Automated sample deposition and staining systems and related methods

Abstract

To provide cell deposition and staining apparatuses and methods, in particular, the deposition and the staining apparatuses provide low-volume automated bench top systems for depositing and staining cell samples on a cytological slide.SOLUTION: A deposition and staining apparatus includes: a housing having an access door; a substrate processing holder located within the housing configured to hold one or more substrates and / or one or more substrate cartridges, the substrate processing holder being accessible when the access door is in an open configuration; at least one opening located at least partially above at least a portion of the substrate processing holder; a spray nozzle configured to dispense a gaseous substance into a substrate processing area; a user interface configured to receive input from a user, and in response to receiving the input, cause execution of a pre-programmed protocol; and a waste and / or reagent holder element.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 696,119, filed on Jul. 10, 2018, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure provides a system, apparatus, and related methods for achieving spray deposition and staining of a cell sample within a single system. In particular, provided herein is an automated system that provides for deposition of a cell sample on a microscope slide and can stain the cell sample for its analysis as well as for clinical, diagnostic, and research purposes.

[0003]

Background Art

[0004]

[0005] Histological or cytological analysis is highly dependent on the quality of the prepared specimen (e.g., cell sample). <000004It depends. If the sample preparation is insufficient, the data will be inaccurate, leading to errors in interpreting the results. This can lead to misdiagnosis. Furthermore, complex, non-automated systems can cause problems. Clogs, diagnostic delays, unintended types of artifacts due to procedural complexity, and This leads to unacceptable per-run variability. These unintended artifacts To reduce and / or eliminate and deliver high-quality results, we use low-cost systems. Therefore, there is a need to develop a simplified and reliable system to obtain rapid and accurate results. There is. [Overview of the project]

[0005] In some embodiments, provided herein are (a) a spray holder and (b) a test A base cartridge comprising (c) a dispensing port and an upper opening for receiving a spray nozzle. It is a ledge. In some embodiments, provided herein are (a) a spray holder and (b) a sample dispensing port, wherein (i) a first sample dispensing port for receiving a sample (ii) the end of the sample, the second end of the sample dispensing port for releasing the sample into the spray holder, and (iii) a sample holding socket located between the first and second ends of the sample dispensing port The sample dispensing port has a second end located on the side of the spray holder, and the sample dispensing port (c) an upper opening for receiving a spray nozzle, and the second of the sample dispensing port. A base cartridge having an upper opening positioned at a certain angle to the opening of the base cartridge That is the case.

[0006] In some embodiments, what is provided herein is disclosed and described herein. An embodiment comprising at least one substrate cartridge and at least one substrate It is a slide holder configured to hold.

[0007] In some embodiments, what is provided herein is disclosed and described herein. A slide holder according to one embodiment, and according to one embodiment disclosed and described herein This kit comprises at least one substrate cartridge and at least one substrate. .

[0008] In some embodiments, the herein provides for depositing and staining cell samples. A device for the purpose of (a) a housing having an access door, and (b) one or more substrates and / or configured to hold one or more substrate cartridges within the housing A substrate processing holder located at the same position, which is accessible when the access door is in an open configuration. (c) a substrate processing holder and at least a portion above the substrate processing holder (d) Dispensing a gaseous substance into the substrate processing area A spray nozzle configured to (e) receive input from the user and receive input In response to this, it is configured to trigger the execution of a pre-programmed protocol. (f) a user interface and a waste and / or reagent holder element, and a device It is placed there.

[0009] In some embodiments, the substrate cartridge has a bottom opening opposite to the top opening. The spray holder is located between the upper opening and the bottom opening.

[0010] In some embodiments, the area of ​​the bottom opening is larger than the area of ​​the top opening.

[0011] In some embodiments, the substrate cartridge further comprises a sealing element disposed near the bottom opening. In some embodiments, the sealing element includes a locking element, an O-ring, and / or a gasket. / and a gasket.

[0012] In some embodiments, the substrate cartridge further comprises at least one reagent port. In some embodiments, the substrate cartridge further comprises at least one drainage reservoir. In some embodiments, the substrate cartridge further comprises at least one waste extraction port. In some embodiments, the substrate cartridge further comprises a gripping element. In some embodiments, the substrate cartridge further comprises at least one alignment element for placing the substrate cartridge within the device and / or on the substrate.

[0013] In some embodiments, the spray retainer has a rectangular prism shape, a cylindrical shape, or a frustum of a cone shape.

[0014] In some embodiments, at least one of the upper opening and / or the bottom opening is rectangular, circular, or elliptical. In some embodiments, the distance between the upper opening and the bottom opening is about 1 cm to about 10 cm. In some embodiments, the upper opening is disposed at an angle of 75 degrees to 90 degrees with respect to the second end of the sample dispensing port. In some embodiments, the sample dispensing port is a detachable sample dispensing port.

[0015] In some embodiments, the slide holder further comprises a handle.

[0016] In some embodiments, the substrate is a slide.

[0017] In some embodiments, the substrate cartridge and the substrate, when in contact, deposit / It forms a staining reservoir.

[0018] In some embodiments, at least a portion of the substrate cartridge is such that the access door is closed. When in position, it protrudes at least partially from at least one opening.

[0019] In some embodiments, the apparatus further comprises an environmental chamber. The environmental chamber is configured to control the humidity level inside the device.

[0020] In some embodiments, the device is located within the waste and / or reagent holder element, At least one waste container and / or fewer waste containers that are in fluid communication with the substrate processing area. Each also includes one additional reagent container.

[0021] In some embodiments, the apparatus further comprises a heating element.

[0022] In some embodiments, the spray nozzle sprays gaseous substances at a pressure of approximately 1 psi to approximately 30 psi. Dispense the substance.

[0023] In some embodiments, the substrate processing holder includes at least one substrate cartridge and It is configured to receive a slide holder having at least one substrate. [Brief explanation of the drawing]

[0024] Many aspects of this disclosure can be better understood by referring to the following drawings. The components in the drawings are not necessarily to scale. Instead, they clearly illustrate the principles of this disclosure. The emphasis is on doing so. Furthermore, the components are specific only to clarify the explanation. The diagram may show something as transparent, but the illustrated components are not necessarily transparent. This does not indicate that the same or lesser information is used throughout this disclosure for the sake of ease of reference. To identify similar, similar, and / or complementary components or features, A reference number may be used.

[0025] [Figure 1] This is an isometric view schematically showing a substrate cartridge according to one embodiment of the present disclosure.

[0026] [Figure 2] This is a perspective view of a substrate cartridge according to one embodiment of the present disclosure.

[0027] [Figure 3] This is an isometric view showing packaging for two substrate cartridges and a slide holder having two substrates according to one embodiment of the present disclosure.

[0028] [Figure 4] This is an isometric view showing a slide holder having two substrate cartridges and two substrates according to one embodiment of the present disclosure.

[0029] [Figure 5] This is an isometric view showing a slide holder having two substrate cartridges and two substrates arranged in a cell deposition and staining apparatus according to one embodiment of the present disclosure.

[0030] [Figure 6] This schematic diagram shows that, after cell deposition and staining using a cell deposition and staining apparatus according to one embodiment of the present disclosure, a slide holder having two substrates is placed on a microscope for visualization.

[0031] [Figure 7] This is an isometric view showing a cell deposition and staining apparatus in an open position for receiving a substrate and / or substrate cartridge, according to one embodiment of the present disclosure. The apparatus is a self-contained device comprising a sample spray deposition system, substrate staining, and onboard waste for preparing and staining substrates for pathological evaluation. The system has a small footprint.

