Unitary biochip providing sample-in to results-out processing and methods of manufacture

• US 9,314,795 B2
• Filed: 05/13/2014
• Issued: 04/19/2016
• Est. Priority Date: 03/09/2010
• Status: Active Grant

• Current Assignee: ANDE Corp.
• Original Assignee: NetBio, Inc.
• Inventors: Selden, Richard F., Tan, Eugene
• Primary Examiner(s): Alexander, Lyle
• Assistant Examiner(s): Wecker, Jennifer
• Application Number:
  US14/276,993
• Publication Number:
  US 20140371108A1
• Time in Patent Office: 707 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502 : with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B29B 11/08 : Injection moulding
• CPC Class Codes: B29C 2045/0027 : Gate or gate mark locations
• CPC Class Codes: B29C 45/0025 : Preventing defects on the moulded article, e.g. weld lines, shrinkage marks preventing defects on the preformed parts or layers B29C45/14836
• CPC Class Codes: B29K 2101/12 : Thermoplastic materials
• CPC Class Codes: B29K 2105/251 : Particles, powder or granules expandable particles B29K2105/046
• CPC Class Codes: B29L 2031/34 : Electrical apparatus, e.g. sparking plugs or parts thereof
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 1/6874 : involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 27/26 : by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/44704 : Details; Accessories
• CPC Class Codes: G01N 27/44721 : by optical means
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 29/4998 : Combined manufacture including applying or shaping of fluent material

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.

Claims

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.