Dry slide assay using reduced read window

Abstract

The present disclosure relates to a method and apparatus for performing an assay on a dry slide or other solid medium using a reduced read window. In one embodiment, the method of performing at least one assay includes acquiring an image of a fluid sample located on a dry slide, positioning a read window to correspond to an area of ​​the fluid sample in the image, determining an interference region within the read window based on light intensity, reducing the read window to eliminate the interference region from the read window, and performing at least one assay using the reduced read window.

Description

Technical Field

[0001] The present disclosure generally relates to a method and apparatus for reducing an initial read window to remove interference areas when performing an assay using an image of a fluid sample on a slide medium such as a dry slide, and more specifically to a method and apparatus for selecting a predetermined shape and / or area for the reduced read window and positioning the predetermined shape and / or area within the initial read window to exclude interference areas. Background Art

[0002] In some cases, the assay is performed by measuring the light intensity of an area of ​​an image of a fluid sample that has been dispensed onto a dry slide or other solid medium. However, a problem with this approach is that when the fluid sample is washed on the dry slide, the washing process can result in inaccuracies due to retention variations in the washing fluid. Some assays, such as the digoxin ("DGXN") assay, have poor accuracy at high analyte levels, particularly in the retention area where the washing fluid has been dispensed, due to free analyte and free marker in the retention area that have not been washed away. Summary of the invention

[0003] The present disclosure relates to a method and apparatus for performing an assay on a dry slide or other solid medium using a reduced read window. In an exemplary embodiment that may be used with any other embodiment disclosed herein, a method of performing at least one assay includes acquiring an image of a fluid sample located on a dry slide, positioning a read window to correspond to an area of ​​the fluid sample in the image, determining an interference region within the read window, reducing the read window to eliminate the interference region from the read window, and performing at least one assay using the reduced read window.

[0004] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window to a predetermined shape.

[0005] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window to a crescent shape.

[0006] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window from a circular shape to a crescent shape.

[0007] In another embodiment, which may be used with any other embodiment disclosed herein, the read window has an initial area, and reducing the read window includes reducing the read window to a predetermined area that is smaller than the initial area.

[0008] In another embodiment which may be used with any other embodiment disclosed herein, the method includes dispensing a washing fluid onto the fluid sample on the dry slide, wherein the disturbed area is caused by the washing fluid.

[0009] In another embodiment, which may be used with any other embodiment disclosed herein, the interference zone is caused by fluid retention resulting from dispensing of cleaning fluid.

[0010] In another exemplary embodiment that may be used with any other embodiment disclosed herein, a method of performing at least one assay includes dispensing a fluid sample onto a dry slide, dispensing a wash fluid onto the fluid sample on the dry slide, acquiring an image of the dry slide, positioning a read window to correspond to an area of ​​the fluid sample in the image, reducing the read window to exclude an area of ​​interference caused by the wash fluid, and performing the at least one assay using the reduced read window.

[0011] In another embodiment that may be used with any other embodiment disclosed herein, the method includes determining an interference region within the read window based on known dispensing locations of the cleaning fluid.

[0012] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window to a predetermined shape.

[0013] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window to a crescent shape.

[0014] In another embodiment, which may be used with any other embodiment disclosed herein, reducing the read window includes reducing the read window from a circular shape to a crescent shape.

[0015] In another embodiment, which may be used with any other embodiment disclosed herein, the read window has an initial area, and reducing the read window includes reducing the read window to a predetermined area that is smaller than the initial area.

[0016] In another embodiment, which may be used with any other embodiment disclosed herein, the interference zone is caused by fluid retention resulting from dispensing of cleaning fluid.

[0017] In another exemplary embodiment that may be used with any other embodiment disclosed herein, an apparatus for performing at least one assay comprises: a slide receiving position configured to receive at least one dry slide having a fluid sample positioned thereon, a dispenser configured to dispense a washing fluid onto the fluid sample on the dry slide, and a control unit configured to: (i) position a read window to correspond to an area of ​​the fluid sample in an image; (ii) reduce the read window to exclude an area of ​​interference caused by the washing fluid; and (iii) perform at least one assay using the reduced read window.

