BIOLOGICAL MICROFLUIDICS CHIP AND RELATED METHODS

• US 20120164679A1
• Filed: 06/15/2010
• Published: 06/28/2012
• Est. Priority Date: 06/16/2009
• Status: Active Grant

• Current Assignee: Universiteit Leiden
• Original Assignee: Universiteit Leiden
• Inventors: Oonk, Johannes, Vrouwe, Elwin Xander, Wielhouwer, Eric Marijn, Olde Riekerink, Marinus Bernardus, Richardson, Michael Keith
• Granted Patent: US 9,315,768 B2
• Time in Patent Office: Days
• US Class Current: 435/29
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 41/18 Heat exchange systems, e.g. heat jackets or outer envelopes

Abstract

A biological microfluidics chip (100) comprising a substrate (102), a microfluidic inlet port (104) defining an opening in a surface of the substrate (102), and a microfluidic outlet port (106) defining an opening in a surface of the substrate (102). The biological microfluidics chip (100) also comprises a plurality of wells (108) extending from a top surface (110) of the substrate, wherein each well (108) is bounded by one or more walls, and an inlet opening (112) and an outlet opening (114) are provided in a wall of each of the plurality of wells (108). An inlet microfluidic channel (116) is provided in the substrate (102) to connect the microfluidic inlet port (104) to each of the inlet openings (112) in the walls of the wells, and an outlet microfluidic channel (118) is provided in the substrate to connect each of the outlet openings (114) in the walls of the wells to the microfluidic outlet port (106).

Claims

1. A biological microfluidics chip comprising:

a substrate;

a microfluidic inlet port defining an opening in a surface of the substrate;

a microfluidic outlet port defining an opening in a surface of the substrate;

a plurality of wells extending from a top surface of the substrate, wherein each well is bounded by one or more walls, and an inlet opening and an outlet opening are provided in a wall of each of the plurality of wells;

one or more microfluidic inlet channels in the substrate that connect the microfluidic inlet port to each of the inlet openings in the walls of the wells; and

one or more microfluidic inlet channels in the substrate that connect each of the outlet openings in the walls of the wells to the microfluidic outlet port.

2. The biological microfluidics chip of claim 1, wherein the length of a microfluidic channel between the microfluidic inlet port and an inlet opening in the wall of a well is substantially the same for each well.

3. The biological microfluidics chip of claim 1, further comprising:

a temperature control inlet port and a temperature control outlet port, and

a temperature control channel configured to transport temperature control fluid from the temperature control inlet port to the temperature control outlet port along a path that is in proximity to one or more of the plurality of wells such that, in use, heat is exchangeable between the temperature control liquid and the contents of the wells.

4. The biological microfluidics chip of claim 3, wherein one or more of the temperature control inlet port, temperature control outlet port and temperature control channels are provided for a subset of the plurality of wells.

5. The biological microfluidics chip of claim 3, wherein the plurality of wells comprises an array of wells, and a separate temperature control inlet port and temperature control channel are provided for each row of the array of wells.

6. The biological microfluidics chip of claim 1, wherein the location of the inlet opening in a wall of each of the wells is lower than the outlet opening.

7. The biological microfluidics chip of claim 1, further comprising:

a second microfluidic inlet port; and

a second inlet opening in the walls of the wells;

wherein the second inlet opening is in fluid communication with the second microfluidic inlet port by a second microfluidic inlet channel.

8. The biological microfluidics chip of claim 7, wherein the second inlet opening in the wall of the wells is located lower than the outlet opening in the wall of the wells.

9. The biological microfluidics chip of claim 1, further comprising a lid, wherein the lid is sliding, self-sealing, removable, and/or heated.

10. The biological microfluidics chip of claim 1, wherein the substrate is, at least in part, D263 glass.

11. The biological microfluidics chip of claim 1, wherein the plurality of wells have a shape in vertical cross-section comprising two frustoconical shapes end to end to end, wherein the narrower ends of the frustoconical shapes are collocated.

12. The biological microfluidics chip of claim 11, wherein the substrate comprises a top and a bottom layer, and the two frustoconical shapes are collected at the boundary between the top and bottom layer.

13. The biological microfluidics chip of claim 12, wherein the first and/or second microfluidic channels are provided between the top and bottom layer of the substrate.

14. The biological microfluidics chip of claim 1, wherein one or more of the microfluidic channels comprises a microfluidic valve.

15. A method of utilizing the biological microfluidics chip of claim 1, the method comprising:

providing cells, embryo'"'"'s or larvae to one or more of the plurality of wells, wherein the cells, embryo'"'"'s or larvae are for use in an experiment;

providing a fluid to the microfluidic inlet port such that the fluid enters the one or more wells;

removing a fluid from the one or more wells via the microfluidic outlet port; and

imaging the contents of the one or more wells in order to obtain results of the experiment in the one or more wells.

16. The method of claim 15, further comprising

developing the cells, embryo'"'"'s or larvae in the one or more of the plurality of wells;

and

expose the cells, embryo'"'"'s or larvae to drugs or other compounds.

17. The method of claim 15, in which the cells are stem cells.

18. The method of claim 15, in which the assay is used for human, animal, micro organism or plant studies or screens.

19. The method of claim 15, in which photosynthetic bodies are cultured within the plurality of wells.

20. The method of claim 15, further comprising providing a temperature control fluid to a temperature control inlet port of the biological microfluidics chip in order to control the temperature of the contents of the one or more wells.