Unitary Biochip Providing Sample-in to Results-out Processing and Methods of Manufacture

Abstract

A biochip for the integration of all steps in a complex process from the insertion of a sample to the generation of a result, performed without operator intervention includes microfluidic and macrofluidic features that are acted on by instrument subsystems in a series of scripted processing steps. Methods for fabricating these complex biochips of high feature density by injection molding are also provided.

What is claimed is: 
     
         1 . A biochip, which upon insertion into an electrophoresis instrument having pneumatic, thermal, high voltage, and optical subsystems, and a process controller, generates a nucleic acid sequencing or sizing profile from at least one sample, said biochip comprising:
 a macrofluidic processing subassembly in connection with a fluidic subassembly and a pneumatic subassembly, comprising at least one chamber adapted to receive a sample;   the fluidic subassembly, comprising a fluidic plate, and at least one fluid transport channel and an amplification chamber adapted to connecting to the thermal subsystem;   the pneumatic subassembly which is adapted to connecting to the pneumatic subsystem of said instrument, and to the subassemblies of said biochip, comprising, a pneumatic plate and one or a plurality of drive lines to pneumatically drive fluids on instructions from said process controller;   a separation and detection subassembly adapted for connecting to the high voltage and optical subsystems and process controller on said instrument, said separation and detection subassembly comprising a separation channel, and further comprising a detection region positioned to send signals from each of said channels to said optical subsystem on said instrument;   wherein the biochip is plastic, stationary, and unitary, and a footprint of the fluidic and/or pneumatic plates is about 86 mm by 128 mm or greater.   
     
     
         2 . The biochip of  claim 1 , wherein the footprint of the fluidic and/or pneumatic plates is about 100×150 mm or greater. 
     
     
         3 . The biochip of  claim 2 , wherein the footprint of the fluidic and/or pneumatic plates is about 115×275 mm or greater. 
     
     
         4 . The biochip of  claim 3 , wherein the footprint of the fluidic and/or pneumatic plates is about 140×275 or greater. 
     
     
         5 . The biochip of  claim 4 , wherein the footprint of the fluidic and/or pneumatic plates is 165×295 or greater. 
     
     
         6 . A biochip, which upon insertion into an electrophoresis instrument having pneumatic, thermal, high voltage, and optical subsystems, and a process controller, generates a nucleic acid sequencing or sizing profile from at least one sample, said biochip comprising:
 a macrofluidic processing subassembly in connection with a fluidic subassembly and a pneumatic subassembly, comprising at least one macrofluidic feature located therein or thereon, further comprising a chamber capable of receiving a sample;   the fluidic subassembly, comprising a fluidic plate, and at least one feature located therein or thereon, the fluidic subassembly further comprising at least one fluid transport channel and an amplification chamber adapted to connecting to the thermal subsystem;   the pneumatic subassembly which is adapted to connecting to the pneumatic subsystem of said instrument, and to the subassemblies of said biochip, comprising, a pneumatic plate and at least one feature located therein or thereon, the pneumatic subassembly further comprising one or a plurality of drive lines to pneumatically drive fluids on instructions from said process controller;   a separation and detection subassembly adapted for connecting to the high voltage and optical subsystems and process controller on said instrument, said separation and detection subassembly comprising at least one feature located therein or thereon, the separation and detection subassembly further comprising a separation channel and a detection region positioned to send signals from each of said channels to said optical subsystem on said instrument;   wherein the biochip is plastic, stationary, and unitary, and a physical state of said one or more features of the fluidic, pneumatic, and/or separation and detection subassemblies are adapted to change in scripted processes of 25 or more steps.   
     
     
         7 . Biochip of  claim 6 , wherein the number of steps is 50 or more. 
     
     
         8 . Biochip of  claim 7 , wherein the number of steps is 100 or more. 
     
     
         9 . Biochip of  claim 8 , wherein the number of steps is 200 or more. 
     
     
         10 . Biochip of  claim 6 , wherein the 25 or more scripted process steps results in two or more resultant processing steps. 
     
     
         11 . A unitary, stationary biochip, which upon insertion into an electrophoresis instrument having pneumatic, thermal, high voltage and optical subsystems, and a process controller, generates a nucleic acid sequencing or sizing profile from at least one sample, said biochip comprising:
 a macrofluidic processing subassembly in connection with a fluidic subassembly and a pneumatic subassembly, comprising at least one chamber adapted to receive a sample;   the fluidic subassembly, comprising a fluidic plate having a top and bottom patterned thermoplastic sheet bonded thereon, to form at least one fluid transport channel on each sides of the plate and an amplification chamber adapted to connecting to the thermal subsystem;   the pneumatic subassembly which is adapted to connecting to the pneumatic subsystem of said instrument, and to the subassemblies of said biochip, comprising a pneumatic plate having a top patterned thermoplastic sheet bonded thereon, and one or a plurality of drive lines to pneumatically drive fluids on instructions from said process controller;   a valve subassembly, positioned between and connected to said fluidic and pneumatic subassemblies; and   a separation and detection subassembly adapted for connecting to the high voltage and optical subsystems and process controller on said instrument, said separation and detection subassembly comprising at least one separation channel, and further comprising a detection region positioned to send signals from each of said at least one separation channels to said optical subsystem on said instrument.   
     
     
         12 . The biochip of  claim 11 , wherein the separation and detection subassembly is plastic. 
     
     
         13 . The biochip of  claim 11 , in which the macrofluidic, pneumatic, fluidic, and separation and detection subsystems are plastic. 
     
     
         14 . The biochip of  claim 11 , wherein the valve subassembly comprises at least one elastomeric valve. 
     
     
         15 . The biochip of  claim 11 , wherein the valve subassembly comprises at least one non-elastomeric valve. 
     
     
         16 . The biochip of  claim 11 , wherein the separation and detection subassembly is oriented such that electrophoresis of the sample within the separation and detection subassembly is conducted in the opposite direction from a general flow of sample through the fluidic plate. 
     
     
         17 . The biochip of  claim 11 , wherein all reagents needed to process the at least one sample are contained within the biochip. 
     
     
         18 . The biochip of  claim 11 , wherein a footprint of the fluidic plate and/or the pneumatic plate is about 86 mm×128 mm or greater. 
     
     
         19 . The biochip of  claim 11  wherein a footprint of the fluidic plate and/or the pneumatic plate is about 115 mm×275 mm or greater. 
     
     
         20 . The biochip of  claim 11  wherein a footprint of the fluidic plate and/or the pneumatic plate is about 165 mm×295 mm or greater.