Methods for manipulating liquid substances in multi-chambered receptacles

Abstract

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. The actuator system can be arranged to concentrate an analyte present in a sample. The detector can be used to detect an optical signal emitted by the contents of the receptacle.

1 . A method of mixing substances contained in a receptacle having a plurality of interconnected chambers, the method comprising the steps of:
 (a) forming a volume in a first chamber of the receptacle, the volume comprising a first substance, a second substance and an immiscible liquid; and   (b) moving the volume through a connection between the first chamber and a second chamber of the receptacle one or more times to facilitate mixing of the first and second substances in the presence of the immiscible liquid.   
     
     
         2 . The method of  claim 1 , wherein the immiscible liquid generally concentrates the first and second substances in the center of each of the first and second chambers. 
     
     
         3 . The method of  claim 1 , wherein the moving step comprises alternately applying substance-moving forces to flexible portions of the first and second chambers. 
     
     
         4 . The method of  claim 3 , wherein the receptacle comprises opposed members configured to define the plurality of interconnected chambers. 
     
     
         5 . The method of  claim 4 , wherein one of the opposed members comprises a flexible sheet, the flexible sheet comprising the flexible portions of the first and second chambers. 
     
     
         6 . The method of  claim 4 , wherein each of the opposed members comprises a flexible sheet, one of the flexible sheets comprising the flexible portions of the first and second chambers. 
     
     
         7 . The method of  claim 4 , wherein the plurality of interconnected chambers are defined by seals between the opposed members. 
     
     
         8 . The method of  claim 3 , wherein the substance-moving forces comprise one or more actuators having compression pads that are arranged to generally conform to the shape of the first flexible portion and one or more actuators having compression pads that are arranged to generally conform to the shape of the second flexible portion. 
     
     
         9 . The method of  claim 8 , wherein the actuators are pneumatic actuators. 
     
     
         10 . The method of  claim 1 , wherein the connection is an openable connection that is altered from a closed state to an open state during step (b). 
     
     
         11 . The method of  claim 10 , 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 substance-moving force is applied to the flexible portion of the first chamber. 
     
     
         12 . The method of  claim 11 , wherein the seal is a heat seal. 
     
     
         13 . The method of  claim 10 , wherein the closed state comprises applying an external force to the connection prior to step (b). 
     
     
         14 . The method of  claim 13 , wherein the external force comprises at least one actuator having a compression pad that extends across the connection. 
     
     
         15 . The method of  claim 14 , wherein the actuator is a pneumatic actuator. 
     
     
         16 . The method of  claim 1 , wherein the first and second substances are liquid substances. 
     
     
         17 . The method of  claim 1 , wherein the immiscible liquid is an oil. 
     
     
         18 . The method of  claim 17 , wherein the oil is a mineral oil. 
     
     
         19 . The method of  claim 1 , wherein the ratio of the immiscible liquid to the remainder of the fluid volume in the first chamber is from about 1:10 to about 10:1. 
     
     
         20 . The method of  claim 1 , wherein the ratio of the immiscible liquid to the remainder of the fluid volume in the first chamber is from about 1:3 to about 10:1. 
     
     
         21 . The method of  claim 1 , wherein the immiscible liquid is not reactive with either of the first and second substances. 
     
     
         22 . The method of  claim 1 , wherein each of the plurality of interconnected chambers is positioned adjacent to at least one other chamber of the receptacle. 
     
     
         23 . A method of mixing substances contained in a receptacle comprising a plurality of interconnected chambers, the method comprising the steps of:
 (a) forming a volume in a chamber of the receptacle, the volume comprising a first substance, a second substance and an immiscible liquid, and the chamber comprising a flexible portion;   (b) closing the chamber to provide a substantially fluid-tight seal; and   (c) applying substance-moving forces to different regions of the flexible portion in an alternating manner to mix the first and second substances in the presence of the immiscible liquid within the closed chamber.   
     
     
         24 . The method of  claim 23 , wherein the immiscible liquid concentrates the first and second substances toward the center of the chamber. 
     
     
         25 . The method of  claim 23 , wherein the receptacle comprises opposed members configured to define the plurality of interconnected chambers. 
     
     
         26 . The method of  claim 25 , wherein one of the opposed members comprises a flexible sheet, the flexible sheet comprising the flexible portion. 
     
     
         27 . The method of  claim 25 , wherein each of the opposed members comprises a flexible sheet, one of the flexible sheets comprising the flexible portion. 
     
     
         28 . The method of  claim 25 , wherein the plurality of interconnected chambers are defined by seals between the opposed members. 
     
     
         29 . The method of  claim 23 , wherein the substance-moving forces comprise a plurality of actuators having compression pads that are arranged to generally conform to the shape of the flexible portion. 
     
     
         30 . The method of  claim 29 , wherein the actuators are pneumatic actuators. 
     
     
         31 . The method of  claim 23 , wherein the first and second substances are liquid substances. 
     
     
         32 . The method of  claim 23 , wherein one of the first and second substances is a dried substance. 
     
     
         33 . The method of  claim 23 , wherein the immiscible liquid is an oil. 
     
     
         34 . The method of  claim 33 , wherein the oil is a mineral oil. 
     
     
         35 . The method of  claim 23 , wherein the ratio of the immiscible liquid to the remainder of the fluid volume in the first chamber is from about 1:10 to about 10:1. 
     
     
         36 . The method of  claim 23 , wherein the ratio of the immiscible liquid to the remainder of the fluid volume in the first chamber is from about 1:3 to about 10:1. 
     
     
         37 . The method of  claim 23 , wherein the immiscible liquid is not reactive with either of the first and second substances. 
     
     
         38 . The method of  claim 23 , wherein each of the plurality of interconnected chambers is positioned adjacent to at least one other chamber of the receptacle.