[0018] In another embodiment, which may be used with any other embodiment disclosed herein, the control unit is configured to determine the interference region within the read window based on known dispensing locations of the cleaning fluid.

[0019] In another embodiment, which may be used with any other embodiment disclosed herein, the control unit is configured to reduce the reading window to a predetermined shape.

[0020] In another embodiment, which may be used with any other embodiment disclosed herein, the control unit is configured to reduce the reading window from a circular shape to a crescent shape.

[0021] In another embodiment, which may be used with any other embodiment disclosed herein, the control unit is configured to reduce the read window to a predetermined area.

[0022] In another embodiment, which may be used with any other embodiment disclosed herein, the interference region is caused by fluid retention caused by a wash fluid dispensed onto the dry slide.

[0023] In another embodiment, which may be used with any other embodiment disclosed herein, in combination with Figures 1 to 11 Any structure and function disclosed may be combined with Figures 1 to 11 Any other structure and function combination disclosed.

[0024]

[0013] It is therefore an advantage of the present disclosure, in accordance with the present disclosure and the above-mentioned aspects, to provide an improved method and apparatus for determining a reduced read window for performing an assay on a biological sample.

[0025] Additionally, according to the present disclosure and the above aspects, an advantage of the present disclosure is thus to use a reduced read window to reduce the effects from sample washing.

[0026] The advantages discussed herein may be found in one or some of the embodiments disclosed herein, and may not be found in all of the embodiments disclosed herein.Additional features and advantages are described herein and will be apparent from the following detailed description and accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Embodiments of the present disclosure will now be explained in further detail, by way of example only, with reference to the accompanying drawings, in which:

[0028] Figure 1 shows a side view of an exemplary embodiment of a dry slide according to the present disclosure;

[0029] Figure 2 Shows Figure 1 An exploded perspective view of a dry slide;

[0030] Figure 3 The present disclosure shows Figure 1 A side view of an exemplary embodiment of a dry slide assay device;

[0031] Figure 4 An exemplary embodiment of a cleaning mechanism for dispensing cleaning fluid onto a dry slide according to the present disclosure is shown;

[0032] Figure 5 An exemplary embodiment of a method of performing at least one assay according to the present disclosure is shown;

[0033] Figure 6 An exemplary embodiment of a read window created within an image according to the present disclosure is shown;

[0034] Figure 7 shows an exemplary embodiment in which an initial read window is reduced to a reduced read window according to the present disclosure;

[0035] Figure 8 An example of how the methods according to the present disclosure can improve digoxin kinetics is shown;

[0036] Fig. 9 An example is shown of how the method according to the invention can improve digoxin kinetics;

[0037] Fig.10 An example showing how the method according to the invention can improve digoxin kinetics; and

[0038] Fig.11 An example of how a reduced read window can be used to improve assay accuracy according to methods of the present disclosure is shown. DETAILED DESCRIPTION

[0039] The present disclosure relates to a method and apparatus for performing an assay on a solid medium using a reduced read window. As discussed in more detail below, the currently disclosed method and apparatus are advantageous, for example, in excluding a retention region from imaging to improve the imaging accuracy of a biological sample. The retention region can be formed by one or more processes for cleaning the sample. By reducing the read window, light intensity variations in the retention region are selectively excluded from image analysis when the sample is assayed.

[0040] Figure 1 and Figure 2 An exemplary embodiment of a solid medium or dry slide that can be used according to the present disclosure is shown. Figure 1 and Figure 2 In the embodiment shown, the reaction cell is a solid medium 10 that can be used with the assay system 20 according to the present disclosure. The solid medium 10 can be, for example, a single layer or a multilayer thin film element, on which a fluid sample can be distributed. In the illustrated embodiment, the solid medium 10 includes a plurality of layers, including a first layer 12, which can be an upper slide mounting layer, and the upper slide mounting layer is configured to provide a top base layer, which has holes passing therethrough to receive a fluid sample. The first layer can also be configured to spread the fluid sample thereon. The solid medium 10 also includes a second layer 14, which can be a reagent layer, which includes reagents configured to react with the fluid sample for a specific assay. The second layer 14 can also include a support layer to provide support or rigidity for the reagent layer. The solid medium also includes a third layer 16, which can be a filter layer, which provides a low wavelength cutoff filter for optical analysis. The third layer 16 can include a lower slide mounting layer, which is configured to provide a bottom base layer, which has holes passing therethrough for optical analysis. Although the solid medium 10 is shown as a dry slide, in other examples, the solid medium may include a reaction dish, a dry slide, or the like.