[0032] [Figure 8] This is an isometric view showing a cell deposition and staining apparatus according to one embodiment of the present disclosure, which is in an open position and holds two substrates and two substrate cartridges. The illustrated apparatus can prepare two substrates (e.g., cytological slides) at once using single-use substrate cartridges (e.g., consumables) that seal the substrates to contain a spray and stain. The substrates and substrate cartridges are joined together and then loaded into the front of the unit. The cell sample is then loaded into the substrate cartridge, and the subassembly is then clamped in place by closing the front cover.

[0033] [Figure 9] This is a schematic diagram for operating a cell deposition and staining apparatus according to one embodiment of the present disclosure.

[0034] [Figure 10] This is a perspective view of a substrate cartridge showing sample deposition on a substrate according to one embodiment of the present disclosure.

[0035] [Figure 11] This is a perspective view of a substrate cartridge showing sample heating according to one embodiment of the present disclosure.

[0036] [Figure 12] This is a perspective view of a substrate cartridge showing sample fixation using a reagent according to one embodiment of the present disclosure.

[0037] [Figure 13] This is a perspective view of a substrate cartridge illustrating waste removal according to one embodiment of the present disclosure.

[0038] [Figure 14] This is a perspective view of a substrate cartridge showing sample staining using a reagent according to one embodiment of the present disclosure.

[0039] [Figure 15] This is a perspective view of a substrate cartridge illustrating waste removal according to one embodiment of the present disclosure.

[0040] [Figure 16] This is a perspective view of a substrate cartridge showing sample staining using a reagent according to one embodiment of the present disclosure.

[0041] [Figure 17] This is a perspective view of a substrate cartridge illustrating waste removal according to one embodiment of the present disclosure.

[0042] [Figure 18] This is a perspective view of a substrate cartridge illustrating sample disposal using a reagent according to one embodiment of the present disclosure.

[0043] [Figure 19] This is a perspective view of a substrate cartridge illustrating waste removal according to one embodiment of the present disclosure.

[0044] [Figure 20] This is a schematic diagram for operating a cell deposition and staining apparatus according to one embodiment of the present disclosure.

[0045] [Figure 21]This is a schematic top view of the interior of a cell deposition and staining apparatus according to one embodiment of the present disclosure. As shown, there are multiple bottles for containing reagents, a large waste bottle, and a pressurized CO2 canister for providing an onboard pressurized air source. A dedicated pump for each bottle provides metering and dispensing of reagents and removal of waste.

[0046] [Figure 22A-C] These are representative images of cells obtained from (a) thyroid fine-needle aspiration (FNA), (b) pleural fluid, and (c) cervical brushing, fixed using PreservCyt solution. The samples were deposited and stained using a cell deposition and staining apparatus according to embodiments of this disclosure.

[0047] [Figure 23A-D] These are representative images of hepatocellular carcinoma cells grown subcutaneously in an Oncopig model. FNA was performed on these subcutaneous tumors using (a) 25 gauge, (b) 22 gauge, (c) 19 gauge, and (d) 18 gauge needles. Samples collected from the FNA procedure were deposited and stained using a cell deposition and staining apparatus according to embodiments of this disclosure.

[0048] [Figure 24A-B] This is a representative image of an unfixed pleural fluid sample deposited and stained using Diff-Quik®. The sample was deposited and stained using a cell deposition and staining apparatus according to embodiments of this disclosure.

[0049] [Figure 25] This is a representative image of lung epithelial cells, obtained after a FNA procedure on a resected lung and prepared using a cell deposition and staining apparatus according to one embodiment of the present disclosure. [Modes for carrying out the invention]

[0050] This disclosure relates to a device for depositing and staining cell material, depositing and staining The present invention relates to apparatus, systems, and methods for color. For example, certain embodiments involve microscopic examination. Cell specimens on a substrate for investigation and other suitable molecular and imaging modalities. This enables spray deposition and staining with various reagents. In particular, the method provided herein This includes a substrate cartridge for guiding cell samples onto a substrate, and the substrate cartridge Hold and run a pre-programmed sample preparation module (e.g., staining module). It is a device for that purpose.

[0051] Specific details of several embodiments of the technology are described below with reference to Figures 1 to 25. Many of the application forms are devices, systems, and methods for producing high-quality sample-supporting substrates. The law is described below, but in addition to what is described herein, other applications and other The embodiments described herein are within the scope of the technology. Furthermore, several other embodiments of the technology are described herein. It may have a different structure, components, or procedures than those described in the book. Therefore, the technology may have other embodiments with additional elements, or the technology may have other embodiments with additional elements. The procedure does not involve some of the features shown and described below with reference to Figures 1 to 25. Those skilled in the art will understand that other embodiments are possible.

[0052] As used herein, the term “automation” means that one or more steps are operated Methods that can be performed without requiring operator intervention (e.g., "automated processes"), or operators A system or device that performs one or more of its functions without the intervention of a data source (for example, This refers to "automation equipment."

[0053] As used herein, the term "fully automated" refers to the steps after the initial setup. This includes capabilities that do not require an operator, and without operator supervision or accompaniment. A system, device, or This refers to a method. In a particular embodiment, the operator provides a sample to the system or apparatus. , and / or initiate acquisition, and sample and / or analysis is performed without subsequent operator intervention. It is generated without any conditions.

[0054] As used herein, the term “cell sample” refers to any biological sample containing cells. This refers to a sample. A cell sample is one or more tissue samples taken from a subject (for example). (or any collection of cells). Tissue samples are intercellular cells that perform similar functions within an organism. It can be a collection of successive cells. Cell samples can also include bacteria, yeast, protozoa, and americana. Single-celled organisms such as butterflies, (healthy or outwardly healthy human subjects, or those diagnosed with cancer, etc.) Plants containing samples from human patients suffering from a condition or disease that should be diagnosed or investigated. Obtained from any living organism, including but not limited to multicellular organisms (such as animals). It could be any solid or liquid sample that has been excreted or secreted by them. In some embodiments, the cell sample can be placed on a microscope slide, and tissue slices can be prepared. This includes organs, tumor smears, frozen smears, cytological preparations, or cell lines, but does not include these. Not limited to: incisional biopsy, core biopsy, excisional biopsy, fine-needle aspiration biopsy (e.g., fine-needle aspiration (FNA)). )) Obtain a sample using core needle biopsy, stereotactic biopsy, direct biopsy, or surgical biopsy. It is possible.

[0055] A system for generating reproducible, high-quality stained cell samples on substrates such as microscope slides. Stems, devices, and methods are provided herein.

[0056] This disclosure also includes (a) a spray holder, (b) a sample dispensing port, and (c) a spray nozzle. The present invention relates to a base cartridge having an upper opening for accommodating a certain amount of material. In some embodiments, The sample dispensing port has (i) a first end for receiving the sample, (i i) The second end of the sample dispensing port for releasing the sample into the spray holder, and (ii) i) Of the sample holding zones located between the first and second ends of the sample dispensing port It has at least one. In some embodiments, the second end of the sample dispensing port is a spray It is located on the side of the mist holder. In some embodiments, the upper opening is the sample dispensing port. It is positioned at a certain angle to the second opening.

[0057] This disclosure further includes (i) at least one embodiment disclosed and described herein. The present invention relates to a slide holder comprising (i) one substrate cartridge and (i) at least one substrate. do.

