Devices, systems and methods to detect viable infectious agents in a fluid sample and susceptibility of infectious agents to anti-infectives

• US 10,174,356 B2
• Filed: 04/07/2017
• Issued: 01/08/2019
• Est. Priority Date: 05/31/2016
• Status: Active Grant

• Current Assignee: Avails Medical, Inc.
• Original Assignee: Avails Medical, Inc.
• Inventors: Knopfmacher, Oren S., Herget, Meike, Laufer, Michael D., Estabrook, August
• Primary Examiner(s): Wecker, Jennifer
• Application Number:
  US15/482,307
• Publication Number:
  US 20170342459A1
• Time in Patent Office: 641 Days
• CPC Class Codes: A61B 5/00 Measuring for diagnostic purposes radiation diagnosis A61B6/00; diagnosis by ultrasonic, sonic or infrasonic waves A61B8/00; Identification of persons
• 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: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/025 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics antimicrobial activity C12Q1/18
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: G01N 27/27 Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

Various devices, systems and methods for detecting infectious agents or determining a susceptibility of an infectious agent to an anti-infective are described herein. One example method comprises introducing a fluid sample to a surface; exposing the surface to a solution; sampling the solution after exposing the solution to the surface; and detecting a change in an electrical characteristic of a sensing device exposed to the solution sampled corresponding to a presence of the infectious agent in the fluid sample.

Claims

1. A method of assessing a susceptibility of an infectious agent to an anti-infective, the method comprising:

introducing a fluid sample to a first surface and a second surface;

exposing the first surface comprising the infectious agent to a first solution;

exposing the second surface comprising the infectious agent to a second solution, wherein at least one of the second surface and the second solution comprises an anti-infective;

sampling the first solution after exposing the first solution to the first surface;

sampling the second solution after exposing the second solution to the second surface;

monitoring a first electrical characteristic of a first sensing device exposed to the first solution sampled;

monitoring a second electrical characteristic of a second sensing device exposed to the second solution sampled; and

comparing the first electrical characteristic, including a change in the first electrical characteristic, with the second electrical characteristic, including any changes in the second electrical characteristic, wherein any differences between the first electrical characteristic and the second electrical characteristic, or lack thereof, is used to assess the susceptibility of the infectious agent to the anti-infective.

2. The method of claim 1, wherein the first sensing device is a first electrochemical cell and monitoring the first electrical characteristic comprises:

determining a first voltage change at a first functionalization layer exposed to the first solution sampled, wherein the first voltage change is with respect to a voltage at a first reference electrode also exposed to the first solution sampled and the first functionalization layer covers a first working electrode of the first electrochemical cell; and

wherein the second sensing device is a second electrochemical cell and monitoring the second electrical characteristic comprises;

determining a second voltage change at a second functionalization layer exposed to the second solution sampled, wherein the second voltage change is with respect to a voltage at a second reference electrode also exposed to the second solution sampled and the second functionalization layer covers a second working of the second electrochemical cell.

3. The method of claim 1, wherein the first reference electrode is a first on-chip reference electrode separated by a first insulator from the first working electrode and the second reference electrode is a second on-chip reference electrode separated by a second insulator from the second working electrode.

4. The method of claim 1, further comprising adding a known concentration of glucose to the first solution before sampling the first solution and adding the same known concentration of glucose to the second solution before sampling the second solution.

5. The method of claim 4, wherein the first sensing device is a first glucose sensor and the second sensing device is a second glucose sensor.

6. The method of claim 5, wherein the first glucose sensor comprises a first working electrode, a first reference electrode, and a first counter electrode.

7. The method of claim 5, wherein the second glucose sensor comprises a second working electrode, a second reference electrode, and a second counter electrode.

8. The method of claim 5, wherein comparing the first electrical characteristic and the second electrical characteristic includes determining a difference between the first electrical characteristic and the second electrical characteristic and wherein the difference between the first electrical characteristic and the second electrical characteristic is a result of a difference in the concentration of glucose in the first solution sampled and the concentration of glucose in the second solution sampled.

9. The method of claim 1, wherein the first sensing device is a first light-addressable potentiometric (LAP) sensor and monitoring the first electrical characteristic comprises:

applying a first bias voltage via a first reference electrode of the first LAP sensor exposed to the first solution sampled;

directing a first modulated light at a first semiconductor layer of the first LAP sensor;

detecting a first photocurrent using a first ammeter coupled to the first LAP sensor; and

determining a first voltage change at a first functionalization layer of the first LAP sensor exposed to the first solution sampled.

10. The method of claim 1, wherein the second sensing device is a second LAP sensor and monitoring the second electrical characteristic comprises:

applying a second bias voltage via a second reference electrode of the second LAP sensor exposed to the second solution sampled;

directing a second modulated light at a second semiconductor layer of the second LAP sensor;

detecting a second photocurrent using a second ammeter coupled to the first LAP sensor; and

determining a second voltage change at a second functionalization layer of the second LAP sensor exposed to the second solution sampled.

11. The method of claim 1, wherein the first surface is a filter surface or a well surface.

12. The method of claim 11, wherein the second surface is separated from the first surface and is another instance of the filter surface or the well surface.

13. The method of claim 1, wherein at least one of the first surface and the second surface is a high-capacity filter.

14. The method of claim 1, wherein at least one of the first surface and the second surface comprises pores of a similar pore size.

15. The method of claim 1, further comprising trapping the infectious agent on the first surface and the second surface and preventing the infectious agent from contacting the first sensing device and the second sensing device.

16. The method of claim 1, wherein comparing the first electrical characteristic and the second electrical characteristic includes determining a difference between the first electrical characteristic and the second electrical characteristic and wherein the difference between the first electrical characteristic and the second electrical characteristic is a result of a difference in a solution characteristic of the first solution and the second solution.

17. The method of claim 16, wherein the difference in the solution characteristic of the first solution and the second solution is a difference in at least one of a molecular count, a concentration of an ion, and a solution temperature.

18. The method of claim 1, wherein the infectious agent is a bacteria, a fungus, a virus, or a prion.

19. The method of claim 1, wherein at least one of the first sensing device and the second sensing device is housed by a protective chamber and the protective chamber is at least one of an electrically isolated environment, a temperature-controlled chamber, and a light controlled chamber.

20. The method of claim 1, further comprising directing the first solution to the first surface or directing the second solution to the second surface using a pump.