Smart disposable plastic lab-on-a-chip for point-of-care testing

• US 7,524,464 B2
• Filed: 09/22/2004
• Issued: 04/28/2009
• Est. Priority Date: 09/26/2003
• Status: Expired due to Fees

• Current Assignee: University of Cincinnati
• Original Assignee: University of Cincinnati
• Inventors: Choi, Jin-Woo, Nevin, Joseph, Beaucage, Gregory, Ahn, Chong H.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Mui; Christine T
• Application Number:
  US10/947,577
• Publication Number:
  US 20050130292A1
• Time in Patent Office: 1,679 Days
• Field of Search: 422/177, 73/10.2
• US Class Current: 422/177
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes

Abstract

Disclosed herein is a fully-integrated, disposable biochip for point-of-care testing of clinically relevant parameters. Specifically, in accordance with an embodiment of the present invention, the biochip is designed for POCT (point-of-care-testing) of an array of metabolic parameters including partial pressure of oxygen, Glucose, and Lactate concentration from venous blood samples. The biochip is fabricated on a low-cost plastic substrate using mass manufacturing compatible fabrication processes. Furthermore, the biochip contains a fully-integrated metallic micro-needle for blood sampling. The biochip also uses smart passive microfluidics in conjunction with low-power functional on-chip pressure generators for microfluidic sequencing. The design, configuration, assembly and operation of the biochip are ideally suited for a disposable biochip specifically targeted towards POCT applications.

Claims

1. A disposable, integrated biochip for clinical diagnostic applications, said biochip comprising:

a. at least one micro-sensor for sensing at least one relevant parameter of said sampled fluid;

b. micro-calibration system connected to said at least one micro-sensor to calibrate said biochip comprising;

i. a metallic calibration solution pouch containing a calibration buffer of at least one known concentration of at least one analyte;

ii. at least one micro-fluidic channel, connecting to said calibration solution pouch, to carry said calibration buffer to said at least one micro-sensor when said calibration solution pouch is ruptured; and

iii. at least one waste reservoir to accept said calibration buffer after said biochip is calibrated;

c. a micro-needle for sampling a fluid from a subject; and

d. a passive micro-fluidic control system, connecting said micro-needle to said at least one micro-sensor, to accept said sampled fluid from said micro-needle and to facilitate movement of said sampled fluid to said at least one micro-sensor.

2. The biochip of claim 1 further comprising a micro-propulsion system connecting to said passive micro-fluidic control system to move said sampled fluid through said passive micro-fluidic control system.

3. The biochip of claim 2 wherein said at least one micro-sensor, said passive micro-fluidic control system, said micro-propulsion system, and said micro-calibration system are collectively fabricated on at least two plastic substrates that are integrated together within said biochip.

4. The biochip of claim 1 wherein said micro-needle is metallic.

5. The biochip of claim 1 wherein said at least one micro-sensor comprises at least one of an electro-chemical oxygen biosensor, an electrochemical glucose biosensor, an electro-chemical lactate biosensor, a pH biosensor, and a hematocrit biosensor.

6. The biochip of claim 1 wherein said passive micro-fluidic system comprises:

a micro-dispenser reservoir;

at least one passive micro-valve;

at least one micro-sensor reservoir connecting to said at least one micro-sensor via at least one semi-permeable membrane of said at least one micro-sensor; and

at least two micro-fluidic channels connecting together said micro-dispenser reservoir, said at least one passive micro-valve, and said at least one micro-sensor reservoir.

7. The biochip of claim 2 wherein said micro-propulsion system comprises:

at least one micro-chamber containing a pressurized gas and being connected to said passive micro-fluidic control system; and

at least one micro-heater positioned next to and being in contact with a thermo-plastic membrane of said micro-chamber to release said pressurized gas into an air inlet of said passive micro-fluidic control system upon melting of said thermo-plastic membrane by said micro-heater when an electrical pulse is applied to said micro-heater.

8. The biochip of claim 2 wherein said micro-propulsion system comprises:

at least one micro-heater; and

at least one solid chemical-propellant positioned on said at least one micro-heater to release an inert gas into an air inlet of said passive micro-fluidic control system upon activation of said at least one solid chemical propellant by said micro-heater when an electrical pulse is applied to said micro-heater.

9. The biochip of claim 3 wherein said at least two plastic substrates comprises at least one of cyclic olefin copolymer, polyimide, polymethylmethaacrylate, PDMS, polyethylene, and polycarbonate.

10. The biochip of claim 5 wherein said oxygen biosensor comprises:

a semi-permeable membrane that is permeable to at least oxygen molecules;

a solid, gel-based layer of electrolyte solution being in contact with said semi-permeable membrane; and

at least two electrodes being in contact with said solid, gel-based layer of electrolyte solution.

11. The biochip of claim 5 wherein said glucose biosensor comprises:

a first semi-permeable membrane that is permeable to at least glucose molecules;

a glucose oxidase enzyme layer being in contact with said first semi-permeable membrane to oxidize said glucose molecules into at least oxygen molecules;

a second semi-permeable membrane being in contact with said glucose oxidase enzyme layer and being permeable to at least said oxygen molecules;

a solid, gel-based layer of electrolyte solution being in contact with said second semi-permeable membrane; and

at least two electrodes being in contact with said solid, gel-based layer of electrolyte solution.

12. The biochip of claim 5 wherein said lactate biosensor comprises:

a first semi-permeable membrane that is permeable to at least lactate molecules;

a lactate oxidase enzyme layer being in contact with said first semi-permeable membrane to oxidize said lactate molecules into at least oxygen molecules;

a second semi-permeable membrane being in contact with said lactate oxidase enzyme layer and being permeable to at least said oxygen molecules;

a solid, gel-based layer of electrolyte solution being in contact with said second semi-permeable membrane; and

at least two electrodes being in contact with said solid, gel-based layer of electrolyte solution.

13. The biochip of claim 1 further comprising at least two conductive traces connected to said at least one micro-sensor for monitoring an electric current generated by said micro-sensor.

14. The biochip of claim 1 wherein said at least one relevant parameter comprises at least one of partial oxygen concentration, glucose level, lactate level, pH, and hematocrit.