparatus or method of any of the foregoing embodiments, wherein at least one of the plates is made of a flexible polymer.

[0617] 216. The apparatus or method of any of the foregoing embodiments, wherein only one of the plates is flexible.

[0618] The apparatus of any of the foregoing embodiments, wherein the region determination device is a camera.

[0619] + The region determining device includes a region within the sample contact area of ​​the plate, wherein the region is smaller than 1 / 100, 1 / 20, 1 / 10, 1 / 6, 1 / 5, 1 / 4, 1 / 3, 1 / 2, 2 / 3 of the sample contact area, or within a range between any two values.

[0620] + The region determination device includes a region in the sample contact area of ​​the camera and plate, wherein the region is in contact with the sample.

[0621] The apparatus or method of any of the foregoing embodiments, wherein the deformable sample comprises a liquid sample.

[0622] The apparatus or method of any of the foregoing embodiments, wherein the variation of the imprecise force is at least 30% of the total force actually applied.

[0623] The apparatus or method of any of the foregoing embodiments, wherein the variation of the imprecise force is at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%, 500% of the total force actually applied, or within any two values.

[0624] 217. The apparatus or method of any of the foregoing embodiments, wherein the spacer has a flat top.

[0625] 218. The apparatus or method of any of the foregoing embodiments, wherein the apparatus is further configured to have a sample thickness with thickness and uniformity substantially the same after the pressure is removed as when the force is applied.

[0626] 219. The apparatus or method of any of the foregoing embodiments, wherein the imprecise force is provided by hand.

[0627] 220. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is substantially constant.

[0628] 221. The apparatus or method of any of the foregoing embodiments, wherein the spacing distance is substantially periodic in the region of uniform sample thickness.

[0629] 222. The apparatus or method of any of the foregoing embodiments, wherein the product of the fill factor and the Young's modulus of the spacer is 2 MPa or greater.

[0630] 223. The apparatus or method of any of the foregoing embodiments, wherein the force is applied directly or indirectly by hand.

[0631] 224. The apparatus or method of any of the foregoing embodiments, wherein the applied force is in the range of 5N to 20N.

[0632] 225. The apparatus or method of any of the foregoing embodiments, wherein the thickness variation of the highly uniform layer is less than 15%, 10%, or 5% of the average thickness.

[0633] 226. The apparatus or method of any of the foregoing embodiments, wherein the imprecise force is applied by clamping the apparatus between the thumb and forefinger.

[0634] 227. The apparatus or method of any of the foregoing embodiments, wherein the predetermined sample thickness is greater than the height of the spacer.

[0635] 228. The apparatus or method of any of the foregoing embodiments, wherein the apparatus retains itself in a closed configuration after the pressure is removed.

[0636] 229. The apparatus or method of any of the foregoing embodiments, wherein the region of the uniform thickness sample layer is larger than the region of applied pressure.

[0637] 230. The apparatus or method of any of the foregoing embodiments, wherein the spacer does not significantly deform during the application of pressure.

[0638] 231. The apparatus or method of any of the foregoing embodiments, wherein the pressure is not predetermined and is not measured.

[0639] 232. The apparatus of any of the foregoing embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0640] 233. The apparatus of any of the foregoing embodiments, wherein the analyte comprises white blood cells, red blood cells and platelets.

[0641] 234. The apparatus of any of the foregoing embodiments, wherein the analyte is stained.

[0642] 235. The method or apparatus of any of the foregoing embodiments, wherein the spacing distance (SD) is equal to or less than about 120 μm (micrometers).

[0643] 236. The method or apparatus of any of the foregoing embodiments, wherein the spacing distance (SD) is equal to or less than about 100 μm (micrometers).

[0644] 237. The method or apparatus of any of the foregoing embodiments, wherein the fourth power of the spacing distance (ISD) is divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below.

[0645] 238. The method or apparatus of any of the foregoing embodiments, wherein the fourth power of the spacing distance (ISD) is divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 5 μm 3 / GPa or below.

[0646] 239. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape, a substantially flat top surface, a predetermined substantially uniform height and a predetermined constant spacing distance, the spacing distance being at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 2 MPa, wherein the fill factor is the ratio of the spacer contact area to the total plate area, and wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (1).

[0647] 240. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape, a substantially flat top surface, a predetermined substantially uniform height, and a predetermined constant spacing distance, the spacing distance being at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 2 MPa, wherein the fill factor is the ratio of the spacer contact area to the total plate area, and wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (1), wherein the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below.

[0648] 241. The apparatus of any of the foregoing embodiments, wherein the ratio of the spacing distance of the spacers to the average width of the spacers is 2 or greater, and the fill factor of the spacers multiplied by the Young's modulus of the spacers is 2 MPa or greater.

[0649] 242. The method or apparatus of any of the foregoing embodiments, wherein the analyte is an analyte for detecting proteins, peptides, nucleic acids, synthetic compounds and inorganic compounds.

[0650] 243. The method or apparatus of any of the foregoing embodiments, wherein the sample is a biological sample selected from amniotic fluid, aqueous humor, vitreous fluid, blood (e.g., whole blood, graded blood, plasma or serum), breast milk, cerebrospinal fluid (CSF), earwax, chyle, chyme, endolymph, perilymph, feces, respiration, gastric acid, gastric juice, lymph, mucus (including nasal drainage and sputum), pericardial fluid, peritoneal fluid, pleural fluid, pus, rheumatic fluid, saliva, exhaled condensate, sebum, semen, sputum, sweat, synovial fluid, tears, vomit, and urine.

[0651] 244. The method or apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape and the ratio of the width to the height of the column is equal to or greater than 1.

[0652] 245. The method of any of the foregoing embodiments, wherein the sample deposited on one or two plates has an unknown volume.

[0653] 246. The method or apparatus of any of the foregoing embodiments, wherein the sample is used to detect, purify and quantify compounds or biomolecules associated with certain disease stages.

[0654] 247. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with infectious and parasitic diseases, injuries, cardiovascular diseases, cancer, mental disorders, neuropsychiatric disorders, lung diseases, kidney diseases, and other organic diseases.

[0655] 248. The method or apparatus of any of the foregoing embodiments, wherein the sample involves the detection, purification and quantification of microorganisms.

[0656] 249. The method or apparatus of any of the foregoing embodiments, wherein the sample involves viruses, fungi, and bacteria from the environment (e.g., water, soil, or biological samples).

[0657] 250. The method or apparatus of any of the foregoing embodiments, wherein the sample involves the detection and quantification of a compound or biological sample (e.g., toxic waste, anthrax) that poses a threat to food safety or national security.

[0658] 251. The method or apparatus of any of the foregoing embodiments, wherein the sample is correlated with the quantification of vital parameters in medical or physiological monitoring.

[0659] 252. The method or apparatus of any of the foregoing embodiments, wherein the sample is related to glucose, blood, oxygen level, or total blood cell count.

[0660] 253. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with the detection and quantification of specific DNA or RNA from a biological sample.

[0661] 254. The method or apparatus of any of the foregoing embodiments, wherein the sample is associated with the sequencing and comparison of genetic sequences of DNA in chromosomes and mitochondria for genomic analysis.

[0662] 255. The method or apparatus of any of the foregoing embodiments, wherein the sample relates to, for example, detecting reaction products during drug synthesis or purification.

[0663] 256. The method or apparatus of any of the foregoing embodiments, wherein the sample is cells, tissue, body fluid, or feces.

[0664] 257. The method or apparatus of any of the foregoing embodiments, wherein the sample is a sample for detecting proteins, peptides, nucleic acids, synthetic compounds, or inorganic compounds.

[0665] 258. The method or apparatus of any of the foregoing embodiments, wherein the sample is a sample in the fields of human, veterinary, agricultural, food, environmental and pharmaceutical testing.

[0666] 259. The method or apparatus of any of the foregoing embodiments, wherein the sample is a biological sample selected from the group consisting of: blood, serum, plasma, nasal swabs, nasopharyngeal washings, saliva, urine, gastric juice, cerebrospinal fluid, tears, feces, mucus, sweat, earwax, oil, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, interstitial fluid derived from tumor tissue, eye discharge, cerebrospinal fluid, throat swabs, respiration, hair, nails, skin, biopsy, placental fluid, amniotic fluid, umbilical cord blood, lymph, cavity fluid, sputum, pus, microbiota, meconium, breast milk, exhaled condensate, nasopharyngeal washings, throat swabs, fecal samples, hair, nails, earwax, respiration, connective tissue, muscle tissue, nerve tissue, epithelial tissue, cartilage, cancer samples, or bone.

[0667] 260. The apparatus or method of any of the foregoing embodiments, wherein the spacer of the layer of uniform thickness has a fill factor of at least 1%, wherein the fill factor is the ratio of the spacer region in contact with the layer of uniform thickness to the total plate region in contact with the layer of uniform thickness.

[0668] Q Card Manufacturing

[0669] One embodiment of the MA1.Q card includes: a first plate, a second plate, and a hinge, wherein...

[0670] i. A first plate having a thickness of approximately 200 nm to 1500 nm, having on its inner surface (a) a sample contact area for contacting the sample, and (b) a sample overflow dam surrounding the sample contact area, configured to present a sample flow outside the dam;

[0671] ii. A second plate, having a thickness of 10 μm to 250 μm, and having on its inner surface (a) a sample contact area for contacting a sample, and (b) a spacer on the sample contact area;

[0672] iii. The hinge connecting the first plate and the second plate; and

[0673] The first and second plates are movable relative to each other about the axis of the hinge.

[0674] One embodiment of the MA2.Q card includes: a first plate, a second plate, and a hinge, wherein...

[0675] i. A first plate having a thickness of approximately 200 nm to 1500 nm, having on its inner surface (a) a sample contact area for contacting a sample, (b) a sample overflow dam surrounding the sample contact area, configured to present a sample flow outside the dam, and (c) a spacer on the sample contact area.

[0676] ii. A second plate, 10 μm to 250 μm thick, having a sample contact area on its inner surface for contacting the sample;

[0677] iii. The hinge connecting the first plate and the second plate; and

[0678] The first and second plates are movable relative to each other about the axis of the hinge.

[0679] One embodiment of the MA3.Q card includes: a first plate, a second plate, and a hinge, wherein...

[0680] i. A first plate having a thickness of about 200 nm to 1500 nm, having on its inner surface (a) a sample contact area for contacting a sample, and (b) a spacer on the sample contact area;

[0681] ii. A second plate, having a thickness of 10 μm to 250 μm, having on its inner surface (a) a sample contact area for contacting the sample, and (b) a sample overflow dam surrounding the sample contact area, configured to present a sample flow outside the dam; and

[0682] iii. The hinge connecting the first plate and the second plate; and

[0683] The first and second plates are movable relative to each other about the axis of the hinge.

[0684] One embodiment of the MA4.Q card includes: a first plate, a second plate, and a hinge, wherein...

[0685] i. A first plate having a thickness of approximately 200 nm to 1500 nm, having on its inner surface (a) a sample contact area for contacting the sample;

[0686] ii. A second plate, having a thickness of 10 μm to 250 μm, having on its inner surface (a) a sample contact area for contacting the sample, (b) a sample overflow dam surrounding the sample contact area, configured to present a sample flow outside the dam; and (c) spacers on the sample contact area; and

[0687] iii. The hinge connecting the first plate and the second plate; and

[0688] The first and second plates are movable relative to each other about the axis of the hinge.

[0689] M1. An embodiment of a method for manufacturing a Q card according to any one of the embodiments of MA1 to MA4, comprising:

[0690] (a) Injection molding of the first plate,

[0691] (b) Nanoimprinting or extrusion printing of the second plate.

