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 system for mixing substances comprising:
a receptacle having a plurality of interconnected chambers, including a first chamber directly connected to an at least partially compressible second chamber; and
an analyzer supporting the receptacle in an operative position and comprising:
one or more actuators constructed and arranged to apply a compressive force to the second chamber, the receptacle being positioned in the analyzer so that gravity will draw a fluid from the first chamber into the second chamber when fluid communication is established between the first and second chambers, wherein the analyzer does not include an actuator constructed and arranged to apply a compressive force to the first chamber;
an optical detector positioned adjacent to the first chamber and configured to detect an optical signal emitted by the contents of the first chamber; and
a controller programmed to control operation of the one or more actuators and to cause the one or more actuators to:
(a) apply a compressive force to the second chamber, thereby displacing at least a portion of the contents of the second chamber into the first chamber;
(b) remove the compressive force from the second chamber, thereby allowing the displaced contents to flow by gravity from the first chamber to the second chamber without applying a compressive force to the first chamber; and
(c) repeat steps (a) and (b) one or more times.
2. The system of claim 1 , wherein the one or more actuators have compression pads that are arranged to generally conform to the shape of the second chamber.
3. The system of claim 1 , wherein the one or more actuators are pneumatic actuators.
4. The system of claim 1 , wherein, prior to applying the compressive force to the second chamber, the first chamber contains a dried substance, the second chamber contains a liquid substance for reconstituting, dissolving or rehydrating the dried substance, and a connection between the first and second chambers is initially blocked to prevent the liquid substance from coming into contact with the dried substance.
5. The system of claim 4 , wherein the dried substance comprises a lyophilized reagent.
6. The system of claim 5 , wherein the second chamber further contains an immiscible liquid, the immiscible liquid being non-reactive with the liquid substance.
7. The system of claim 6 , wherein the immiscible liquid is an oil.
8. The system of claim 7 , wherein the oil is a mineral oil.
9. The system of claim 1 , wherein:
each of the chambers of the receptacle is an at least partially compressible chamber to facilitate substance movement between chambers,
the analyzer comprises a plurality of actuators, each of the actuators being associated with at least one of the chambers; and
the controller is programmed to control operation of the actuators and to cause the actuators to move substances among the interconnected chambers by selective application of external force by the actuators to their associated chambers to compress the associated chambers and displace the contents of the chambers into interconnected chambers.
10. The system of claim 1 , wherein the receptacle comprises opposed members, at least one of the opposed members comprising a flexible sheet.
11. The system of claim 10 , wherein each of the opposed members comprises a flexible sheet.
12. The system of claim 1 , wherein an openable connection directly connecting the first and second chambers is altered from a closed state to an open state when the compressive force is applied to the second chamber, the open state of the connection providing fluid communication between the first and second chambers.
13. The system of claim 12 , 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.
14. The system of claim 13 , wherein the burstable seal is a heat seal.
15. The system of claim 12 , wherein each of the plurality of interconnected chambers is positioned adjacent to at least one other chamber of the receptacle.
16. The system of claim 12 , wherein the analyzer further comprises an actuator adjacent the connection between the first and second chambers, and wherein the controller is programmed to control operation of the actuator to cause the actuator to block the connection between the first and second chambers after step (c).
17. The system of claim 1 further comprising:
an actuator system that includes an actuator plate for operatively positioning a plurality of actuators relative to the receptacle, the actuator plate having an opening,
wherein the opening in the actuator plate is located adjacent to the first chamber, and the detector is positioned adjacent to the opening to permit the detector to detect an optical signal emitted by the contents of the first chamber.
18. The system of claim 1 , wherein the detector is a fluorometer.