SINGLE-CHANNEL, HYBRID BIOSENSOR AND SENSOR SYSTEM INCLUDING THE SAME

• US 20190321818A1
• Filed: 04/19/2019
• Published: 10/24/2019
• Est. Priority Date: 04/19/2018
• Status: Active Grant

• Current Assignee: Korea University Research and Business Foundation
• Original Assignee: Korea University Research and Business Foundation
• Inventors: PAEK, Se-Hwan
• Granted Patent: US 11,154,857 B2
• Time in Patent Office: Days
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 2201/0221 Portable; cableless; compact; hand-held
• CPC Class Codes: G01N 2333/76 Assays involving albumins other than in routine use for blocking surfaces or for anchoring haptens during immunisation
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 33/523 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/54306 Solid-phase reaction mechanisms
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin

Abstract

A single-channel, chemical-immunological hybrid biosensor is disclosed. According to an embodiment, the hybrid biosensor includes a reaction strip 100 in the form of a porous membrane through which a sample 1 moves by capillary action. the reaction strip 100 is in the form of a porous membrane through which the sample 1 moves by capillary action. Biomarkers in the sample 1 are independently detected based on a chemical reaction and binding reactions on the reaction strip 100.

Claims

1. A single-channel, chemical-immunological hybrid biosensor comprising a reaction strip in the form of a porous membrane through which a sample moves by capillary action wherein the reaction strip comprises:

a sample transfer pad having a predetermined length and along which the sample is transferred from one end to the other in the lengthwise direction;

one or more immuno-reaction zones comprising capture recognition elements specifically binding to binding reaction markers in the sample to generate first reaction signals on the sample transfer pad; and

at least one chemical reaction zone comprising a matrix to supply substrate(s) chemically reacting with a chemical reaction marker in the sample to generate a second reaction signal, where the sample is received in a manner that is spatially separated from the sample transfer pad and, thus, the chemical reaction occurs independently from the binding reactions.

2. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the sample is blood, one of the binding reaction markers is glycated hemoglobin (HbA1c), the chemical reaction marker is total hemoglobin, and the ratio of the concentration of the glycated hemoglobin analyzed as the first reaction signal to the concentration of the total hemoglobin analyzed as the second reaction signal (“

% HbA1c”

) is used to diagnose diabetes.

3. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the sample is blood, one of the binding reaction markers is glycated albumin, the chemical reaction marker is total albumin, and the ratio of the concentration of the glycated albumin analyzed as the first reaction signal to the concentration of the total albumin analyzed as the second reaction signal (“

% glycated albumin”

) is used to diagnose diabetes.

4. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the matrix comprises a signal-generating substrate that directly chemically reacts with the chemical reaction marker to generate the second reaction signal.

5. The single-channel, chemical-immunological hybrid biosensor according to claim 4, wherein the sample is blood, the chemical reaction marker is total albumin, and the signal-generating substrate is bromocresol green (BCG) or bromocresol purple (BCP) that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

6. The single-channel, chemical-immunological hybrid biosensor according to claim 4, wherein the sample is blood, the chemical reaction marker is total hemoglobin, and the signal-generating substrate is Triton X-100 or sodium lauryl sulphate (SLS) that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

7. The single-channel, chemical-immunological hybrid biosensor according to claim 4, wherein the matrix comprises a pre-reactive substrate chemically reacting with the chemical reaction marker to produce an intermediate and the signal-generating substrate chemically reacts with the intermediate to generate the second reaction signal.