[0692] M2. An embodiment of a method for manufacturing a Q card according to any one of the embodiments of MA1 to MA4, comprising:

[0693] (a) Laser cutting of the first plate.

[0694] (b) Nanoimprinting or extrusion printing of the second plate.

[0695] M3. An embodiment of a method for manufacturing a Q card for any of the embodiments of MA1 to MA4, comprising:

[0696] (a) Injection molding and laser cutting of the first plate.

[0697] (b) Nanoimprinting or extrusion printing of the second plate.

[0698] M4. An embodiment of a method for manufacturing a Q card according to any of the embodiments of MA1 to MA4, comprising: nanoimprinting or extrusion printing to manufacture both a first plate and a second plate.

[0699] M5. An embodiment of a method for manufacturing a Q card for any of the embodiments of MA1 to MA4, comprising: manufacturing a first plate or a second plate using injection molding, laser cutting of a first plate, nanoimprinting, extrusion printing, or a combination thereof.

[0700] The method of any one of embodiments M1-M5, wherein the method further includes the step of attaching the hinge to the first plate and the second plate after manufacturing the first plate and the second plate.

[0701] Apparatus and system for collecting and analyzing vapor condensate, particularly exhaled respiration condensate, and method of use thereof. This invention provides an apparatus for collecting and analyzing vapor condensate (VC) samples, the apparatus comprising:

[0702] Collection plate, cover plate and spacer, wherein:

[0703] i. The plates can be moved relative to each other to form different configurations;

[0704] ii. One or both plates are flexible;

[0705] iii. Each plate has a sample contact area on its respective inner surface for contacting the vapor condensate (VC) sample containing the analyte;

[0706] iv. Spacers are fixed to one or both of the corresponding inner surfaces of the plates and have a predetermined substantially uniform height and a predetermined constant spacing distance, wherein at least one of the spacers is located inside the sample contact area;

[0707] One of the configurations is an open configuration, in which the two plates are completely or partially separated, the spacing between the plates is not adjusted by spacers, and the VC sample is deposited on one or both plates; and

[0708] Another aspect of the configuration is a closed configuration configured after the VC sample is deposited in the open configuration; and in this closed configuration: at least a portion of the VC sample is between and in contact with the two plates, and has a very uniform thickness, which is adjusted by the spacer and the two sample surfaces of the plates and is equal to or less than 30 μm with minimal variation.

[0709] Another apparatus for collecting and analyzing vapor condensate (VC) samples is provided herein, the apparatus comprising:

[0710] Collection plate and cover plate, wherein:

[0711] i. The plates can be moved relative to each other to form different configurations;

[0712] ii. One or both plates are flexible; and

[0713] iii. Each plate has a sample contact area on its respective surface for contacting the vapor condensate (VC) sample containing the analyte;

[0714] One of the structures is an open structure, in which the two plates are completely or partially separated, and the VC sample is deposited on one or both plates; and

[0715] Another aspect of the configuration is a closed configuration configured after the VC sample is deposited in the open configuration; and in the closed configuration, at least a portion of the VC sample is between and in contact with the two plates, and has a thickness adjusted by the plate spacing.

[0716] In some embodiments, the device further includes one or more dry binding sites and / or one or more reagent sites on one or two plates. In some embodiments, the sample is exhaled condensate.

[0717] In some embodiments, the sample is a vapor from a biological sample, environmental sample, chemical sample, or clinical sample. In some embodiments, the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids, or other molecules), cells, tissues, viruses, and nanoparticles of different shapes. In some embodiments, the analyte comprises volatile organic compounds (VOCs). In some embodiments, the analyte comprises nitrogen, oxygen, CO2, H2O, and inert gases. In some embodiments, the analyte is stained.

[0718] In some embodiments, the device may include a drying reagent coated on one or two plates. In some embodiments, the drying reagent may bind to an analyte in the blood and immobilize the analyte on the surface of one or two plates. In these embodiments, the reagent may be, for example, an antibody or other specific binding agent. The drying reagent may have a predetermined area. In other embodiments, the device may include a releasable drying reagent, such as a labeled reagent like a cell dye or a labeled detection reagent like an antibody, on one or more plates. In some cases, a release time control material may be present on the plates containing the releasable drying reagent, wherein the release time control material delays the time it takes for the releasable drying reagent to be released into the blood sample.

[0719] In some cases, the release time control material delays the release of the drying reagent into the blood sample by at least 3 seconds, such as at least 5 seconds or at least 10 seconds. In some embodiments, the actuator may contain multiple dry binding sites and / or multiple reagent sites, thereby allowing for multiple assays. In some cases, when the plate is in the closed position, the area occupied by the dry binding sites may be opposite the area occupied by the reagent sites.

[0720] In some embodiments, the reagent comprises a labeling or staining reagent.

[0721] In some embodiments, the spacers of the uniformly thick layer (i.e., spacers that separate the plates from each other in the layer) have a “fill factor” of at least 1%, for example at least 2% or at least 5%, wherein the fill factor is the ratio of the spacer area in contact with the uniformly thick layer to the total plate area in contact with the uniformly thick layer. In some embodiments, for the spacers of the uniformly thick layer, the Young's modulus of the spacers multiplied by the fill factor of the spacers is equal to or greater than 10 MPa, for example at least 15 MPa or at least 20 MPa, wherein the fill factor is the ratio of the spacer area in contact with the uniformly thick layer to the total plate area in contact with the uniformly thick layer. In some embodiments, the thickness of the flexible plate multiplied by the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm, for example 100 to 300 GPa-μm, 300 to 550 GPa-μm, or 550 to 750 GPa-μm. In some embodiments, for a flexible plate, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) of the flexible plate, ISD 4 / (hE) equals or is less than 10 6 μm 3 / GPa, for example, less than 10 5 μm 3 / GPa, less than 10 4 μm 3 / GPa or less than 10 3 μm 3 / GPa.

[0722] In some embodiments, one or both plates include position marks located on or within the surface of the plates, providing information about the plate's position, such as the location to be analyzed or the location where blood should be deposited. In some cases, one or both plates may include scale marks on or within the surface of the plates, providing information about the lateral dimensions of the blood sample and / or the plate's structure. In some embodiments, one or both plates include imaging marks on or within the surface of the plates, which facilitate the imaging of the sample. For example, imaging marks can help focus an imaging device or guide the imaging device to a location on the device. In some embodiments, spacers can be used as position marks, scale marks, imaging marks, or any combination thereof.

[0723] In some embodiments, one of the sample surfaces further includes a sealing spacer encapsulating part or all of the VC sample deposited on the collection plate.

[0724] In some embodiments, the very uniform thickness has a value equal to or less than 0.5 μm. In some embodiments, the very uniform thickness has a value of 0.5 μm-1 μm, 1 μm-2 μm, 2 μm-10 μm, 10 μm-20 μm, or 20 μm-30 μm.

[0725] In some embodiments, the thickness of at least a portion of the VC sample in a closed configuration is greater than the thickness of the VC sample deposited on the collection plate in an open configuration.

[0726] In some embodiments, the thickness of at least a portion of the VC sample in a closed configuration is less than the thickness of the VC sample deposited on the collection plate in an open configuration.

[0727] In some embodiments, the spacer is fixed to the plate by a direct imprint plate or an injection-molded plate.

[0728] In some embodiments, the materials of the plates and spacers are selected from polystyrene, PMMA, PC, COC, COP, or another plastic.

[0729] In some embodiments, the interval distance is 1μm-50μm, 50μm-100μm, 100μm-200μm, or 200μm-1000μm.

[0730] In some embodiments, the VC sample is exhaled condensate from a human or animal.

[0731] In some embodiments, the spacers of the uniformly thick layer have a fill factor of at least 1%, wherein the fill factor is the ratio of the spacer region in contact with the uniformly thick layer to the total plate region in contact with the uniformly thick layer.

[0732] In some embodiments, for spacers with a uniform thickness layer, the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 10 MPa, wherein the fill factor is the ratio of the spacer region in contact with the uniform thickness layer to the total plate region in contact with the uniform thickness layer.

[0733] In some embodiments, for flexible plates, the thickness of the flexible plate multiplied by the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm.

[0734] In some embodiments, for a flexible plate, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) of the flexible plate, ISD 4 / (hE) equals or is less than 10 6 μm 3 / GPa.

[0735] In some embodiments, one or both plates include location markers located on or inside the surface of the plates, the location markers providing information about the position of the plates.

[0736] In some embodiments, one or two plates may include scale markings on or inside the plates that provide information on the lateral dimensions of the sample and / or plate structure.

[0737] In some embodiments, one or both plates contain imaging markers on or inside the plates that facilitate the imaging of the sample.

[0738] In some embodiments, the spacer is used as a position marker, scale marker, imaging marker, or any combination thereof.

[0739] In some embodiments, the average thickness of the uniform thickness layer is approximately equal to the minimum size of the analyte in the sample.

[0740] In some embodiments, the interval distance is 1 μm or less, 5 μm or less, 7 μm or less, 10 μm or less, 20 μm or less, 30 μm or less, 40 μm or less, 50 μm or less, 60 μm or less, 70 μm or less, 80 μm or less, 90 μm or less, 100 μm or less, 200 μm or less, 300 μm or less, 400 μm or less, or within any two of these values.

[0741] In some embodiments, the interval is substantially periodic.

[0742] In some embodiments, the interval is non-periodic.

[0743] In some embodiments, the spacer is a column with a cross-sectional shape selected from a circle, polygon, annular, square, rectangular, oval, elliptical, or any combination thereof.

[0744] In some embodiments, the spacer has a columnar shape and a substantially flat-topped surface, wherein for each spacer, the ratio of its lateral dimension to its height is at least 1.

[0745] In some embodiments, each spacer has a ratio of the spacer's lateral dimension to its height of at least 1.

[0746] In some embodiments, the minimum lateral dimension of the spacer is less than or substantially equal to the minimum dimension of the analyte in the sample.

[0747] In some embodiments, the minimum lateral dimension of the spacer is in the range of 0.5 μm to 100 μm.

[0748] In some embodiments, the minimum lateral dimension of the spacer is in the range of 0.5 μm to 10 μm.

[0749] In some embodiments, the spacer has a thickness of at least 100 mm. 2 The density. In some embodiments, the spacers have a density of at least 1000 / mm. 2 The density. In some embodiments, at least one of the plates is transparent.

[0750] In some embodiments, at least one plate is made of a flexible polymer.

[0751] In some embodiments, the spacers are incompressible and / or, independently, only one of the plates is flexible, in response to the pressure that compresses these plates.

[0752] In some embodiments, the thickness of the flexible plate is from 10 μm to 200 μm (e.g., about 10 μm, 25 μm, 50 μm, 75 μm, 100 μm, 125 μm, 150 μm, 175 μm).

[0753] In some embodiments, the variation is less than 30%, 10%, 5%, 3%, or 1%.

[0754] In some embodiments, the first plate and the second plate are connected and configured to change from an open structure to a closed structure by folding the plate.

[0755] In some embodiments, the first plate and the second plate are connected by a hinge and configured to change from an open configuration to a closed configuration by folding the plate along the hinge.

[0756] In some embodiments, the first plate and the second plate are connected to the plate by a hinge, the hinge being a separate material and configured to change from an open configuration to a closed configuration by folding the plate along the hinge.

[0757] In some embodiments, the first and second plates are made of a single piece of material and are configured to change from an open structure to a closed structure by folding the plates.

[0758] In some embodiments, the uniform thickness of the sample layer is at least 100 μm. 2 The horizontal area is uniform.

[0759] In some embodiments, the uniform thickness of the sample layer is at least 1 mm. 2 The horizontal area is uniform.

