Thermocycling system and manufacturing method

Abstract

A system for thermocycling biological samples within detection chambers comprising: a set of heater-sensor dies, each heater-sensor die comprising a heating surface configured to interface with a detection chamber and a second surface, inferior to the heating surface, including a first connection point; an electronics substrate, comprising a first substrate surface coupled to the second surface of each heater-sensor die, an aperture providing access through the electronics substrate to at least one heater-sensor die, and a second substrate surface inferior to the first substrate surface, wherein the electronics substrate comprises a set of substrate connection points at least at one of the first substrate surface, an aperture surface defined within the aperture, and the second substrate surface, and wherein the electronics substrate is configured to couple heating elements and sensing elements of the set of heater-sensor dies to a controller; and a set of wire bonds, including a wire bond coupled between the first connection point of at least one of the set of heater-sensor dies and one of the set of substrate connection points.

What is claimed: 
     
         1 . A method of manufacturing a system for thermocycling biological samples within detection chambers, the method comprising:
 at a substrate, forming a first insulating layer coupled to exposed surfaces of the substrate;   depositing a heating region onto the first insulating layer of the substrate;   removing material of the heating region, thereby forming a heating array with a pattern that defines a set of heating elements and a set of sensing elements within the heating array;   dividing the heating array into a set of heater-sensor dies, each heater-sensor die comprising a heating surface, including a heating element of the set of heating elements and a sensing element of the set of sensing elements, configured to interface with a detection chamber, and each heater-sensor die comprising a second surface, inferior to the heating surface, including a first connection point;   providing an electronics substrate having a first substrate surface configured to couple to the second surface of each of the set of heater-sensor dies, an aperture providing access through the electronics substrate to at least one of the set of heater-sensor dies, and a second substrate surface inferior to the first substrate surface; and   coupling a wire bond from the first connection point of at least one of the set of heater-sensor dies, into the aperture of the electronics substrate, and to a second connection point of the electronics substrate.   
     
     
         2 . The method of  claim 1 , wherein depositing the heating region comprises coupling an adhesion material layer to the first insulating layer, and coupling a noble material layer to the adhesion material layer. 
     
     
         3 . The method of  claim 2 , wherein forming the heating array with a pattern comprises defining a pattern of voids through the adhesion material layer and the noble material layer, wherein coarse elements of the pattern define heating elements of the heating array and fine elements of the pattern, integrated within coarse elements of the pattern, define sensing elements of the heating array. 
     
     
         4 . The method of  claim 3 , wherein the pattern of the heating array comprises boustrophedonic segments including wide segments associated with heating elements of the heating array and fine segments, surrounded by wide segments, associated with sensing elements of the heating array. 
     
     
         5 . The method of  claim 1 , wherein coupling the wire bond comprises coupling a first end of the wire bond to the first connection point, passing the wire bond through the aperture, and coupling a second end of the wire bond to the second connection point at the second substrate surface. 
     
     
         6 . The method of  claim 1 , wherein coupling the wire bond comprises coupling a first end of the wire bond to the first connection point, passing the wire bond into the aperture, and coupling a second end of the wire bond to a surface of the aperture within the electronics substrate. The method of  claim 1 , wherein providing the electronics substrate comprises defining a set of apertures longitudinally spaced across the electronics substrate and a set of recesses, each recess of the set of recesses contiguous with at least one aperture of the set of apertures. 
     
     
         8 . The method of claim  7 , further comprising coupling the second surface of each of the set of heater-sensor dies, within a recess of the set of recesses, with an adhesive layer configured to maintain coupling between the set of heater-sensor dies and the electronics substrate. 
     
     
         9 . The method of claim  7 , wherein coupling the wire bond comprises coupling a heater- sensor dies of the set of heater-sensor dies to the first substrate surface with an adhesive layer, and coupling a first end of the wire bond to the first connection point, passing the wire bond into a recess of the set of recesses, and coupling a second end of the wire bond to the second connection point at a surface of at least one of the recess and an aperture contiguous with the recess. 
     
     
         10 . The method of  claim 1 , further comprising coupling a coating, proximal to the heating surface of at least one heater-sensor die of the set of heater-sensor dies, wherein the coating is configured to mitigate reflection of light from the heating surface toward photodetectors of an optical subsystem, in a configuration wherein the set of heater- sensor dies is opposed to photodetectors of the optical subsystem. 
     
