IP Library Granted Patent US 9,315,768
Granted Patent B2
US 9,315,768 · App. 13/378,924 · Granted Apr 19, 2016

Biological microfluidics chip and related methods

Inventors: Elwin Xander Vrouwe (Enschede, NL); Eric Marijn Wielhouwer (Leiden, NL); Johannes Oonk (Enschede, NL); Marinus Bernardus Olde Riekerink (Enschede, NL); Michael Keith Richardson (Leiden, NL)
Assignee: Universiteit Leiden
C12M23/12B01L3/5027C12M23/16C12M41/18B01L3/50851B01L3/50853B01L2300/0829B01L2300/0877B01L2300/185
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Quick Facts
Patent No.
US 9,315,768
App. No.
13/378,924
Granted
Apr 19, 2016
Kind
B2
Abstract

A biological microfluidics chip comprising a substrate, a microfluidic inlet port defining an opening in a surface of the substrate, and a microfluidic outlet port defining an opening in a surface of the substrate. The biological microfluidics chip also comprises 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. An inlet microfluidic channel is provided in the substrate to connect the microfluidic inlet port to each of the inlet openings in the walls of the wells, and an outlet microfluidic channel is provided in the substrate to connect each of the outlet openings in the walls of the wells to the microfluidic outlet port.

Claims (43)

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, wherein the length of the channel between the main artery of the microfluidic inlet channel and the inlet opening in the wall of a well varies such that the entire 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 every well of the plurality of wells within the substrate;

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;

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.

2. The biological microfluidics chip of claim 1 , 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.

3. The biological microfluidics chip of claim 2 , 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.

4. 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.

5. 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.

6. The biological microfluidics chip of claim 5 , wherein the second inlet opening in the wall of the wells is located lower than the outlet opening in the wall of the wells.

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

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

9. 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.

10. The biological microfluidics chip of claim 9 , 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.

11. The biological microfluidics chip of claim 10 , wherein the first and/or second microfluidic channels are provided between the top and bottom layer of the substrate.

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

13. The biological microfluidics chip of claim 7 , wherein the lid is sliding, self-sealing, removable, and/or heated.

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

providing cells, embryos or larvae to one or more of the plurality of wells, wherein the cells, embryos 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.

15. The method of claim 14 , further comprising:

developing the cells, embryos or larvae in the one or more of the plurality of wells; and

expose the cells, embryos or larvae to drugs or other compounds.

16. The method of claim 14 , in which the cells are stem cells.

17. The method of claim 14 , in which the assay is used for human, animal, microorganism or plant studies or screens.

18. The method of claim 14 , in which photosynthetic bodies are cultured within the plurality of wells.

19. The method of claim 14 , 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.

20. 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 outlet channels in the substrate that connect each of the outlet openings in the walls of the wells to the microfluidic outlet port, wherein the length of the channel between the main artery of the microfluidic inlet channel and the inlet opening in the wall of a well varies such that the entire 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 every well of the plurality of wells within the substrate.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE ADDRESS INFORMATION PREVIOUSLY RECORDED ON REEL 027999 FRAME 0573. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNEE ADDRESS INFORMATION SHOULD READ: UNIVERSITEIT LEIDEN RAPENBURG 70 LEIDEN, NETHERLANDS 2311-EZ. Recorded May 23, 2012
From: VROUWE, ELWIN XANDER; WIELHOUWER, ERIC MARIJN; OONK, JOHANNES; OLDE RIEKERINK, MARINUS BERNARDUS; RICHARDSON, MICHAEL KEITH
To: UNIVERSITEIT LEIDEN
Reel/Frame 028260/0596 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT ADDRESS IDENTIFIED FOR THE ASSIGNEE PREVIOUSLY RECORDED ON REEL 027872 FRAME 0639. ASSIGNOR(S) HEREBY CONFIRMS THE UNIVERSITEIT LEIDEN RAPENBURG 70 EZ LEIDEN, NETHERLANDS NL-2311. Recorded Apr 5, 2012
From: VROUWE, ELWIN XANDER; WIELHOUWER, ERIC MARIJN; OONK, JOHANNES; OLDE RIEKERINK, MARINUS BERNARDUS; RICHARDSON, MICHAEL KEITH
To: UNIVERSITEIT LEIDEN
Reel/Frame 027999/0573 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2012
From: VROUWE, ELWIN XANDER; WIELHOUWER, ERIC MARIJN; OONK, JOHANNES; OLDE RIEKERINK, MARINUS BERNARDUS; RICHARDSON, MICHAEL KEITH
To: UNIVERSITEIT LEIDEN
Reel/Frame 027872/0639 →
Priority Claims (1)
GB 0910330.0 · Jun 16, 2009 · national
Continuity (1)
Related Publication 20120164679A1 · Jun 28, 2012