[0760] In some embodiments, the device is configured to analyze a sample in 60 seconds or less.

[0761] In some embodiments, in a closed configuration, the final sample thickness device is configured to analyze the sample in 60 seconds or less.

[0762] In some embodiments, the device further includes one or more amplification sites on one or two plates, each amplification site being capable of amplifying the signal from the analyte or the analyte's label when the analyte or label is within 500 nm of the amplification site.

[0763] In some embodiments, in a closed configuration, the final sample thickness device is configured to analyze the sample in 10 seconds or less.

[0764] In some embodiments, the dry binding site comprises a trapping agent.

[0765] In some embodiments, the drying binding site comprises an antibody or nucleic acid. In some embodiments, the releasable drying agent is a labeling agent. In some embodiments, the releasable drying agent is a fluorescently labeled agent. In some embodiments, the releasable drying agent is a dye. In some embodiments, the releasable drying agent is a bead. In some embodiments, the releasable drying agent is a quantum dot. In some embodiments, the releasable drying agent is a fluorescently labeled antibody.

[0766] In some embodiments, the first plate further includes a first predetermined measurement site and a second predetermined measurement site on its surface, wherein when the plate is in a closed position, the distance between the edges of the measurement sites is significantly greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the predetermined measurement sites, and wherein the sample has one or more analytes that are capable of diffusing in the sample.

[0767] In some embodiments, the first plate has at least three analyte measurement sites on its surface, and when the plate is in a closed position, the distance between the edges of any two adjacent measurement sites is much greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes that are capable of diffusing in the sample.

[0768] In some embodiments, the first plate has at least two adjacent analyte measurement sites (not separated by a certain distance) on its surface, the distance being substantially greater than the thickness of a uniform thickness layer when the plate is in a closed position, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes that are capable of diffusing in the sample.

[0769] In some embodiments, the releasable drying reagent is a cell staining agent. In some embodiments, the device further includes a detector, which is a photodetector for detecting light signals. In some embodiments, the device further includes a detector, which is an electrodetector for detecting electrical signals.

[0770] In some embodiments, the device includes discrete spacers not fixed to either of the plates, wherein in the closed configuration, the discrete spacers are between the inner surfaces of the two plates, and the thickness of the sample is defined by the inner surfaces of the two plates and adjusted by the discrete spacers and the plates.

[0771] In some embodiments, the device further includes a binding site having a chemical sensor made of a material selected from the group consisting of: silicon nanowires (SiNW); single-walled carbon nanotubes (SWCNT); random networks of carbon nanotubes (RN-CNT); molecularly capped metal nanoparticles (MCNP); metal oxide nanoparticles (MONP); and chemically sensitive field-effect transistors (CHEM-FET).

[0772] A system for rapidly analyzing vapor condensate samples using a mobile phone is provided herein, comprising:

[0773] (a) The apparatus as claimed in any of the preceding claims;

[0774] (b) A mobile communication device comprising:

[0775] i. One or more cameras for detecting and / or imaging vapor condensate samples; and

[0776] ii. Electronic devices, signal processors, hardware, and software for receiving and / or processing detected signals and / or images of vapor condensate samples and for remote communication;

[0777] In some embodiments, the system further includes a light source from a mobile communication device or an external source.

[0778] In some embodiments, one of the plates has binding sites for the analyte, wherein at least a portion of the uniform sample thickness layer is above the binding sites and is substantially smaller than the average lateral linear dimension of the binding sites.

[0779] In some embodiments, the system further includes:

[0780] (d) Housing configured to hold the sample and to be installed on the mobile communication device.

[0781] In some embodiments, the housing includes optics for facilitating imaging and / or signal processing of the sample by the mobile communication device, and a base configured to hold the optics on the mobile communication device.

[0782] In some embodiments, the components of the optical devices within the housing may be movable relative to the housing.

[0783] In some embodiments, the mobile communication device is configured to transmit test results to medical professionals, healthcare institutions, or insurance companies.

[0784] In some embodiments, the mobile communication device is further configured to transmit information about the test and the subject to medical professionals, healthcare institutions, or insurance companies.

[0785] In some embodiments, the mobile communication device is further configured to transmit test information to a cloud network, and the cloud network processes the information to improve the test results.

[0786] In some embodiments, the mobile communication device is further configured to transmit test and subject information to a cloud network, which processes the information to improve test results, and the improved test results are sent back to the subject.

[0787] In some embodiments, the mobile communication device is configured to receive prescriptions, diagnoses, or advice from medical professionals.

[0788] EBC analysis

[0789] Breathing tests are among the least invasive methods available for clinical diagnosis, disease state monitoring, health surveillance, and environmental exposure assessment. Exemplary methods and devices for analyzing EBC are described below. Figure 9-11 As shown in the image.

[0790] EBC analysis can be used to detect inflammatory markers reflecting the status of chronic airway diseases such as chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF). EBC analysis can also be used to identify metabolic, proteomic, and genomic fingerprints of the respiratory system, with the aim of diagnosing not only respiratory diseases but also systemic diseases at an early stage.

[0791] The respiratory matrix from the subjects was a mixture of nitrogen, oxygen, CO2, H2O, and inert gases. The remaining small portion consisted of trace amounts of volatile organic compounds (VOCs) exceeding 1000, with concentrations ranging from parts per million (ppm) to parts per trillion (ppt) by volume. These volatiles can be produced in the body (endogenous) or absorbed from the environment as pollutants (exogenous). The composition of VOCs in respiration varies from person to person, both qualitatively and quantitatively.

[0792] Although more than 1,000 VOCs have been identified in human respiration to date, only a small number are common to all individuals. These common VOCs, including isoprene, acetone, ethane, and methanol, are products of core metabolic processes and are highly informative for clinical diagnosis. The lung-blood-air interface contains a large amount of matrix and trace amounts of VOCs in the respiratory exchange between blood and alveolar air. One exception is NO, which is released into the airways in cases of airway inflammation.

[0793] Endogenous compounds found in human respiration, such as inorganic gases (e.g., NO and CO), VOCs (e.g., isoprene, ethane, pentane, acetone), and other typical non-volatile substances like isoprostane, peroxynitrite, or cytokines, can be measured in respiratory condensate. Testing for endogenous compounds can provide valuable information about possible disease states. Furthermore, exogenous molecules, particularly halogenated organic compounds, can indicate recent exposure to drugs or environmental pollutants.

[0794] Volatile organic compounds (VOCs) are organic substances that have high vapor pressures and therefore evaporate at room temperature. VOCs that can be analyzed as target analytes by the methods and apparatus provided by this invention include, but are not limited to, bio-derived VOCs (e.g., terpenes, isoprene, methane, chlorophyll volatiles) and anthropogenic VOCs (e.g., typical solvents used in paints and coatings, such as ethyl acetate, glycol ethers, and acetone; vapors from adhesives, paints, adhesive removers, building materials, etc., such as dichloromethane, MTBE, and formaldehyde; chlorofluorocarbons and perchloroethylene used in dry cleaning; vapors and exhaust gases from fossil fuels, such as benzene and carbon monoxide).

[0795] Table 1 provides a detailed discussion of certain respiratory markers for diseases and other health conditions.

[0796] In addition to the diseases listed in Table 1, various VOCs contained in exhaled breath are also associated with different types of cancer. A non-exclusive list of respiratory VOCs identified as cancer biomarkers is shown in Table 2.

[0797] In addition to some of the nonvolatile compounds listed in Table 1, various other nonvolatile compounds have also been listed or identified as biomarkers for various diseases / symptoms. Specifically, the apparatus and method provided in this disclosure are used to determine glucose levels in EBCs. Other applications include, but are not limited to, the detection of nitrogen-reactive substances, arachidonic acid metabolites (e.g., isoprostane, leukotrienes, prostaglandins), cytokines, glutathione, proteins and metabolites, small molecules (e.g., chloride, sodium, potassium, urea, and small organic acids), and pH levels.

[0798] In some embodiments, the apparatus and method of the present invention are also applied to the detection of abused drugs in EBC samples. Abused drugs detected using the apparatus and method of the present invention include, but are not limited to, ethanol, cannabis, methadone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, codeine, 6-acetylmorphine, diazepam, oxazepam, morphine, benzoyl styrene, cocaine, buprenorphine, and tetrahydrocannabinol.

[0799] Table 1. Respiratory markers in certain diseases or conditions

[0800]

[0801]

[0802] Table 2. VOCs from exhalation identified among biomarkers for various cancers

[0803]

[0804]

[0805]

[0806]

[0807]

[0808]

[0809] EBC-3.2. Collection and analysis of other vapor condensates.

[0810] Some embodiments of the present invention relate to the application of SiEBCA methods and apparatus for collecting and analyzing vapor condensates other than EBC. Other humidity includes, but is not limited to, fog, clouds, and steam. Targeted analysis of these vapor condensates can be used for various purposes such as environmental monitoring and emission control. In some embodiments, the sample is vapor from biological, environmental, chemical, or clinical samples.

[0811] EBC-3.3. Automation and High Throughput.

[0812] In some embodiments, the apparatus and method of the present invention are automatic and high-speed, wherein the steps are performed by machines. In some embodiments, the sheets are in the form of sheet rolls and are controlled by rollers to place certain areas of the sheets in an open or closed configuration.

[0813] EBC-3.4. Identification and Verification of Condensate Gas Reservoir Markers

[0814] In some embodiments, the apparatus and methods of the present invention are particularly useful for identifying and confirming biomarkers for human diseases / conditions, or other markers for environmental, food safety, or other conditions / events. Due to the ease of use, speed, small sample volume, and multiple potential of the apparatus and methods of the present invention, they are readily adaptable for high-throughput, and even automated, screening and validation of these markers. In some embodiments, the apparatus and methods of the present invention are particularly useful when coupled with data processing systems capable of pattern recognition for such purposes.

[0815] In some embodiments, the apparatus and method of the present invention are also advantageous for creating large sample datasets for improving algorithms for pattern recognition through machine learning and / or other methods.

[0816] EBC-4. Collection and Analysis of Spacerless EBCs

[0817] Another aspect of the present invention is to provide an apparatus and method for collecting and analyzing vapor condensate using the aforementioned collection plate and cover plate but without spacers.

[0818] In some embodiments of the invention, spacers for adjusting the relevant volume of a sample or EBC sample are replaced by (a) a positioning sensor capable of measuring the internal space of the plate, and / or (b) a device capable of controlling the plate position and moving the plate into the desired internal space of the plate based on information provided by the sensor. In some embodiments, all spacers are replaced by a translation stage, monitoring sensors, and a feedback system.

[0819] In some embodiments, the collection plate and cover plate do not contain spacers at all, and the EBC sample is compressed into a thin layer by the two plates, the thickness of which is adjusted by the spacing between the inner surfaces of the plates (plate spacing).

[0820] A4. A device for collecting EBCs without spacers, comprising:

[0821] The first board and the second board, of which:

[0822] i. The plates can be moved relative to each other to form different configurations, and one or both plates are flexible;

[0823] ii. Both plates include a sample contact area on the respective surface of each plate for contacting the EBC sample;

[0824] One of the aforementioned configurations is an open configuration, wherein: two plates are separated, and an EBC sample is deposited on one or both plates from the subject; and

[0825] Another structure in the configuration is a closed structure constructed in the open configuration after EBC sample deposition; and in the closed configuration: at least a portion of the EBC sample is compressed into a thin layer by two plates, wherein the thin layer is in contact with and defined by the inner surfaces of the two plates.