[0058] Other aspects of the present disclosure are apparatus for depositing and staining cell samples, (a) (b) Housing with a recessed door, (b) one or more substrates and / or one or more substrates A substrate processing holder located within the housing, configured to hold the tinder, (c) At least one located at least partially above at least a portion of the substrate processing holder (d) an opening, a spray nozzle configured to dispense the base gaseous substance into the base processing area. (e) receive input from the user, and in response to receiving the input, pre-program A user interface configured to trigger the execution of a protocol, and (f) an apparatus comprising at least one of waste and / or reagent holder elements. Regarding this, in some embodiments, the substrate processing holder is configured when the access door is open. It is accessible.

[0059] The substrate cartridge of this disclosure provides several functions. Cell samples are dispensed when the sprayer is activated. A substrate cartridge with a precise shape to ensure that the sample is held until it is removed. It is loaded into the upper part. The base cartridge also ensures that the aerosolized sample is not lost. It has a feature part that includes a spray to prevent the substrate, and uses a flexible material or the shape itself The reagent is sealed and held in contact with the substrate, so that the staining agent (i.e., the reagent) can be applied to the sample. A cavity (i.e., a deposit and staining reservoir) that allows penetration and staining. The base cartridge is attached to the base and mechanically clamped when the lid is closed. And so, fluid connections between the substrate cartridge, device, reagents, and waste lines. This is done. The base cartridge can be made from any suitable material. Suitable material Non-limiting examples of materials include biocompatible plastics, such as polycarbonate and polystyrene. Contains len or polypropylene.

[0060] Figure 1 shows a substrate for depositing and staining a cell sample on a substrate according to one embodiment of the present disclosure. This is an isometric view showing a schematic representation of cartridge 100. The substrate cartridge 100 contains cell samples. It may include a spray holder 101 for directing and guiding the spray. Base cartridge 10 0 is a sample dispensing port having a first end of a sample dispensing port 103 for receiving a sample. 102 can be further provided. The base cartridge 100 has an upper opening 104. The base cartridge also has at least a partially upper opening 10 It may have a bottom opening 105 located on the opposite side of 4, and the spray holder 101 is above It is positioned between the opening 104 and the bottom opening 105.

[0061] In some embodiments, all or part of the substrate cartridge 100 is disposable. The disposable nature of the substrate cartridge 100 helps prevent contamination between different samples. This is possible. In some cases, disposable may be all or specific of the base cartridge 100. This can indicate that the components are suitable for single use. In other embodiments, the substrate car Cartridge 100 can be reused or used multiple times (e.g., after cleaning and / or sterilization). It is possible. In certain cases, the base cartridge 100 is not disposable. There is a base cartridge, and the other parts are disposable and / or need to be replaced. The J100 can be made from a variety of materials such as plastic, metal, rubber, and silicone. This is possible. The base cartridge 100 is not limited to one or more human-readable It may further include a machine-readable label.

[0062] Returning to Figure 1, the spray holder 101 can have any suitable shape and dimensions. In some embodiments, the spray holder 101 is connected to the base 204 and / or other drainage containers. This design originates from the fact that it promotes flow that slopes downward toward the surface of the reservoir and diverges radially. It has the following shape. Non-limited shapes include rectangular prism, cylindrical, or frustoconical. In some embodiments, the spray holder 101 contains the cell material during the spray deposition process. A protective chamber is provided that encapsulates the spray of the material.

[0063] The upper opening 104 and / or the bottom opening 105 may be any preferred shape and dimensions. This is possible. In some embodiments, the upper opening 104 and / or the bottom opening Part 105 can be rectangular, circular, or elliptical. The area of ​​the bottom opening 105 is The area can be made larger than the area of ​​the upper opening 104. In some embodiments, the bottom The opening 105 is approximately 1.25 times larger (for example, in area) than the upper opening 104. 0.5, approximately 1.75, approximately 2, approximately 2.25, approximately 2.5, approximately 2.75, approximately 3, approximately 3.25, approximately 3 0.5, approximately 3.75, approximately 4, approximately 4.25, approximately 4.5, approximately 4.75, approximately 5, approximately 5.25, approximately 5 0.5, approximately 5.75, approximately 6, approximately 6.25, approximately 6.5, approximately 6.75, approximately 7, approximately 7.25, approximately 7 0.5, approximately 7.75, approximately 8, approximately 8.25, approximately 8.5, approximately 8.75, approximately 9, approximately 9.25, approximately 9 0.5, approximately 9.75, approximately 10 times, or larger. Upper opening 104 and / or The bottom openings 105 can be at any suitable distance from each other. Therefore, the distance between the upper opening 104 and the bottom opening 105 is approximately 0.1 cm to approximately 20 cm. It is between. In some embodiments, the distance between the upper opening 104 and the bottom opening 105 Distance: approx. 0.1cm, approx. 0.2cm, approx. 0.3cm, approx. 0.4cm, approx. 0.5cm, approx. 0 .6cm, approx. 0.7cm, approx. 0.8cm, approx. 0.9cm, approx. 1cm, approx. 2cm, approx. 3cm , approx. 4cm, approx. 5cm, approx. 6cm, approx. 7cm, approx. 8cm, approx. 9cm, approx. 10cm, approx. 11 cm, approx. 12cm, approx. 13cm, approx. 14cm, approx. 15cm, approx. 16cm, approx. 17cm, approx. It is 18cm, approximately 19cm, or approximately 20cm.

[0064] The substrate cartridge 100 has at least one reagent port 106 and at least one outlet Liquid reservoir 107, at least one waste removal port 108, gripping element 109, small It may further include at least one alignment element 110, or any combination thereof. Yes, it is possible. In some embodiments, the substrate cartridge 100 has at least one reagent port Port 106, at least one drain reservoir 107, at least one waste removal port Each of the following elements comprises a 108, a gripping element 109, and at least one alignment element 110. This is possible. The alignment element 110 aligns the substrate cartridge within the device and / or on the substrate. Place the drainage reservoir to hold the cell sample and / or staining process during the deposition and / or staining process. This can be suitable for capturing and / or retaining reagent overflow or excessive spray. ru.

[0065] In some embodiments, the sample dispensing port 102 is a removable sample dispensing port 1 It is 02.

[0066] Figure 2 shows a suitable substrate for depositing a cell sample onto a substrate according to one embodiment of the present disclosure. This is a perspective view of cartridge 100. The base cartridge 100 is located at the sample dispensing port 103. Sample holding zone 20 located between the first end and the second end of the sample dispensing port 202 It may include 1, and the second end of the sample dispensing port 202 is on the side of the spray holder 101 It is located. The base cartridge 100 has an upper opening for receiving the spray nozzle 205. The part 104 may be further provided. In some embodiments, the spray nozzle 205 is They are aligned on the surface of the substrate 204.

[0067] The spray nozzle 205 dispenses any suitable gaseous substance, for example, CO2 or O2. It is possible. In some embodiments, the spray nozzle 205 can reach approximately 1 psi to approximately 60 Between psi, between approximately 5 psi and 40 psi, between approximately 10 psi and 20 psi, and around 1 p si, approx. 2psi, approx. 3psi, approx. 4psi, approx. 5psi, approx. 6psi, approx. 7psi, approx. 8psi, approx. 9psi, approx. 10psi, approx. 15psi, approx. 20psi, approx. 25psi, approx. 30psi, approx. 35psi, approx. 40psi, approx. 45psi, approx. 50psi, approx. 55psi The spray nozzle 205 dispenses gaseous substances at a pressure of approximately 60 psi or higher. It consists of multiple subcomponents that function as a single assembly. It is possible. The spray nozzle 205 may be equipped with a gas port. Spray nozzle 20 5 may also have one or more filters to prevent contamination of the substrate. The shape is modified to limit the material and to allow for adaptation and size reduction. obtain.