[0041] Figure 3 An exemplary embodiment of an assay system 20 configured to receive and analyze a solid medium 10 to perform an assay is shown. As shown, the assay system 20 may include a solid medium receiving position 22 configured to receive at least one solid medium 10 having a fluid sample positioned thereon, a cleaning mechanism 40 configured to dispense a cleaning fluid onto the solid medium 10, an imaging device 24 positioned and arranged relative to the solid medium receiving position 22 to acquire at least one image of the fluid sample positioned on the solid medium 10, a light source 26 (e.g., one or more light emitting diode lights) configured to project light onto the solid medium 10 such that the light may be modulated by the liquid sample dispensed onto the solid medium 10, and optionally, an optical filter 28 configured to modulate light from the light source 28 to a specific wavelength specific to the assay being performed.

[0042] In the illustrated embodiment, the slide receiving position 22 is configured to receive and hold the solid medium 10 when a fluid sample is added to the first layer 12 of the solid medium 10, when a cleaning fluid is added to the first layer 12 of the solid medium 10, and / or when the solid medium 10 is illuminated by the light source 26 and imaged by the imaging device 24. In the illustrated embodiment, the solid medium receiving position 22 includes at least one bracket that creates a first opening 22a and a second opening 22b. The fluid sample and the cleaning fluid can be added to the solid medium 10 at the first opening 22a of the solid medium receiving position 22 (e.g., through a hole in the first layer 11), and once the fluid sample has reacted with the reagent, the second opening 22b of the solid medium receiving position 22 allows the solid medium 10 to be illuminated and imaged (e.g., through a hole in the sixth layer 16). It should also be understood that the addition of fluid sample and cleaning fluid can occur before the solid medium 10 is received by the solid medium receiving position 22, and that illumination and imaging of the solid medium 10 can occur at a first opening 22a at the top of the solid medium receiving position 22, as opposed to a second opening 22b at the bottom of the solid medium receiving position 22.

[0043] The analysis system 20 may also include a control unit 30 configured to control one or more elements of the analysis system 20 and analyze the fluid sample on the solid medium 10 according to the method described herein. The control unit 30 may include a processor and a non-transitory memory storing instructions for performing the method, wherein the processor executes the instructions to control one or more elements of the assay system 20 and perform the assay.

[0044] Figure 4 An exemplary embodiment of a cleaning fluid dispensed onto a solid medium 10 according to an exemplary embodiment of the present disclosure is shown. In the illustrated embodiment, the cleaning fluid may be dispensed onto the solid medium 10 via a cleaning mechanism 40 controlled by a control unit 30, but the cleaning fluid may also be dispensed before the solid medium 10 is received at the solid medium receiving position 22. As shown, the cleaning mechanism 40 is located above the solid medium 10 including the fluid sample, and the cleaning fluid is dispensed onto the solid medium 10 at the cleaning dispensing position 42 (e.g., Figure 6 and Figure 7 In one embodiment, the cleaning fluid is applied by a nozzle (e.g., a tip having a small orifice with a diameter of about 0.4 millimeters (mm)) of a cleaning mechanism 40, which is located at a distance from the sample dispensing position 34 ( Figure 6 and Figure 7 The cleaning fluid may be dispensed at a dispensing rate and total dispensing volume specific to the type of assay being performed.

[0045] like Figure 4 As shown in the example of FIG. 4 , when the cleaning fluid is dispensed, a small liquid meniscus is formed between the nozzle and the solid medium 10. The cleaning fluid enters the solid medium 10 near the edge of the meniscus. Below the meniscus, a retention area 44 with a small amount of fluid flow is formed, so that the free markers and analytes are retained in the retention area 44 without significant displacement. Outside the meniscus, lateral fluid flow moves soluble materials (including free markers and free analytes) out of the center under the nozzle of the cleaning mechanism 40.