[0826] A5. A method for collecting EBCs without spacers, comprising the following steps:

[0827] (a) Obtain the collection plate and cover plate of section A4;

[0828] (b) When the plate is configured in an open configuration, EBC samples are deposited by exhaling breath from the object toward the collection plate, wherein the exhaled breath condenses on the collection surface of the collection plate to form droplets and / or pools with different lateral dimensions and different heights, depending on the surface wetting properties of the collection surface.

[0829] (c) Following (b), the cover plate is brought onto the collecting surface and then the two plates are brought into a closed structure by pressing the plate, wherein in the closed structure:

[0830] (i) At least a portion of the EBC sample is located between the cover plate and the collection plate, and the relevant area of ​​the collection surface of the collection plate is covered by a concave plate; and

[0831] (ii) In the relevant region, the large number or all of the droplets or pools formed in the open structure in step (b) merge into (1) pools that are much larger in lateral dimension than in the open structure but fewer in number and (2) simultaneously contact the inner surfaces of the cover plate and the collection plate, whereby the thickness of the pool is defined by the inner surfaces of the plates and equal to the spacing between the inner surfaces, and the total surface area of ​​the deposited EBC exposed to the surrounding environment is significantly reduced; and

[0832] Among them, the plate spacing is the distance between the inner surface of the cover plate and the collecting plate, the relevant area is a part or the entire surface of the collecting surface, and the collecting surface is a part or the entire surface of the collecting plate.

[0833] A6. A method for analyzing EBC without spacers, comprising the following steps:

[0834] (a) Obtain the collection plate and cover plate of segment A4;

[0835] (b) When the plate is configured in an open configuration, EBC samples are deposited by exhaling breath from the object toward the collection plate, wherein the exhaled breath condenses on the collection surface of the collection plate to form droplets and / or pools with different lateral dimensions and different heights, depending on the surface wetting properties of the collection surface.

[0836] (c) Following (b), the cover plate is brought onto the collecting surface and then the two plates are brought into a closed structure by pressing the plate, wherein in the closed structure:

[0837] (i) At least a portion of the EBC sample is located between the cover plate and the collection plate, and the relevant area of ​​the collection surface of the collection plate is covered by a concave plate; and

[0838] (ii) In the relevant region, the large number or all of the droplets or pools formed in the open structure in step (b) merge into (1) pools that are much larger in lateral dimension than in the open structure but fewer in number and (2) simultaneously contact the inner surfaces of the cover plate and the collection plate, whereby the thickness of the pool is defined by the inner surfaces of the plates and equal to the spacing between the inner surfaces, and the total surface area of ​​the deposited EBC exposed to the surrounding environment is significantly reduced; and

[0839] (d) Analyze EBC;

[0840] Among them, the plate spacing is the distance between the inner surface of the cover plate and the collecting plate, the relevant area is a part or the entire surface of the collecting surface, and the collecting surface is a part or the entire surface of the collecting plate.

[0841] In some embodiments, it is not possible to obtain a layer with a very uniform thickness without using the spacers described above. However, it remains advantageous to collect and analyze EBC samples using the apparatus and methods of segments A4-A5 because of their ease of handling, rapid processing, lack of specialized training, and very small sample volume.

[0842] In some embodiments, analysis step (d) of segment A6 includes determining the thickness of the EBC sample collected in the closed configuration after the thin layer is formed during step (c). In some embodiments, the thickness of the EBC sample collected in the closed configuration is equal to the distance between the inner surfaces of the two plates.

[0843] In some embodiments, measuring the spacing between the inner surfaces involves using optical interference. Optical interference can use multiple wavelengths. For example, the optical signal caused by the interference of light reflected at the inner surfaces of the first and second plates oscillates with the wavelength of the light. Based on the oscillation, the spacing between the inner surfaces can be determined. To enhance the interference signal, one or both inner surfaces can be coated with a light-reflective material.

[0844] In some embodiments, measuring the spacing between inner surfaces includes obtaining optical imaging (e.g., obtaining a 2D / 3D image of the sample, and image acquisition may be multiple times with different viewpoints, different wavelengths, different phases and / or different polarizations) and image processing.

[0845] In some embodiments, the analysis step (d) of segment A6 includes measuring the volume of the collected EBC sample based on the lateral region and thickness of the thin layer determined after the thin layer is formed during step (c).

[0846] In some embodiments, measuring the entire sample region or volume involves obtaining optical imaging (e.g., obtaining a 2D / 3D image of the sample, and image acquisition may be performed multiple times with different viewpoints, wavelengths, phases, and / or polarizations) and image processing. The lateral region of the sample refers to the area in a direction substantially parallel to the first and second plates. 3D imaging can be performed using fringe projection profilometry (FPP), one of the most common methods for acquiring three-dimensional (3D) images of objects.

[0847] In some embodiments, measuring a sample region or volume by imaging includes: (a) calibrating the image scale by using a sample of known region or volume (e.g., the imager is a mobile phone smartphone, and the size of the image taken by the mobile phone can be calibrated by comparing images of samples of known size taken by the same mobile phone); (b) comparing the image with scale markings (rulers) placed on or near a first plate and a second plate (discussed further here); and (c) combinations thereof.

[0848] As used herein, light may include visible light, ultraviolet light, infrared light, and / or near-infrared light. Light may include wavelengths in the range of 20 nm to 20,000 nm.

[0849] In some embodiments, the pressing during step (c) of segments A5-A6 is performed by hand.

[0850] In some embodiments, the formation and properties of the thin layer depend on the pressure applied during step (c) of segments A5-A6 to bring the two plates into the closed configuration. In some embodiments, the pressure applied during step (c) of segments A5-A6 is well-adjusted to form a thin layer of the EBC sample between the two plates having prerequisite parameters. Further examples of EBC collection and analysis experiments.

[0851] Further exemplary experimental tests and observations of the present invention are provided, as well as further preferred embodiments.

[0852] All exemplary experimental tests and demonstrations of the invention described in Part 4 (Examples) were conducted under the following conditions and have the following common observations.

[0853] Plates: Of the two plates in the SiEBCA device, only one (referred to as the "X plate") has spacers fixed to the sample surface of the plate, while the other plate (referred to as the "substrate") has a flat surface and no spacers.

[0854] EBC formation without spacers under open and closed structures

[0855] In a separate set of experiments, we tested the possibility of collecting EBC samples using spacerless plates.

[0856] As shown here, the exemplary SiEBCA device also includes a collection plate and a cover plate. The collection plate we used is a 25mm × 25mm × 1mm PMMA plate with an untreated surface, and the cover plate is a 25mm × 25mm × 0.175mm PMMA plate with an exposed untreated surface. EBC samples are collected by having the subject breathe over the collection plate for 2 seconds, and the cover plate is immediately placed over the collection plate and pressed onto it as described above. Subsequently, the SiEBCA device, along with the sample collected therein, is used for optical measurements and microscopic imaging.

[0857] Figure 15 of U.S. Provisional Patent Application 62 / 459,972, filed February 16, 2017, schematically illustrates optical measurements and imaging used to measure the thickness and lateral region of an EBC sample, the entire contents of which are incorporated herein by reference. As shown in Figure (A), the FP cavity resonance in the reflection spectrum of 25 points on an artificially generated 4×4 grid at the center of the SiEBCA device was measured using a Fabry-Perot interferometer, from which the plate spacing (and sample thickness) was derived. Each of the 25 measurement points has a region of approximately 2 μm × 2 μm, and all 25 points cover a 20 mm × 20 mm region. The average plate spacing over the 25 points was taken as an estimate of the sample thickness. As shown in Figure (B), a photograph of the SiEBCA device was taken directly to depict the general profile of the EBC sample between the two plates and to measure the total lateral area (S).t Then, microscopic images were taken at each of the 25 points (each image covering an area S of 1.6 mm × 1.1 mm). i Then, these images are analyzed using image processing software to identify and measure the total area (S) of bubbles in each image. b ).

[0858] To estimate the total lateral region of the EBC sample, firstly, the lateral area of ​​the EBC liquid at each measurement point (a i The percentage of (Si-Sb) is calculated as (Si-Sb) / Si×100%; secondly, the average value... Taken from all 25 points; finally, the total EBC sample lateral region (S EBC Estimated as

[0859] EBC sample (V) EBC The volume of ) was therefore determined to be

[0860] Figure 16 of U.S. Provisional Patent Application 62 / 459,972, filed February 16, 2017, demonstrates the principle of plate spacing measurement based on FP cavity resonance, the entire contents of which are incorporated herein by reference. Figure (a) shows a schematic diagram of the FP cavity from the SiEBCA device; Figure (b) shows a typical reflection spectrum and resonance from the device. The plate spacing (h) at each measurement point is calculated as follows:

[0861]

[0862] Where h is the plate spacing, c is the speed of light, Δv is the period in the frequency domain, and n is the reflectivity of the EBC liquid.

[0863] As mentioned above, the average EBC sample thickness is equal to

[0864] EBC sample thickness uniformity calculation is as follows

[0865] Figure 17 of U.S. Provisional Patent Application 62 / 459,972, filed February 16, 2017, shows a microscopic image of an EBC sample collected using an exemplary SiEBCA device without spacers, the entire contents of which are incorporated herein by reference. Figures (a)-(b) show images of EBC samples in a closed configuration after two plates have been manually pressed with low, medium, and high compressive strengths, respectively. Low strength is less than 10 kg, high strength is greater than 15 kg, and medium strength is between low and high strengths.

[0866] Under these three different conditions, the performance of the spacerless exemplary SiEBCA device was examined and summarized in Table 3 based on the measurement and calculation methods described above. As shown in Table 3 and Figure 17, low intensity yields a thicker liquid thickness and a larger bubble region, while high intensity yields a thinner EBC sample layer and a smaller bubble region.

[0867] Table 3. Performance of spacerless SiEBCA

[0868]

[0869] AA0. An apparatus for collecting and analyzing vapor condensate (VC) samples, comprising:

[0870] Collection plate and cover plate, wherein:

[0871] i. The plates can be moved relative to each other to form different configurations;

[0872] ii. One or both plates are flexible; and

[0873] iii. Each plate has a sample contact area on its respective inner surface for contacting the vapor condensate (VC) sample containing the analyte;

[0874] One of the structures is an open structure, in which the two plates are completely or partially separated, and the VC sample is deposited on one or both plates; and

[0875] Another component of the structure is a closed structure configured after the VC sample is deposited in the open structure; and in this closed structure: at least a portion of the VC sample is between and in contact with the two plates, and has a thickness that is adjusted by the two sample surfaces of the plates and is equal to or less than 30 μm with minimal variation.

[0876] AA1. An apparatus for collecting and analyzing vapor condensate (VC) samples, comprising:

[0877] Collection plate, cover plate and spacer, wherein:

[0878] i. The plates can be moved relative to each other to form different configurations;

[0879] ii. One or both plates are flexible;

[0880] iii. Each plate has a sample contact area on its respective inner surface for contacting the vapor condensate (VC) sample containing the analyte;

[0881] iv. Spacers are fixed to one or both of the corresponding inner surfaces of the plates and have a predetermined substantially uniform height and a predetermined constant spacing distance, wherein at least one of the spacers is located inside the sample contact area;

[0882] One of the configurations is an open configuration, in which the two plates are completely or partially separated, the spacing between the plates is not adjusted by spacers, and the VC sample is deposited on one or both plates; and

[0883] Another aspect of the structure is a closed structure configured after the VC sample is deposited in the open structure; and in this closed structure: at least a portion of the VC sample is between and in contact with the two plates, and has a very uniform thickness, which is adjusted by the spacer and the two sample surfaces of the plates and is equal to or less than 30 μm with minimal variation.

[0884] AA2. The apparatus of example AA0 or AA1, wherein the apparatus further comprises a drying agent coated on one or two plates.

