WO2021201858A1

WO2021201858A1 - Matrix dispense patterns

Info

Publication number: WO2021201858A1
Application number: PCT/US2020/026136
Authority: WO
Inventors: Anita Rogacs; Beverly CHOU
Original assignee: Hewlett-Packard Development Company, L.P.
Priority date: 2020-04-01
Filing date: 2020-04-01
Publication date: 2021-10-07

Abstract

Example implementations relate to matrix dispense patterns. For example, an apparatus can include a controller communicatively coupled to a droplet dispenser to deposit a plurality of reagents on a matrix, wherein the controller is to: determine a dispense pattern for the plurality of reagents to be deposited on the matrix, align the droplet dispenser with the matrix to deposit the plurality of reagents along the dispense pattern to generate a plurality of samples on the matrix, wherein the plurality of samples include a differential variable that affects a test performance of the corresponding sample, and select a differential variable for the matrix based on the test performance of the plurality of samples when exposed to a challenge solution.

Description

MATRIX DISPENSE PATTERNS

Background

[0001] Lateral flow assays can be relatively simple cellulose-based devices intended to detect the presence of a target analyte in a liquid sample without the need for specialized and costly equipment, though many lab-based applications exist that are supported by reading equipment. These tests can run a liquid along a surface of a pad with reactive molecules that show a visual positive or negative result. Typically, these tests are used for medical diagnostics for home testing, point of care testing, or laboratory use. Adapting these tests to particular target analytes can include performing a plurality of tests utilizing different variables, which can utilize a large quantity of analytes and/or testing materials.

Brief Description of the Drawings

[0002] Figure 1 illustrates an example system including a controller and a dispense device for matrix dispense patterns consistent with the present disclosure. [0003] Figure 2 illustrates an example of a memory resource for matrix dispense patterns, in accordance with the present disclosure.

[0004] Figure 3 illustrates an example system including a controller and a digital microfluidic array for matrix dispense patterns consistent with the present disclosure. [0005] Figure 4 illustrates an example of matrix dispense patterns, in accordance with the present disclosure.

[0006] Figure 5 illustrates an example of a matrix dispense pattern, in accordance with the present disclosure. [0007] Figure 6 illustrates an example of a matrix dispense pattern, in accordance with the present disclosure.

[0008] Figure 7 illustrates an example of a matrix dispense pattern, in accordance with the present disclosure.

Detailed Description

[0009] A lateral flow assay (LFA) can include a matrix (e.g., paper-based platform, etc.) that can be utilized for the detection and/or quantification of analytes in a mixture (e.g., reagents, etc.). In some examples, the sample can be placed on a test device and the results can be displayed in a relatively short period of time (e.g., 5-30 minutes, etc.). In some examples, LFAs can include a relatively long shelf life and may not need refrigeration, which can allow LFAs to utilized in areas with relatively lower resources (e.g., disaster zone, developing countries, etc.).

[0010] In some examples, LFAs can have a relatively labor-intensive development process. That is, an LFA can be relatively difficult to optimize test performance of the LFA for different applications (e.g., testing different types of samples, testing different reagents, etc.). For example, there can be a relatively large parametric space for optimization of different reagent compositions, different dispense patterns, and/or different reagent positioning. As used herein, reagent composition options can include, but are not limited to, capture reagent options (e.g., buffer reagent composition, etc.), membrane treatment options, conjugate chemistry and composition options, and/or sample pretreatment options (e.g., challenge solution options, etc.). In addition, as used herein, the test performance of the LFA can be measured or analyzed by test performance metrics that can include, but is not limited to: a capillary flow time (CFT), line intensity, line width, reagent depth, and/or coefficient of variation (CV) of the reagent sample patterns when exposed to a challenge solution. With a plurality of reagent composition options and/or a plurality of different reagent pattern positioning options, it can be difficult to determine a combination that may provide better test performance for the LFA with a particular application.

[0011] The present disclosure relates to determining a differential variable of a reagent composition for a LFA or similar device by utilizing a controller coupled to a droplet dispenser (e.g., an inkjet printhead, digital microfluidic system, etc.) to deposit a particular dispense pattern on to a matrix to generate a particular sample on the matrix. In this way, a test performance of the different reagent compositions and/or differential variables can be determined. In some examples, the test performance of the different reagent compositions and/or differential variables can be utilized to select a particular combination of reagent compositions and/or reagent positioning to increase a performance for the LFA or similar device. In this way, the development time and cost for producing an LFA or similar device can be relatively lower compared to previous systems and methods.

[0012] As used herein, the term “reservoir” refers to a container capable of including a reagent within the container. A controller can be utilized to align a droplet dispenser with a particular portion or particular area of the matrix and deposit the reagent from a coupled reservoir to generate a sample on the matrix with a particular dispense pattern. As used herein, the term “matrix” refers to a material that can form a structure suitable for the transfer and/or separation of molecules. For example, a matrix can be a nitrocellulose membrane that can be compatible with a variety of detection methods. Although LFA devices utilizing nitrocellulose membranes are used as specific examples, examples of the present disclosure are not so limited. For example, the dispense patterns utilized to determine a particular reagent composition or differential variable to be utilized for a particular test can be utilized by other similar devices or with a similar matrix without departing from the present disclosure.

[0013] Examples of the present disclosure include an apparatus that can include a controller communicatively coupled to a droplet dispenser to deposit reagents on a matrix (e.g., matrix of a lateral flow assay, etc.). In these examples, the controller can include instructions to determine a dispense pattern for the plurality of reagents to be deposited on the matrix. As described further herein, the dispense pattern can be a pattern of samples that can be utilized to compare a test performance of the samples. In some examples, the controller can include instructions to align the droplet dispenser with the matrix to deposit the plurality of reagents along the dispense pattern to generate a sample on the matrix. In some examples, the plurality of reagents include a differential variable that affects a test performance of the sample. In these examples, the controller can include instructions to select a differential variable for the matrix based on the test performance of the sample when exposed to a challenge solution. In this way, the apparatus can be utilized to test a plurality of samples on an LFA matrix to determine what differential variable is to be utilized for a particular LFA test based on the test performance of the plurality of samples positioned on the matrix in the dispense pattern.

