Microfluidic probe head with aspiration posts

Patent metadata

Field	Value
Publication number	US-12201974-B2
Application number	US-202016984852-A
Country	US
Kind code	B2
Filing date	Aug 4, 2020
Priority date	Feb 5, 2018
Publication date	Jan 21, 2025
Grant date	Jan 21, 2025

Abstract

The present disclosure is notably directed to a microfluidic probe head ( 202 ), or MFP head, comprising a processing surface ( 204 ) having liquid injection and liquid aspiration apertures, as well as projections ( 205 ) extending from the processing surface ( 204 ). The arrangement of injection and aspiration apertures provides for a hydrodynamic flow confinement within a processing region that is formed between the processing surface ( 204 ) and a substrate ( 104 ) or sample surface (for example, the bottom of a microtiter plate sample well ( 102 )), typically located beneath the processing surface ( 204 ). The disclosure is further directed to related microfluidic probe devices, and methods of operation of such an MFP head, notably to deposit cells on a surface.

First claim

What is claimed is:

1. A microfluidic probe head configured to operate with a sample well, comprising:
a processing surface at one end of the microfluidic probe head, configured to interact with fluids within a processing region proximate to the processing surface, the processing surface comprising a center and an outer edge defining a perimeter of the processing surface;
one or more injection apertures disposed within an inner region located at or around the center of the processing surface;
a plurality of aspiration apertures disposed within an outer region spaced from the inner region and extending to the outer edge of the processing surface, the plurality of aspiration apertures being radially distributed around the one or more injection apertures, wherein a distance of the plurality of aspiration apertures from the outer edge of the processing surface is from 10% to 80% of a diameter of the sample well; and
two or more posts extending outward from the processing surface, the two or more posts being configured to form a fluidic barrier comprising a turbulent flow at the plurality of aspiration apertures and establishing a height of the processing region, wherein at least a portion of a wall of a post of the two or more posts is located about an equal radial distance along with at least one of the plurality of aspiration apertures from the center of the processing surface such that the fluid interacts with the posts during aspiration to form the fluidic barrier comprising the turbulent flow.

2. The microfluidic probe head of claim 1 , wherein the processing surface has three injection apertures arranged in a triangular configuration.

3. The microfluidic probe head of claim 2 , wherein the three injection apertures are spaced apart from each other such that, the processing region includes a stagnation space formed between the three injection apertures.

4. The microfluidic probe head of claim 2 , wherein the three injection apertures are each connected to different fluid sources.

5. The microfluidic probe head of claim 1 , wherein the processing surface has four injection apertures arranged in a square configuration.

6. The microfluidic probe head of claim 5 , wherein the four injection apertures are spaced apart from each other such that, the processing region includes a stagnation space formed between the four injection apertures.

7. The microfluidic probe head of claim 5 , wherein two or more of the four injection apertures are connected to different fluid sources.

8. The microfluidic probe head of claim 1 , wherein the plurality of aspiration apertures comprise one or more circular holes arrayed along the perimeter of the processing surface and are located within the outer region.

9. The microfluidic probe head of claim 1 , wherein the plurality of aspiration apertures are located within a recess formed within the processing surface.

10. The microfluidic probe head of claim 1 , wherein the two or more posts extend 0.1 mm outward from the processing surface.

11. The microfluidic probe head of claim 1 , comprising four posts, arranged equidistantly from each other around the perimeter of the processing surface and located within the outer region.

12. The microfluidic probe head of claim 11 , wherein the plurality of aspiration apertures are positioned in between the four posts, arranged around the perimeter of the processing surface and located within the outer region.

13. The microfluidic probe head of claim 11 , wherein each of the four posts is paired with an aspiration aperture positioned adjacent to each post on a side of the post facing the one or more injection apertures.

14. The microfluidic probe head of claim 1 , further comprising a probe interface section at an end of the microfluidic probe head distal from the processing surface, the probe interface section comprising fluid contact ports configured to connect the microfluidic probe head with one or more fluid sources and a vacuum source.

15. The microfluidic probe head of claim 14 , wherein the probe interface section includes four fluid contact ports, wherein three of the fluid contact ports are connected to one or more fluid source reservoirs, and wherein a fourth fluid contact port is connected to the vacuum source.

16. The microfluidic probe head of claim 1 , wherein the at least a portion of the wall of a post of the two or more posts is flush with fluidic channel surface associated with at least one of the plurality of aspiration apertures.

17. A method of operating the microfluidic probe head according to claim 1 , the method comprising:
positioning the microfluidic probe head in proximity with a substrate holding material to be processed, such that the processing surface faces the substrate; and
injecting a processing liquid via the one or more injection apertures while aspirating liquid from the plurality of aspiration apertures, to process the substrate.

18. The method according to claim 17 , wherein the processing liquid is a heterogeneous suspension comprising cells, and wherein injecting processing liquid is performed so as to deposit cells of this heterogeneous suspension onto a sample surface.

19. The method according to claim 17 , wherein the steps of injecting the processing liquid and aspirating liquid are performed so as to maintain a hydrodynamic flow confinement of the injected processing liquid between the one or more injection apertures and the plurality of aspiration apertures.

20. The microfluidic probe head of claim 1 , wherein a distance of aspiration apertures from the outer edge of the processing surface of the microfluidic probe (MFP) head is configured to be from about 10% to about 20% of a diameter of a sample well in which the MFP head is designed to operate.

21. The microfluidic probe head of claim 1 , wherein a size of the one or more injection apertures is a function of the height of each of the two or more posts.

Assignees

• Bio Rad Laboratories Inc

Inventors

• Uri Yochanan
• Barak Itay
• Lovchik Robert
• Taylor David P
• Buerge Marcel
• Kaigala Govind V

Classifications

• B01L2400/049

  vacuum · CPC title

• B01L2200/0636

  Focussing flows, e.g. to laminate flows · CPC title

• B01L3/502769

  characterised by multiphase flow arrangements · CPC title

• C12M23/16

  Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title

• C12M33/04

  by injection or suction, e.g. using pipettes, syringes, needles (pipettes in general B01L3/02) · CPC title