[0885] AA3. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises dry binding sites having predetermined regions on one or two plates, wherein the dry binding sites bind and immobilize analytes in the sample.

[0886] AA4. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises a releasable desiccant and a release time control material on one or two plates, the release time control material delaying the time for the releasable desiccant to be released into the sample.

[0887] AA5. The apparatus of Example 4, wherein the release time control material delays the time at which the drying reagent begins to be released into the sample by at least 3 seconds.

[0888] AA6. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises one or more dry binding sites and / or one or more reagent sites on one or two plates.

[0889] AA7. The apparatus of any of the foregoing embodiments, wherein the sample is exhaled condensate.

[0890] AA8. The apparatus of any of the foregoing embodiments, wherein the sample is a vapor from a biological sample, an environmental sample, a chemical sample, or a clinical sample.

[0891] AA9. The apparatus of any of the foregoing embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0892] AA10. The apparatus of any of the foregoing embodiments, wherein the analyte comprises a volatile organic compound (VOC).

[0893] AA11. The apparatus of any of the foregoing embodiments, wherein the analyte comprises nitrogen, oxygen, CO2, H2O and an inert gas.

[0894] AA12. The apparatus of any of the foregoing embodiments, wherein the analyte is stained.

[0895] AA13. The apparatus of any of the foregoing embodiments, wherein on one of the sample surfaces, it further comprises a sealing spacer encapsulating part or all of the VC sample deposited on the collection plate.

[0896] AA14. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value equal to or less than 0.5 μm.

[0897] AA15. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value in the range of 0.5 μm to 1 μm.

[0898] AA16. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value in the range of 1 μm to 2 μm.

[0899] AA17. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value in the range of 2 μm to 10 μm.

[0900] AA18. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value in the range of 10 μm to 20 μm.

[0901] AA19. The apparatus of any of the foregoing embodiments, wherein the very uniform thickness has a value in the range of 20 μm to 30 μm.

[0902] AA20. The apparatus of any of the foregoing embodiments, wherein at least a portion of the thickness of the VC sample in the closed configuration is greater than the thickness of the VC sample deposited on the collection plate in the open configuration.

[0903] AA21. The apparatus of any of the foregoing embodiments, wherein at least a portion of the thickness of the VC sample in the closed configuration is less than the thickness of the VC sample deposited on the collection plate in the open configuration.

[0904] AA22. The apparatus of any of the foregoing embodiments, wherein the spacing is fixed on the plate by a direct imprint plate or an injection-molded plate.

[0905] AA23. The apparatus of any of the foregoing embodiments, wherein the materials of the plates and spacers are selected from polystyrene, PMMA, PC, COC, COP or another plastic.

[0906] AA24. The apparatus of any of the foregoing embodiments, wherein the spacing distance is in the range of 1 μm to 200 μm.

[0907] AA25. The apparatus of any of the foregoing embodiments, wherein the spacing distance is in the range of 200 μm to 1000 μm.

[0908] AA26. The apparatus of any of the foregoing embodiments, wherein the VC sample is exhaled condensate from a human or animal.

[0909] AA27. The apparatus of any of the foregoing embodiments, wherein the spacers of the uniformly thick layer have a fill factor of at least 1%, wherein the fill factor is the ratio of the spacer region in contact with the uniformly thick layer to the total plate region in contact with the uniformly thick layer.

[0910] AA28. The apparatus of any of the foregoing embodiments, wherein for the spacer of the uniform thickness layer, the Young's modulus of the spacer multiplied by the fill factor of the spacer is equal to or greater than 10 MPa, wherein the fill factor is the ratio of the spacer region in contact with the uniform thickness layer to the total plate region in contact with the uniform thickness layer.

[0911] AA29. The apparatus of any of the foregoing embodiments, wherein for the flexible plate, the thickness of the flexible plate multiplied by the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm.

[0912] AA30. The apparatus of any of the foregoing embodiments, wherein for the flexible plate, the fourth power of the spacing distance (ISD) divided by the thickness (h) of the flexible plate and the Young's modulus (E) of the flexible plate, ISD 4 / (hE) equals or is less than 10 6 μm 3 / GPa,

[0913] AA31. The apparatus of any of the preceding paragraphs, wherein one or both plates include position marks located on or inside the surfaces of the plates, the position marks providing information about the position of the plates.

[0914] AA32. The apparatus of any of the preceding paragraphs, wherein one or both plates include scale markings on or inside the surface of the plates, the scale markings providing information on the lateral dimensions of the sample and / or the structure of the plates.

[0915] AA33. The apparatus of any of the foregoing embodiments, wherein one or both plates include imaging markers located on or inside the surfaces of the plates, the imaging markers assisting in imaging the sample.

[0916] AA34. The apparatus of any of the foregoing embodiments, wherein the spacer serves as a position marker, a scale marker, an imaging marker, or any combination thereof.

[0917] AA35. The apparatus of any of the foregoing embodiments, wherein the average thickness of the uniform thickness layer is approximately equal to the minimum size of the analyte in the sample.

[0918] AA36. The apparatus of any of the foregoing embodiments, wherein the spacing distance is in the range of 1 μm to 50 μm.

[0919] AA37. The apparatus of any of the foregoing embodiments, wherein the spacing distance is in the range of 50 μm to 120 μm.

[0920] AA38. The apparatus of any of the foregoing embodiments, wherein the spacing distance is in the range of 120 μm to 200 μm.

[0921] AA39. The apparatus of any of the foregoing embodiments, wherein the spacing distance is substantially periodic.

[0922] AA40. The apparatus of any of the foregoing embodiments, wherein the interval is non-periodic.

[0923] AA41. The device of any of the foregoing embodiments, wherein the spacer is a column having a cross-sectional shape selected from a circle, polygon, annulus, square, rectangle, oval, ellipse or any combination thereof.

[0924] AA42. The apparatus of any of the foregoing embodiments, wherein the spacer has a columnar shape and a substantially flat-topped surface, wherein for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1.

[0925] AA43. The apparatus of any of the foregoing embodiments, wherein each spacer has a ratio of the spacer's lateral dimension to its height of at least 1.

[0926] AA44. The apparatus of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is less than or substantially equal to the minimum dimension of the analyte in the sample.

[0927] AA45. The apparatus of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is in the range of 0.5 μm to 100 μm.

[0928] AA46. The apparatus of any of the foregoing embodiments, wherein the minimum lateral dimension of the spacer is in the range of 0.5 μm to 10 μm.

[0929] AA47. The device of any of the foregoing embodiments, wherein the spacer has a thickness of at least 100 mm. 2 The density.

[0930] AA48. The device of any of the foregoing embodiments, wherein the spacer has a diameter of at least 1000 mm. 2 The density.

[0931] AA49. The apparatus of any of the foregoing embodiments, wherein at least one of the plates is transparent.

[0932] AA50. The apparatus of any of the foregoing embodiments, wherein at least one of the plates is made of a flexible polymer.

[0933] AA51. The apparatus of any of the foregoing embodiments, wherein for pressure on the compression plates, the spacers are incompressible and / or independently, only one of the plates is flexible.

[0934] AA52. The apparatus of any of the foregoing embodiments, wherein the thickness of the flexible plate is in the range of 10 μm to 200 μm.

[0935] AA53. The apparatus of any of the foregoing embodiments, wherein the variation is less than 30%.

[0936] AA54. The apparatus as described in any of the foregoing embodiments, wherein the variation is less than 10%.

[0937] AA55. The apparatus of any of the foregoing embodiments, wherein the variation is less than 5%.

[0938] AA56. The apparatus of any of the foregoing embodiments, wherein the first plate and the second plate are connected and configured to change from an open configuration to a closed configuration by means of a folding plate.

[0939] AA57. The apparatus of any of the foregoing embodiments, wherein the first plate and the second plate are connected by a hinge and configured to change from an open configuration to a closed configuration by folding the plate along the hinge.

[0940] AA58. The apparatus of any of the foregoing embodiments, wherein the first plate and the second plate are connected to the plate by a hinge, the hinge being a separate material and configured to change from an open configuration to a closed configuration by folding the plate along the hinge.

[0941] AA59. The apparatus of any of the foregoing embodiments, wherein the first plate and the second plate are made of a single sheet material and are configured to change from an open configuration to a closed configuration by folding the plate.

[0942] AA60. The apparatus of any of the foregoing embodiments, wherein the uniform thickness of the sample layer is at least 100 μm. 2 The horizontal area is uniform.

[0943] AA61. The apparatus of any of the foregoing embodiments, wherein the uniform thickness of the sample layer is at least 1 mm. 2 The horizontal area is uniform.

[0944] AA62. The apparatus of any of the foregoing embodiments, wherein the apparatus is configured to analyze a sample in 60 seconds or less.

[0945] AA63. The apparatus of any of the foregoing embodiments, wherein, in a closed configuration, the final sample thickness device is configured to analyze the sample in 60 seconds or less.

[0946] AA64. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises one or more amplification sites on one or two plates, each amplification site being capable of amplifying a signal from the analyte or a label of the analyte when the analyte or label is within 500 nm of the amplification site.

[0947] AA65. The apparatus of any of the foregoing embodiments, wherein, in a closed configuration, the final sample thickness device is configured to analyze the sample in 10 seconds or less.

[0948] AA66. The apparatus of any of the foregoing embodiments, wherein the dry binding site comprises a trapping agent.

[0949] AA67. The apparatus of any of the foregoing embodiments, wherein the stem binding site comprises an antibody or a nucleic acid.

[0950] AA68. The apparatus of any of the foregoing embodiments, wherein the releasable drying agent is a labeled agent.

[0951] AA69. The apparatus of any of the foregoing embodiments, wherein the releasable drying reagent is a fluorescently labeled reagent.

[0952] AA70. The apparatus of any of the foregoing embodiments, wherein the releasable drying reagent is a fluorescently labeled antibody.

[0953] AA71. The apparatus of any of the foregoing embodiments, wherein the first plate further includes a first predetermined measurement site and a second predetermined measurement site on its surface, wherein when the plate is in a closed position, the distance between the edges of the measurement sites is significantly greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the predetermined measurement sites, and wherein the sample has one or more analytes capable of diffusing in the sample.

[0954] AA72. The apparatus of any of the preceding embodiments, wherein the first plate has at least three analyte measurement sites on its surface, and when the plate is in the closed position, the distance between the edges of any two adjacent measurement sites is much greater than the thickness of the uniform thickness layer, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes that are capable of diffusing in the sample.

[0955] AA73. The apparatus of any of the preceding embodiments, wherein the first plate has at least two adjacent analyte measurement sites (not separated by a distance) on its surface, the distance being substantially greater than the thickness of a uniform thickness layer when the plate is in the closed position, wherein at least a portion of the uniform thickness layer is on the measurement sites, and wherein the sample has one or more analytes capable of diffusing in the sample.

[0956] AA74. The apparatus of any of the foregoing embodiments, wherein the releasable drying agent is a cell staining agent.

[0957] AA75. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises a detector, the detector being a photodetector for detecting an optical signal.

[0958] AA76. The apparatus of any of the foregoing embodiments, wherein the apparatus further comprises a detector, the detector being an electrical detector for detecting electrical signals.

[0959] AA77. The apparatus of any of the foregoing embodiments, wherein the apparatus includes a discrete spacer not fixed to either of the plates, wherein in the closed configuration, the discrete spacer is between the inner surfaces of the two plates, and the thickness of the sample is defined by the inner surfaces of the two plates and adjusted by the discrete spacer and the plates.

