Cover member, method and treatment module for treating a biological sample on a substrate

Patent metadata

Field	Value
Publication number	US-12157118-B2
Application number	US-202217869645-A
Country	US
Kind code	B2
Filing date	Jul 20, 2022
Priority date	Nov 16, 2011
Publication date	Dec 3, 2024
Grant date	Dec 3, 2024

Abstract

A cover member for a substrate supporting a biological sample comprises first and second opposing ends, first and second opposing surfaces, a void in the second surface which, when juxtaposed with a substrate, forms a chamber, and a fluid inlet toward the first end and in fluid communication with the void. The void is bounded by void walls having one or more contoured regions for enhancing fluid movement within the chamber. A treatment module for a biological sample comprises the cover member, a support surface for a substrate bearing the biological sample and clamp means operable to releasably retain the cover member in juxtaposition with the substrate for an incubation period. A method for incubating the biological sample with one or more reagents uses the cover member.

First claim

The invention claimed is:

1. A treatment module for use with a biological sample disposed on a substrate, the module comprising:
a cover member having:
opposing ends comprising a first end and a second end;
opposing surfaces comprising a first surface and a second surface;
a cover member body, wherein the cover member body provides the first surface;
a cover member insert removably coupled to the cover member body, wherein the cover member insert provides the second surface, and wherein the cover member insert includes a void which, when juxtaposed with the substrate, forms a chamber; and
a fluid inlet toward the first end and in fluid communication with the void;

a support surface configured to support the substrate and the biological sample thereon; and
a pivot arm operable to pivot the cover member between an open condition and a closed condition relative to the substrate.

2. The treatment module according to claim 1 , wherein the cover member body has grooves into which opposing tongue portions of the cover member insert is slidingly received.

3. The treatment module according to claim 1 , wherein the cover member body and the cover member insert are couplable by one or more of magnetic, suction and friction couplings.

4. The treatment module according to claim 1 , wherein the cover member insert is disposable.

5. The treatment module according to claim 1 , wherein the cover member insert has an inlet extension arranged to couple with the cover member fluid inlet to facilitate dispensing of reagent into the chamber formed by the cover member insert.

6. The treatment module according to claim 1 , wherein the cover member has a fluid outlet toward the second end and the cover member insert has an outlet extension arranged to couple with the cover member fluid outlet.

7. The treatment module according to claim 1 , further comprising a substrate retention member configured to retain the substrate on the support surface during opening of the chamber or separation of the cover member and the substrate.

8. The treatment module according to claim 1 , further including a wash bay for exposing a surface of the cover member to a wash reagent, wherein optionally, the support surface is shaped to receive the substrate having the sample thereon and, in the absence of a substrate, to form the wash bay.

9. The treatment module according to claim 1 , wherein the cover member insert void is bounded by void walls having one or more contoured regions and the one or more contoured regions comprise rounded corners connecting side walls of the void with an end wall of the cover member insert to encourage fluid flow within the chamber.

10. The treatment module according to claim 1 , wherein the cover member insert void is bounded by void walls having one or more contoured regions and wherein the one or more contoured regions comprise a rounded taper connecting side walls of the void with an end wall of the cover member insert to encourage fluid flow within the chamber.

11. The treatment module according to claim 1 , wherein the cover member insert void is bounded by void walls having one or more contoured regions and wherein the one or more contoured regions comprise rounded cornices connecting the walls of the void with a void ceiling in the second surface of the cover member insert.

12. The treatment module according to claim 1 , wherein a void ceiling in the cover member insert has a finish configured to enhance reagent propagation from the fluid inlet extension to the fluid outlet extension, and optionally, wherein the finish is at least one of etched, corrugated, dimpled, sloped, bowed, and rippled.

13. The treatment module according to claim 1 , wherein the treatment module is configured for use with an automated sample processing instrument comprising a plurality of treatment modules operable independently under control of a controller of the instrument; and wherein operation of one or more of a clamp, a thermal exchanger, a robot, a negative pressure source and fluid dispenser is under the control of the instrument controller.

14. The treatment module according to claim 13 , wherein the robot is configured to position one or both of the substrate and the cover member in the treatment module and optionally, wherein the robot is configured to dispense reagent into the fluid inlet of the cover member during a treatment protocol.

15. The treatment module according to claim 1 wherein the cover member body is removable from the treatment module.

16. The treatment module according to claim 1 , wherein the pivot arm is operable to pivot the cover member about a dispersing edge causing fluid to move from the inlet along the substrate from the dispersing edge toward a fluid outlet.

17. The treatment module according to claim 1 , wherein the pivot arm is operable to tilt the cover member about a tilt axis extending between the first and second ends.

18. A method of using the treatment module of claim 1 , including the steps of:
a. providing the sample on the substrate;
b. positioning the substrate and the cover member coupled with the cover member insert to form the chamber;
c. positioning a dispensing probe tip in mating contact with the fluid inlet of the cover member; and
d. driving a first volume of a first reagent into the inlet with force sufficient for the first reagent to substantially cover the sample on the substrate; and optionally
e. agitating reagent within the chamber.

19. The method according to claim 18 , including one or more further steps comprising:
a. applying a negative pressure at a fluid outlet of the cover member to draw reagent within the chamber toward the outlet; and
b. removing the substrate from a support surface and immersing a second surface of the cover member insert in a wash reagent.

20. A treatment module for use with a biological sample disposed on a substrate, the treatment module comprising:
a cover member formed from at least two parts including a cover member body and a cover member insert coupled to the cover member body, the cover member having:
opposing ends comprising a first end and a second end;
opposing surfaces comprising a first surface and a second surface; and
a fluid inlet toward the first end, extending through the cover member body and the cover member insert, and in fluid communication with the void;

a support surface configured to support the substrate and a biological sample thereon; and
a pivot arm operable to pivot the cover member between an open condition and a closed condition relative to the substrate,
wherein the cover member insert is removably couplable with the cover member body, and wherein the cover member insert includes a void which, when juxtaposed with the substrate, forms a chamber.

21. The treatment module according to claim 20 , wherein the pivot arm is operable to pivot the cover member about a dispersing edge causing fluid to move from the inlet along the substrate from the dispersing edge toward a fluid outlet.

22. The treatment module according to claim 20 , wherein the pivot arm is operable to tilt the cover member about a tilt axis extending between the first and second ends.

23. A method of using the treatment module of claim 20 , including the steps of:
a. providing the sample on the substrate;
b. positioning the substrate and the cover member with the cover member insert to form the chamber;
c. positioning a dispensing probe tip in mating contact with the fluid inlet

Assignees

• Leica Biosystems Melbourne Pty

Inventors

• Dockrill Mark Brian
• Favaloro Anthony
• Ng Kenneth He-Cho
• Limon Martin
• Toogood Peter
• Bagnato Stephen John

Classifications

• B01L2300/0851

  Bottom walls · CPC title

• B01L2300/0877

  Flow chambers · CPC title

• B01L3/5027

  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 · CPC title

• B01L2300/0822

  Slides · CPC title

• B01L2300/1827

  using resistive heater · CPC title