[0046] The size of the retention area 44 is affected by the flow rate of the fluid from the nozzle, the flow rate through the solid medium 10, and the size of the gap between the nozzle and the solid medium 10. Although the flow rate from the nozzle can be controlled by the control unit 30, the flow rate in the solid medium 10 is significantly affected by the viscosity of the sample fluid, which varies between patients. The flow rate in the solid medium 10 can also be affected by the specific properties (e.g., wettability, permeability, and porosity) of the solid medium 10, which depend on the specific composition of the solid medium 10. As a result, the size of the retention area 44 has a large variability between samples, which means that the amount of free markers and free analytes that are not washed also varies between samples. The changes in the free markers and free analytes in the retention area 44 contribute to the changes in the image reflection density, and therefore contribute to the changes in the rate of the determination of the binding marker.

[0047] To correct for free markers and free analytes in the stagnant region 44, the control unit 30 may employ an algorithm to actively identify and utilize regions on the solid medium 10 that are least disturbed by undesired signals, such as free markers and free analytes from the wash fluid. The algorithm results in an initial read window 50 ( Figure 7 The initial circular reading window 50 can be reduced to a reduced crescent reading window 60 in the embodiment explained in more detail below to avoid interference areas from washing variations, thereby eliminating variations in the washing retention area from the assay signal and improving assay accuracy.

[0048] Figure 5 A method 100 for performing at least one assay using, for example, a solid medium 10 and an assay system 20 is shown. One of ordinary skill in the art will appreciate that the method 100 may also be used with different types of solid media and assay systems. It should also be appreciated that the method 100 may be omitted without departing from the spirit and scope of the present disclosure. Figure 5 One or more of the steps shown in the drawings may be changed, and / or additional steps may be added, and / or the order of certain steps may be rearranged.

[0049] Beginning at step 102, a solid medium 10 is received at a solid medium receiving position 22. In one embodiment, the solid medium 10 includes antibodies that are either coated throughout a beaded spreading layer (non-receptor form, such as a digoxin assay form) or coated in a thin receptor layer (receptor form, such as carbamipine). For example, an HRP (horseradish peroxidase) label can be gravure coated with or without pre-binding (in non-receptor form). One of ordinary skill in the art will appreciate that different types of solid medium 10 can be used for different types of assays, and the composition and coating of the solid medium 10 can be varied accordingly. In the illustrated embodiment, the assay system 20 is configured to receive a plurality of different types of solid media, and to perform different types of assays and / or multiple assays depending on which type of solid media is inserted into the solid medium receiving position 22.

[0050] In step 104, the fluid sample to be analyzed is dispensed onto the solid medium 10 at the sample dispensing position 34. For example, a small amount (e.g., about 11 μL) of sample fluid with free analyte can be quantitatively dispensed onto the solid medium 10 at the sample dispensing position 34. In one embodiment, the sample fluid is added at the sample dispensing position 34 of the solid medium 10, for example, by a pipette controlled by the control unit 30. In another embodiment, the fluid sample can be added by the user before the solid medium 10 is inserted into the solid medium receiving position 22. The fluid sample can then be spread on the first layer 12 and mixed with the reagent included in the second layer 14. In the HRP embodiment described above, the gravure-coated HRP label can be hydrated and dissolved by the sample fluid, and the analyte in the sample fluid and the dissolved HRP label can compete with the antibody for a certain amount of time (e.g., typically 5 minutes) for the restricted antibody site.

[0051] At step 106, a wash fluid is dispensed onto the fluid sample on the solid medium 10, for example, at a wash dispensing location 42 that is proximate to but distinct from the sample dispensing location 34 (e.g., about 2 mm from the center of the location where the fluid sample is dispensed onto the solid medium). Figure 4 The washing mechanism 40 shown applies the washing fluid. Alternatively, the washing fluid can be added by the user before the solid medium 10 is inserted into the solid medium receiving position 22. In the HRP embodiment discussed above, the unbound label and unbound analyte can be washed away by the washing fluid containing H2O2 to initiate the dye generation reaction, wherein the concentration of the bound label is monitored by the dye generation rate.