[0960] AA78. The device of any of the foregoing embodiments, wherein the device further comprises a binding site having a chemical sensor made of a material selected from the group consisting of: silicon nanowires (SiNW); single-walled carbon nanotubes (SWCNT); random network of carbon nanotubes (RN-CNT); molecularly capped metal nanoparticles (MCNP); metal oxide nanoparticles (MONP); and chemically sensitive field-effect transistors (CHEM-FET).

[0961] BB1. A system for rapidly analyzing vapor condensate samples using a mobile phone, comprising:

[0962] (a) The apparatus as described in any of the preceding AA embodiments;

[0963] (b) A mobile communication device comprising:

[0964] i. One or more cameras for detecting and / or imaging vapor condensate samples; and

[0965] ii. Electronic devices, signal processors, hardware, and software for receiving and / or processing detected signals and / or images of vapor condensate samples and for remote communication;

[0966] BB2. The system of any of the foregoing BB embodiments, wherein the system further includes a light source from a mobile communication device or an external source.

[0967] BB3. The system of any of the foregoing BB embodiments, wherein one of the plates has binding sites for the analyte, wherein at least a portion of the uniform sample thickness layer is above the binding sites and is substantially smaller than the average lateral linear dimension of the binding sites.

[0968] BB4. The system of any of the foregoing BB embodiments further includes:

[0969] (d) Housing configured to hold the sample and to be installed on the mobile communication device.

[0970] BB5. The system of any of the foregoing BB embodiments, wherein the housing includes optics for facilitating imaging and / or signal processing of the sample by the mobile communication device, and a base configured to hold the optics on the mobile communication device.

[0971] BB6. The system of any of the foregoing BB embodiments, wherein the elements of the optics in the housing are movable relative to the housing.

[0972] BB7. A system as described in any of the preceding BB embodiments, wherein the mobile communication device is configured to transmit test results to medical professionals, medical institutions, or insurance companies.

[0973] BB8. A system as described in any of the foregoing BB embodiments, wherein the mobile communication device is further configured to transmit information about the test and the subject to medical professionals, medical institutions, or insurance companies.

[0974] BB9. The system of any of the foregoing BB embodiments, wherein the mobile communication device is further configured to transmit test information to a cloud network, and the cloud network processes the information to improve the test results.

[0975] BB10. The system of any of the foregoing BB embodiments, wherein the mobile communication device is further configured to transmit information of the test and the subject to a cloud network, the cloud network processes the information to improve the test results, and the improved test results are sent back to the subject.

[0976] BB11. A system as described in any of the foregoing BB embodiments, wherein the mobile communication device is configured to receive prescriptions, diagnoses, or advice from a medical professional.

[0977] BB12. The system of any of the foregoing BB embodiments, wherein the mobile communication device is configured with hardware and software to:

[0978] (a) Capture an image of the sample;

[0979] (b) Analyze the test and control positions in the image;

[0980] (c) The values ​​obtained from the analysis of the test location are compared with the thresholds that characterize the rapid diagnostic test.

[0981] BB13. The system of any of the foregoing BB embodiments, wherein at least one of the plates includes a storage site for storing the assay reagent.

[0982] BB14. In any of the foregoing BB embodiments of the system, at least one camera reads signals from the CROF device.

[0983] BB15. The system of any of the foregoing BB embodiments, wherein the mobile communication device communicates with a remote location via Wi-Fi or a cellular network.

[0984] BB16. The system of any of the foregoing BB embodiments, wherein the mobile communication device is a mobile phone.

[0985] CC1. A method for rapidly analyzing analytes in a sample using a mobile phone, comprising:

[0986] (a) Deposit the sample onto the apparatus of any of the aforementioned BB embodiments;

[0987] (b) to determine the analytes in the sample deposited on the device to produce results; and

[0988] (c) Transmit the results from the mobile communication device to a location remote from the mobile communication device.

[0989] CC2. The method of any of the preceding CC embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[0990] CC3. The method of any of the foregoing CC embodiments, wherein the analytes comprise leukocytes, erythrocytes and platelets.

[0991] CC4. The method as described in any of the foregoing CC embodiments, wherein the method comprises:

[0992] Analyze results at a remote location to provide analysis results; and transmit analysis results from a remote location to a mobile communication device.

[0993] CC5. The method of any of the foregoing CC embodiments, wherein the analysis is performed by a medical professional at a remote location.

[0994] CC6. The method of any of the foregoing CC embodiments, wherein the mobile communication device receives a prescription, diagnosis, or advice from a medical professional at a remote location.

[0995] CC7. The method of any of the preceding CC embodiments, wherein the thickness of at least a portion of the VC sample in the closed configuration is greater than the thickness of the VC sample deposited on the collection plate in the open configuration.

[0996] CC8. The method of any of the preceding CC embodiments, wherein the thickness of at least a portion of the VC sample in the closed configuration is less than the thickness of the VC sample deposited on the collection plate in the open configuration.

[0997] CC9. The method of any of the preceding CC segments, wherein the analytical step comprises detecting an analyte in the sample.

[0998] CC10. As in any of the preceding CC segments, wherein the analyte is a biomarker.

[0999] CC11. The method of any of the preceding CC embodiments, wherein the analyte is a protein, nucleic acid, cell, or metabolite.

[1000] CC12. The method of any of the preceding CC embodiments, wherein the determination performed in step (b) is a binding assay or a biochemical assay.

[1001] DD1. A method for analyzing an analyte in a vapor condensate sample, comprising:

[1002] To obtain the apparatus as claimed in any of the preceding apparatus claims;

[1003] Deposit vapor condensate samples onto one or two plates of the apparatus;

[1004] Placing the plate in a closed structure and applying an external force to at least a portion of the plate; and

[1005] Analyze the analytes in a uniform thickness layer when the plate is in a closed structure.

[1006] DD2. The method as described in any of the foregoing DD embodiments, wherein the method comprises:

[1007] (a) Obtaining a sample;

[1008] (b) Obtaining a first plate and a second plate movable relative to each other in different configurations, wherein each plate has a substantially flat sample contact surface, one or both plates are flexible, and one or both plates include spacers fixed to the respective sample contact surfaces, wherein the spacers have:

[1009] i. A predetermined, substantially uniform height.

[1010] ii. The shape of a column having a substantially uniform cross-section and a flat-topped surface;

[1011] iii. The ratio of width to height is equal to or greater than 1;

[1012] iv. A predetermined constant interval distance in the range of 10 μm to 200 μm;

[1013] v. The fill factor is equal to or greater than 1%;

[1014] (c) Depositing a sample on one or two plates, wherein the plates are configured in an open configuration, wherein the open configuration is a configuration in which two plates are partially or completely separated and the spacing between the plates is not adjusted by spacers;

[1015] (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, and has an average value equal to or less than 30 μm and varying by less than 10%, wherein the compression comprises:

[1016] Place the two boards together; and

[1017] A region of at least one of these plates is conformally pressed in parallel or sequentially to press the plates together into a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to unfold laterally between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in a uniform thickness region layer is adjusted by spacers; and

[1018] (e) Analyze uniform thickness layers when the plate is in a closed structure;

[1019] The fill factor is the ratio of the spacer contact area to the total plate area; conformal pressing is a method that ensures a substantially constant pressure applied to a region, regardless of variations in the shape of the plate's outer surface; and

[1020] The parallel presses simultaneously apply pressure to the target area, while the sequential presses apply pressure to a portion of the target area and gradually move to other areas.

[1021] DD3. The method as described in any of the foregoing DD embodiments, wherein the method comprises:

[1022] After the plate is in a closed structure, the external force is removed; and when the plate is in a closed structure, the analyte in a layer of uniform thickness is imaged; and

[1023] Count the number of analytes or markers in the image area.

[1024] DD4. The method of any of the foregoing DD embodiments, wherein the method includes removing the external force after the plate is in a closed configuration; and measuring the optical signal in a uniform thickness layer when the plate is in a closed configuration.

[1025] DD5. The method of any of the foregoing DD embodiments, wherein the spacing distance is in the range of 20 μm to 200 μm.

[1026] DD6. The method of any of the foregoing DD embodiments, wherein the spacing distance is in the range of 5 μm to 20 μm.

[1027] DD7. The method of any of the foregoing DD embodiments, wherein the product of the fill factor and the Young's modulus of the spacer is 2 MPa or greater.

[1028] DD8. The surface change is less than 50 nm as in any of the foregoing DD embodiments.

[1029] DD9. The method of any of the foregoing DD embodiments further includes the step of calculating the concentration of the analyte in the relevant volume of the sample, wherein the calculation is based on the relevant sample volume defined by a predetermined region of the storage site, the uniform sample thickness under the closed structure, and the amount of the detected target entity.

[1030] DD10. The method of any of the foregoing DD embodiments, wherein the analytical step includes counting the analytes in the sample.

[1031] DD11. The method of any of the foregoing DD embodiments, wherein imaging and counting are accomplished by:

[1032] i. Irradiate cells in a layer of uniform thickness;

[1033] ii. Take one or more images of the cells using a CCD or CMOS sensor;

[1034] iii. Using computers to identify cells in images; and

[1035] iv. Count the number of platelets in the image region.

[1036] DD12. The method of any of the foregoing DD embodiments, wherein the external force is provided by hand.

[1037] DD13. The method of any of the foregoing DD embodiments, wherein it further comprises a drying agent coated on one or two plates.

[1038] DD14. The method of any of the foregoing DD embodiments, wherein the uniform thickness sample layer has a thickness uniformity of up to + / - 5%.

[1039] DD15. The method of any of the foregoing DD embodiments, wherein the spacer is a column having a cross-sectional shape selected from a circle, polygon, annulus, square, rectangle, oval, ellipse or any combination thereof.

[1040] DD16. The method of any of the foregoing DD embodiments, wherein the spacing between the spacers is approximately the minimum size of the analyte.

[1041] EE1. The method of any of the foregoing CC or DD embodiments, wherein one or both plate sample contact surfaces contain one or more amplification sites, each amplification site being capable of amplifying the signal from the analyte or the analyte's label when the analyte or label is within 500 nm of the amplification site.

[1042] EE2. The method of any of the foregoing CC or DD embodiments, wherein the sample is exhaled condensate.

[1043] EE3. The method of any of the foregoing CC or DD embodiments, wherein the sample is a vapor from a biological sample, an environmental sample, a chemical sample, or a clinical sample.

[1044] EE4. The method of any of the foregoing CC or DD embodiments, wherein the analyte comprises molecules (e.g., proteins, peptides, DNA, RNA, nucleic acids or other molecules), cells, tissues, viruses and nanoparticles of different shapes.

[1045] EE5. The method of any of the foregoing CC or DD embodiments, wherein the analyte comprises a volatile organic compound (VOC).

[1046] EE6. The method of any of the foregoing CC or DD embodiments, wherein the analyte comprises nitrogen, oxygen, CO2, H2O and an inert gas.

[1047] EE7. The method of any of the foregoing CC or DD embodiments, wherein the analyte is stained.

[1048] EE8. The method of any of the foregoing CC or DD embodiments, wherein on one of the sample surfaces, it further comprises a sealing spacer encapsulating part or all of the VC sample deposited on the collection plate.

[1049] EE9. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value equal to or less than 0.5 μm.

[1050] EE10. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value in the range of 0.5 μm to 1 μm.

[1051] EE11. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value in the range of 1 μm to 2 μm.

[1052] EE12. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value in the range of 2 μm to 10 μm.

[1053] EE13. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value in the range of 10 μm to 20 μm.

[1054] EE14. The method of any of the foregoing CC or DD embodiments, wherein the very uniform thickness has a value in the range of 20 μm to 30 μm.