[0014] The figures herein follow a numbering convention in which the first digit corresponds to the drawing figure number and the remaining digits identify an element or component in the drawing. Elements shown in the various figures herein may be capable of being added, exchanged, and/or eliminated so as to provide a number of additional examples of the present disclosure. In addition, the proportion and the relative scale of the elements provided in the figures are intended to illustrate the examples of the present disclosure and should not be taken in a limiting sense.

[0015] As used herein, designators such as “B”, “M”, “N,” “P,” “Q”, “R”, and “T”, etc., particularly with respect to reference numerals in the drawings, indicate that any quantity of the particular feature so designation can be included. It is also to be understood that the terminology used herein is for the purpose of describing particular examples only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” can include both singular and plural referents, unless the context clearly dictates otherwise.

[0016] Figure 1 illustrates an example system 100 including a controller 104 and a dispense device 102 for matrix dispense patterns consistent with the present disclosure. In some examples, the dispense device 102 (e.g., droplet dispenser, digital microfluidic system, etc.) can include a reservoir 108 that can be utilized to store a fluid. As used herein, the term “fluid” refers to a substance that can be deposited by a droplet dispenser such as the dispense device 102.

[0017] Some examples of fluids that can be contained in the reservoir 108 include a reagent fluid, an antibody fluid, a fluidic barrier, a washing buffer, a stain (e.g., a generic visualization stain), etc. For example, the dispense device 102 can include multiple antibody fluids, a hydrophobic fluid for a fluidic barrier, different concentrations of antibody fluids, reagents, stains, and combinations thereof. The dispense device 102 can include a dispense head 110 that can be utilized to deposit a fluid as a droplet 112. The dispense head 110 can deposit the droplet 112 from a reservoir 108 onto the matrix 114 positioned on a stage 116.

[0018] As used herein, “communicatively coupled” refers to various wired and/or wireless connections between devices such that data and/or signals may be transferred in various directions between the devices. The controller 104 can transmit control signals to the dispense device 102 and/or the stage 116 related to an operation of the stage 116. The controller 104 can receive information from the stage 116 or the matrix 114 (e.g., imaging system, optical device, humidity information, temperature information, etc.).

[0019] The controller 104 can control the movement and operation of the stage 116, the dispense head 110, or both. The stage 116 can be communicatively coupled to the controller 104 to support the matrix 114 of the LFA or similar matrix, where the stage 116 is moveable to align the matrix 114 with the dispense head 110. The controller 104 can be a component of a computing device such as a processor, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a metal- programmable cell array (MPCA), or other combination of circuitry and/or logic to orchestrate execution of instructions. In other examples, the controller 104 can be a computing device that can include instructions stored on a machine-readable medium (e.g., memory resource, etc.) and executable by a processing resource.

[0020] The dispense head 110 can be a modified inkjet printhead. In an example, this modified inkjet printhead is a thermal inkjet (TIJ) which uses a heating resistor to form an ejection bubble to propel a liquid droplet 112. In another example, the dispense head 110 (e.g., the modified inkjet printhead) is a piezoelectric inkjet (PI J) which uses a piezoelectric actuator to eject the droplet 112.

[0021] The dispense head 110 can alter the droplet 112 to a particular volume to be deposited onto the matrix 114 when instructed by the controller 104. For example, based on a dispense pattern, the droplet 112 can be customized by the dispense head 110 to deposit a precise volume. In some examples, dispense patterns can utilize relatively small volumes (e.g., pico, nano, and/or micro liters) of reagent fluid. In some examples, the controller 104 can be communicatively coupled to a humidity and temperature control 118. In these examples, the humidity and temperature control 118 can be a system that can alter a humidity and/or temperature of the dispense device 102. For example, the humidity and temperature control 118 can be utilized to maintain a temperature and/or humidity of the area around the matrix 114 within a particular range to ensure the operation of the matrix 114.

[0022] The controller 104 can move the dispense head 110 to a position that is aligned with a dispense pattern to be generated on the matrix 114. In some examples, a user of the dispense device 102 can be prompted to place the matrix 114 in a predetermined position and/or orientation relative to the stage 116. For example, the predetermined position can be prompted to the user by utilizing pre-placed markings on the stage 116 which can direct the user to position the matrix 114 on the stage 116. In another example, instead of or in addition to the pre-placed markings on the stage 116, a physical protrusion and/or indentation on the stage 116 can prevent incorrect placement of the matrix 114 on to the stage 116.

[0023] In some examples, the controller 104 can include instructions 120, 122, 124. In some examples, the controller 104 can be a computing device that include a memory resource to store the instructions 120, 122, 124 and the instructions 120, 122, 124 can be executed by a processing resource (e.g., central processing unit (CPU), processor, etc.) to instruct the dispense device 102 to perform particular functions. [0024] In some examples, the controller 104 can include instructions 120 to determine a dispense pattern for the plurality of reagents to be deposited on the matrix 114. In some examples, the dispense pattern can include a pattern of dispensed reagents (e.g., reagent sample pattern, etc.) within a particular portion of the matrix 114. The dispense pattern can include a plurality of dispense locations to deposit a droplet 112 onto the matrix 114 to generate a sample in the determined dispense pattern. As used herein, a sample can include a deposited droplet 112 that has been positioned on or within the matrix 114. That is, the sample can be a combination of reagents and/or other fluids to be tested on the matrix 114. In some examples, the dispense pattern can include a pattern of droplets 112 that can include generating a plurality of portions utilizing a barrier solution (e.g., hydrophobic solution, etc.) or identifying a plurality of locations on the matrix 114 that can correspond to a deposit location (e.g., location of deposited fluid, etc.) of a particular sample. For example, the dispense head 110 can deposit the barrier solution to generate fluidic barriers along the matrix 114 that can be used to separate the matrix 114 into a plurality of portions. In these examples, each of the plurality of portions can include a particular dispense pattern of reagents to generate particular samples. In some examples, each sample within each of the plurality of portions can utilize reagents with a corresponding differential variable.