[0068] In various configurations, the spray deposition process can be optimized for each cell sample. Yes, it is possible. Spray deposition parameters (e.g., distance of spray nozzle from substrate, air pressure, air flow rate) (Nozzle design, amount per spray, total volume, drying temperature, air drying time) Cell type, cell It can be a function of various sample properties, such as concentration and transport or suspension characteristics. ,therefore,

[0069] Distance, air pressure, airflow rate, nozzle design, amount per spray, total volume, temperature drying, air drying] =f(cell type, concentration, liquid type).

[0070] The preparation and deposition of cell samples are based on cellular characteristics such as shape, size, and sensitivity (e.g., fragility). It can be changed based on: Cell type / sample type Examples of parameters that can be used include the following:

[0071] 1a. Distance between the spray nozzle and the substrate surface: The spray pattern changes at different distances. Therefore, for cells of different sizes and shapes, the distance between the spray nozzle and the substrate can be adjusted. This can be changed. In certain embodiments, the distance can be changed by increasing / decreasing the air pressure. It may be necessary to adapt to the changes.

[0072] 1b. Maximum gas / air pressure: Vary the pressure at which cells are deposited, allowing for different cell types to be detected. It can accommodate various sizes and shapes.

[0073] 1c. Gas flow rate: Optimize the speed at which the gas (compressed air) flows for each cell type. It is possible. The size, shape, and sensitivity of each cell type may differ, and each cell type may be preferred. The appropriate flow rate can be utilized / programmed.

[0074] 1d. Nozzle design: A method for obtaining a uniform layer of cells that do not overlap, based on the cell sample. It can be deposited on the surface of the body. In some embodiments, the cell deposition is on the surface of the substrate. To obtain cells isolated from other deposited cells (e.g., separated and not in contact with other cells) It can be designed to uniformly deposit a specific sample type. We can provide individual nozzle designs that are suitable for that purpose.

[0075] 1e. Amount per spray: The amount deposited per spray from each cell sample is controlled to achieve various results. It can accommodate the unique size and shape of the cutting cell type. Several embodiments Therefore, the desired deposition yield can be obtained by spraying the sample onto the substrate surface multiple times.

[0076] 1f. Total volume: Since both the size and shape of each cell type vary, the cells being sprayed will vary. The total amount of material can also depend on the determined cell type.

[0077] 1g. Temperature-based drying: Introduce and control sample drying (e.g., on the surface of a substrate). This allows for a reduction in sample preparation time by changing the drying / heating mechanism. This can promote evaporation. In some embodiments that incorporate multiple spray passes, The system raises the temperature around the substrate between each spray deposition process, on the surface of the substrate. The system can be configured to dry the sample.

[0078] 1. Air drying: In some embodiments, the cell sample is air-dried to allow time for sample preparation. It can be shortened.

[0079] The preparation and deposition of cell samples can be varied based on cell concentration. The apparatus incorporates mechanisms and processes for quantitatively evaluating each sample before deposition. Steps can be set. Examples of parameters that can be changed based on cell concentration. This may include the following:

[0080] 2a. Distance between the spray nozzle and the substrate surface: The distance between the spray nozzle and the substrate varies. It can be varied with respect to the cell concentration. In certain embodiments, the distance is the substrate surface. It can be adjusted to prevent the overlapping of cells that have accumulated.

[0081] 2b. Maximum gas / air pressure: The pressure at which cells are deposited is changed to accommodate the cell concentration. It is possible.

[0082] 2c. Gas flow rate: The air flow rate needs to be adjusted for various concentrations.

[0083] 2d. Nozzle design: A method for obtaining a uniform layer of cells that do not overlap, based on a cell sample. It can be deposited on the surface of the body. In some embodiments, the cell deposition is on the surface of the substrate. To obtain cells isolated (e.g., separated and not in contact) from other deposited cells. It can be designed to uniformly extract cells from samples of varying concentrations. We can provide individual nozzle designs that are suitable for deposition.

[0084] 2e. Amount per spray: The amount deposited per spray from each cell sample is controlled to achieve various results. It can correspond to the cell concentration. In some embodiments, the sample is applied to the surface of the substrate. By spraying several times, the desired yield can be obtained.

[0085] 2f. Total volume: The total volume of cellular material to be sprayed can be varied or spread across multiple spray passes. It can be increased. For example, if the sample concentration is low, the total volume of the spray pass can be increased. This is possible. Conversely, if the concentration is high, a smaller amount can be deposited.

[0086] 2g. Temperature-based drying: Introduce and control sample drying (e.g., on the surface of a substrate). This allows for a reduction in sample preparation time by changing the drying / heating mechanism. This can promote evaporation. In some embodiments that incorporate multiple spray passes, The system is designed to prevent (for example, the aggregation and / or migration of cells on the substrate surface) Between each spray deposition process, the temperature around the substrate is increased to dry the sample on the substrate surface. It can be configured in such a way.

[0087] 2h. Air drying: In some embodiments, the cell sample is air-dried to allow time for sample preparation. This can be shortened. In some embodiments, air drying of the sample is performed in response to environmental changes. It may be suitable for cells that show high sensitivity to it.

[0088] The above spray deposition parameters, and other parameters (e.g., liquid temperature, biological sample) (Temperature, etc.) The device user can determine the spray setting suitable for the type of cells or liquid in a particular cell sample. Pre-program the fog deposition program so that it can be selected and / or optimized. This is possible. In some embodiments, the apparatus 500 supports a substrate 204 that carries a cell sample. Clean the sample and check if the spray deposition meets the program criteria (for example, It is possible to determine (for example, whether sufficient cells have accumulated and whether the cells are overlapping). A screening method involves screening the substrate using laser and / or spectroscopic techniques. This may include .

[0089] Referring back to Figure 2, the base cartridge is also located near the bottom opening 105. It can be equipped with a sealing element 203. As shown in Figure 2, the substrate (for example, slide When Id)204 is placed together with the substrate cartridge 100, it forms a deposition / staining reservoir. 206 can be made. The base cartridge 100 is all or part of the base 204. It can surround the sample. For example, the substrate cartridge 100 is at least the sample deposition area The surface of the substrate 204 selected for this purpose (for example, a part of the slide separate from the label part) is wrapped around it. It can be enclosed.

[0090] The sealing element 203 can be of any suitable design. The suitable design is not limited to any particular design. Typical examples include locking elements, O-rings, gaskets, snaps, fasteners, friction, and adhesives. Included. In some embodiments, the sealing element 203 includes a locking element, an O-ring, and / Or includes a gasket.

[0091] The upper opening 104 is positioned at any suitable angle with respect to the second end of the sample dispensing port 202. It can be positioned as follows: For example, the upper opening 104 is the second end of the sample dispensing port 202. For the part, between approximately 25 degrees and 100 degrees, between approximately 50 degrees and 95 degrees, or between approximately 75 degrees and 100 degrees. It can be positioned at a 90-degree angle. In some embodiments, the upper opening 104 is It can be positioned at an angle of approximately 75 to 90 degrees relative to the second end of the sample dispensing port 202. Cut.

[0092] Returning to Figure 2, the substrate cartridge has at least one reagent port 106, at least It may have one waste port 108, or both.

