# US 12,760,256 B2 · Confined migration microfluidic device for cell culture and drug screening > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,760,256 B2 - Document ID: US12760256B2 - Status: Granted - Kind: B2 - Application number: 17/822,209 - Filed: 2022-08-25 - Published: 2023-11-23 - Granted: 2026-10-13 - Earliest claimed: 2022-05-19 - Assignees: City Unversity of Hong Kong - Applicants: City University of Hong Kong - Inventors: Mengsu Yang; Zihan Yang; Zhihang Zhou; Tongxu Si; Zhengdong Zhou - Web page: https://patentgrep.com/patent/US12760256B2 ## CPC - C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)} - C12M 23/42: {Integrated assemblies, e.g. cassettes or cartridges} - C12M 23/48: {Holding appliances; Racks; Supports (holding devices for laboratory apparatus B01L9/00)} - C12M 25/00: {Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings} - 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} ## Abstract Provided is a confined migration microfluidic device for cell culture and drug screening, including a chip including a plurality of parallel channels, where each pair of it is connected through a plurality of the confined migration channels; a depth of the confined migration channel is lower than the first channel and second channel; a first/second inlet and a first/second outlet are provided at two ends of the first/second channel, respectively; and a pyramid-like structure for diverging flow to the first channels to ensure evenly distribution. During the usage, cells to be cultured are added into one of the first channel and the second channel, and drugs or cells which can influence confined migration of the target cells are added into the other channel; the inhibitory effect of the drugs or cells on the confined migration will be evaluated, thereby screening/studying effective drugs and cells in relation to the confined migration. ## Claims ### Claim 1 A confined migration microfluidic device for cell culture and drug screening, comprising: at least one microfluidic chip, each of the at least one microfluidic chip comprising: a plurality of first channels; a plurality of second channels each being disposed in parallel with one of the first channels thereby providing a plurality of pairs of the first channels and the second channels; a plurality of confined migration channels; a plurality of two extension channels; each of the plurality of pairs of the first channels and the second channels being connected through the confined migration channels, each of the confined migration channels having a depth smaller than that of each of the first channels and second channels; two opposite ends of each of the first channels being provided with a first inlet and a first outlet, respectively; two opposite ends of each of the second channels being provided with a second inlet and a second outlet, respectively; and an upper chip and a lower chip, wherein the plurality of confined migration channels between each of the plurality of pairs of the first channel and the second channel being identical in terms of shape and dimension; the plurality of two extension channels each composed of a first extension channel and a second extension channel being respectively disposed at two opposite ends of each of the confined migration channels; the first extension channel communicating with the first channel and the confined migration channel; the second extension channel communicating with the second channel and the confined migration channel; each of the first extension channel and the second extension channel having a depth greater than that of the confined migration channel; and wherein the upper chip is provided therethrough with the first inlet, the second inlet, the first outlet, and the second outlet, and wherein the upper chip and the lower chip are associated with each other to form each of the at least one microfluidic chip, and wherein the first channels, the second channels, the first extension channels, the second extension channels, and the confined migration channels are formed between the upper chip and the lower chip, and wherein the upper chip comprises upper channel portions; the lower chip comprises lower channel portions, and wherein the upper channel portions and the lower channel portions are combined to form all channels, and wherein the upper chip further comprises an upper set of the first channels, an upper set of the second channels, and an upper set of the confined migration channels; the lower chip further comprises a lower set of the first channels, a lower set of the second channels, and a lower set of the confined migration channels, and wherein a sum of a depth of each of the upper first channels and that of each of the lower first channels is equal to a sum of a depth of each of the first channels; a sum of a depth of each of the upper second channels and that of each of the lower second channels is equal to a sum of a depth of each of the second channels; a sum of a depth of each of the confined migration channels of the upper set of the confined migration channels and that of each of the confined migration channels of the lower set of the confined migration channels is equal to a sum of a depth of each of the confined migration channels. ### Claim 2 (depends on 1) The microfluidic device according to claim 1, wherein the plurality of identical confined migration channels comprises four to ten identical confined migration channels provided between each of the plurality of pairs of the first channel and the second channel. ### Claim 3 (depends on 2) The microfluidic device according to claim 2, wherein the four to ten identical confined migration channels comprises four, six, eight, or ten identical confined migration channels between each of the plurality of pairs of the first channel and the second channel. ### Claim 4 (depends on 1) The