[0025] In some examples, the controller 104 can include instructions 122 to align the droplet dispenser with the matrix 114 to deposit the plurality of reagents along the dispense pattern to generate a plurality of samples on the matrix 114, wherein the plurality of samples include a differential variable that affects a test performance of the corresponding sample. In some examples, the plurality of portions can each utilize a corresponding sample with a differential variable such that the plurality of portions can be compared to determine or select a differential variable (e.g., reagent composition, reagent combination, etc.) based on a test performance of the samples within the plurality of portions. In some examples, the controller 104 can identify properties of the differential variable for a selected differential variable based on the dispense pattern of the samples. That is, the controller 104 can identify the corresponding features of a sample with a relatively high test performance. In some examples, the test performance can be based on test performance metrics. The test performance metrics can include, but are not limited to: a capillary flow time (CFT), line intensity, line width, reagent depth, and/or coefficient of variation (CV) of the samples when exposed to a challenge solution. In some examples, the dispense pattern and/or sample can be a pattern of droplets 112 positioned along a patterned location on the matrix 114.

[0026] The differential variable can include, but is not limited to: a differential capture reagent (e.g., differential buffer reagent composition, etc.), a differential membrane treatment, a differential conjugate chemistry and composition, a differential sample pretreatment, a differential location of a challenge solution, a differential challenge solution, among other differential features that can be utilized to alter a test performance of a sample on the matrix 114. In some examples, the differential variable can be a component or feature that is being tested to increase a test performance of a sample on the matrix 114. For example, the differential variable can be different reagent concentrations. In this example, each of the plurality of portions can utilize a different sample that includes a different reagent concentration along the dispense pattern to determine a particular reagent concentration that corresponds to a relatively high test performance. In another example, the differential variable can include a differential membrane treatment. In this example, each of the plurality of portions can include a sample that utilizes a different membrane treatment such that a particular membrane treatment can be selected based on the test performance of the samples within the plurality of portions.

[0027] In some examples, the controller 104 can include instructions 124 to select a differential variable for the matrix 114 based on the test performance of the plurality of samples when exposed to a challenge solution. In some examples, the challenge solution can be deposited by the dispense device 102 in a similar way that reagents can be deposited on the matrix 114 by the dispense head 110. However, in other examples, the challenge solution can be deposited by a different device or system. For example, a pipette can be utilized to deposit a challenge solution onto the matrix 114 at a particular challenge solution position. As described herein, the challenge solution can be a fluid provided to the matrix 114 that utilizes a known composition that can be compared to the sample. For example, the challenge solution can be utilized to generate a control line on the matrix 114 during a test utilizing the matrix 114.

[0028] As described herein, the system 100 can be utilized to determine or select a particular combination of features (e.g., differential variable, etc.) for an LFA test for a particular use (e.g., combination of reagents, concentration of reagents, depth of the reagents positioned in the matrix 114, and/or other features that can affect a test performance of the matrix 114). In some examples, the system 100 can be utilized to more easily increase performance of an LFA for a particular use while also utilizing less reagents and/or fewer matrices compared to previous systems and methods.

[0029] Figure 2 illustrates an example of a memory resource 230 for matrix dispense patterns, in accordance with the present disclosure. In some examples, the memory resource 230 can be a part of a computing device or controller that can be communicatively coupled to a dispense device. In some examples, the memory resource 230 can be communicatively coupled to a processing resource 242 that can execute instructions 232, 234, 236, 238 stored on the memory resource 230. For example, the memory resource 230 can be communicatively coupled to the memory resource 230 through a communication path 240. As used herein, a communication path 240 can include a wired or wireless connection that can allow communication between devices.

[0030] The memory resource 230 may be electronic, magnetic, optical, or other physical storage device that stores executable instructions. Thus, non-transitory machine readable medium (e.g., a memory resource 230) may be, for example, a non- transitory MRM comprising Random Access Memory (RAM), an Electrically-Erasable Programmable ROM (EEPROM), a storage drive, an optical disc, and the like. The non- transitory machine readable medium (e.g., a memory resource 230) may be disposed within a controller and/or computing device. In this example, the executable instructions 232, 234, 236, 238 can be “installed” on the device. Additionally, and/or alternatively, the non-transitory machine readable medium (e.g., a memory resource 684) can be a portable, external or remote storage medium, for example, that allows the system 680 to download the instructions 232, 234, 236, 238 from the portable/external/remote storage medium. In this situation, the executable instructions may be part of an “installation package”. As described herein, the non-transitory machine readable medium (e.g., a memory resource 230) can be encoded with executable instructions for array droplet manipulations.

[0031] The instructions 232, when executed by a processing resource such as the processing resource 242, can include instructions to determine a dispense pattern for a plurality of reagents to be deposited on a matrix of a lateral flow assay. In some examples, the dispense pattern can include information relating to a location of a plurality of fluid droplets to be dispensed on the matrix. For example, the dispense pattern can include a quantity of reagents to be deposited at particular locations, a depth of the reagents to be deposited at particular locations, a quantity of barrier solution to be deposited at particular locations, and/or a spacing distance between reagents and/or barrier solutions. In this way, the instructions 232 can determine which reagents are to be deposited at what locations on the matrix, which barrier solutions are to be deposited at what locations on the matrix, and/or how much area of the matrix will not include a deposited fluid.

[0032] In some examples, the dispense pattern can be based on a particular test that is being performed on the matrix. For example, a test for a first reagent may utilize a first dispense pattern and a test for a second reagent may utilize a second dispense pattern that is a different pattern than the first dispense patter. In some examples, the dispense pattern can be based on a predicted flow or test performance for particular reagents. For example, a first reagent may have a first travel distance and a second reagent may have a second travel distance. In this example, the first travel distance and the second travel distance can be predicted travel distances. In this example, the dispense pattern for the first reagent can be based on the first predicted travel distance and the dispense pattern for the second reagent can be based on the second predicted travel distance. In this way, the dispense pattern can prevent contamination between a plurality of tests being performed on samples of the same matrix based on a predicted travel distance of reagents.