[1055] Biomarkers and Applications

[1056] Other aspects of this disclosure include CROF devices comprising multiple trapping agents, each binding multiple analytes in a sample, i.e., multiplex CROF devices. In this case, CROF devices containing multiple trapping agents can be configured to detect different types of analytes (proteins, nucleic acids, antibodies, etc.). Different analytes can be distinguished from each other on the array based on their position within the array, or by combinations of emission wavelengths or more of the detectable labels bound to different analytes.

[1057] Other pathogens that can be detected in diagnostic samples using the apparatus, system, and method of the present invention include, but are not limited to: varicella-zoster virus; Staphylococcus epidermidis, Escherichia coli, methicillin-resistant Staphylococcus aureus (MSRA), Staphylococcus aureus, Staphylococcus hominis, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus capitulata, Staphylococcus wartii, Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus mimicus, Streptococcus pneumoniae, and Candida albicans, gonorrhea (Neisseria gonorrhoeae), syphilis (Treponema pallidum), and Chlamydia trachomatis. Tracomitis), non-gonococcal urethritis (Ureaplasma urealyticum), chancroid (Haemophilus ducreyi), trichomoniasis (Trichomonas vaginalis); Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MSRA), Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Stenotrophomonas maltophilia, Haemophilus parainfluenzae, Escherichia coli, Enterococcus faecalis, Serratia marcescens, Haemophilus parahemolyticus, Enterococcus cloacae, Candida albicans, Moraxella catarrhalis, Streptococcus pneumoniae, Citrobacter freundii, Enterococcus, Klebsiella pneumoniae, Pseudomonas fluorescens, Neisseria meningitidis, Streptococcus pyogenes, Pneumocystis carinii, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Mycobacterium tuberculosis, as well as those listed in Tables B2 and 6.

[1058] Table B1: Diagnostic Markers

[1059]

[1060]

[1061]

[1062] Table B2. Diagnostic Markers

[1063]

[1064]

[1065]

[1066]

[1067]

[1068]

[1069]

[1070]

[1071]

[1072]

[1073]

[1074]

[1075]

[1076]

[1077]

[1078]

[1079]

[1080] In some cases, this method is used to inform the subject to whom the sample belongs about their health condition. Health conditions that can be diagnosed or measured by this method, device, and system include, but are not limited to: chemical balance; nutritional health; exercise; fatigue; sleep; stress; prediabetes; allergies; aging; exposure to environmental toxins, pesticides, herbicides, synthetic hormone analogs; pregnancy; menopause; and male menopause. Table B3 below provides a list of biomarkers that can be detected using this invention and their associated health conditions.

[1081] Table B3: Diagnostic Markers

[1082]

[1083]

[1084]

[1085]

[1086]

[1087]

[1088]

[1089] In some cases, the biomarkers that can be detected by this method are antibodies in a sample (e.g., a diagnostic sample), which can be used to diagnose diseases or health conditions in the subject from whom the sample originated.

[1090] Table B4 provides a list of autoantibody targets, which can be used in whole or as epitope fragments as capture agents in this method to measure the amount of epitope-binding antibody analytes in a sample, thereby diagnosing related diseases or health conditions, such as autoimmune diseases. In some cases, the disease or health condition is related to an immune response to an allergen. Table B5 provides a list of allergens, which can be used in whole or as epitope fragments as capture agents in the method of the present invention to measure the amount of epitope-binding antibody analytes in a sample, thereby diagnosing related diseases or health conditions, such as allergies. In some cases, the disease or health condition is related to an infectious disease, where the causative agent can be diagnosed based on information including measurements of antibodies against one or more epitopes (e.g., lipopolysaccharides, toxins, proteins, etc.) derived from the causative agent. Table B6 provides a list of epitopes of causative agents, which can be used in whole or as epitope fragments as capture agents in this method to measure the amount of epitope-binding antibody analytes in a sample, thereby diagnosing related diseases or health conditions, such as infections. Other epitopes or antigens applicable to this diagnostic method are described, for example, in PCT application publication number WO2013164476, which is incorporated herein by reference.

[1091] Table B4: Diagnostic Autoantibody Epitopes

[1092]

[1093]

[1094]

[1095]

[1096]

[1097] Table B5: Epitopes of Allergens

[1098]

[1099]

[1100]

[1101]

[1102] Table B6: Epitopes derived from pathogenic factors

[1103]

[1104]

[1105] In some cases, the biomarkers detected using this method are microRNA (miRNA) biomarkers associated with diseases or health conditions. Table B7 below provides a list of miRNA biomarkers that can be detected using this invention and their associated diseases / health conditions.

[1106] Table B7: Diagnostic miRNA Markers

[1107]

[1108]

[1109]

[1110]

[1111]

[1112]

[1113] *The miRNA marker in parentheses was downregulated.

[1114] Environmental Testing. As described above, the apparatus, systems, and methods of the present invention can be used to analyze the presence of environmental markers in environmental samples, such as samples from water, soil, industrial waste, etc. Environmental markers can be any suitable marker that can be captured by a trapping agent, which specifically binds to the environmental marker in a CROF device configured with the trapping agent. Environmental samples can be obtained from any suitable source, such as rivers, oceans, lakes, rain, snow, sewage, wastewater treatment runoff, agricultural runoff, industrial runoff, tap water, or drinking water, etc. In some embodiments, the apparatus and systems of the present invention detect the concentration of lead or toxins in water. In some embodiments, the presence or absence of environmental markers in the sample, or the quantification level, can indicate the state of the environment from which the sample was obtained. In some cases, environmental markers can be substances that are toxic or harmful to organisms exposed to the environment, such as humans, companion animals, plants, etc. In some cases, environmental markers can be allergens that can cause allergic reactions in some individuals exposed to the environment. In some cases, the presence or absence of environmental markers in the sample, or the quantification level, can be related to the general health of the environment. In this case, the overall health of the environment can be measured over a period of time, such as a week, months, years, or decades.

[1115] In some embodiments, the apparatus, systems, and methods of the present invention further include receiving or providing a report indicating the safety or harmfulness of an object exposed to the environment from which the sample was obtained, based on information including the quantity of measured environmental markers. Information used to assess environmental safety risks or health may include data in addition to the type and quantity of environmental markers. This other data may include location, altitude, temperature, time of day / month / year, pressure, humidity, wind direction and speed, weather, etc. The data may represent averages or trends over specific time periods (minutes, hours, days, weeks, months, years, etc.) or instantaneous values ​​over shorter time periods (milliseconds, seconds, minutes, etc.).

[1116] The report can be generated by a device configured to read the CROF device, or it can be generated at a remote location while sending data containing measured environmental markers. In some cases, experts can be at a remote location or have access to data sent to a remote location, and can analyze or view that data to generate a report. Experts can be scientists or managers from government agencies such as the U.S. Centers for Disease Control and Prevention (CDC) or the U.S. Environmental Protection Agency (EPA), research institutions such as universities, or private companies. In some embodiments, experts can issue instructions or recommendations to users based on data sent by the device and / or analyzed at a remote location.

[1117] A list of exemplary environmental labels is set forth in Table 8 of U.S. Provisional Application Serial No. 62 / 234,538, filed September 29, 2015, which is incorporated herein by reference.

[1118] Table B8: Environmental Labels

[1119]

[1120]

[1121]

[1122]

[1123]

[1124] Food Detection. As described above, the apparatus, system, and method of the present invention can be used to analyze food samples, such as samples from unprocessed foods, processed foods, cooked foods, drinking water, etc., for the presence of food markers. Food markers can be any suitable marker, such as those shown in Table B9 below, which can be captured by a capture agent that specifically binds to the food markers in a CROF device constructed together with the capture agent. Environmental samples can be obtained from any suitable source, such as tap water, drinking water, prepared foods, processed foods, or raw foods, etc. In some embodiments, the presence or absence, or quantitative level, of food markers in a sample can indicate the safety or hazard to a subject if the food is consumed. In some embodiments, food markers are substances derived from pathogens or microorganisms that indicate the presence of organisms in the food from which the sample was obtained. In some embodiments, food markers are toxic or harmful substances if consumed by a subject. In some embodiments, food markers are bioactive compounds that may unintentionally or accidentally alter physiology if consumed by a subject. In some embodiments, food markers are indicators of the manner in which the food was obtained (growth, acquisition, capture, harvesting, processing, cooking, etc.). In some embodiments, food markers indicate the nutritional content of the food. In some embodiments, if the food sample is consumed by a subject, the food label is an allergen that can induce an allergic reaction.

[1125] In some embodiments, the apparatus, systems, and methods of the present invention further include receiving or providing a report that, based on information including measurement levels of food markings, indicates the safety or hazard of a subject consuming a food sample from which the sample was obtained. The information used to assess the safety of food intended for consumption may include data different from the type and measurement of food markings. This additional data may include any health conditions relevant to the consumer (allergies, pregnancy, chronic or acute illnesses, currently prescribed medications, etc.).

[1126] The report can be generated by a device configured to read the CROF device, or it can be generated at a remote location when data containing the amount of measured food tags is transmitted. In some cases, food safety experts can be at a remote location or have access to data transmitted to a remote location, and can analyze or view that data to generate a report. Food safety experts can be scientists or managers of government agencies (e.g., the U.S. Food and Drug Administration (FDA) or the CDC), research institutions (e.g., universities), or private companies. In some embodiments, food safety experts can issue instructions or recommendations to users based on data transmitted by the device and / or analyzed at a remote location.

[1127] Table B9: Food Labelling

[1128]

[1129]

[1130]

[1131] Table B10. Analytes for POC

[1132]

[1133]

[1134]

[1135]

[1136]

[1137]

[1138] Health conditions that can be diagnosed or measured by subject-specific methods, devices, and systems include, but are not limited to: chemical balance; nutritional health; exercise; fatigue; sleep; stress; prediabetes; allergies; aging; exposure to environmental toxins, pesticides, herbicides, synthetic hormone analogs; pregnancy; menopause; and menopause.

[1139] In some implementations, the methods described above can be used to obtain and compare the relative levels of nucleic acids in two or more different nucleic acid samples. In these embodiments, the results obtained from the methods described above are typically normalized to the total amount of nucleic acids (e.g., constitutive RNA) in the samples and then compared. This can be done by comparing ratios or by any other means. In specific embodiments, the nucleic acid profiles of two or more different samples can be compared to identify nucleic acids associated with a specific disease or condition.

[1140] In some embodiments, the different samples may consist of an "experimental" sample (i.e., the sample of interest) and a "control" sample to which the experimental sample can be compared. In many embodiments, the different samples are a pair of cell types or portions thereof, one cell type being the cell type of interest, such as abnormal cells, and the other being a control, such as normal cells. If two portions of a cell are compared, these portions are typically the same parts from each of the two cells. However, in some embodiments, two portions of the same cell may be compared. Exemplary cell types include, for example, cells isolated from tissue biopsies (e.g., from tissue suffering from diseases such as colon, breast, prostate, lung, skin cancer, or infected with pathogens, etc.) and normal cells from the same tissue, typically from the same patient; cells grown in tissue incubators that are immortalized (e.g., cells with proliferative mutations or immortalized transgenes), infected with pathogens, or treated (e.g., with environmental or chemical agents such as peptides, hormones, altered temperature, growth conditions, physical stress, cell transformation, etc.) and normal cells (e.g., cells that are otherwise identical to the experimental cells except that they are not infinitely proliferating, infected, or treated, etc.); cells isolated from mammals suffering from cancer, disease, old age, or exposed to the disease, and cells from the same species, preferably from the same family, healthy or young mammals; and differentiated and undifferentiated cells from the same mammal (e.g., one cell is a progenitor cell of another mammal). In one embodiment, different types of cells, such as neurons and non-neurons, or cells in different states (e.g., before and after stimulation of the cells), may be used. In another embodiment of the invention, the experimental material is cells susceptible to infection by pathogens such as viruses, such as human immunodeficiency virus (HIV), and the control material is cells resistant to infection by the pathogen. In another embodiment of the invention, the sample pairs are represented by undifferentiated cells, such as stem cells, and differentiated cells.