[0093] Figure 3 shows two substrate cartridges 101 and two substrates according to one embodiment of the present disclosure. This is an isometric view showing the packaging 301 of a slide holder 300 having 204. The Idoholder 300 can hold one, two, three, four, five, six, or more base carts. The system may include a cartridge 101 and / or a substrate 204. In some embodiments, The slide holder 300 is designed to allow a technician or robot to move the slide holder. It is equipped with a handle 302 configured to allow the following. In some embodiments, the handle 302 indicates that a technician or robot can perform the operation using at least one base cartridge 101 and a small A slide holder including at least one substrate 204 is disclosed and described herein. Moving the device from either of the application forms and from a second device (e.g., a microscope). It is configured to allow this. In some embodiments, the slide holder 300 is Apparatus according to any of the embodiments disclosed and described in the specification, and a second apparatus (e.g.) It is configured to fit a microscope.

[0094] In some embodiments, the slide holder holds at least one substrate cartridge and It is packaged as a kit with at least one substrate. Several implementations In this configuration, the slide holder, at least one substrate cartridge, and / or at least Another substrate can be configured for immediate use, as shown in Figure 3. In some embodiments, a slide holder, at least one substrate cartridge, and and / or at least one substrate can be packaged in any suitable packaging material. Yes, it is possible. In other embodiments, a slide holder, at least one substrate cartridge, and and at least one substrate, either in one package or in multiple and / or separate It can be packaged within each individual package.

[0095] Figure 4 shows two substrate cartridges 101 and two substrates according to one embodiment of the present disclosure. This is an isometric view showing a slide holder 300 having 204. In some embodiments, The slide holder 300 allows the slide holder to be moved by a technician or robot. It is equipped with a handle 302 configured in such a way.

[0096] Figure 5 shows two cells arranged inside a cell deposition and staining apparatus 500 according to one embodiment of the present disclosure. A slide holder 300 having two base cartridges 101 and two bases 204 is generally This is a simplified isometric view. The slide holder 300 further includes a handle 302. The apparatus for depositing and staining cellular samples is a housing 50 having an access door 502. 1 and, located within the housing 501, one or more substrates 204 and / or one or more substrates A substrate processing holder 503 configured to hold the body cartridge 101, A substrate processing holder 503 is accessible when the recess door 502 is in an open configuration, and At least partially located above at least a portion of the body processing holder 503 One opening 504, and receiving input from the user, and in response to receiving input, A user interface configured to trigger the execution of a pre-programmed protocol. It may include a face 505 and a waste and / or reagent holder element 506. .

[0097] In various embodiments, the housing 501 is configured such that contaminants can be transferred to the substrate processing holder 503. To suppress, limit, or substantially prevent entry into the substrate processing area. The housing 501 is a substrate processing area. Access door 502 (for example, side-swing) to allow access to door 503 This can include various types of doors (such as swing doors, up-swing doors, and sliding panels). In the configuration, the housing 501 also includes robotic components (e.g., robotic arms). ), transport devices (e.g., conveyors, actuators, etc.), fluid components, sample deposition Stations, base platforms, mixed components (e.g., vibration or vortex-forming components) Materials), pressurizing devices (e.g., air compressors and fluid lines, pumps, vacuums, etc.), drying Internal components including, but not limited to, machines, controllers, and power systems. Access panel 509 to enable access (for example, side swing door, etc.) It can include (top swing doors, sliding panels, etc.). Housing 501 also , to suppress, limit, or prevent residual spray from contaminating the external environment surrounding the housing 501. It can be practically prevented.

[0098] In some embodiments, the apparatus 500 further comprises a substrate and a substrate cartridge. It is possible that when the substrate cartridge 100 and substrate 204 are in contact, deposition / contamination occurs. A color reservoir 206 is formed.

[0099] In some embodiments, at least a portion of the substrate cartridge 100 is accessed When A502 is in the closed position, at least one opening 504 protrudes at least partially. To discharge. In some embodiments, the apparatus 500 may further include an environmental chamber. The environmental chamber is located within the apparatus 500, particularly the substrate processing holder 503 and / or the deposition / The system can be configured to control the humidity level within the staining reservoir 206.

[0100] Referring back to Figure 5, the apparatus 500 includes the waste and / or reagent holder element 506. Inside are at least one waste container 507 and / or at least one reagent container 508 It may further include at least one waste container 507 and / or fewer Each reagent container 508 is a substrate processing holder 503 and / or a deposit / staining reservoir. It can communicate with 206 via fluid.

[0101] In some embodiments, software, code, or other executable instructions are used by the system. Automated cell sample deposition and / or sample staining using the TEM500 (e.g., controller) (or together with the processor) provided for instruction and / or control. Some actual In this configuration, automation and / or high-throughput software is integrated into the System 500. Cell sample uptake, spray deposition, sample exchange, substrate index creation, other sample supporting groups We provide one or more of the following: body processing, dyeing, washing, etc.

[0102] Figure 6 shows cell deposition and cell deposition using the staining apparatus 500 according to one embodiment of the present disclosure. And after staining, for visualization, the slide holder 300 having two substrates 204 is visible. This is a schematic diagram showing the arrangement on a microscope. Figure 7 shows a substrate according to one embodiment of the present disclosure. Cell deposits in an open position to receive 204 and / or the substrate cartridge 101. Figure 8 is an isometric view showing the substrate 2 according to one embodiment of the present disclosure. Cell deposition and staining in the open position, having 04 and / or substrate cartridge 101. This is an isometric view showing device 500.

[0103] Figure 9 shows an overview of how to operate the cell deposition and staining apparatus 500 according to one embodiment of the present disclosure. This is a schematic diagram.

[0104] After the user deposits the sample into the substrate cartridge 100, the programmed module Start the process, for example, by depositing a cell sample and / or adding a reagent to the deposited cell sample. It can be provided. Figures 10 to 18 show the program executed by the device 500. This is a schematic diagram.

[0105] Figure 10 shows a controlled spray from a spray nozzle 205 according to one embodiment of the present disclosure. The substrate cartridge 100 is shown, illustrating the deposition of a cell sample onto substrate 204. Several implementations In terms of form, the system is a part of the sample dispensing port 102, particularly the part of the sample dispensing port 202. Air is guided above the end of 2 to draw the sample into the air channel and place the cells on the substrate 204. Includes a controlled spraying system. In some embodiments, the system self It is equipped with a CO2 canister to provide a self-contained, onboard pressurized air source. The air is at a known pressure. The force is adjusted to (for example, approximately 100 to approximately 300 kPa), and timed dispensing is performed (for example, approximately 0.2 to approximately It is sprayed using 1 second to provide a known amount of sample onto the substrate. In some embodiments The sample is introduced into the spray nozzle at an angle of approximately 10 to 90 degrees. Several embodiments Then, at least a portion of the second end of the sample dispensing port 202 is approximately 0.4 to approximately 1.2 m It has an orifice dimension between m.

[0106] In some embodiments, the spray nozzle converts the liquid sample into an aerosol, and then... This is then transferred to the substrate. The liquid thin film dries in a few seconds, leaving a uniform monolayer of high-quality cells. The deposition technique is highly adaptable and can deposit a large number of cell samples. Non-limiting examples of cell samples include cell cultures, human epithelial cells (e.g., squamous epithelial cells and This includes casts (and other cells) and fine-needle aspiration.