[0033] In some examples, a dispense pattern can include information relating to a location of fluids to be deposited within a particular portion of the matrix. For example, a first dispense pattern can be a pattern of fluid deposit locations on the matrix that corresponds to a first test being performed on the matrix. In this example, a second dispense pattern can be a pattern of fluid deposit locations on the matrix that corresponds to a second test being performed on the matrix. In some examples, the first test and the second test can be testing for the same differential variable and can be compared to each other to determine which test performance is greater. For example, the first test can include a pattern of fluid deposits with a first concentration of reagents and the second test can include a pattern of fluid deposits with a second concentration of reagents. In this example, the differential variable can be the concentration of the reagents and the test performance of the first test can be compared to the test performance of the second test to select a particular concentration of reagents to be utilized for a test condition or select a particular differential variable. In some examples, the first test and the second test can be separated by a fluidic barrier to prevent elements of the first test from interacting with elements of the second test. [0034] In some examples, the memory resource 230 can include instructions to generate fluidic barriers to separate the matrix into a plurality of portions. As used herein, generating fluidic barriers can include depositing a barrier solution on the matrix such that a barrier of fluidic barrier solution is generated between a first area of the matrix and a second area of the matrix. In some examples, the fluidic barriers can be generated by a dispense device (e.g., dispense device 102, etc.) depositing fluidic barrier solution on the matrix to divide the matrix into a plurality of portions.

[0035] In some examples, the quantity of the plurality of portions can correspond to a quantity of tests to be performed on the matrix. For example, the instructions 234 can include instructions to determine a quantity of tests to perform on a particular matrix. In some examples, the quantity of tests to be performed can correspond to a size of each of the plurality of tests and/or a size of the matrix. As described herein, each of the plurality of portions can include a corresponding dispense pattern of fluid to be deposited on the matrix to generate corresponding samples within each of the plurality of portions. In addition, the dispense pattern can correspond to a particular test being performed and the size of the dispense pattern can correspond to the dispense pattern and/or reagents being utilized. In some examples, a fluidic barrier can include a continuous or substantially continuous line or path of fluidic barrier solution. In some examples, each of the plurality of portions can include edges that are a fluidic barrier or an edge of the matrix. In this way, a particular test within a particular portion is prevented from interacting with a different test within a different portion of the matrix. [0036] The instructions 236, when executed by a processing resource such as the processing resource 242, can include instructions to align a droplet dispenser with the matrix to deposit the plurality of reagents along the dispense pattern to generate a plurality of samples at a plurality of locations (e.g., plurality of portions, plurality of different areas, etc.) on the matrix, wherein the plurality of locations include a corresponding sample of the plurality of samples that utilizes a corresponding differential variable that affects a test performance of the corresponding sample. As described herein, the memory resource 230 can be communicatively coupled to a dispense device. For example, the memory resource 230 can be a component of controller 104 as illustrated in Figure 1 and be communicatively coupled to the dispense device 102 as illustrated in Figure 1.

[0037] In some examples, the instructions 236 can utilized to align the droplet dispenser (e.g., dispense device 102 as illustrated in Figure 1, etc.) with particular portions of the matrix to deposit droplets of the reagents based on the dispense pattern. As described herein, the dispense pattern can include an orientation of droplets at specific locations to generate a pattern of droplets or samples within a particular portion of the matrix. In some examples, the pattern of droplets or samples can be utilized to illustrate a test performance of a particular differential variable. In some examples, each of the plurality of portions can utilize the same or similar dispense pattern to compare a test performance of a first portion or first sample with a test performance of a second portion or second sample. In this way, the differential variable of the plurality of reagents can be compared based on a test performance that is performed under the same or similar conditions since they are performed on the same matrix and during the same testing period.

[0038] In some examples, the dispense pattern can be based on the differential variable of the plurality of reagents. As will be described further herein, the dispense pattern can be one of a plurality of different dispense pattern types including, but not limited to: a linear dispense pattern, a radial dispense pattern, and/or a circular or oval dispense pattern. In some examples, the dispense pattern of a first portion of the matrix can be a first dispense pattern type and a second portion of the matrix can be a second dispense pattern type. In this way, a first portion of the matrix can be utilized to compare a test performance for a first differential variable and a second portion of the matrix can be utilized to compare a test performance of a second differential variable. In this way, the same matrix and test run can be utilized to compare a plurality of different differential variables simultaneously. In this way, a first differential variable for the plurality of samples can be selected utilizing a second differential variable that may affect the test performance of the first differential variable. Thus, a particular differential variable can be selected based on a comparison of test performance for a plurality of other differential variables, which can increase the overall test performance of the LFA that is generated to test similar samples. [0039] The instructions 238, when executed by a processing resource such as the processing resource 242, can include instructions to select a differential variable for the lateral flow assay based on the test performance of the plurality of samples when exposed to a challenge solution. As described herein, the challenge solution can be provided on the matrix as a control solution to ensure that a flow or lack of flow of samples is performing as expected. In some examples, the challenge solution can be deposited at a particular location on the matrix by the dispense device communicatively coupled to the memory resource 230 and/or deposited utilizing a different method or system. As described herein, the sample or differential variable that is selected for the lateral flow assay can be a sample that is utilized for production of a lateral flow assay test. In this way, a lateral flow assay test can be generated that utilizes particular differential variables of the samples that promote a relatively higher test performance. [0040] Figure 3 illustrates an example system 300 including a controller 304 and a dispense device 302 (e.g., digital microfluidic array, etc.) for matrix dispense patterns consistent with the present disclosure. In some examples, the system 300 can include a controller 304 that is communicatively coupled to the dispense device 302 through communication path 306 and/or communicatively coupled to an optical sensor 350 through communication path 352. In some examples, the optical sensor 350 can be utilized to determine a test performance of a plurality of samples deposited on to a matrix associated with the dispense device 302.

[0041] In some examples, the controller 304 can include instructions 354, 356, 358, 360. In some examples, the controller 304 can be a computing device that include a memory resource to store the instructions 354, 356, 358, 360 and the instructions 354, 356, 358, 360 can be executed by a processing resource (e.g., central processing unit (CPU), processor, etc.) to instruct the dispense device 302 to perform particular functions.