     
         11 . A thermocycling system, comprising:
 a first insulating layer at exposed surfaces of a substrate;   a heating region on the first insulating layer of the substrate;   a heating array having a pattern that defines a set of heating elements and a set of sensing elements therein;   a set of heater-sensor dies, each heater-sensor die comprising a heating surface, including one of the heating elements and one of the sensing elements, and each heater sensor die comprising a second surface, inferior to the heating surface, the second surface including a first connection point;   an electronics substrate having a first substrate surface configured to couple to the second surface of each of the set of heater-sensor dies, and a second substrate surface inferior to the first substrate surface;   an aperture in the electronics substrate providing access through the electronics substrate to at least one of the set of heater-sensor dies, and   a conductor extending from the first connection point of at least one of the set of heater-sensor dies, through the aperture to a second connection point of the electronics substrate.   
     
     
         12 . A method of manufacturing a thermocycling system, comprising:
 forming, on an electronics substrate having a first substrate surface and a second substrate surface inferior to the first substrate surface, a set of heater-sensor dies, each heater-sensor die including a heating element and a sensing element, a first surface of each heater-sensor die configured to interface with a detection chamber during operation, and a second surface of each heater-sensor die, inferior to the first surface, including a heater- sensor die connection point;   coupling the second surface of each heater-sensor die to the first substrate surface;   forming, in the electronics substrate, a plurality of longitudinally-spaced apertures that provide access through the electronics substrate to the set of heater-sensor dies;   forming, on the second substrate surface a set of substrate connection points;   coupling a conductor between corresponding ones of the heater-sensor die connection points and the substrate connection points, each conductor passing through an aperture; and   forming a set of heat sink supports operable to dissipate heat generated by the set of heater-sensor dies, wherein a base surface of each of the set of heat sink supports is coupled to an elastic element that transmits a biasing force through the electronics substrate, thereby maintaining thermal communication between the set of heater-sensor dies and a set of detection chambers during operation of the thermocycling system.   
     
     
         13 . A method of manufacturing a thermocycling system, the method comprising:
 forming a first insulating layer at exposed surfaces of a substrate;   depositing a heating region onto the first insulating layer of the substrate;   removing material of the heating region, thereby forming a heating array with a pattern that defines a set of heating elements and a set of sensing elements within the heating array;   dividing the heating array into a set of heater-sensor dies, each heater-sensor die comprising a heating surface, including a heating element of the set of heating elements and a sensing element of the set of sensing elements, and each heater-sensor die comprising a second surface, inferior to the heating surface, including a first connection point;   providing an electronics substrate having a first substrate surface configured to couple to the second surface of each of the set of heater-sensor dies, an aperture providing access through the electronics substrate to at least one of the set of heater-sensor dies, and a second substrate surface inferior to the first substrate surface; and   coupling a conductor from the first connection point of at least one of the set of heater-sensor dies, to a second connection point of the electronics substrate, through the aperture of the electronics substrate.   
     
     
         14 . The method of  claim 13 , wherein coupling the conductor comprises coupling a first end of the conductor to the first connection point, passing the conductor through the aperture, and coupling a second end of the conductor to the second connection point at the second substrate surface. 
     
     
         15 . The method of  claim 13 , wherein coupling the conductor comprises coupling a first end of the conductor to the first connection point, passing the conductor into the aperture, and coupling a second end of the conductor to an internal surface of the aperture. 
     
     
         16 . The method of  claim 13 , wherein providing the electronics substrate comprises defining a set of apertures spaced across the electronics substrate and defining a set of recesses, each recess of the set of recesses contiguous with at least one aperture of the set of apertures. 
     
     
         17 . The method of  claim 16 , further comprising coupling the second surface of each of the set of heater-sensor dies, within a corresponding recess of the set of recesses, with an adhesive layer that maintains coupling between the set of heater-sensor dies and the electronics substrate. 
     
     
         18 . The method of  claim 16 , wherein coupling the conductor comprises coupling a heater- sensor die of the set of heater-sensor dies to the first substrate surface with an adhesive layer, and coupling a first end of the conductor to the first connection point, passing the conductor into a recess of the set of recesses, and coupling a second end of the conductor to the second connection point at a surface of at least one of the recess and an aperture contiguous with the recess. 
     
     
         19 . The method of  claim 13 , further comprising coupling a coating, proximal to the heating surface of at least one heater-sensor die of the set of heater-sensor dies, wherein the coating is operable to mitigate reflection of light from the heating surface toward photodetectors of an optical subsystem opposed to the heating surface during operation of the thermocycling system. 
     
     
         20 . The method of  claim 13 , wherein depositing the heating region comprises
 coupling an adhesion material layer to the first insulating layer, and coupling a noble material layer to the adhesion material layer, and   wherein forming the heating array with the pattern comprises defining a pattern of voids through the adhesion material layer and the noble material layer, wherein coarse elements of the pattern define heating elements of the heating array and fine elements of the pattern, integrated within coarse elements of the pattern, define sensing elements of the heating array.