8. The single-channel, chemical-immunological hybrid biosensor according to claim 7, wherein the sample is blood, the chemical reaction marker is total hemoglobin, the pre-reactive substrate is potassium ferricyanide (K₃Fe(CN)₆), and the signal-generating substrate is potassium cyanide (KCN) that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

9. The single-channel, chemical-immunological hybrid biosensor according to claim 7, wherein the sample is blood, the chemical reaction marker is total hemoglobin, the pre-reactive substrate is sodium nitrite (NaNO₂), and the signal-generating substrate is sodium azide (NaN₃) that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

10. The single-channel, chemical-immunological hybrid biosensor according to claim 7, wherein the sample is blood, the chemical reaction marker is total hemoglobin, the pre-reactive substrate is hydrogen peroxide (H₂O₂), and the signal-generating substrate is luminol that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

11. The single-channel, chemical-immunological hybrid biosensor according to claim 7, wherein the sample is blood, the chemical reaction marker is total albumin, the pre-reactive substrate comprises at least one of methoxy-N-methyl phenazinium methyl sulphate and dithiothreitol, and the signal-generating substrate is 2-(2′

-benzothiazolyl)-5-styryl-3-phthalhydrazidyl)-tetrazolium chloride (BSPT) that generates the second reaction signal suitable as a chromogenic signal for the diagnosis of diabetes.

12. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the reaction strip further comprises at least one chemical reaction pad through which the sample is supplied to the chemical reaction zone;

and the chemical reaction zone is arranged on one side of the chemical reaction pad.

13. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the number of the immuno-reaction zones is two or more and the capture recognition elements react with the corresponding binding reaction markers in a one-to-one relationship in the immuno-reaction zones.

14. The single-channel, chemical-immunological hybrid biosensor according to claim 1, wherein the reaction strip further comprises a sample absorption pad arranged at the other end of the sample transfer pad to absorb the sample transferred along the sample transfer pad.

15. The single-channel, chemical-immunological hybrid biosensor according to claim 1, further comprising a sample addition pad absorbing the sample loaded from the outside;

and a conjugate pad comprising detection elements specifically binding to the binding reaction markers in the sample and a signal generator to be conjugated with the detection elements, and connecting one end of the sample transfer pad to the sample addition pad, wherein the signal generator generates the first reaction signals when the detection elements, the binding reaction markers, and the capture recognition elements bind together.

16. The single-channel, chemical-immunological hybrid biosensor according to claim 15, wherein the conjugate pad is disposed on one end of the sample transfer pad and the sample addition pad is disposed on the conjugate pad.

17. The single-channel, chemical-immunological hybrid biosensor according to claim 1, further comprising:

a sample addition pad absorbing the sample loaded from the outside and connected to one end of the sample transfer pad;

a signal-generating substrate addition pad arranged adjacent to one side of the sample transfer pad and supplying a signal-generating substrate to the sample transfer pad where the signal-generating substrate reacts with reaction complexes formed by binding reactions between the binding reaction markers and the capture recognition elements to generate the first reaction signals; and

a signal-generating substrate absorption pad adjacent to the other side of the sample transfer pad to absorb the signal-generating substrate transferred across the sample transfer pad.

18. The single-channel, chemical-immunological hybrid biosensor according to claim 1, further comprising a cartridge having an accommodation space in which the reaction strip is arranged, a detection window through which the immuno-reaction zones and the chemical reaction zone are exposed, and a sample injection hole through which the sample is loaded into the sample addition pad.

19. A sensor system comprising:

the single-channel, chemical-immunological hybrid biosensor according to claim 1, a smart device in which a camera is accommodated to capture chromogenic signals and/or luminescent signals from the single-channel, chemical-immunological hybrid biosensor as an image; and

a smart device holder having a slot into which the single-channel, chemical-immunological hybrid biosensor is inserted and adapted to hold the smart device.

20. The sensor system according to claim 19, further comprising a light source arranged in the smart device holder to emit light.

21. The sensor system according to claim 19, wherein the captured signal image is converted into digital data by an application on the smart device.

22. The sensor system according to claim 19, further comprising a focusing lens arranged between the camera and at least one of the immuno-reaction zones and the chemical reaction zone to control the focal distance of the camera.

23. A sensor system comprising the single-channel, chemical-immunological hybrid biosensor according to claim 1 and a CMOS image sensor (CIS) capable of capturing chromogenic signals and/or luminescent signals from the single-channel, chemical-immunological hybrid biosensor as an image.