[0042] In some examples, the controller 304 can include instructions 354 to deposit a fluidic barrier onto the matrix to separate the matrix into a plurality of portions. As described herein, the fluidic barrier can include a fluidic barrier solution that is deposited on the matrix to separate the matrix into a plurality of portions. In some examples, the dispense device 302 can include a reservoir that includes the fluidic barrier. As described herein, the size and/or dimensions of the plurality of portions can be based on the dispense pattern to be positioned within each of the plurality of portions. For example, a particular dispense pattern that utilizes a particular quantity of reagents can be a particular size that can be different than a different dispense pattern. In this way, the controller 304 can include instructions to determine the dispense pattern to be deposited within each portion of the matrix and utilize the determined dispense patterns to determine a corresponding size for each of the portions.

[0043] In some examples, the controller 304 can include instructions 356 to deposit a first reagent from the plurality of reagents within a first portion of the matrix in a selected dispense pattern to generate a first sample. In some examples, the plurality of reagents can be stored within the reservoir of the dispense device 302. In some examples, the plurality of reagents can each include a differential variable. For example, each of the plurality of reagents can include a different concentration of a particular element (e.g., antigen, buffer solution, etc.). In some examples, the differential variable can affect a test performance of the corresponding sample. In some examples, the selected dispense pattern can be based on the differential variable to be tested.

[0044] In some examples, the controller 304 can include instructions 358 to deposit a second reagent from the plurality of reagents within a second portion of the matrix in the selected dispense pattern to generate a second sample. As described herein, the first reagent and the second reagent from the plurality of reagents can include differential variables that can make the first sample have a test performance that is different than the second sample. In this way, the differential variable can be tested by comparing a test performance of the first sample to a test performance of the second sample. In these examples, the test performance of the first sample can be separated from the test performance of the second sample when the first portion and second portion are separated by the generated fluidic barrier.

[0045] In some examples, the controller 304 can include instructions 360 to determine a test performance of the first sample and the second sample when exposed to a challenge solution, wherein the test performance is based on a starting location and stopping location of the first sample and second sample. As described herein, a test performance of the first sample and the second sample can be compared against the same conditions by testing on the same matrix during the same test run. In some examples, the test performance of the first sample and the second sample can be based on a flow of the first sample and a flow of the second sample.

[0046] In some examples, the test performance of the first sample and the second sample can be based on an image generated by the optical sensor 350 and/or results generated by the optical sensor 350. For example, the optical sensor 350 can track a flow performance of the first sample and the second sample over a period of time. In some examples, the optical sensor 350 can be utilized to determine a level of protein binding, a level of capillary flow rate, a level of striping consistency, and/or a level of stripe width for the first reagent and the second reagent. In some examples, the optical sensor 350 can be utilized to determine relatively small test performance differences between the first sample and the second sample.

[0047] In some examples, an expected flow of the first sample and/or the second sample can be a lack of flow. In these examples, the starting location and the stopping location can be the same location of the matrix. In other examples, the starting location and stopping location can be different locations. In these examples, a distance between the starting location and the stopping location can be utilized to compare the test performance of the first sample and the second sample. For example, an expected flow for the first sample and the second sample can be 1 millimeter (mm). In this example, the first sample and the second sample can include a differential variable that can affect the flow of the sample. In this example, a determination can be made to increase the flow distance of a sample for production of the lateral flow assay. In this way, the test performance of the first sample and the second sample can be based on the flow distance of the samples. In this way, a sample that results in a greater distance can be selected and a corresponding differential variable can be utilized for the production of a lateral flow assay.

[0048] Figure 4 illustrates an example of matrix dispense patterns 472, in accordance with the present disclosure. As described herein, the matrix dispense patterns 472 can be deposited onto a matrix (e.g., lateral flow assay matrix, etc.) to determine a test performance of a plurality of different samples that include differential variables. In some examples, the matrix dispense patterns 472 can include a first matrix dispense pattern 472-1 and a second matrix dispense pattern 472-2. In these examples, the first matrix dispense pattern 472-1 can be utilized to generate a first sample and the second matrix dispense pattern 472-2 can be utilized to generate a second sample. In some examples, the first matrix pattern 472-1 can be utilized to determine a test performance for a first differential variable and the second matrix pattern 472-2 can be utilized to determine a second differential variable.

[0049] In some examples, the first matrix pattern 472-1 can be utilized to test a first differential variable. For example, the first matrix pattern 472-1 can be utilized to determine an optimal detergent concentration for the matrix. In some examples, the optimal detergent level can be based on the test performance of different detergent concentrations. In some examples, the matrix can utilize a surfactant or detergent to make the matrix wettable. In these examples, an increase in surfactant or detergent concentration may have little impact on wettability, however a relatively higher concentration can correspond to a relatively higher uniform capillary flow. The concentration of the detergent or surfactant can also affect protein adsorption, reagent striping, band width, and/or maintaining wettability during reagent application.

[0050] In some examples, the test performance can be based on a level of protein binding, a level of capillary flow rate, a level of striping consistency, and/or a level of stripe width for a sample. As used herein, a level of protein binding can be a percentage of protein binding of a reagent sample during and/or after a test of a sample. As used herein, a level of capillary flow rate can be a rate of speed of a sample moving from a first position to a second position over a period of time. Since reagents such as surfactants or detergents can affect multiple metrics of the test performance, it can be beneficial to compare a plurality of different dispense patterns or samples simultaneously to see how the overall test performance is affected by different reagent combinations.

[0051] As used herein, a level of striping consistency can include a consistency level of a stripe between a plurality of samples. For example, a first stripe can be relatively clear with relatively well defined edges while a second stripe can be relatively foggy with relatively low defined edges. In this example, the first stripe and the second stripe would not have a high level of stripe consistency since the samples are not consistently high or low. In other examples, a plurality of samples may each include a relatively high level of edge definition and/or strip clarity, which may be utilized to determine that the plurality of samples have a relatively high level of stripe consistency. As used herein, a stripe width can correspond to a distance between a leading edge of a stripe and a trailing edge of a stripe.

[0052] As described herein, a first dispense pattern 472-1 can be positioned on a matrix that can include a plurality of portions 476-1 , 476-2, 476-3, 476-4 that can be separated by a fluidic barrier. As described herein, the fluidic barrier can be deposited on to the matrix to generate the first dispense pattern 472-1. In some examples, the plurality of portions 476-1 , 476-2, 476-3, 476-4 can each include a reagent with a differential variable to generate corresponding samples. For example, the first portion 476-1 can include a first concentration of detergent dispensed in a clustered or cross dispense pattern, the second portion 476-2 can include a second concentration of detergent dispensed in a clustered or cross dispense patter, the third portion 476-3 can include a third concentration of detergent dispensed in a clustered or cross dispense pattern, and the fourth portion 476-4 can include a fourth concentration of detergent dispensed in a clustered or cross dispense pattern.

