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US 2012/0055798 A1Published application
Unitary Biochip Providing Sample-in to Results-out Processing and Methods of Manufacture
AssigneeNetBio, Inc.
InventorsRichard F. Selden, Eugene Tan
Life of this patent
Estimating the term…
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.
Claims8
A plastic, stationary, unitary biochip for processing at least one unprocessed sample, said biochip comprising:
- a macrofluidic processing subassembly in connection with a fluidic subassembly and a drive mechanism, comprising at least one macrofluidic processing subassembly feature located therein or thereon, further comprising a chamber capable of receiving a sample, and at least a first solution;
- the fluidic subassembly, comprising a fluidic plate, and at least one fluidic subassembly feature located therein or thereon, the fluidic subassembly further comprising at least one fluid transport channel and a chamber capable of receiving at least a second solution;
- a drive mechanism to transfer said at least said first solution within said macrofluidic processing subassembly and at least said second solution within said fluidic subassembly and at least one of said first or second solutions between said two subassemblies;
- wherein a physical state of said one or more features of the fluidic and/or macrofluidic processing subassemblies are adapted to change in scripted processes of 25 or more steps so as to perform at least two manipulations selected from the group consisting of:
- nucleic acid extraction;
- cell lysis;
- cell separation;
- differential cell lysis;
- differential filtration;
- total nucleic acid purification;
- DNA purification;
- RNA purification;
- mRNA purification;
- protein purification;
- pre-nucleic acid amplification cleanup;
- nucleic acid amplification;
- end-point PCR;
- Real-time PCR;
- reverse transcription PCR;
- asymmetric PCR;
- nested PCR;
- LATE PCR;
- touchdown PCR;
- digital PCR;
- rolling circle amplification;
- strand displacement amplification;
- multiple displacement amplification;
- Y-STR amplification;
- mini-STR amplification;
- single nucleotide polymorphism analysis;
- VNTR analysis;
- RFLP analysis;
- post-nucleic acid amplification cleanup;
- pre-nucleic acid sequencing cleanup;
- Sanger sequencing;
- pyrosequencing;
- and single molecule sequencing;
- post-nucleic acid sequencing cleanup;
- reverse transcription;
- pre-reverse transcription cleanup;
- post-reverse transcription cleanup;
- nucleic acid ligation;
- SNP analysis;
- nucleic acid hybridization;
- electrophoretic separation and detection;
- immunoassay;
- binding assay;
- protein assay;
- enzymatic assay;
- mass spectroscopy;
- nucleic acid quantification and protein quantification.
48 more elements
A plastic, stationary, unitary biochip for processing at least one unprocessed sample, said biochip comprising:
- a macrofluidic processing subassembly in connection with a fluidic subassembly and a drive mechanism, comprising at least one macrofluidic processing subassembly feature located therein or thereon, further comprising a chamber capable of receiving a sample, and at least a first solution;
- the fluidic subassembly, comprising a fluidic plate, and at least one fluidic subassembly feature located therein or thereon, the fluidic subassembly further comprising at least one fluid transport channel and a chamber capable of receiving at least a second solution;
- a drive mechanism to transfer said at least said first solution within said macrofluidic processing subassembly and at least said second solution within said fluidic subassembly and at least one of said first or second solutions between said two subassemblies;
- wherein said one or more features of the fluidic and/or macrofluidic processing subassemblies has an initial physical state adapted to change to a second physical state in scripted processes of 25 or more steps so as to perform at least two manipulations selected from the group consisting of:
- nucleic acid extraction;
- cell lysis;
- cell separation;
- differential cell lysis;
- differential filtration;
- total nucleic acid purification;
- DNA purification;
- RNA purification;
- mRNA purification;
- protein purification;
- pre-nucleic acid amplification cleanup;
- nucleic acid amplification;
- end-point PCR;
- Real-time PCR;
- reverse transcription PCR;
- asymmetric PCR;
- nested PCR;
- LATE PCR;
- touchdown PCR;
- digital PCR;
- rolling circle amplification;
- strand displacement amplification;
- multiple displacement amplification;
- Y-STR amplification;
- mini-STR amplification;
- single nucleotide polymorphism analysis;
- VNTR analysis;
- RFLP analysis;
- post-nucleic acid amplification cleanup;
- pre-nucleic acid sequencing cleanup;
- Sanger sequencing;
- pyrosequencing;
- and single molecule sequencing;
- post-nucleic acid sequencing cleanup;
- reverse transcription;
- pre-reverse transcription cleanup;
- post-reverse transcription cleanup;
- nucleic acid ligation;
- SNP analysis;
- nucleic acid hybridization;
- electrophoretic separation and detection;
- immunoassay;
- binding assay;
- protein assay;
- enzymatic assay;
- mass spectroscopy;
- nucleic acid quantification and protein quantification.
