Biological Analysis Systems, Devices, and Methods

Abstract

A device for performing biological sample reactions may include a plurality of flow cells configured to be mounted to a common microscope translation stage, wherein each flow cell is configured to receive at least one sample holder containing biological sample. Each flow cell also may be configured to be selectively placed in an open position for positioning the at least one sample holder into the flow cell and a closed position for reacting biological sample contained in the at least one sample holder. The plurality of flow cells may be configured to be selectively placed in the open position and the closed position independently of each other.

1 . A device for performing biological sample reactions, the device comprising:
 a plurality of flow cells configured to be mounted to a common microscope translation stage, each flow cell being configured to receive at least one sample holder containing biological sample,   wherein each flow cell is configured to be selectively placed in an open position for positioning the at least one sample holder into the flow cell and a closed position for reacting biological sample contained in the at least one sample holder, and   wherein the plurality of flow cells are configured to be selectively placed in the open position and the closed position independently of each other.   
     
     
         2 . The device of  claim 1 , wherein the plurality of flow cells are removably mounted to the common microscope stage. 
     
     
         3 . The device of  claim 2 , further comprising a frame mounted to the microscope stage, wherein the plurality of flow cells are configured to be removably mounted to the frame. 
     
     
         4 . The device of  claim 1 , further comprising thermal components associated with each of the plurality of flow cells, wherein the thermal components are configured to be independently controlled. 
     
     
         5 . The device of  claim 4 , wherein the thermal components comprise a circulating cooling fluid system associated with each of the plurality of flow cells, each cooling fluid system being configured to circulate a cooling fluid proximate each reaction chamber to provide cooling thereto. 
     
     
         6 . The device of  claim 4 , wherein the thermal components comprise ductwork associated with each of the plurality of flow cells, the ductwork being configured to deliver air from a remote source proximate each reaction chamber to provide cooling thereto. 
     
     
         7 . The device of  claim 1 , wherein, in the open position, each flow cell is configured to receive the at least one sample holder in a substantially vertical position. 
     
     
         8 . The device of  claim 1 , wherein, in the open position, each flow cell is configured to receive the at least one sample holder in a substantially horizontal position. 
     
     
         9 . The device of  claim 8 , wherein, in the closed position, each flow cell is configured to hold the at least one sample holder in a substantially vertical position. 
     
     
         10 . The device of  claim 1 , wherein each flow cell is configured to be engageable with a bench top fixture for supporting the flow cell while positioning the at least one sample holder therein. 
     
     
         11 . The device of  claim 1 , wherein each flow cell is configured to receive a substrate comprising a microarray of nucleic acids for performing nucleic acid sequencing. 
     
     
         12 . The device of  claim 1 , wherein each flow cell comprises a heater block and is configured to define a reaction chamber between the heater block and the at least one sample holder positioned in each flow cell. 
     
     
         13 . The device of  claim 1 , further comprising an adjusting mechanism associated with each flow cell, the adjusting mechanism being configured to adjust a position of each flow cell in the closed position to move a portion of the at least one sample holder being imaged by a microscope to a focal plane of the microscope. 
     
     
         14 . The device of  claim 1 , wherein the flow cells are configured to be moved from the open position to the closed position by rotating the flow cells about a hinge relative to the microscope stage. 
     
     
         15 . The device of  claim 1 , wherein each flow cell is mounted to the microscope stage via a spherical bearing. 
     
     
         16 . The device of  claim 1 , further comprising a plurality of dampers, each damper being secured to a respective flow cell and the microscope stage. 
     
     
         17 . The device of  claim 1 , wherein each flow cell comprises a lever lock configured to lock the flow cell in the closed position. 
     
     
         18 . The device of  claim 17 , wherein each lever lock is configured to engage with a respective flange mechanism mounted relative to the microscope stage. 
     
     
         19 . A carrier for retaining a substrate holding at least one biological sample, the carrier comprising:
 a frame defining a recess configured to receive a substrate holding at least one biological sample on a surface thereof;   a plurality of retaining fingers configured to move into and out of engagement with the substrate to retain the substrate in the recess;   at least two extension portions extending from the frame in a direction away from the recess, each of the extension portions comprising a surface with which a respective clamping mechanism can engage to clamp the frame in position in a reaction chamber.   
     
     
         20 . The carrier of  claim 19 , wherein the frame is configured to receive a heater block to form a reaction chamber between the heater block and a substrate held by the carrier. 
     
     
         21 . The carrier of  claim 19 , wherein the frame is configured to contain substance that runs off a surface of a substrate received in the recess. 
     
     
         22 . The carrier of  claim 19 , wherein the surfaces of the extension portions with which the clamping mechanisms are configured to engage are ramped. 
     
     
         23 . The carrier of  claim 19 , wherein the plurality of extension portions comprise a pair of extension portions disposed diagonally opposite each other on the frame. 
     
     
         24 . The carrier of  claim 19 , wherein the recess is substantially rectangular. 
     
     
         25 . The carrier of  claim 19 , further comprising an opening surrounded by the recess. 
     
     
         26 . The carrier of  claim 19 , further comprising a radio-frequency identification mechanism. 
     
     
         27 . The carrier of  claim 19 , wherein the retaining fingers are configured to rotate relative to the frame into and out of engagement with the substrate. 
     
     
         28 . A flow cell configured to hold the carrier of  claim 19 , the flow cell comprising:
 a heater block configured to mate with the frame of the carrier, wherein a reaction chamber is formed between the heater block and a substrate in the recess of the carrier; and   a plurality of clamping mechanisms configured to engage with the plurality of extension portions to hold the carrier on the heater block.   
     
     
         29 . The flow cell of  claim 28 , wherein the plurality of clamping mechanisms are configured to rotate relative to a support plate on which the heater block is supported. 
     
     
         30 . The flow cell of  claim 28 , wherein the plurality of clamping mechanisms are spring-loaded to provide a clamping force on the extension portions. 
     
     
         31 . The flow cell of  claim 28 , further comprising a release knob configured to actuate a linkage system configured to engage with and rotate the plurality of clamping mechanisms. 
     
     
         32 . The flow cell of  claim 28 , further comprising a plurality of spacers on the heater block, the spacers being configured to support a substrate retained in the carrier when the heater block and frame mate with each other. 
     
     
         33 . The flow cell of  claim 28 , wherein the spacers are configured to support the substrate above a surface of the heater block to define a reaction volume between the substrate and the surface of the heater block. 
     
     
         34 . The flow cell of  claim 28 , wherein the flow cell is configured to be pivotably mounted relative to a microscope stage to move between an open position for loading a substrate and a closed position for performing reactions, and wherein abutment mechanisms on the microscope stage are configured to prevent the flow cell from being placed in the closed position unless the clamping mechanisms are engaged with the carrier.