[0053] In a specific example, a first portion 476-1 of the plurality of dispense patterns can utilize a first type of capture reagent and conjugate reagent and a second portion 476-2 of the plurality of dispense patterns can utilize a second type of capture reagent and conjugate reagent. In another example, a first portion 476-1 of the plurality of dispense patterns can be exposed to a first type of challenge solution and a second portion 476-2 of the plurality of dispense patterns can be exposed to a second type of challenge solution. In addition, a first portion 478-1 of the plurality of dispense patterns can be exposed to a first type of membrane treatment and a second portion 478-2 of the plurality of dispense patterns can be exposed to a second type of membrane treatment.

[0054] In some examples, the clustered or cross dispense pattern can include a pattern of droplets that includes a central droplet with a plurality of surrounding droplets. In some examples, the clustered or cross pattern can include a plurality of droplets of reagent that are a particular distance or threshold distance away from other droplets within the same portion of the plurality of portions 476-1 , 476-2, 476-3, 476-4. For example, in the case where there is a central droplet (e.g., droplet positioned at a relative center of a plurality of droplets, etc.), the central droplet can be a threshold distance from the other droplets deposited within the same portion of the plurality of portions 476-1 , 476-2, 476-3, 476-4. In some examples, each of the droplets can be positioned the same distance from the nearest droplets. For example, a central droplet can be positioned at a particular distance from the surrounding droplets. In this way, the test performance can be determined for each of the plurality of droplets within a particular portion of the plurality of portions 476-1 , 476-2, 476-3, 476-4. For example, the test performance can include a striping consistency and capillary flow rate. By utilizing the first dispense pattern 472-1 , the striping consistency for a particular portion or particular differential variable can be determined by comparing the plurality of droplets within a particular portion. That is, a first droplet can have a first capillary flow rate, which can be compared to the capillary flow rate of the other plurality of droplets. This type of comparison can be utilized to determine the striping consistency for a particular portion or particular differential variable.

[0055] In some examples, the first dispense pattern 472-1 can utilize a flow direction 474-1. In some examples, the flow direction 474-1 can be designed based on a position of a sample pad and/or absorbent pad when the matrix is an LFA matrix. For example, the bottom edge of the matrix can include a sample pad and the top edge of the matrix can include an absorbent pad to provide the flow direction 474-1 toward the absorbent pad. In some examples, the flow direction can be utilized to determine the test performance of the samples deposited within each of the plurality of portions 476-1 , 476-2, 476-3, 476-4.

[0056] In some examples, the second dispense pattern 472-2 can utilize the same or similar dispense device to generate a linear pattern. As used herein a linear pattern can include a plurality of droplets that are arranged in a substantially linear pattern within a particular portion of the matrix. As used herein, substantially linear can be a shape that is more linear than non-linear. In some examples, the matrix can include a plurality of portions 478-1 , 478-2, 478-3, 478-4 that are separated by a fluidic barrier. In some examples, each of the droplets can be positioned the same distance from the nearest droplets. For example, an edge droplet (e.g., droplet positioned at an edge of the linear dispense pattern, etc.) can be positioned at a particular distance from a first interior droplet or droplet that is adjacent to the edge droplet. In this way, the test performance can be determined for each of the plurality of droplets within a particular portion of the plurality of portions 478-1 , 478-2, 478-3, 478-4. For example, the test performance can include a stripe width. By utilizing the second dispense pattern 472-2, the stripe width for a particular portion or particular differential variable can be determined by comparing the plurality of droplets within a particular portion. That is, a first droplet can have a first stripe width, which can be compared to the stripe width of the other plurality of droplets. This type of comparison can be utilized to determine the stripe width for a particular portion or particular differential variable.

[0057] In some examples, the second dispense pattern 472-2 can utilize a flow direction 474-2. In some examples, the flow direction 474-2 can be designed based on a position of a sample pad and/or absorbent pad when the matrix is an LFA matrix. For example, the bottom edge of the matrix can include a sample pad and the top edge of the matrix can include an absorbent pad to provide the flow direction 474-2 toward the absorbent pad. In some examples, the flow direction can be utilized to determine the test performance of the samples deposited within each of the plurality of portions 478-1 , 478-2, 478-3, 478-4.

[0058] Figure 5 illustrates an example of a matrix dispense pattern 572, in accordance with the present disclosure. In some examples, the matrix dispense pattern 572 can be generated by a dispense device (e.g., dispense device 102 as illustrated in Figure 1, etc.). In some examples, the matrix dispense pattern 572 can be a radial dispense pattern. As used herein, a radial dispense pattern can include a plurality of reagents that are deposited around a central challenge solution point (e.g., challenge solution is deposited between a plurality of samples, challenge solution point 582, etc.). In some examples, the plurality of samples can surround or substantially surround the central challenge solution point (e.g., challenge solution point 582, etc.).

[0059] In some examples, the plurality of samples can be separated into a plurality of portions 584-1, 584-2, 584-3, 584-4, 584-5. In some examples, the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 may not be separated by a fluidic barrier as described herein since the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 are deposited to move radially outward, which should prevent the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 from interacting or contaminating other portions. In some examples, each of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 can be testing for a different differential variable. For example, the first portion 584-1 can be testing for detergent concentration and the second portion 584-2 can be testing different blocking reagents. Thus, a challenge solution can be deposited at the challenge solution point 582 and the challenge solution can disperse across the matrix in a radial direction of arrows 574 surrounding the challenge solution point 582.

[0060] In some examples, each of the plurality of portions 584-1, 584-2, 584-3, 584-4, 584-5 can be split into a plurality of samples (e.g., sample (1), sample (2), sample (3), sample (4), etc.). Although four samples are illustrated for each of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 the disclosure is not so limited. For example, each of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 can utilize a different quantity of samples for a particular test to be performed.