[0107] Figure 11 shows the substrate 204 being heated using the heating element 1001. 4. The substrate cartridge 100 is shown, illustrating the processing (e.g., drying) of the deposited sample. Although heating is shown only in Figure 11, the heating step is performed in multiple steps of the module. Those skilled in the art will understand that this is possible. For example, the sample is, for example, a cell in substrate 20 Immediately after contact with 4, after the fixation step, after the washing step, or after the staining step, It can be heated. In some embodiments, the substrate 204 is heated surface 100 1. Placed on top of, and providing controlled heat to the slide via a Peltier or similar device, This provides accelerated drying of the sample on substrate 204. The temperature can be controlled from approximately 0 to approximately 75 degrees. Yes, it is possible. In some embodiments, the temperature can be controlled so that it is activated when needed. It is possible.

[0108] The apparatus 500 handles deposited cell samples and / or reagents (e.g., staining or washing reagents). To shorten the drying time of the substrate, heating of the ambient air, heating of the substrate 204, and the wet substrate Any mechanism known to those skilled in the art, including but not limited to laminar flow of dry air above It can provide a sm. In a further embodiment, the apparatus 500 provides a wet substrate 204 It may include a sensor (e.g., optical) for monitoring drying. Other embodiments include Furthermore, through repeated deposition cycles accompanied by drying cycles between each deposition cycle, the substrate 204 This may include means for increasing the amount of cell and / or tissue material. The cycle is performed with or without the various drying mechanisms discussed herein. It is possible.

[0109] Referring to Figure 12, the perspective view of the substrate cartridge 100 shows that the fixative reagent is, in this disclosure In one embodiment, the substrate cartridge 100 and substrate 2 are supplied through the reagent port 106. This shows that the staining and deposition reservoir 206, created by 04, is dispensed. The setting agent covers, or at least partially covers, the cell sample. In some embodiments, The programmed module delay in this step is due to the fixative being finely compressed for a predetermined amount of time. This allows the fixative to remain on the cell sample, enabling it to penetrate the cell sample. (Figure) 13, according to one embodiment of the present disclosure, through the waste port 108 of the substrate cartridge 100 A perspective view of the base cartridge 100 showing the removal of waste (e.g., used fixative). Figure 14 shows a reagent (for example, the first reagent) according to one embodiment of the present disclosure. Through port 106, the substrate cartridges 100 and 204 produced Oblique view of substrate cartridge 100, showing dispensing into staining and deposition reservoir 206. This is a diagram. The reagent is dispensed and covers, or at least partially covers, the cell sample. In some embodiments, the delay of the programmed module in this step is an attempt. This allows the drug to remain on the cell sample for a predetermined time, and the reagent to penetrate the cell sample. This makes it possible.

[0110] In some embodiments, the staining module uses the substrate cartridge 100 to test A staining and deposition reservoir filled with the drug and in close contact with the substrate 204 for staining cells. Prepare B206. The reagents are filled into the cavities using a dedicated peri-pump for each reagent. Reagent port 106 on substrate cartridge 100 (until it is filled or partially filled) In other words, it is delivered through the inlet port. The reagent is only used for the time specified in the protocol. It is held in place and then automatically removed by the waste disposal system. Unidirectional The reagent flow and substrate cartridge 100 facilitate the phase transition from one substrate 204 to another substrate 204. Mutual contamination is prevented.

[0111] Figure 15 shows a waste port 108 of a substrate cartridge 100 according to one embodiment of the present disclosure. A perspective view of the substrate cartridge 100 showing the removal of reagents through several implementations. In this configuration, waste is transported via a dedicated peri-pump to the waste port on the substrate cartridge 100. It is removed from the stained and deposited reservoir 206 through the 108.

[0112] The pump speed is controlled to ensure that the fluid is completely removed from the slide. The pump can be reversed to provide further agitation.

[0113] Figure 16 shows a reagent (e.g., a second reagent) being supplied to reagent port 1 according to one embodiment of the present disclosure. Through 06, the staining produced by substrate cartridge 100 and substrate 204 This is a perspective view of the substrate cartridge 100, showing that it is dispensed into the deposition reservoir 206. The reagents are dispensed and cover, or at least partially cover, the cell sample. In this embodiment, the delay of the programmed module in this step is determined when the reagent is predetermined This allows the reagent to remain on the cell sample for a limited time, enabling it to penetrate the cell sample. Figure 17 shows the waste port of the substrate cartridge 100 according to one embodiment of the present disclosure. Figure 18 is a perspective view of the substrate cartridge 100, showing the removal of reagents through 108. , a washing reagent (e.g., water) is passed through the reagent port 106 according to one embodiment of the present disclosure. Staining and deposition reservoirs created by substrate cartridges 100 and 204 Figure 19 is a perspective view of the substrate cartridge 100, showing that it is dispensed into 206. According to one embodiment of the present disclosure, waste is disposed of through the waste port 108 of the substrate cartridge 100. This is a perspective view of the base cartridge 100, showing the removal of waste material.

[0114] Figure 20 is a schematic diagram for operating a cell deposition and staining apparatus according to one embodiment of the present disclosure. The illustrated steps involve lifting the handle and the used base car This includes removing and discarding the cartridge and removing the contaminated substrate from the device. The stained substrate can then be analyzed immediately or after a certain period of time.

[0115] The substrate 100 containing stained cell material is prepared by any preferred method well known to those skilled in the art. It can be analyzed. Non-limiting examples of suitable analytical methods include microscopy, mass spectrometry, and visual analysis. Visual inspection, fluorescence visualization, trace analysis, imaging (e.g., digital imaging), or other analyses. This includes an imaging method. For example, a substrate 100 containing stained cell material is stained ( For example, H&E staining, antigen recovery, or other types of protocols (e.g., immunohistochemistry) Further processing, including in situ hybrid formation methods, can be performed. In some embodiments, the substrate 100 comprising stained cell material produced according to this disclosure is , for acquiring partial wave spectroscopy (PWS) microscope images and for their clinical, diagnostic, and research applications. Suitable for use. Examples of PWS devices, systems, and methods of using them are, for example, , U.S. Patent No. 7,667,832, U.S. Patent No. 7,800,746, U.S. Patent No. 7, U.S. Patent No. 652,772, U.S. Patent No. 8,131,348, U.S. Patent No. 8,735,075 , U.S. Patent Application Publication No. 2006 / 0155178, and U.S. Patent Application Publication No. 2018 It is described in publication / 0127833, which is incorporated herein by reference in its entirety. In some embodiments, the apparatus further comprises a microscope for visualizing and analyzing cells. In some embodiments, the microscope is a robotic microscope.

[0116] In some embodiments, one or more components of the deposition and staining apparatus 500 are one or more It is under the control of the electronic controller or computer processor above. In certain embodiments This enhances the deposition of cell samples and enables automation and / or high throughput capabilities. The components and processes are controlled by the processor. In some embodiments, The Rossessa controls numerous components of the deposition and staining apparatus 500 and coordinates their operation. This allows the desired / instructed function to be achieved. For example, in some embodiments, one or more The movement of the drive mechanism and / or motors (for example, all of them) is automated. In this embodiment, the movement is to a processor located within or communicating with the device 500. Therefore, it is controlled and / or directed. In some embodiments, the movement of the device 500 Synchronized with other operations. In some embodiments, steps are combined and / or synchronized. Therefore, the automation and speed of the process for obtaining high-quality substrates 204 for supporting cell samples It will be strengthened.

