Method and apparatus for purifying gel droplets supporting biological tissues

Abstract

The present invention provides a device for forming gel droplets containing biological tissues (e.g., cells), and in particular, a device for removing oil from gel droplets containing dissociated cells (containing microorganospheres). [Solution] A device for forming gel droplets is provided, comprising: a fluid processor including a plurality of channels: a first channel configured to receive a dissociated tissue sample containing dissociated cells and an unpolymerized matrix material; a second channel configured to receive oil and intersect with the first channel to form polymerized gel droplets suspended in the oil; a demulsification portion including a hydrophobic membrane configured to remove oil from the polymerized gel droplets and in fluid communication with the fluid processor; and an elution channel configured to elute the polymerized gel droplets from the demulsification portion.

Claims

1. Method: The formation of multiple gel droplets in oil, the gel droplets containing cells from a dissociated tissue sample distributed within polymerized spheres of a matrix material, and the gel droplets having the cells distributed within them; The process involves bringing the gel droplets into contact with the hydrophobic film such that the oil is removed from the gel droplets through or into the hydrophobic film, including, A method for processing gel droplets containing cells.

2. The method according to claim 1, wherein the gel droplets comprise microorganospheres having a diameter between 50 and 500 μm.

3. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film removes at least 99% of the oil from the gel droplet.

4. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film includes passing an organoid through a chamber formed at least partially by the hydrophobic film.

5. The method according to claim 4, wherein the chamber includes a tunnel or tube formed by a hydrophobic membrane.

6. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film is performed to dissolve the gel droplet into a funnel formed by the hydrophobic film.

7. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film includes filtering the gel droplet with respect to the hydrophobic film.

8. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film includes passing a solution containing the gel droplet over the hydrophobic film.

9. The method according to claim 1, wherein the hydrophobic film has a pore size between 0.1 and 5 μm.

10. The method according to claim 1, wherein contacting a gel droplet with a hydrophobic film is performed to retain the gel droplet in an aqueous medium.

11. Furthermore, the method according to claim 1, wherein each gel droplet contains cells between 1 and 200 distributed therein.

12. The method according to claim 1, further comprising washing the gel droplets on the hydrophobic film with an aqueous medium.

13. The method according to claim 1, further comprising culturing the gel droplets in a culture medium.

14. Method: The formation of multiple gel droplets in oil, the gel droplets containing cells from a dissociated tissue sample distributed within spheres of matrix material, the gel droplets having diameters between 50 and 500 μm, and having between 1 and 200 cells distributed therein; and Bringing a gel droplet into contact with a hydrophobic film such that at least 98% of the oil is removed from the gel droplet on or within the hydrophobic film; Washing gel droplets on a hydrophobic film with an aqueous medium; and Culturing gel droplets in a culture medium. including, A method for processing gel droplets.

15. The method according to claim 14, wherein the gel droplets comprise microorganospheres having a diameter between 50 and 500 μm.

16. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film is performed to remove at least 99% of the oil from the gel droplet.

17. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film includes passing an organoid through a chamber formed at least partially by the hydrophobic film.

18. The method according to claim 17, wherein the chamber includes a tunnel or tube formed by a hydrophobic membrane.

19. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film is performed to dissolve the gel droplet into a funnel formed by the hydrophobic film.

20. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film includes filtering the gel droplet with respect to the hydrophobic film.

21. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film includes passing a solution containing the gel droplet over the hydrophobic film.

22. The method according to claim 14, wherein the hydrophobic film has a pore size between 0.1 and 5 μm.

23. The method according to claim 14, wherein contacting a gel droplet with a hydrophobic film is performed to retain the gel droplet in an aqueous medium.

24. The method according to claim 14, further comprising washing the gel droplets on the hydrophobic film with an aqueous medium.

25. The device: A first channel configured to receive a dissociated tissue sample containing dissociated cells and unpolymerized matrix material, A second channel is configured to receive oil and to intersect with the first channel to form polymerized gel droplets suspended in the oil, A fluid processor containing multiple channels; A demulsifying portion comprising a hydrophobic membrane configured to remove oil from gel droplets and in fluid communication with a fluid processor; and An elution channel configured to elute gel droplets from the demulsified portion using an aqueous solution. including, A device for forming gel droplets.

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