[0061] In some examples, each of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 can utilize a corresponding dispense pattern. For example, the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 are illustrated as utilizing a linear dispense pattern within the radial dispense pattern. However, a cluster dispense pattern could also be utilized within each of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 based on the type of differential variable is being tested.

[0062] In some examples, the test performance of the plurality of portions 584-1 , 584-2, 584-3, 584-4, 584-5 can be determined as described herein. Utilizing the radial dispense pattern as illustrated in Figure 5, a plurality of different reagents can be tested and compared under the same conditions to determine which differential variables are to be utilized for a matrix such as an LFA matrix.

[0063] Figure 6 illustrates an example of a matrix dispense pattern 672, in accordance with the present disclosure. In some examples, the matrix dispense pattern 672 can include a plurality of rows 698-1 , 698-2, 698-3 that each include a plurality of dispense patterns. In some examples, the plurality of rows 698-1, 698-2, 698-3 and/or the plurality of dispense patterns within the plurality of rows 698-1 , 698-2, 698-3 can be separated by a fluidic barrier as described herein. [0064] In some examples, each of the plurality of rows 698-1 , 698-2, 698-3 can be utilized to determine a test performance for a particular differential variable. For example, the first row 698-1 can include a plurality of radial dispense patterns. In this example, the first row 698-1 can be utilized to test for capture reagent and conjugate sample chemistry. In this example, the challenge solution point 682-1 can be positioned within a circle of reagent samples 692-1. In this example, the plurality of radial dispense patterns within the first row 698-1 can each include a different capture reagent and conjugate for reagent samples that are deposited as the circle of reagent samples 692- 1. As described herein, the circle of reagent samples 692-1 can be exposed to a challenge solution that is deposited at the challenge solution point 682-1 that is radiating in a radial direction to interact with the circle of reagent samples 692-1. In some examples, the challenge solution can include, but is not limited to: a conjugate label, a detection Abs concentration, a buffer concentration, detergent concentration, blocking reagents, biological sample with different pretreatments, and/o/r a target concentration. In some examples, the capture chemistry composition of the circle of reagent samples 692-1 can include, but is not limited to: an Abs concentration, a buffer ID, a buffer concentration, and/or a detergent concentration.

[0065] In some examples, a capture buffer reagent composition can affect a plurality of different test performances. For example, the capture buffer reagent composition can affect protein adsorption, reagent reactivity, and/or flow properties. By utilizing the dispense pattern 672 and/or other dispense patterns described herein, a plurality of different capture buffer reagent compositions can be tested simultaneously on the same matrix and compared to determine a test performance that is acceptable for production of an LFA or similar device.

[0066] In another example, the second row 698-2 can include a plurality of radial dispense patterns. In this example, the second row 698-2 can be utilized to test for blocking reagents. In this example, the challenge solution point 682-2 can be positioned within a circle of reagent samples 692-2. In this example, the plurality of radial dispense patterns within the second row 698-2 can each include a different blocking reagent for reagent samples that are deposited as the circle of reagent samples 692-2. As described herein, the circle of reagent samples 692-2 can be exposed to a challenge solution that is deposited at the challenge solution point 682-2 that is radiating in a radial direction to interact with the circle of reagent samples 692-2.

[0067] In one example, a first portion of the plurality of dispense patterns of the third row 698-3 can utilize a first distance 695-1 of capture chemistry and a second portion of the plurality of dispense patterns can utilize a second distance 695-2 of capture chemistry. In these examples, the third row 698-3 can include a plurality of radial dispense patterns. The third row 698-3 can be utilized to test for a position of capture chemistry and/or a distance between the challenge solution point 682-3 and the circle of reagent samples 692-3. In this example, the challenge solution point 682-3 can be positioned within a circle of reagent samples 692-3 that are each a different distance away from the challenge solution point 682-3. In this example, the plurality of radial dispense patterns within the third row 698-3 can each include a different distance between the challenge solution point 682-3 and the circle of reagent samples 692-3. For example, the distance 695-1 can be relatively shorter than the distance 695-2. In this way, the plurality of radial dispense patterns within the third row 698-3 can be compared to determine a distance to be utilized based on the test performance. As described herein, the circle of reagent samples 692-3 can be exposed to a challenge solution that is deposited at the challenge solution point 682-3 that is radiating in a radial direction to interact with the circle of reagent samples 692-3.

[0068] Figure 7 illustrates an example of a matrix dispense pattern 772, in accordance with the present disclosure. In some examples, the matrix dispense pattern 772 can include a plurality of rows 701 , 703, 705 that each include a plurality of dispense patterns. In some examples, the plurality of rows 701, 703, 705 and/or the plurality of dispense patterns within the plurality of rows 701 , 703, 705 can be separated by a fluidic barrier as described herein.

[0069] In some examples, each of the plurality of rows 701 , 703, 705 can be utilized to determine a test performance for a particular differential variable. For example, the first row 701 can be utilized to test multiple distances of capture chemistry. For example, the challenge solution point 782-1 can be at a first position that makes the challenge solution a different distance from the circle of reagent samples 792-1. In a similar way, the challenge solution point 782-2 can be at a second position that makes the challenge solution a different distance from the circle of reagent samples 792-2. [0070] In another examples, the second row 703 can be utilized to test an order of capture chemistry. That is, a first portion of the plurality of dispense patterns within the second row 703 can utilize a first multiplexing order of capture chemistry and a second portion of the plurality of dispense patterns within the second row 703 can utilize a second multiplexing order of capture chemistry. In some examples, the second row 703 can include a plurality of circles of reagent samples 792-3 where each circle represents a different capture chemistry. In this way, each of the dispense patterns within the second row 703 can include a particular inner circle, a particular mid circle, and/or a particular outer circle of reagents. In some examples, the circles of reagent samples 792-3 can be greater than or less than three circles to test additional orders of capture chemistry. As described herein, the circle of reagent samples 792-3 can be exposed to a challenge solution that is deposited at the challenge solution point 782-3 that is radiating in a radial direction to interact with the circle of reagent samples 792-3. Since the challenge solution is radiating, an inner circle can be exposed to the challenge solution first, followed by the mid circle, and then followed by the outer circle. In this way, the order or sequence of capture chemistry can be tested and compared to different orders or sequences of capture chemistry. That is, the first inner circle can be a first reagent for a first dispense pattern within the second row 703 and a second inner circle can be a second reagent for the second dispense pattern within the second row 703.