[0052] At step 108, the light source 26 may project light onto the solid medium 10 such that the light may be modulated by the fluid sample dispensed onto the solid medium 10. In one embodiment, the light is modulated by the optical filter 28 and / or a filter provided by the solid medium 10 (e.g., at the third layer 16) so as to project a specific wavelength for the assay being performed. In one embodiment, the desired wavelength may be programmed into the control unit 30, which may then control the light source 26 and the optical filter 28 so that light of the correct wavelength for the assay being performed is projected onto the solid medium 10.

[0053] At step 110, the imaging device 24 records at least one image of the fluid sample dispensed onto the solid medium 10. For example, the image may be recorded when the light source 26 projects light onto the solid medium 10 to be modulated by the liquid sample dispensed onto the solid medium 10 and / or when the optical filter 28 modulates the light from the light source 28. The imaging device 24 may be, for example, a charge coupled device ("CCD") camera, which may, for example, record a two-dimensional image showing an approximately elliptical or circular fluid sample on the solid medium 10. In one embodiment, the image is captured at a specified wavelength, and then the light intensity (e.g., AD counts) is converted into a reflection density at a 4.5 mm diameter in the central region (i.e., at the sample dispensing position 34).

[0054] In step 112, the control unit 30 positions the read window 50 to the area corresponding to the fluid sample in the image. For example, the read window 50 can be positioned by selecting a target position and then forming a read window 50 having a predetermined area and / or shape around the target position. The target position can be, for example, a sample distribution position 34 or another default position (e.g., the default center of the solid medium 10), or the target position can be selected based on light intensity. U.S. Provisional Application No. 62 / 693,110, entitled "Method and Apparatus for Selecting Dry Slide Image Read Position" filed on the same day as this application, also describes a method for locating a target position on a solid medium, and is incorporated herein by reference and relied upon. In one embodiment, the known sample distribution position 34 can be used as a center point to place the initial read window 50. In an alternative embodiment, for example, the read window 50 can be positioned or the size of the read window 50 can be determined based on the light intensity detected from the image, wherein the read window 50 is drawn to include or exclude a certain range of light intensity / reflection density.

[0055] Figure 6 An exemplary embodiment of an initial read window 50 positioned within an image 46 captured by the imaging device 30 is shown. Figure 6, the left graph shows the light intensity (e.g., AD counts) of a larger area of ​​the solid medium 10, while the right graph shows the light intensity once the area outside the initial read window 50 is excluded. In the illustrated embodiment, the initial read window 50 is positioned by taking the sample dispensing position 34 and generating a circle with a specified diameter around the sample dispensing position 34 so that all light intensity outside the circle (or substantially at least 90% of the original light intensity) is thereafter excluded. One of ordinary skill in the art will recognize that other shapes may also be used for the read window 50, although when the sample is added to the solid medium 10, the circular flow of the sample from the sample dispensing position 34 forms a circle that is particularly representative of the entire sample.

[0056] Back to Figure 5 At step 114, the interference region within the initial read window 50 may be determined. The interference region may be focused, for example, at the center of the wash dispense location 42, where a retention region 44 is formed due to changes in free label and analyte, which contributes to changes in dye generation and, therefore, changes in the light intensity signal. Figure 6 As shown, the light intensity in the retention area 44 is significantly different from the light intensity of the rest of the reading window 50, where most of the free labels and free analytes are removed in the case of lateral fluid flow. Since the cleaning fluid is distributed eccentrically from the position where the sample is distributed, the retention area 44 is also positioned to be eccentric from the center of the reading window 50, and the reading window is focused on the center of the fluid sample. Since both the bound label and the free label produce dyes, the retention area 44 is darker. The changes caused by the retention area 44 have a relatively large contribution to the image signal, making the assay less accurate and prone to error. In an alternative embodiment, the interference area can be determined based on the light intensity profile without knowing the cleaning distribution position 42, wherein the peak or valley of the light intensity profile is the center of the interference.

[0057] exist Figure 5 In step 116, the initial read window 50 is reduced to a smaller area (eg, Figure 6In one embodiment, the control unit 30 is configured to place the crescent-shaped reading window 60 by selecting the center of the crescent-shaped reading window 60 to correspond to the center of the circular reading window 50, and rotating the crescent-shaped reading window 60 so that the detected interference area is located in the excluded portion of the crescent-shaped reading window 60. In another embodiment, the control unit 30 is configured to place the crescent-shaped reading window 60 by selecting the center of the excluded area to correspond to the cleaning distribution position 42, and excluding the circular area smaller than the reading window around the cleaning distribution position 42.