48 more elements
A plastic, stationary, unitary biochip for processing at least one unprocessed sample, said biochip comprising:
- a macrofluidic processing subassembly in connection with a fluidic subassembly and, comprising at least one macrofluidic feature located therein or thereon for the performance of at least one sample manipulation selected from the group consisting of nucleic acid extraction;
- cell lysis;
- cell separation;
- differential cell lysis;
- differential filtration;
- total nucleic acid purification;
- DNA purification;
- RNA purification;
- mRNA purification;
- protein purification and pre-nucleic acid amplification cleanup, and
- 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 a chamber adapted for amplification selected from the group consisting of:
- end-point PCR;
- Real-time PCR;
- reverse transcription PCR;
- asymmetric PCR;
- nested PCR;
- LATE PCR;
- touchdown PCR;
- digital PCR;
- rolling circle amplification;
- strand displacement amplification;
- multiple displacement amplification;
- Y-STR amplification;
- and mini-STR amplification;
- a drive mechanism to transfer said at least a first solution within said macrofluidic processing subassembly and at least a second solution within said fluidic subassembly and at least one of said first or second solutions between said two subassemblies;
- wherein a physical state of said one or more features of the fluidic, and/or macrofluidic processing subassemblies are adapted to change in scripted processes of 25 or more steps so as to perform at least two manipulations selected from the group consisting of:
- Sanger sequencing;
- pyrosequencing;
- and single molecule sequencing;
- post-nucleic acid sequencing cleanup;
- reverse transcription;
- pre-reverse transcription cleanup;
- post-reverse transcription cleanup;
- nucleic acid ligation;
- SNP analysis;
- nucleic acid hybridization;
- electrophoretic separation and detection;
- and nucleic acid quantification.
36 more elements
A electrophoretic system for processing a biological sample, the system comprising:
- a biochip and a process controller, the biochip, which upon insertion into an instrument having pneumatic and thermal subsystems, and the process controller, generates amplified, electrophoretically separated nucleic acid fragments from at least one sample, the 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 at least one fluid transport channel and an amplification chamber adapted to connect to the thermal subsystem;
- a valve subassembly, positioned between and connected to said fluidic and pneumatic subassemblies;
- and
- wherein the process controller of the instrument includes instructions to perform 25 or more automated scripted process steps.
3 more elements
A method of manufacturing a biochip, said method comprising:
- injection molding a macrofluidic block for receiving at least one unprocessed sample, comprising at least one reagent storage chamber having a top end and a bottom end, a first foil seal bonded to one of said ends and a second foil seal bonded to the other of said ends;
- injection molding a fluidic plate to include a fluidic top surface, a fluidic bottom surface and at least one through hole extending from the fluidic top surface to the fluidic bottom surface to connect the fluidic top surface to the bottom surface, each of the fluidic top and bottom surfaces comprise a plurality of microfluidic features;
- injection molding a pneumatic plate to include a pneumatic top surface, a pneumatic bottom surface and at least one through hole extending from the pneumatic top surface to the pneumatic bottom surface to connect the pneumatic top surface to the bottom surface, each of the pneumatic top and bottom surfaces comprise a plurality of microfluidic features;
- aligning said macrofluidic block and said fluidic plate so that sample processed in said macrofluidic block is transferred to said fluidic plate;
- aligning the pneumatic and fluidic plates;
- wherein a footprint of the fluidic and/or pneumatic plates is 86 mm by 128 mm or greater.
3 more elements
A method of manufacturing a biochip, said method comprising:
- injection molding a macrofluidic block for receiving at least one unprocessed sample, comprising at least one reagent storage chamber having a top end and a bottom end, a first foil seal bonded to one of said ends and a second foil seal bonded to the other of said ends;
- injection molding a fluidic plate to include a fluidic top surface, a fluidic bottom surface and at least one through hole extending from the fluidic top surface to the fluidic bottom surface to connect the fluidic top surface to the bottom surface, each of the fluidic top and bottom surfaces comprise a plurality of microfluidic features;
- injection molding a pneumatic plate to include a pneumatic top surface, a pneumatic bottom surface and at least one through hole extending from the pneumatic top surface to the pneumatic bottom surface to connect the pneumatic top surface to the bottom surface, each of the pneumatic top and bottom surfaces comprise a plurality of microfluidic features;
- aligning said macrofluidic block and said fluidic plate so that sample processed in said macrofluidic block is transferred to said fluidic plate;
- aligning the pneumatic and fluidic plates;
- wherein at least one of the plurality of microfluidic features of the fluidic plate and/or the pneumatic plate comprises a draft angle of less than 2 degrees.
3 more elements
A method of manufacturing a biochip, said method comprising:
- fabricating a macrofluidic block for receiving at least one unprocessed sample, comprising at least one reagent storage chamber having a top end and a bottom end, a first foil seal bonded to one of said ends and a second foil seal bonded to the other of said ends;
- fabricating a fluidic plate to include a fluidic top surface, a fluidic bottom surface and at least one through hole extending from the fluidic top surface to the fluidic bottom surface to connect the fluidic top surface to the bottom surface, each of the fluidic top and bottom surfaces comprise a plurality of microfluidic features;
- fabricating a pneumatic plate to include a pneumatic top surface, a pneumatic bottom surface and at least one through hole extending from the pneumatic top surface to the pneumatic bottom surface to connect the pneumatic top surface to the bottom surface, each of the pneumatic top and bottom surfaces comprise a plurality of microfluidic features;
- aligning said macrofluidic block and said fluidic plate so that sample processed in said macrofluidic block is transferred to said fluidic plate;
- aligning the pneumatic and fluidic plates;
- wherein at least one of the macrofluidic block, fluidic plate or pneumatic plate is fabricated by injection molding.
3 more elements
Dependencies are inferred from the claim text.