[0117] For clinical, diagnostic, and research purposes, high performance is necessary to derive useful and accurate data from samples. High sample quality is desired. The apparatus 500 and method described herein are for high quality including cell samples. This facilitates the production of high-quality and reproducible substrates. For example, the apparatus 500 mixes the sample. (Alternatively, similar techniques such as stirring, vortex formation, or shaking) and counting the cell concentration of each sample. It can be configured to do both to make a decision and to make a decision. Each collected cell sample is They may contain different amounts of cells, which can lead to variability between samples. To standardize the number of cells deposited on substrate 204, each sample can be quantified. The apparatus 500 can adjust the deposition parameters based on this information and desired criteria. Yes, it is possible. For example, if a sample is evaluated and it is determined that it contains 10,000 cells per 1 mL of sample, The desired cell concentration on the substrate is determined to be 1 square centimeter per square centimeter. If there are approximately 1,000 cells per unit, the system will be about 1 / 10 (or 100 units). It will deposit (1 chloroliter). In another example, the second cell sample will be per 1 mL of sample. It is determined that it has approximately 5,000 cells. In this example, the desired number of cells on the substrate 204 Assuming the cell concentration is the same, the device 500 will hold approximately 1 / 5 (or 200 microliters) of the contents. It will accumulate. The amount of cells present in the cell sample varies within the sample holding zone 201. Since it is expected to have, the spray volume will govern the amount of cells deposited on the substrate. For example, it may be desirable to adjust parameters such as the amount per spray and the total spray volume. Further adjustments to the spray volume can be made based on the cell type in the cell sample. For example, large In the case of samples containing cells, the desired cell concentration on the substrate may decrease.

[0118] In some embodiments, the apparatus disclosed and described herein is used, for example, BD PrepStain slide processor, Hologic ThinPrep, and - Deposits cell samples in a shorter time than conventional methods, including Mo Fisher CytoSpin. and can be stained. In some embodiments, disclosed and described herein The device took approximately 1 minute, 2 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 25 minutes. Approximately 30 minutes, approximately 35 minutes, approximately 40 minutes, approximately 45 minutes, approximately 50 minutes, approximately 55 minutes, or less than 60 minutes. Cell samples can be prepared. In some embodiments, these are disclosed and described herein. The device can prepare cell samples in less than one minute.

[0119] In one embodiment, electrical impedance is used to determine the cell concentration in a sample. This is possible. For example, when cells are introduced through the chamber, the impedance is It changes, but this can correlate with the amount of cells in the test sample. To determine the cell concentration in the sample... An alternative approach involves detecting the presence of shadows (for example, those detected by optical sensors). This would include the use of lasers and sensors to detect the resulting changes in intensity. When this changes, the voltage changes, allowing for an accurate assessment of the number of cells per unit volume. [Examples]

[0120] Example 1 Cell collection and spray deposition The quality and reproducibility of the spray deposition of different cell samples onto microscope slides were verified by experiments on collected thyroid FNA, pleural effusion, and neck brushing according to aspects of the present disclosure. Cells were collected, deposited, and stained using the apparatus disclosed and described herein.

[0121] Figures 22A - 22C are 20 - fold images of thyroid FNA (a), pleural effusion (b), and neck brushing (c) fixed using ThinPrep PerservCyt solution. As shown in Figures 22A - 22B, the cells are isolated, undamaged, not folded, and round. Thus, this data shows that the apparatus of the present disclosure provides high - quality cells suitable for analysis.

[0122] Figures 23A - 23D are 20 - fold images of hepatocellular carcinoma cells grown subcutaneously in an Oncopig model. FNA was performed on these subcutaneous tumors using needles of (a) 25 - gauge, (b) 22 - gauge, (c) 19 - gauge, and (d) 18 - gauge. Specimens collected from the FNA procedure were deposited using the apparatus of the present disclosure. These data show that a sufficient number of hepatocellular carcinoma tumor cells were present in specimens collected using 25 - gauge, 22 - gauge, and 19 - gauge needles and prepared using the apparatus of the present disclosure for diagnosis. However, the cells collected with the 18 - gauge needle clogged the system when attempting to spray the 18 - gauge needle material, and thus only limited cell material was released onto the slide. ​​​​​​​​​​​​​​

[0123] Figures 24A to 24B are 20-fold images of an unfixed pleural effusion sample deposited and Diff-Quik (registered trademark) stained using the device of the present disclosure. The quality of the specimen slides prepared using the device of the present disclosure is comparable to currently available techniques. Figure 25 is a 20-fold image of unfixed lung epithelial cells obtained by performing FNA on an excised lung tumor. The FNA sample was deposited and Diff-Quik (registered trademark) stained using the device of the present disclosure. The quality of this specimen slide is considered to be equal to or better than currently available techniques.

[0124] Tests were conducted to compare the performance of the device of the present disclosure with currently available commercially available systems, and (a) concordance in diagnosis, (b) staining quality, and (c) cellularity of the samples were evaluated. [Table 1]

[0125] These results were obtained from a blind test on samples of 20 patients comparing the performance of the device of the present disclosure with currently available commercially available systems. The results show 100% concordance in diagnosis and staining quality. The reason for the low concordance in cellularity is due to the difference in storage time between the two devices (1 day for the commercially available system vs. 8 days for the specimen preparation system).

[0126] The above detailed description of the embodiments of the technology is not intended to be exhaustive or to limit the technology to the exact form disclosed above. Specific embodiments of the technology and examples of the It is possible within the scope of the technique. The various embodiments described herein are also further practical They may be combined to provide a specific application form.

[0127] As described above, specific embodiments of the technology have been described herein for illustrative purposes, but well known structures And the functions are described in detail to avoid unnecessarily obscuring the description of the technical embodiments. Not shown or explained. Singular or plural terms, where the context allows. These terms may each include plural or singular terms.