[0058] Figure 7 An exemplary embodiment is shown, in which Figure 6 The read window 50 is reduced to remove the stagnation region 44. Figure 7 , the left graph shows the light intensity for a larger area of ​​the solid medium 10, while the right graph shows the light intensity once the reduced read window 60 is placed to exclude the stagnant area 44. In the illustrated embodiment, at the sample dispensing position 42, an area having a diameter of 3 mm and centered 1.4 mm from the sample dispensing position 34 is removed from the original 4.5 mm initial circular read window 50. That is, the initial read window 50 can be formed as a circle around the sample dispensing position 34 (e.g., a 4.5 mm perimeter around the sample dispensing position 34), and the reduced read window can then be formed to exclude a smaller circle around the wash dispensing position 42 (e.g., a 3 mm perimeter around the wash dispensing position 42).

[0059] In the illustrated embodiment, both the initial circular reading window 50 and the reduced crescent-shaped reading window 60 are predetermined shapes. Figure 7 A circular read window is shown reduced to a crescent, but it should be understood that different types of reductions can be envisioned. For example, an elliptical read window can be reduced to a crescent or other smaller area, a square, rectangular or other uniform or symmetrical window can be reduced to a smaller square, rectangular or other uniform or non-uniform area with a portion excluded, or an abstract or non-uniform shape can be reduced to include the excluded portion to remove dark interference areas caused by fluid retention. Removing a circle from the initial read window to produce a reduced read window is advantageous because the purge flow is nearly axisymmetric with respect to the purge dispense position.

[0060] In another embodiment, one or both of the shapes of the initial read window 50 and the reduced read window 60 may not be predetermined. For example, the area and / or shape of the reduced read window 60 may be determined when performing step 116, for example, by excluding a portion of the initial read window 50 based on the light intensity detected from the image being above or below a threshold or within a certain range.

[0061] exist Figure 5 In step 118, the assay is performed using the reduced read window 60. For example, the assay can be performed by taking the average light intensity over the reduced read window 60. In one embodiment, the reduced read window 60 is used to determine the light intensity as a function of time. For example, the rate at which the light intensity (signal) changes can be used to calculate a response (rate of change) for predicting the assay concentration.

[0062] It has been determined that reducing the read window as disclosed herein effectively reduces variations from free label and free analyte and thus improves assay accuracy.

[0063] Figure 8 The kinetics (signal change as a function of time) of the DGXN assay with calibrant level 3 are shown. As shown, the change is smaller with the reduced crescent-shaped reading window compared to the circular reading window. The lower current reading curve corresponds to the circular reading window centered at the predetermined sample distribution position. The upper crescent-removed reading curve corresponds to the crescent-shaped reading window. As shown, the upper curve is more reproducible (tighter distribution) while the lower curve is less reproducible. Figure 8 In the figure, the left and right graphs compare the results of the same sample but from different cups. As shown, the crescent-shaped read window produces better accuracy between the two cups compared to the circular read window.

[0064] Fig. 9 The kinetics (signal change as a function of time) of the DGXN assay with calibrant level 3 are shown. As shown, the change is smaller with the reduced crescent-shaped reading window compared to the circular reading window. The lower current reading curve corresponds to the circular reading window centered at the predetermined sample distribution position. The upper crescent-removed reading curve corresponds to the crescent-shaped reading window. As shown, the upper curve is more reproducible (tighter distribution) while the lower curve is less reproducible. Fig. 9 In the figure, the left and right graphs compare the results of the same sample but from different cups. As shown, the crescent-shaped read window produces better accuracy between the two cups compared to the circular read window.

[0065] Fig.10The kinetics (signal change as a function of time) of the DGXN assay with calibrant level 3 are shown. As shown, the change is smaller with the reduced crescent-shaped reading window compared to the circular reading window. The lower current reading curve corresponds to the circular reading window centered at the predetermined sample distribution position. The upper crescent-removed reading curve corresponds to the crescent-shaped reading window. As shown, the upper curve is more reproducible (tighter distribution) while the lower curve is less reproducible. Fig.10 In the figure, the left and right graphs compare the results of the same sample but from different cups. As shown, the crescent-shaped read window produces better accuracy between the two cups compared to the circular read window.