[0071] In some examples, the dispense pattern 772 can include a third row 705 that includes a plurality of radial dispense patterns. In some examples, the third row 705 can utilize a plurality of screens 707-1 , 707-2 that can be utilized to prevent an interaction between the challenge solution deposited at the challenge solution point 782-4. In some examples, the screens can be utilized to illustrate how a challenge solution will react with a particular circle of reagents 792-4, 792-5 and how the challenge solution will react without a particular circle of reagents 792-4, 792-5. In some examples, the screens 707-1, 707-2 can be utilized to increase the number of combinations for the order of capture chemistry. For example, the screen 707-1 can be used to illustrate how a challenge solution will interact without the circle of reagents 792-4. In this way, the same radial dispense pattern within the third row 705 can be utilized to test the challenge solution with and without the circle of reagents 792-4.

[0072] In another example, the screen 707-2 can be utilized to select a particular circle from the circles of reagents 792-5. For example, the screen 707-2 covers the mid circle and not the inner circle or the outer circle of the circles of reagents 792-5. In this way, the radial dispense pattern within the third row 705 can be utilized to test a first order of capture chemistry (e.g., inner circle, mid circle, and outer circle) as well as a second order of capture chemistry (e.g., inner circle and outer circle). Many combinations can be utilized to allow a plurality of combinations to be tested on the same radial dispense pattern.

[0073] The figures herein follow a numbering convention in which the first digit corresponds to the drawing figure number and the remaining digits identify an element or component in the drawing. Elements shown in the various figures herein can be added, exchanged, and/or eliminated so as to provide a number of additional examples of the present disclosure. In addition, the proportion and the relative scale of the elements provided in the figures are intended to illustrate the examples of the present disclosure and should not be taken in a limiting sense. As used herein, the designator “N”, particularly with respect to reference numerals in the drawings, indicates that a number of the particular feature so designated can be included with examples of the present disclosure. The designators can represent the same or different numbers of the particular features. Further, as used herein, "a number of an element and/or feature can refer to one or more of such elements and/or features.

[0074] In the foregoing detailed description of the present disclosure, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration how examples of the disclosure may be practiced. These examples are described in sufficient detail to enable those of ordinary skill in the art to practice the examples of this disclosure, and it is to be understood that other examples may be utilized and that process, electrical, and/or structural changes may be made without departing from the scope of the present disclosure.

Claims

What is claimed:

1. An apparatus, comprising: a controller communicatively coupled to a droplet dispenser to deposit a plurality of reagents on a matrix, wherein the controller is to: determine a dispense pattern for the plurality of reagents to be deposited on the matrix; align the droplet dispenser with the matrix to deposit the plurality of reagents along the dispense pattern to generate a plurality of samples on the matrix, wherein the plurality of samples include a differential variable that affects a test performance of the corresponding sample; and select a differential variable for the matrix based on the test performance of the plurality of samples when exposed to a challenge solution.

2. The apparatus of claim 1 , wherein the plurality of samples are divided into a plurality of portions on the matrix with a barrier solution such that a corresponding sample of the plurality of samples are positioned within the plurality of portions.

3. The apparatus of claim 2, wherein a first portion utilizes a first type of capture reagent and conjugate reagent and a second portion utilizes a second type of capture reagent and conjugate reagent.

4. The apparatus of claim 2, wherein a first portion is exposed to a first type of challenge solution and a second portion is exposed to a second type of challenge solution.

5. The apparatus of claim 2, wherein a first portion is exposed to a first type of membrane treatment and a second portion is exposed to a second type of membrane treatment.

6. The apparatus of claim 2, wherein a first portion utilizes a first distance of capture chemistry and a second portion utilizes a second distance of capture chemistry.

7. The apparatus of claim 2, wherein a first portion utilizes a first multiplexing order of capture chemistry and a second portion utilizes a second multiplexing order of capture chemistry.

8. A non-transitory machine-readable storage medium comprising instructions executable by processing resource to: determine a dispense pattern for a plurality of reagents to be deposited on a matrix of a lateral flow assay; align a droplet dispenser with the matrix to deposit the plurality of reagents along the dispense pattern to generate a plurality of samples at a plurality of locations on the matrix, wherein the plurality of locations include a corresponding sample of the plurality of samples that utilizes a corresponding differential variable that affects a test performance of the corresponding sample; and select a differential variable for the lateral flow assay based on the test performance of the plurality of samples when exposed to a challenge solution.

9. The medium of claim 8, further comprising instructions executable to identify properties of the selected differential variable.

10. The medium of claim 8, wherein the dispense pattern is a radial pattern positioned at the plurality of locations

11. The medium of claim 8, wherein the differential variable includes reagent composition and reagent positioning.

12. The medium of claim 8, further comprising instructions executable to evaluate the plurality of samples based on a capillary flow time (CFT), line intensity, line width, reagent depth, and coefficient of variation (CV) of the sample when exposed to a challenge solution.

13. A system, comprising: a controller communicatively coupled to a droplet dispenser to deposit a plurality of reagents onto a matrix of a lateral flow assay, wherein the controller is to cause the droplet dispenser to: deposit a fluidic barrier onto the matrix to separate the matrix into a plurality of portions; deposit a first reagent from the plurality of reagents within a first portion of the matrix in a selected dispense pattern to generate a first sample; deposit a second reagent from the plurality of reagents within a second portion of the matrix in the selected dispense pattern to generate a second sample; and determine a test performance of the first sample and the second sample when exposed to a challenge solution, wherein the test performance is based on a starting location and stopping location of the first sample and second sample.

14. The system of claim 13, wherein the test performance of the first sample is compared to a first plurality of samples deposited within corresponding portions of the matrix, wherein the first sample and the first plurality of samples each include a differential variable with a corresponding composition that affects the test performance.

15. The system of claim 14, wherein the controller is to select a first differential variable associated with the first sample when the first sample includes a corresponding test performance that is greater than a test performance of the first plurality of samples.