Gravity-assisted mixing methods
View Patent ↗A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector.
1. A method of mixing substances within a receptacle having a plurality of interconnected chambers, the method comprising the steps of:
(a) orienting the receptacle in an analyzer so that gravity can draw the contents of a first chamber of the receptacle into a second chamber of the receptacle when fluid communication is established between the first and second chambers;
(b) establishing fluid communication between the first and second chambers;
(c) applying a compressive force to the contents of the second chamber so that the contents of the second chamber are moved into the first chamber;
(d) removing the compressive force of step (c) so that gravity draws the contents of the first chamber into the second chamber without applying a compressive force to the first chamber,
(e) repeating steps (c) and (d) one or more times; and
(f) detecting with an optical detector positioned adjacent to the first camber an optical signal emitted by the contents of the first chamber.
2. The method of claim 1 , wherein the receptacle remains stationary during the method.
3. The method of claim 1 , wherein the fluid communication is established by the formation of a narrow opening between the first and second chambers.
4. The method of claim 1 , wherein, prior to step (b), the first chamber contains a dried substance and the second chamber contains a liquid substance for reconstituting, dissolving or rehydrating the dried substance.
5. The method of claim 4 , wherein the dried substance is a lyophilized substance.
6. The method of claim 4 further comprising the step of reconstituting, dissolving or rehydrating the dried substance contained in the first chamber.
7. The method of claim 4 , wherein the second chamber further contains an immiscible liquid, the immiscible liquid being non-reactive with the liquid substance.
8. The method of claim 7 , wherein the immiscible liquid is an oil.
9. The method of claim 8 , wherein the oil is a mineral oil.
10. The method of claim 1 , wherein the substance-moving force is one or more compressive forces applied to a flexible portion of the second chamber.
11. The method of claim 10 , wherein the receptacle comprises opposed members configured to define the plurality of interconnected chambers.
12. The method of claim 11 , wherein at least one of the opposed members comprises a flexible sheet, the flexible sheet including the flexible portion of the second chamber.
13. The method of claim 12 , wherein each of the opposed members comprises a flexible sheet.
14. The method of claim 10 , wherein step (b) comprises altering an openable connection between the first and second chambers from a closed state to an open state when the compressive force is applied to the second chamber.
15. The method of claim 14 , wherein the plurality of interconnected chambers are defined by seals formed between the opposed members.
16. The method of claim 15 , wherein the first and second chambers are adjacent to each other, and wherein the openable connection is an opening blocked by a burstable seal that is altered from the closed state to the open state when the compressive force is applied to the second chamber.
17. The method of claim 16 , wherein the burstable seal is a heat seal.
18. The method of claim 14 , wherein the compressive force is applied by one or more actuators having compression pads that are arranged to generally conform to the shape of the second chamber.
19. The method of claim 18 , wherein the actuators are pneumatic actuators.
20. The method of claim 14 , further comprising, after step (e), the step of blocking the connection between the first and second chambers to prevent substance movement between the first and second chambers.
21. The method of claim 20 , wherein the connection between the first and second chambers is blocked by one or more compressive forces applied to the connection.
22. The method of claim 1 , wherein each of the plurality of interconnected chambers is adjacently positioned next to at least one other chamber of the receptacle.
23. The method of claim 1 , wherein the detector is in a stationary position adjacent the first chamber during the method.
24. The method of claim 1 , wherein the detector is a fluorometer.