[0066] Fig.11 is a graph showing the performance with different read window shapes. Fig.11 The graph shown shows seven different instruments and four different fluid types with high digoxin concentrations used in the trial (patients 1, 2, 3, and TDM3 fluid). Fig.11 , "Default" is a 4.5 mm circular read window. "Ellipse Wt6" is an elliptical read window of 4.5 mm by 3.4 mm. "Ellipse / Moon" is an elliptical read window of 4.5 mm by 3.4 mm with the wash hold-up area removed. "Moon 3.0 mm" is a 4.5 mm circular read area with 3 mm of the wash hold-up area removed and offset by 1.4 mm (crescent moon read window). "Moon 4.0 mm" is a 4.5 mm circular read area with 4 mm of the wash hold-up area removed and offset by 2.5 mm. The best performance comes from a 4.5 mm circular read window with 3 mm of the hold-up area removed and offset by 1.4 mm (crescent moon read window). Therefore, Fig.11 The crescent-shaped reading windows with circular removal of 1.4 mm and 3 mm offsets were shown to have the best accuracy on all analyzers and all fluids.

[0067] It should be understood that various changes and modifications to the currently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the present subject matter and without reducing its expected advantages. Therefore, these changes and modifications are intended to be covered by the appended claims.

[0068] Unless otherwise stated, all numerals used in the specification and claims to represent the amount of components, properties (such as molecular weight, reaction conditions, etc.) should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters set forth in the following specification and the appended claims are approximate values, which can vary according to the desired characteristics sought to be obtained by the present disclosure. At least, and without attempting to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be interpreted at least according to the number of reported significant digits and by applying ordinary rounding techniques. Although the numerical ranges and parameters setting forth the wide range of the present disclosure are approximate values, the numerical values ​​set forth in the specific examples are reported as accurately as possible. However, any numerical value inherently contains certain errors, which are necessarily caused by the standard deviation found in their respective test measurements.

[0069] The terms "one" and "an" and similar indicators used in the context of the present disclosure (especially in the context of the appended claims) should be interpreted as covering the singular and the plural, unless otherwise indicated herein or clearly contradicted by the context. The numerical ranges recorded herein are intended only to serve as a shorthand method for referring to each individual numerical value falling within the range, respectively. Unless otherwise specified herein, each individual value is incorporated into this specification as if it were recorded separately herein. Unless otherwise specified herein or clearly contradicted by the context, all methods described herein can be performed in any suitable order. The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the present disclosure, and does not impose limitations on the scope of the present disclosure otherwise claimed. The language in the specification should not be interpreted as indicating that any unclaimed element is necessary for the practice of the present disclosure.

[0070] Use of the term "or" in the claims is intended to mean "and / or" unless explicitly stated to refer only to alternatives or the alternatives are mutually exclusive, although the present disclosure supports the reference to alternatives and the definition of "and / or."

[0071] The grouping of the alternative elements or embodiments of the present disclosure disclosed herein should not be construed as limiting. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It can be expected that, for convenience and / or patentability reasons, one or more members of the group can be included in the group or deleted from the group. When any such inclusion or deletion occurs, this specification is considered to include the group modified here, so as to meet the written description of all Markush groups used in the appended claims.

[0072] Preferred embodiments of the present disclosure are described herein, including the best mode known to the inventor for carrying out the present disclosure. Of course, after reading the foregoing description, variations of those preferred embodiments will become apparent to those of ordinary skill in the art. The inventors expect that those of ordinary skill in the art will appropriately adopt such variations, and the inventors intend to implement the present disclosure in a manner different from that specifically described herein. Therefore, the present disclosure includes all modifications and equivalents of the subject matter recorded in the appended claims as permitted by applicable law. In addition, unless otherwise specified herein or clearly contradictory to the context, the present disclosure encompasses any combination of the elements described above with all possible variations thereof.