[0128] Furthermore, the term "or" refers to a list of two or more items, and other items Unless explicitly limited to meaning only a single item that is excluded, The use of "or" in a list means (a) a single item in the list, or (b) an item in the list (c) This includes all items, or any combination of items in the list. It is interpreted as follows. Furthermore, the term "comprising" has the same function. To ensure that no more than a certain number of additional types of calls and / or other features are excluded, It is used throughout to mean that it includes the listed functions. Specific implementation Although the forms described herein are illustrative, various forms can be described without departing from the Art. It will also be understood that modifications may be made. Furthermore, the benefits related to specific embodiments of this technology While the points are described in the context of those embodiments, other embodiments are similar. Such advantages may also be demonstrated, and all embodiments must not necessarily fall within the scope of this technology. However, it is not necessary to demonstrate such advantages. Therefore, this disclosure and related technologies The technique may include other embodiments not explicitly shown or described in this specification. It can include other embodiments not explicitly shown or described in this specification. This application provides an invention in the following aspects. (Aspect 1) A substrate cartridge, (a) a spray holder, (b) a sample dispensing port having (i) a first end of the sample dispensing port for receiving a sample, (ii) a second end of the sample dispensing port for discharging the sample into the spray holder, and (iii) a sample holding zone located between the first end and the second end of the sample dispensing port, wherein the second end of the sample dispensing port is located on a side surface of the spray holder, the sample dispensing port; the first end of the sample dispensing port for receiving a sample, (ii) the second end of the sample dispensing port for discharging the sample into the spray holder, and (iii) a sample holding zone located between the first end and the second end of the sample dispensing port, and the second end of the sample dispensing port is located on a side surface of the spray holder. the second end of the sample dispensing port for discharging the sample into the spray holder, and (iii) a sample holding zone located between the first end and the second end of the sample dispensing port, and the second end of the sample dispensing port is located on a side surface of the spray holder. and having a sample holding zone located between the first end and the second end of the sample dispensing port, and the second end of the sample dispensing port is located on a side surface of the spray holder. the sample dispensing port; (c) an upper opening for receiving a spray nozzle, the upper opening being arranged at an angle with respect to the second opening of the sample dispensing port. The substrate cartridge is provided with an upper opening arranged at an angle with respect to the second opening of the sample dispensing port. ridge. (Aspect 2) The substrate cartridge has a bottom opening on the side opposite to the upper opening, and the spray holder is disposed between the upper opening and the bottom opening. The substrate cartridge according to Aspect 1. The spray holder is disposed between the upper opening and the bottom opening. The substrate cartridge according to Aspect 1. cartridge. (Aspect 3) The area of the bottom opening is larger than the area of the upper opening. The substrate cartridge according to Aspect 2. cartridge. (Aspect 4) The substrate cartridge according to Aspect 2 further includes a sealing element disposed near the bottom opening. cartridge. (Aspect 5) The sealing element includes a locking element, an O-ring, and / or a gasket. The substrate cartridge according to Aspect 3. cartridge. (Aspect 6) A substrate according to any one of embodiments 1 to 5, further comprising at least one reagent port cartridge. (Aspect 7) A base according to any one of embodiments 1 to 6, further comprising at least one drain reservoir Body cartridge. (Pattern 8) Any one of embodiments 1 to 7 further comprises at least one waste removal port. The base cartridge as described. (Aspect 9) A substrate cartridge according to any one of embodiments 1 to 8, further comprising a gripping element. (Aspect 10) At least one of the following means of placing the substrate cartridge inside and / or on the substrate A substrate cartridge according to any one of embodiments 1 to 9, further comprising alignment elements. (Aspect 11) The spray holder has a rectangular prism shape, a cylindrical shape, or a frustoconical shape. A base cartridge as described in any one of items 1 through 10. (Aspect 12) At least one of the upper opening and / or the bottom opening may be rectangular, circular, or elliptical. The substrate cartridge described in Embodiment 1. (Aspect 13) The distance between the upper opening and the bottom opening is approximately 1 cm to approximately 10 cm. The base cartridge described in 2. (Aspect 14) The upper opening is at an angle of 75 to 90 degrees with respect to the second end of the sample dispensing port. A substrate cartridge according to embodiment 1, arranged at a certain degree. (Aspect 15) The sample dispensing port is a detachable sample dispensing port, as described in Embodiment 1 of the substrate cart. ridge. (Aspect 16) (i) at least one substrate cartridge as described in any of embodiments 1 to 15, and (ii A slide holder configured to hold at least one substrate. (Aspect 17) The slide holder according to embodiment 16, further comprising a handle. (Aspect 18) The slide holder according to embodiment 16, wherein the base is a slide. (Aspect 19) (i) the slide holder described in embodiment 16 or 17, and (ii) any of embodiments 1 to 15 (iii) at least one substrate cartridge as described in item 1, and at least one substrate A kit that includes the following. (Aspect 20) The kit according to embodiment 19, wherein the substrate is a slide. (Aspect 21) An apparatus for depositing and staining cell samples, (a) Housing having an access door, (b) A configuration that holds one or more substrates and / or one or more substrate cartridges A substrate processing holder is constructed, located within the housing, wherein the access door opens A substrate processing holder that is accessible when in configuration, (c) A small portion located at least partially above at least a portion of the substrate processing holder At least one opening, (d) A spray nozzle configured to dispense a gaseous substance into the substrate processing area, (e) receive input from the user and, in response to receiving said input, pre-program A user interface configured to trigger the execution of a programmed protocol, (f) A device comprising waste and / or reagent holder elements. (Aspect 22) The present invention further comprises a substrate and a substrate cartridge, wherein the substrate cartridge and the substrate are The apparatus according to embodiment 21, which forms a deposit / stain reservoir when in contact. (Aspect 23) At least a portion of the base cartridge is such that when the access door is in the closed position, The apparatus according to embodiment 22, wherein the device protrudes at least partially from the at least one opening. (Aspect 24) The apparatus according to embodiment 21, further comprising an environmental chamber. (Aspect 25) The environmental chamber is configured to control the humidity level within the apparatus, The apparatus described in 24. (Aspect 26) Located within the waste and / or reagent holder element and in fluid communication with the substrate processing region. This includes at least one waste container and / or at least one reagent container. The apparatus according to embodiment 21, which is provided for the following. (Aspect 27) The apparatus according to embodiment 21, further comprising a heating element. (Aspect 28) The spray nozzle dispenses the gaseous substance at a pressure of approximately 1 psi to approximately 30 psi. The device described in item 21. (Aspect 29) The substrate processing holder comprises at least one substrate cartridge and at least one substrate The apparatus according to embodiment 21, configured to receive a slide holder having a body.

Claims

1. An apparatus for depositing and staining cell samples, A housing having an access panel, A substrate processing holder located within the housing, configured to hold a substrate and a substrate cartridge, A waste and dye holder element configured to hold waste bottles and reagent containers, comprising: The substrate cartridge comprises (a) a first port configured for depositing the cell sample on the substrate, and (b) a second port configured for staining the cell sample, The aforementioned staining is performed following the deposition. The apparatus wherein the waste bottle is configured to hold waste from the staining of the cell sample, and the reagent container is configured to hold reagents or fixatives used for staining the cell sample.

2. The apparatus according to claim 1, further comprising a user interface configured to receive input from a user and, in response to the receipt of said input, to execute a pre-programmed protocol for the deposition and / or staining.

3. The apparatus according to claim 1, further comprising a spray nozzle configured to dispense an aerosolized cell sample into a substrate processing area including the substrate and the substrate cartridge.

4. The aforementioned first port, (i) A first end for receiving the cell sample, (ii) A second end for releasing the cell sample into the spray holder of the substrate cartridge, (iii) comprising a sample holding zone located between the first end and the second end, The base cartridge further comprises an upper opening configured to receive the spray nozzle, The apparatus according to claim 3, wherein the upper opening is positioned at an angle with respect to the opening at the second end of the first port.

5. The apparatus according to claim 4, wherein the spray holder has a rectangular prism shape, a cylindrical shape, or a frustoconical shape.

6. The apparatus according to claim 3, wherein the distance between the spray nozzle and the surface of the substrate is based on the size and / or shape of the cells in the cell sample.

7. The apparatus according to claim 3, wherein a uniform layer is obtained in which the cells of the cell sample do not overlap by depositing the cell sample onto the substrate.

8. The apparatus according to claim 7, wherein the deposition of a uniform layer on the substrate in which the cells of the cell sample do not overlap is based on the design of the spray nozzle and the distance between the spray nozzle and the surface of the substrate.

9. The apparatus according to claim 1, further comprising an environmental chamber configured to control the humidity level within the apparatus.

10. The apparatus according to claim 1, further comprising a heating element configured to dry the cell sample on the substrate following the staining.

11. The apparatus according to claim 10, wherein the drying of the cell sample is monitored using an optical sensor.

12. The apparatus according to claim 1, wherein the staining of the cell sample is performed using hematoxylin-eosin (H&E) staining.

13. The apparatus according to claim 1, wherein the staining of the cell sample is performed using at least two different reagents.

14. The apparatus according to claim 1, wherein at least one imaging method is performed on the substrate containing the cell sample, following the deposition and staining.

15. The apparatus according to claim 14, wherein the at least one imaging method includes microscopy, mass spectrometry, visual inspection, and / or fluorescence visualization.

16. The apparatus according to claim 1, wherein the cell sample includes a cell culture, a sample of human epithelial cells, or a fine-needle aspiration (FNA).

17. The apparatus according to claim 1, wherein the waste from the staining of the cell sample includes the fixative used.

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