Device for rapid detection of tuberculosis-lipoarabinomannan (TB-LAM) with enhanced sensitivity

Patent metadata

Field	Value
Publication number	US-11726078-B2
Application number	US-202017091501-A
Country	US
Kind code	B2
Filing date	Nov 6, 2020
Priority date	Dec 20, 2017
Publication date	Aug 15, 2023
Grant date	Aug 15, 2023

Abstract

A device for rapid detection of a tuberculosis lipoarabinomannan (TB-LAM) is provided. The device includes a pre-concentrator unit for concentrating the TB-LAM comprising: an ion-exchange medium comprising one or more ligands configured to capture the TB-LAM from the source biological sample, wherein the captured-TB-LAM is eluted from the ion-exchange medium as an eluate comprising a concentrated form of TB-LAM; a cassette; a lateral flow assay unit disposed in the cassette; and an integration unit attached to the pre-concentrator unit and the cassette. The integration unit is configured to operatively couple and de-couple the pre-concentrator unit and the cassette. The pre-concentrator unit and the lateral flow assay unit disposed in the cassette are in a fluidic communication in a coupled form. The device for rapid detection of TB-LAM further comprises a dilutor unit.

First claim

The invention claimed is:

1. A method comprising the steps of:
introducing a source biological sample to a detection device, the detection device comprising:
a pre-concentrator unit for concentrating tuberculosis lipoarabinomannan (TB-LAM) comprising:
an ion-exchange medium comprising one or more ligands configured to capture the TB-LAM from the source biological sample, wherein the captured-TB-LAM is eluted from the ion-exchange medium as an eluate comprising a concentrated form of the TB-LAM;

a cassette;
a lateral flow assay unit disposed in the cassette; and
an integration unit attached to the pre-concentrator unit and the cassette at a pivot point,
wherein the integration unit comprises a clamp to hold the pre-concentrator unit, wherein the integration unit is coupled to a lever that is adjacent to the clamp, and wherein the cassette is configured to transition from an uncoupled position to a coupled position via rotation of the integration unit about the pivot point relative to the pre-concentrator unit, wherein the pre-concentrator unit and the lateral flow assay unit disposed in the cassette are in a fluidic communication in the coupled position; and

detecting a presence of the TB-LAM in the source biological sample.

2. The method of claim 1 , further comprising a dilutor unit configured to dilute the source biological sample between 2× to 6× dilution compared to the source biological sample to form a diluted biological sample.

3. The method of claim 2 , wherein the dilutor unit is configured to dilute the source biological sample to 4× dilution compared to the source biological sample to form the diluted biological sample.

4. The method of claim 2 , wherein the dilutor unit and the pre-concentrator unit are operatively coupled to each other.

5. The method of claim 1 , wherein the integration unit is configured to align the pre-concentrator unit and the cassette such that an angle between the pre-concentrator unit and the cassette is between 0 degree to 180 degrees.

6. The method of claim 5 , wherein the integration unit is configured to align the pre-concentrator unit and the cassette such that the angle between the pre-concentrator unit and the cassette is 0 degree.

7. The method of claim 5 , wherein the integration unit is configured to align the pre-concentrator unit and the cassette such that the angle between the pre-concentrator unit and the cassette is 90 degrees.

8. The method of claim 1 , wherein the ion-exchange medium comprises an ion exchange membrane, an ion exchange resin, an ion-exchange matrix, an ion exchange filter, or combinations thereof.

9. The method of claim 1 , wherein the one or more ligands comprise anionic ligands.

10. The method of claim 9 , wherein the anionic ligands are selected from quaternary ammonium ions, dimethyl aminoethyl (DEAE) groups, or a combination thereof.

11. The method of claim 1 , wherein the pre-concentrator unit comprises a column, a syringe, a channel, a filter unit, or a conduit.

12. A method comprising the steps of:
introducing a source urine sample comprising tuberculosis lipoarabinomannan (TB-LAM) to a rapid diagnostic testing device, the rapid diagnostic testing device comprising:
a dilutor unit configured to dilute the source urine sample and form a diluted urine sample;
a pre-concentrator unit configured to concentrate the TB-LAM from the diluted urine sample, comprising:
an ion-exchange medium comprising one or more ligands configured to capture the TB-LAM from the source urine sample, wherein the captured-TB-LAM is eluted from the ion-exchange medium as an eluate comprising a concentrated form of the TB-LAM;
a cassette;
a lateral flow assay unit disposed in the cassette; and
an integration unit attached to the pre-concentrator unit and the cassette, wherein the integration unit comprises a swivel connector coupled to the pre-concentrator unit such that rotation of the pre-concentration unit relative to the cassette causes at least a portion of the pre-concentrator unit to move away from the cassette to transition from an uncoupled position to a coupled position, and
wherein the cassette is configured to transition from the uncoupled position to the coupled position via rotation of the swivel connector to cause the integration unit to move relative to the pre-concentrator unit, and wherein the integration unit operatively provides a fluidic communication from the pre-concentrator unit to the lateral flow assay unit disposed in the cassette when the pre-concentrator unit and the cassette are coupled to each other; and
detecting a presence of the TB-LAM in the source urine sample.

13. The method of claim 12 , wherein the integration unit is configured to align the pre-concentrator unit and the cassette such that an angle between the pre-concentrator unit and the cassette is 0 degree.

14. The method of claim 12 , wherein the integration unit is configured to align the pre-concentrator unit and the cassette such that an angle between the pre-concentrator unit and the cassette is 90 degrees.

15. The method of claim 12 , wherein the ion-exchange medium comprises an ion exchange membrane, an ion exchange resin, an ion-exchange matrix, an ion exchange filter, or combinations thereof.

16. The method of claim 12 , wherein the one or more ligands comprise anionic ligands.

17. The method of claim 16 , wherein the anionic ligands comprise quaternary ammonium ions, dimethyl aminoethyl (DEAE) groups, or a combination thereof.

18. The method of claim 12 , wherein the lateral flow assay unit comprises one or more TB-LAM specific antibodies.

19. The method of claim 18 , wherein the one or more TB-LAM specific antibodies are reporter-linked.

20. The method of claim 12 , wherein the dilutor unit is configured to dilute the source urine sample between 2× to 6× dilution compared to the source urine sample to form the diluted urine sample.

21. The method of claim 1 , wherein the integration unit is rotatably attached to the pre-concentrator unit and the cassette at the pivot point, and wherein the pre-concentrator unit is configured to rotate from the uncoupled position to the coupled position relative to the cassette.

22. The method of claim 1 , wherein the pivot point is a fulcrum configured to rotate such that the integration unit and the cassette are configured to move relative to the pre-concentrator unit.

Assignees

• Gen Electric
• Tokitae Llc

Inventors

• Misner Matthew Jeremiah
• Grossmann Gregory Andrew
• Olsen Cathryn Ellen
• Nelson John Richard
• Moore David Roger
• Smigelski Jr Paul Michael
• Connelly John Thomas
• Grant Benjamin David
• Weigl Bernhard Hans

Classifications

• G01N33/54388

  based on lateral flow · CPC title

• G01N33/493 Primary

  urine · CPC title

• A61B10/007

  for taking urine samples (measuring urological functions A61B5/20; genital receptacles A61F5/451; urinals for bed-ridden persons A61G9/006) · CPC title

• B01D15/08

  Selective adsorption, e.g. chromatography · CPC title

• B01D63/02

  Hollow fibre modules · CPC title