Unitary biochip providing sample-in to results-out processing and methods of manufacture
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.
1. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
2. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features at least two of which have a draft angle of less than 2 degrees, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
3. A biochip made from the method comprising:
fabricating a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
fabricating said fluidic plate having a top surface and a bottom surface, each of top and bottom surfaces comprising at least one microfluidic feature, and at least one through hole extending from said top surface to said bottom surface to connect the top surface to the bottom surface;
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 in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein at least one of the macrofluidic block, fluidic plate or pneumatic plate is fabricated by injection molding.
4. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, at least two of which have a draft angle of less than 2 degrees, and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
5. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one of said surfaces comprises a region of at least one square centimeter in which at least two of the plurality of microfluidic features are at a pitch of at least 1.00 mm, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
6. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one of said surfaces comprises a region of at least one square centimeter in which at least two of the plurality of microfluidic features are at a pitch of at least 1.00 mm, and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
7. A biochip made from the method comprising:
injection molding a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate, (iii) at least one molded feature therein, said feature having a top end and a bottom end, and (iv) a plurality of microfluidic features in a region of at least one square centimeter in which at least two of said plurality are at a pitch of at least 1.00 mm;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
injection molding said fluidic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the fluidic top surface to the bottom surface;
injection molding a pneumatic plate having a top surface and a bottom surface, each of said top and bottom surfaces comprising a plurality of microfluidic features, and at least one through hole extending from said top surface to said bottom surface to connect the pneumatic top surface to the bottom surface;
aligning said macrofluidic block and said fluidic plate so that in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein said reagent storage chamber may be filled prior or subsequent to the first or second aligning steps and said macrofluidic block, fluidic and pneumatic plates may be injected molded in any order or sequence.
8. A biochip made from the method comprising:
fabricating a macrofluidic block, said block comprising: (i) a means for receiving at least one unprocessed sample, (ii) a fluid transfer means positioned and configured so that in the fully manufactured biochip said fluid transfer means is in fluid communication with a fluidic plate; and (iii) at least one molded feature therein, said feature having a top end and a bottom end;
bonding a first foil seal to either said top end or said bottom end to form at least one reagent storage chamber having an open end;
filling said at least one reagent storage chamber with a liquid reagent;
bonding a second foil seal to said open top end to form at least one filled reagent storage chamber in said macrofluidic block;
fabricating said fluidic plate having a top surface and a bottom surface, each of top and bottom surfaces comprising at least one microfluidic feature, and to include a fluidic top surface, a fluidic bottom surface and at least one through hole extending from said top surface to said bottom surface to connect the top surface to the bottom surface;
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 in the fully manufactured biochip sample processed in said macrofluidic block is transferred to said fluidic plate by the fluid transfer means;
aligning the pneumatic and fluidic plates using said at least one through hole;
wherein at least one of the macrofluidic block, fluidic plate or pneumatic plate is fabricated by injection molding and wherein at least one of the injection molded parts has at least one square centimeter region which contains at least two microfluidic features at a pitch of at least 1.0 mm.