Diagnostic devices, systems, and methods

• US 10,444,232 B2
• Filed: 08/13/2015
• Issued: 10/15/2019
• Est. Priority Date: 08/13/2014
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Guo, Tiffany, Sia, Samuel K., Xie, Jeisun Shi, Meng, Fanxing, Yeager, Keith
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US15/503,512
• Publication Number:
  US 20170227537A1
• Time in Patent Office: 1,524 Days
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/56988 HIV or HTLV
• CPC Class Codes: G01N 33/571 for venereal disease, e.g. syphilis, gonorrhoea herpes G01N33/56994; chlamydia G01N33/56927
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/6827 Total protein determination, e.g. albumin in urine

Abstract

Diagnostic systems, methods, and devices employing low-cost handheld components are disclosed herein. A diagnostic system can include a diagnostic device that is configured to perform one or more assays on a fluid sample, such as a whole blood sample, in one or more microfluidic channels or chambers. The diagnostic device can move the fluid sample into or through the one or more microfluidic channels or chambers without using any electrical power, for example, using manual actuation to generate a positive or negative pressure within the diagnostic device. The diagnostic device can have a connector for interfacing with a separate handheld unit that can provide power and data processing. For example, the separate handheld unit can be a smartphone or PDA, and the connector can interface with an existing input/output port of the unit to draw power and/or transmit data.

Claims

1. A handheld diagnostic system, comprising:

a reagent cassette comprising a microfluidic network having an inlet, an outlet, and a detection region, the detection region including at least one detection zone; and

a diagnostic dongle comprising a recess, a manually-actuated pressure system configured to generate negative pressure and store the negative pressure in a pressure chamber, at least one light source, at least one photodetector, a control module, and an input/output connector; and

a smartphone or personal digital assistant (PDA) coupled to the input/output connector of the diagnostic dongle and configured to provide electrical power to the diagnostic dongle and to transmit data from the diagnostic dongle;

wherein the at least one detection zone is aligned with a respective photodetector when the reagent cassette is inserted into the recess of the diagnostic dongle;

wherein the manually-actuated pressure system is configured to apply the negative pressure to the microfluidic network of the reagent cassette to move fluids therethrough;

wherein the reagent cassette includes reagents and/or a lysis agent for whole blood; and

wherein the control module is programmed to control the at least one light source and the at least one photodetector to interrogate the respective detection zone to perform at least one of a colorimetric assay, an immunoassay, an electrochemical assay, and absorbance detection.

2. The diagnostic system of claim 1, wherein the input/output connector is configured to interface with an audio port or a USB port of the smartphone or PDA.

3. The diagnostic system of claim 2, wherein the input/output connector comprises an audio jack.

4. The diagnostic system of claim 1, wherein the diagnostic dongle and the smartphone or PDA are constructed to be held and operated by a user at the same time using a single hand.

5. The diagnostic system of claim 1, wherein the diagnostic dongle and the smartphone or PDA are constructed to be held and operated by a user at the same time using one hand to operate the manually-actuated pressure system and another hand to operate the smartphone or PDA.

6. The diagnostic system of claim 1, wherein electrical power for the diagnostic dongle is provided exclusively via said input/output connector.

7. The diagnostic system of claim 1, wherein the control module is configured to convert data of results of the colorimetric assay and immunoassay by frequency-shift keying (FSK) and to transmit FSK-converted data via the input/output connector.

8. The diagnostic system of claim 1, further comprising an antibody holder having a plurality of labeled antibodies therein and an outlet configured to interface with the inlet of the reagent cassette to deliver the antibodies to the microfluidic network.

9. The diagnostic system of claim 1, wherein antigens in the at least one detection zone comprise disease-specific capture proteins that have been adhered to channel walls of the microfluidic network via physisorption.

10. The diagnostic system of claim 1, wherein the detection region further includes detection zones operating as negative and positive control zones.

11. The diagnostic system of claim 1, wherein the manually-actuated pressure system comprises a manually displaceable bulb covering the pressure chamber with a spring therein, wherein said negative pressure is generated by manually depressing said bulb to compress the spring and subsequently the spring exerting a force on the manually displaceable bulb.

12. The diagnostic system of claim 10, wherein a pinhole aperture is provided in an optical path between each of the detection zones and its corresponding photodetector.

13. The diagnostic system of claim 1, wherein the manually-actuated pressure system applies a negative pressure to the microfluidic network.

14. A diagnostic method, comprising:

using one hand to hold and manually actuate a manually-actuated pressure system of a diagnostic device to generate a negative pressure and store the negative pressure in a pressure chamber, and which pulls a sample into a detection zone of a reagent cassette;

performing an assay on the sample in the detection zone to generate data; and

transmitting said data from the diagnostic device to a smart-enabled device via a connection dongle disposed between the diagnostic device and the smart-enabled device while also receiving power for the diagnostic device via said connection dongle.

15. The diagnostic method of claim 14, wherein the manually-actuated pressure system to generate the negative pressure comprises a bulb covering a pressure chamber with a spring therein, wherein said negative pressure is generated by depressing said bulb.

16. The diagnostic method of claim 14, wherein the connection dongle between the diagnostic device and the smart-enabled device comprises an audio jack.

17. The diagnostic method of claim 14, wherein the transmitting said data comprises converting the data via frequency-shift keying for transmission via said connection dongle.

18. The diagnostic method of claim 14 wherein the assay includes at least one of absorbance measurements, immunoassay, colorimetry, and electrochemical detection.

19. The diagnostic method of claim 14, wherein the assay comprises a diagnostic test for at least one of human immunodeficiency virus (HIV), syphilis, anemia, glucose, total protein, and serum iron.

20. The diagnostic method of claim 14, wherein the diagnostic device obtains all of its electrical power requirements via the power received via the connection dongle.

21. The diagnostic method of claim 14, wherein at least three assays for detecting different diseases are simultaneously performed on the sample.

22. The diagnostic method of claim 14, wherein the assay uses gold-labeled IgM antibodies.

23. The diagnostic method of claim 22, further comprising, prior to the performing an assay, lyophilizing the antibodies within the reagent cassette used by the diagnostic device and/or sealing the reagent cassette with a stabilizer and/or anticoagulant.

24. The diagnostic method of claim 14, further comprising adding disease-specific capture proteins on channel walls in the reagent cassette via physisorption.