IP Library Granted Patent US 12,669,416
Granted Patent B2
US 12,669,416 · App. 19/369,905 · Granted Jun 30, 2026

Methods and devices for manipulating biological samples

Inventors: Yuji Ishitsuka (San Diego, CA); Jaekyung Koh (San Diego, CA); Robert James Stover (San Diego, CA); Pavel Shekhtmeyster (San Diego, CA); Sandor Kovacs (Middletown, DE); Hu Cang (San Diego, CA); Valeria Rascon (San Diego, CA)
Assignee: Singular Genomics Systems, Inc.
G01N1/30G01N1/286G01N1/312G16B20/00G16B40/20G01N2001/288G01N2001/305G01N2001/315
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Quick Facts
Patent No.
US 12,669,416
App. No.
19/369,905
Granted
Jun 30, 2026
Kind
B2
Abstract

Disclosed herein, inter alia, are devices and methods for efficient transfer and analyses of cellular material, tissue samples, such as tissue sections, using carrier substrates and devices.

Claims (31)

1 . A method for manipulating a biological sample, comprising:

positioning a punch device against a sample-carrier construct formed of a tissue section and carrier substrate, wherein the tissue is mounted on the carrier substrate, the punch device formed of an outer wall having a top edge, a bottom edge, and an internal lumen;

pushing the bottom edge of the punch device through the sample-carrier construct to cut through the sample-carrier construct such that an excised tissue section is positioned within the internal lumen of the punch device to form a loaded punch device;

positioning the loaded punch device against a slide;

positioning a piston relative to the loaded punch device so that the piston can be inserted into the loaded punch device; and

using the piston to push the excised tissue section out of the loaded punch device toward the slide.

2 . The method of claim 1 , wherein the piston is part of a piston array formed of a plurality of pistons.

3 . The method of claim 2 , further comprising loading a plurality of loaded punch devices onto a corresponding plurality of pistons of the piston array.

4 . The method of claim 3 , wherein using the piston to push the excised tissue out of the loaded punch device toward the slide comprises using the piston array to simultaneously push excised tissues of a plurality of loaded punch devices toward the slide.

5 . The method of claim 1 , further comprising incubating the slide.

6 . The method of claim 5 , wherein the slide is incubated while the loaded punch device is positioned on the slide.

7 . The method of claim 6 , further comprising, after incubating the slide, removing the loaded punch device from the slide such that the excised tissue section is retained on the slide.

8 . The method of claim 5 , wherein the slide is incubated on a heat plate.

9 . The method of claim 1 , wherein positioning the loaded punch device against a slide comprises positioning a top edge of the loaded punch device against the slide.

10 . The method of claim 9 , wherein the loaded punch device is positioned in a perpendicular orientation relative to the slide.

11 . The method of claim 1 , further comprising removably attaching the punch device to a punch tool formed an outer housing that removably receives the punch device, wherein the housing serves as a handle for manipulating the punch device.

12 . The method of claim 11 , wherein the punch tool is a spring-loaded tool that can be actuated by a user to expel, eject, or otherwise transition the punch device toward the sample carrier-construct.

13 . The method of claim 12 , wherein pushing the bottom edge of the punch device through the sample-carrier construct comprises actuating the punch tool.

14 . The method of claim 1 , wherein the bottom edge of the punch device is sharp.

15 . The method of claim 1 , wherein the bottom edge of the punch device is a blade.

16 . The method of claim 1 , wherein the punch device is cylindrical.

17 . The method of claim 16 , wherein the punch device is cuboid, cylindrical, pyramidal, conical, or frustoconical.

18 . The method of claim 1 , wherein the slide forms part of a flow cell.

19 . The method of claim 1 , wherein the carrier substrate comprises agarose, gelatin, polyacrylamide, or any suitable hydrogel.

20 . The method of claim 1 , wherein the tissue is mounted on top of the carrier substrate.

21 . The method of claim 1 , wherein the tissue is mounted on top of an uppermost surface of the carrier substrate.

22 . The method of claim 1 , wherein the sample-carrier construct comprises interfacial water, wherein the interfacial water is positioned between the carrier substrate and the tissue section.

23 . A method for manipulating a biological sample, comprising:

positioning a loaded punch device against a glass solid support, wherein said loaded punch device comprises an outer wall having a top edge, a bottom edge, and an internal lumen, wherein a tissue sample is positioned within the internal lumen;

inserting a plunger through the top edge into the internal lumen and advancing the plunger through the internal lumen to push the tissue sample to contact the glass solid support; and

while the tissue sample remains in contact with the glass solid support, heating the glass solid support to a temperature of 30° C. or greater.