[1141] 7. Sample thickness control and measurement without spacers

[1142] In some embodiments of the invention, the spacers used to adjust the sample or a related volume of the sample are replaced by (a) a positioning sensor capable of measuring the internal space of the plate, and (b) a device capable of controlling the position of the plate and moving the plate into the desired internal space of the plate based on information provided by the sensor. In some embodiments, all spacers are replaced by a translation stage, monitoring sensors, and a feedback system.

[1143] The spacing and / or sample thickness are measured using optical methods. In some embodiments, the measurement (f) of the spacing between the inner surfaces includes the use of optical interference. Optical interference can use multiple wavelengths. For example, the optical signal caused by the interference of light reflected at the inner surfaces of the first and second plates oscillates with the wavelength of the light. Based on the oscillation, the spacing between the inner surfaces can be determined. To enhance the interference signal, one or both inner surfaces can be coated with a light-reflective material.

[1144] In some embodiments, the measurement (f) of the spacing between the inner surfaces includes obtaining optical imaging (e.g., obtaining a 2D / 3D image of the sample, and the image acquisition may be multiple times with different viewpoints, different wavelengths, different phases and / or different polarizations) and image processing.

[1145] The entire sample region or volume is measured using optical methods. In some embodiments, the measurement of the entire sample region or volume (f) includes obtaining optical imaging (e.g., obtaining a 2D / 3D image of the sample, and image acquisition may be multiple times with different viewpoints, wavelengths, phases, and / or polarizations) and image processing. The sample region refers to the area in a direction generally parallel to the first and second plates. 3D imaging can be performed using fringe projection profilometry (FPP), one of the most common methods for acquiring three-dimensional (3D) images of objects.

[1146] In some embodiments, measuring a sample region or volume by imaging includes (a) calibrating the image scale by using a sample of known region or volume (e.g., the imager is a smartphone, and the size of the image taken by the phone can be calibrated by comparing images of samples of known size taken by the same phone); (b) comparing the image with scale markings (rulers) placed on or near a first plate and a second plate (discussed further here); and (c) combinations thereof.

[1147] As used herein, light can include visible light, ultraviolet light, infrared light, and / or near-infrared light. Light can contain wavelengths in the range of 20 nm to 20,000 nm.

[1148] It must be noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise, such as when the word “single” is used. For example, reference to “analyte” includes a single analyte and multiple analytes, reference to “capture agent” includes a single capture agent and multiple capture agents, reference to “detector” includes a single detector and multiple detectors, reference to “reagent” includes a single reagent and multiple reagents, and reference to “camera” includes a single camera and multiple cameras.

[1149] As used herein, the terms “adapter” and “construction” mean that an element, component, or other subject is designed and / or intended to perform a given function. Therefore, the use of the terms “adapter” and “construction” should not be construed as meaning that a given element, component, or other subject is only “capable” of performing a given function. Similarly, a subject stated as constructed to perform a particular function may additionally or optionally be described as operable to perform that function.

[1150] As used herein, when reference is made to one or more components, features, details, structures, embodiments, and / or methods according to this disclosure, the phrases “for example,” “as an example,” and / or simply the terms “example” and “exemplary” are intended to convey illustrative, non-exclusive examples of the described components, features, details, structures, embodiments, and / or methods according to this disclosure. Therefore, the described components, features, details, structures, embodiments, and / or methods are not intended to be limiting, essential, or exclusive / exhaustive; and other components, features, details, structures, embodiments, and / or methods, including those that are structurally and / or functionally similar and / or equivalent, are also within the scope of this disclosure.

[1151] As used herein, the phrases “at least one” and “one or more” for a list of more than one entity refer to any one or more entities in the entity list, and are not limited to at least one of each and every entity specifically listed in the entity list. For example, “at least one of A and B” (or equivalently, “at least one of A or B”, or equivalently, “at least one of A and / or B”) could refer to A alone, B alone, or a combination of A and B.

[1152] As used herein, the term “and / or” placed between the first entity and the second entity refers to (1) the first entity, (2) the second entity, and (3) one of the first entity and the second entity. Multiple entities listed using “and / or” should be interpreted in the same way, i.e., “one or more” of the entities thus combined. Other entities may optionally exist besides those specifically identified by the “and / or” clause, whether related to or unrelated to those specifically identified. Thus, as a non-limiting example, when used in conjunction with open-ended language (e.g., “contains”), a reference to “A and / or B” may in some embodiments refer only to A (optionally containing entities other than B); in some embodiments only to B (optionally containing entities other than A); and in some embodiments refer to both A and B (optionally containing other entities). These entities may refer to elements, actions, structures, steps, operations, values, etc.

[1153] If any patent, patent application or other reference is incorporated herein by reference and (1) defines a term in a manner inconsistent with any part of this disclosure or any other incorporated reference and / or (2) otherwise is inconsistent with any part of this disclosure or any other incorporated reference, the part of this disclosure shall prevail, and the term or any disclosure in which it is incorporated shall be determined solely by the reference in which the term is first defined and / or in which the incorporated disclosure first appears.

[1154] It is believed that the following claims specifically point to certain combinations and sub-combinations of one of the disclosed inventions and are novel and non-obvious. Inventions embodied in other combinations and sub-combinations of features, functions, elements, and / or characteristics may be claimed by amending these claims or by setting new claims in this application or related applications. These amended or new claims, whether they pertain to different or the same invention, and whether their scope differs from, is broader, narrower, or equal to that of the original claims, are also considered to be included within the subject matter of the invention disclosed herein.

Claims

1. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps: (a) Obtain the first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes an inner surface having a sample contact area for contacting the fluid sample; iv. Each plate includes a stress zone on its respective outer surface, the stress zone being used to apply an imprecise pressure that forces the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height of 200 micrometers or less and a predetermined fixed spacing distance; vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below; and viii. At least one of the spacers is located inside the sample contact area; (b) Obtain a fluid sample; (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer; (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises: Place the two boards together; and At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together to form a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample shortens the time required for mixing the reagent at the storage site with the sample, and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

2. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising: The first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates; Another of the aforementioned configurations is a closed configuration configured after the sample deposition; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and adjusted by the plates and the spacer; and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

3. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps: (a) Obtain the first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; (b) Obtain a fluid sample; (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer; (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises: Place the two boards together; and At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together to form a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample shortens the time required for mixing the reagent at the storage site with the sample, and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

4. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising: The first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates; Another of the aforementioned configurations is a closed configuration configured after the sample deposition; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer; The force used to press the two plates into a closed structure is imprecise and is provided by hand.

5. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the following steps: (a) Obtain the first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; (b) Obtain a fluid sample; (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer; (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises: Place the two boards together; and At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together to form a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample shortens the time required for mixing the reagent at the storage site with the sample, and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

6. An apparatus for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise force, comprising: The first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; and One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates; Another of the aforementioned configurations is a closed configuration configured after the sample deposition; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer; The force used to press the two plates into a closed structure is imprecise and is provided by hand.

7. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the steps of: (a) Obtain the first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing the fluid sample; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height, a predetermined width, and a predetermined spacing distance equal to or less than 200 micrometers; vii. The ratio of the spacing distance to the width of the spacer is 1.5 or greater; viii. At least one of the spacers is located inside the sample contact area; and (b) Obtain a fluid sample; (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer; (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises: Place the two boards together; and At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together to form a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample shortens the time required for mixing the reagent at the storage site with the sample, and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

8. An apparatus for determining the volume of a relevant sample by pressing with an imprecise force provided by a human hand, comprising: The first plate, the second plate, the spacer, and the area determination device, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacers have a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance; vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD) 4 / (hE)) is 5×10 6 μm 3 / GPa or below; viii. At least one of the spacers is located inside the sample contact area; and ix. The region determining device is configured to determine a lateral region of the relevant volume; One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates; Another of the aforementioned configurations is a closed configuration configured after the sample deposition; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer; The relevant volume of the sample is a portion or the entire volume of the uniform thickness layer, and the value of the relevant volume is determined by the uniform thickness and the defined lateral region; and The force used to press the two plates into a closed structure is imprecise and is provided by hand.

9. A method for forming a thin fluid sample layer of uniform predetermined thickness by pressing with imprecise pressure, comprising the steps of: (a) Obtain the first plate, the second plate, and the spacer, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance; vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD4 / (hE)) is 5 × 10⁻⁶. 6 μm 3 / GPa or below; viii. At least one of the spacers is located inside the sample contact area; and ix. The region determining device is configured to determine a lateral region of the relevant volume; (b) Obtain a fluid sample; (c) Depositing the sample on one or two plates; when the plates are configured in an open configuration, wherein the open configuration is a configuration in which the two plates are partially or completely separated and the spacing between the plates is not adjusted by the spacer; (d) Following (c), the two plates are used to compress at least a portion of the sample into a layer of substantially uniform thickness, the layer being defined by the sample contact surface of the plates, wherein the uniform thickness of the layer is adjusted by the spacer and the plates, wherein the compression comprises: Place the two boards together; and At least one region of these plates is conformally pressed in parallel or sequentially to press the plates together to form a closed configuration, wherein the conformal pressing on at least a portion of the sample generates substantially uniform pressure on the plates, and the pressing causes at least a portion of the sample to laterally expand between the sample contact surfaces of the plates, and wherein the closed configuration is a configuration in which the spacing between the plates in the uniform thickness region layer is adjusted by the spacer; and wherein the reduced thickness of the sample shortens the time required for mixing the reagent at the storage site with the sample, and The force that compresses the two plates into a closed structure is an imprecise pressure provided by human hands.

10. An apparatus for determining the volume of a relevant sample by pressing with an imprecise force provided by a human hand, comprising: The first plate, the second plate, the spacer, and the area determination device, wherein: i. The plates can be moved relative to each other to different configurations; ii. One or both plates are flexible; iii. Each plate includes a sample contact area on its respective inner surface for contacting and / or compressing a fluid sample with the relevant volume to be measured; iv. Each plate contains a region on its respective outer surface for applying forces that force the plates together; v. One or two plates include spacers permanently fixed to the inner surfaces of the respective plates; vi. The spacer has a predetermined substantially uniform height of 200 micrometers or less and a predetermined constant spacing distance; vii. The fourth power of the spacing distance (IDS) divided by the thickness (h) of the flexible plate and Young's modulus (E) (ISD4 / (hE)) is 5 × 10⁻⁶. 6 μm 3 / GPa or below; viii. At least one of the spacers is located inside the sample contact area; and ix. The region determining device is configured to determine a lateral region of the relevant volume; One of the configurations is an open configuration, in which the two plates are partially or completely separated, the spacing between the plates is not adjusted by spacers, and the sample is deposited on one or both of the plates; Another of the aforementioned configurations is a closed configuration configured after the sample deposition; and in the closed configuration: at least a portion of the sample is compressed by the two plates into a layer of very uniform thickness and is substantially stationary relative to the plates, wherein the uniform thickness of the layer is defined by the sample contact area of ​​the two plates and is adjusted by the plates and the spacer; The relevant volume of the sample is a part or all of the volume of the uniform thickness layer, and the value of the relevant volume is determined by the uniform thickness and the defined lateral region. The force used to press the two plates into a closed structure is imprecise and is provided by hand.

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