[0073] Certain embodiments disclosed herein may be further limited in the claims using "consisting of" or "consisting essentially of" language. When used in a claim, whether as filed or added pursuant to amendment, the transition term "consisting of" excludes any element, step, or ingredient not specified in the claim. The transition term "consisting essentially of" limits the scope of the claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s). The embodiments of the present disclosure so claimed are inherently or expressly described and enabled herein.

[0074] In addition, it should be understood that the embodiments of the present disclosure disclosed herein are illustrations of the principles of the present disclosure. Other modifications that may be adopted are also within the scope of the present disclosure. Therefore, by way of example and not limitation, alternative configurations of the present disclosure may be utilized according to the teachings herein. Therefore, the present disclosure is not precisely limited to what is shown and described.

Claims

1. A method of performing at least one assay, comprising: causing, in a processor of the control unit, a wash fluid to be dispensed onto the fluid sample on the dry slide, wherein a disturbance region is caused by the wash fluid; In the processor of the control unit, acquiring an image of the fluid sample located on the dry slide; in the processor of the control unit, positioning a reading window to correspond to a region of the fluid sample in the image; In the processor of the control unit, determining the interference region within the read window based on light intensity; In the processor of the control unit, reducing the area of ​​the read window to eliminate the interference area from the read window; and In the processor of the control unit, at least one assay is performed using the reduced read window.

2. The method of claim 1, wherein: Reducing the read window includes reducing the read window to a predetermined shape.

3. The method of claim 2, wherein: Reducing the read window includes reducing the read window to a crescent shape.

4. The method of claim 3, wherein: Reducing the read window includes reducing the read window from a circular shape to the crescent shape.

5. The method according to any one of claims 1 to 4, wherein: The read window has an initial area, and wherein reducing the read window includes reducing the read window to a predetermined area that is smaller than the initial area.

6. The method according to any one of claims 1 to 4, wherein: The interference area is caused by fluid retention caused by dispensing the cleaning fluid.

7. A method of performing at least one assay, comprising: dispensing the fluid sample onto a dry slide; dispensing a cleaning fluid onto the fluid sample on the dry slide; In a processor of a control unit, acquiring an image of the dry slide; in the processor of the control unit, positioning a reading window to correspond to a region of the fluid sample in the image; In the processor of the control unit, reducing the area of ​​the reading window to exclude an interference area caused by the cleaning fluid; as well as In the processor of the control unit, at least one assay is performed using the reduced read window.

8. The method of claim 7, comprising determining the interference region within the read window based on known dispensing locations of the cleaning fluid.

9. The method according to claim 7 or 8, wherein: Reducing the read window includes reducing the read window to a predetermined shape.

10. The method of claim 9, wherein: Reducing the read window includes reducing the read window to a crescent shape.

11. The method of claim 10, wherein: Reducing the read window includes reducing the read window from a circular shape to the crescent shape.

12. The method of any one of claims 7, 8, 10 and 11, wherein: The read window has an initial area, and wherein reducing the read window includes reducing the read window to a predetermined area that is smaller than the initial area.

13. The method of any one of claims 7, 8, 10 and 11, wherein: The interference area is caused by fluid retention caused by dispensing the cleaning fluid.

14. An apparatus for performing at least one assay, comprising: a slide receiving support configured to receive at least one dry slide having a fluid sample positioned thereon; a dispenser configured to dispense a cleaning fluid onto the fluid sample on the dry slide; as well as A control unit configured to: (i) acquire an image of the fluid sample located on the dry slide; (ii) position a read window to correspond to an area of ​​the fluid sample in the image; (iii) reduce the area of ​​the read window to exclude an area of ​​interference caused by a wash fluid; and (iv) perform at least one assay using the reduced read window.

15. The apparatus of claim 14, wherein: The control unit is configured to determine the interference region within the read window based on known dispensing locations of the cleaning fluid.

16. The apparatus of claim 14 or 15, wherein: The control unit is configured to reduce the read window to a predetermined shape.

17. The apparatus of claim 14 or 15, wherein: The control unit is configured to reduce the reading window from a circular shape to a crescent shape.

18. The apparatus of claim 14 or 15, wherein: The control unit is configured to reduce the read window to a predetermined area.

19. The apparatus of claim 14 or 15, wherein: The interference region is caused by fluid retention caused by the washing fluid dispensed onto the dry slide.

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