# US 11,994,515 B2 · Method of performing an assay > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,994,515 B2 - Document ID: US11994515B2 - Status: Granted - Kind: B2 - Application number: 16/467,661 - Filed: 2017-12-01 - Published: 2019-12-05 - Granted: 2024-05-28 - Earliest claimed: 2016-12-12 - Assignees: Minq Solutions B.V. - Applicants: Minq Solutions B.V. - Inventors: Jan Willem Weener; Edin Sarajlic - Web page: https://patentgrep.com/patent/US11994515B2 ## CPC - G01N 33/5304: {Reaction vessels, e.g. agglutination plates (for solid-phase systems G01N33/543)} - B01L 3/5085: {for multiple samples, e.g. microtitration plates} - C12M 23/12: {Well or multiwell plates (C12M25/04 takes precedence)} - G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics} - B01J 2219/00317: Microwell devices, i.e. having large numbers of wells - B01J 2219/00722: Nucleotides - B01J 2219/00743: Cells - B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles - B01L 2300/0829: Multi-well plates; Microtitration plates - B01L 2300/0851: Bottom walls - C12Q 1/686: Polymerase chain reaction [PCR] - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract The invention relates to a method of performing an assay for a compound. The method makes use of a device (390) which has a plurality of wells (340) which contain cells, and according to the method a liquid is transferred from the wells (340) to a substrate which is used to perform the assay. Each well (340) of the device comprises a bottom provided with a through-hole (370) extending from the well (340) to the backside of the device (390). Liquid containing the compound is transferred via the through-holes (370) to the substrate. ## Claims ### Claim 1 A method of selecting a biological cell by performing assays on a compound excreted by biological cells, the method being performed using a device, wherein the device comprises: a frontside with a plurality of wells; and a backside wherein each respective well of the plurality of wells comprises a respective bottom provided with a respective through-hole extending from the respective well to the backside, wherein the wells of the plurality of wells contain biological cells, and wherein each respective through-hole has smaller dimensions than the biological cells in the plurality of wells and thereby physically retains the biological cells in the wells, wherein at least 10% of the plurality of wells contain only a single biological cell; wherein said method comprises: contacting the backside of the device with a substrate such that a substantially respective straight passage from each respective through-hole to the substrate is established wherein each respective straight passage is substantially coaxial with each respective through-hole and is substantially perpendicular to the backside, wherein the biological cells excrete a compound in the plurality of wells and following excretion of the compound by the cells in the plurality of wells, the method further comprises: transferring a liquid from the plurality of wells via the through-holes to the substrate; performing a first assay using the substrate; and selecting a biological cell from a well of the plurality of wells, wherein the device is held in a position with the backside oriented substantially downward between the transferring of the liquid from the plurality of wells to the substrate via the through-holes and performing the first assay using the substrate. ### Claim 2 (depends on 1) The method according to claim 1, wherein the first assay is an immunoassay. ### Claim 3 (depends on 1) The method according claim 1, wherein the substrate comprises a micro-porous substrate. ### Claim 4 (depends on 3) The method according to claim 3, comprising transferring the liquid using a pressure difference wherein a pressure at a side of the substrate facing opposite from the backside of the device is lower than a pressure at a side of the substrate facing the backside of the device. ### Claim 5 (depends on 1) The method according to claim 1, wherein the substrate is a polymer. ### Claim 6 (depends on 1) The method according to claim 1, wherein the backside comprises a plurality of protruding capillaries, the capillaries running in a direction transverse to a main plane of the substrate and through the device from the frontside to the backside. ### Claim 7 (depends on 1) The method according to claim 1, wherein the backside of the device is a hydrophobic backside. ### Claim 8 (depends on 1) The method according to claim 1, wherein the compound is an antibody. ### Claim 9 (depends on 1) The method according to claim 1, further comprising propagating the selected biological cell. ### Claim 10 (depends on 1) The method according to claim 1, wherein the selected biological cell contains a poly nucleic acid sequence and the method further comprises at least one further step chosen from i) multiplying the poly nucleic acid sequence, ii) sequencing the poly nucleic acid sequence, and iii) isolating the poly nucleic acid sequence. ### Claim 11 (depends on 1) The method according to claim 1, further comprising separating the device from the substrate after transferring the liquid to the device and before performing the first assay using the substrate. ### Claim 12 (depends on 5) The method of claim 5, wherein the polymer is chosen from i) polyvinylidene difluoride, and ii) nitrocellulose. ### Claim 13 (depends on 1) The method of claim 1, further comprising retaining the selected biological cell in the well for performing a second assay. ### Claim 14 (depends on 1) The method of claim 1, further comprising keeping the selected biological cell physically from the substrate. ### Claim 15 (depends on 1) The method of claim 1, wherein each through-hole is adapted to transfer liquid containing the compound to a spot of a size smaller than a surface area of the well in a main plane of the device. ### Claim 16 (depends on 15) The method of claim 15, wherein the backside comprises a plurality of protruding capillaries, the capillaries running in a direction transverse to a main plane of the substrate and through the device from the frontside to the backside wherein the capillaries define the through-holes.