microfluidic device according to claim 1, wherein each of the first extension channels has a depth identical to that of each of the first channels; each of the second extension channels has a depth identical to that of each of the second channels. ### Claim 5 (depends on 4) The microfluidic device according to claim 4, wherein the first extension channels and the second extension channels are identical to each other. ### Claim 6 (depends on 1) The microfluidic device according to claim 1, further comprising converging channels provided on each of the at least one microfluidic chip, and the converging channels being disposed at two opposite ends of each of the first channels and configured to channelize all of the first channels. ### Claim 7 (depends on 6) The microfluidic device according to claim 6, wherein each of the converging channels has an inlet converging channel and an outlet converging channel, and wherein the first inlet connects to the inlet converging channel and the first outlet connects to the outlet converging channel, and wherein each of the at least one microfluidic chip further comprises an outlet connection channel provided at a central part of the outlet converging channel; the outlet connection channel connects the first outlet and the outlet converging channel. ### Claim 8 (depends on 6) The microfluidic device according to claim 6, further comprising a pyramid-shaped flow diverging structure provided on each of the at least one microfluidic chip, wherein the number of flow channels at a last level of the pyramid-shaped flow diverging structure is equal to the number of the first channels, and wherein a top end of the pyramid-shaped flow diverging structure connects to the first inlet. ### Claim 9 (depends on 8) The microfluidic device according to claim 8, wherein the pyramid-shaped flow diverging structure is a gradient flow diverging structure, and wherein each subsequent gradient layer is added with one flow channel with respect to a preceding layer. ### Claim 10 (depends on 8) The microfluidic device according to claim 8, wherein the pyramid-shaped flow diverging structure comprises multiple levels of flow diverging channels, and each level of the flow diverging channels comprises a lateral channel and a longitudinal channel, wherein the longitudinal channel of a preceding level connects to the lateral channel of a subsequent level, wherein the lateral channel of the last level connects all the first channels, and wherein the pyramid-shaped flow diverging structure has a top layer comprising only a first longitudinal channel, and the first longitudinal channel connects the first inlet and the lateral channel of a second stage of the pyramid-shaped flow diverging structure, and wherein each of the longitudinal channels and the lateral channels has a depth equal to that of the first channel. ### Claim 11 (depends on 1) The microfluidic device according to claim 1, wherein the upper channel portions and the lower channel portions are identical, and each of the confined migration channels are centered between each of their corresponding first extension channel and their corresponding second extension channel. ### Claim 12 (depends on 1) The microfluidic device according to claim 1, wherein a depth of all the upper channel portions and the lower channel portions is equal to that of the confined migration channels. ### Claim 13 (depends on 12) The microfluidic device according to claim 12, wherein the depth of all channel portions of the lower chip is equal to that of the confined migration channels, and no channel is provided in the corresponding portion of the upper chip with respect to the confined migration channels. ### Claim 14 (depends on 1) The microfluidic device according to claim 1, wherein each of the confined migration channels has a depth in a range of 4-10 microns; each channel other than the confined migration channels has a depth in a range of 20-40 microns; a width of the all the channels is in a range of 40-60 microns; a length of the first extension channels or a length of the second extension channels are in a range of 60-80 microns; a length of the confined migration channels are in a range of 40-60 microns; each of the confined migration channels has identical length, width, and cross-section with each other. ### Claim 15 (depends on 1) The microfluidic device according to claim 1, further comprising a material that enhances cell adhesion and is incorporated into all channels, wherein the material is selected from fibronectin. ### Claim 16 (depends on 1) The microfluidic device according to claim 1, further comprising an accommodation structure capable of accommodating the at least one microfluidic chips, wherein the accommodation structure is provided with at least one microfluidic chip placement holes or slots each for accommodating one of the at least one microfluidic chips, and wherein the at least one microfluidic chip placement holes or slots are circular holes capable of accommodating the at least one microfluidic chip to enable placing and removal of the at least one microfluidic chip. ### Claim 17 (depends on 1) The microfluidic device according to claim 1, wherein cells of the cell culture are normal cells or disease cells; and wherein the normal cells comprise kidney cells, lung cells, digestive tract cells, brain cells, liver cells, fibroblasts, endothelial cells, immune cells, and macrophages; and wherein the disease cells are tumor cells derived from abnormal cells, tumor-associated macrophages, or tumor-associated fibroblasts; and wherein the tumor cells derived from abnormal cells comprise gastric cancer cells, pancreatic cancer cells, colorectal cancer cells, liver cancer cells, bone cancer cells, lung cancer cells, kidney cancer cells, prostate cancer cells, breast cancer cells, brain cancer cells, and neuroendocrine tumor cells.