Device, system and method for cancer prognosis and uses thereof

Patent metadata

Field	Value
Publication number	US-10801073-B2
Application number	US-201715674922-A
Country	US
Kind code	B2
Filing date	Aug 11, 2017
Priority date	Feb 12, 2015
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

Abstract

Modules, devices, systems and methods for measuring or detecting cysteine and/or methionine metabolite levels in a sample from a subject are disclosed. Various embodiments of the present invention concern modules, devices, systems and methods for prognosing or diagnosing cancer, for example, prostate, colon, ovarian or breast cancer; predicting the risk or probability of cancer recurrence; and/or for predicting, detecting and/or monitoring cystinuria or cystine stone disease.

First claim

We claim:

1. A system, comprising:
an enzyme reaction module comprising an enzyme reaction chamber comprising at least one inlet and at least one outlet, wherein the enzyme reaction chamber is configured to conduct a fluid flow from the at least one inlet, through the enzyme reaction chamber, to the at least one outlet;
a sequestration-liberation module comprising a sequestration-liberation chamber comprising at least one second inlet and at least one second outlet and having gold particles located therein, wherein the sequestration-liberation chamber is configured to conduct a fluid flow from the at least one second inlet, through the sequestration-liberation chamber, to the at least one second outlet, and further comprising a set of electrodes configured to conduct an electric current through the gold particles; and
a detection module comprising a detection channel comprising at least one third inlet and at least one third outlet, wherein the detection channel is configured to conduct a fluid flow from the at least one third inlet, through the detection channel, to the at least one third outlet, and a first aperture and a second aperture, wherein the detection channel is located between the first and second apertures, and wherein the first and second apertures are configured to conduct a light beam from the first aperture, across the detection channel, to the second aperture; and
wherein the system is configured to conduct a fluid flow from the enzyme reaction module, through the sequestration-liberation module, to the detection module.

2. The system of claim 1 , further comprising a biological sample obtained from a subject, cystathionine synthase, cystathionine lyase, wash or exchange buffer, and detection reagent.

3. The system of claim 1 , wherein the enzyme reaction chamber is shaped as a column having a length of about 1-1000 mm and a diameter of about 0.1-100 mm.

4. The system of claim 2 , wherein the cystathionine synthase and/or cystathionine lyase is immobilized on a solid support.

5. The system of claim 1 , wherein the enzyme reaction module further comprises a filter located before the enzyme reaction chamber along a fluid flow pathway, and configured to filter a biological sample, enzyme, reagent, buffer, fluid flow, and/or reaction mixture.

6. The system of claim 1 , wherein the sequestration-liberation chamber is shaped as a column having a length of about 1-1000 mm and/or a diameter of about 0.1-100 mm.

7. The system of claim 1 , wherein the set of electrodes is configured to apply a voltage of about 1-10V.

8. The system of claim 1 , further comprising a buffer cartridge configured to hold a wash or exchange buffer having a pH of about 8-14, and to supply the wash or exchange buffer to at least one inlet of the sequestration-liberation chamber.

9. The system of claim 1 , wherein the detection channel has a width of about 0.1-1000 mm.

10. The system of claim 1 , wherein the at least one third inlet of the detection channel is configured to receive a detection reagent.

11. The system of claim 1 , wherein the detection module further comprises a third aperture and an optical filter located between the second and third apertures, wherein the second and third apertures are configured to conduct a light beam from the second aperture, across the optical filter which filters the light beam, to the third aperture.

12. The system of claim 11 , wherein the detection module further comprises a light source configured to emit a light beam into the first aperture, and a photosensor configured to detect the light beam transmitted out of the third aperture, the photosensor configured to generate a current or voltage output from detected transmission light.

13. The system of claim 11 , further comprising a spectrometer configured to emit a light beam into the first aperture and to detect transmission light intensity out of the third aperture.

14. A system, comprising:
an enzyme reaction module comprising an enzyme reaction chamber comprising at least one inlet and at least one outlet, wherein the enzyme reaction chamber is configured to conduct a fluid flow from the at least one inlet, through the enzyme reaction chamber, to the at least one outlet;
a sequestration-liberation module comprising a sequestration-liberation chamber comprising at least one second inlet and at least one second outlet, wherein the sequestration-liberation chamber is configured to conduct a fluid flow from the at least one second inlet, through the sequestration-liberation chamber, to the at least one second outlet, gold particles inside the sequestration-liberation chamber, and electrodes configured to conduct an electric current through the gold particles; and
a detection module comprising a detection channel comprising at least one third inlet and at least one third outlet, wherein the detection channel is configured to conduct a fluid flow from the at least one third inlet, through the detection channel, to the at least one third outlet;
a first aperture, a second aperture, a third aperture, and an optical filter, wherein the detection channel is located between the first aperture and the second aperture, wherein the optical filter is located between the second aperture and the third aperture, and wherein the three apertures and the optical filter are configured to conduct a light beam from the first aperture, across the detection channel, to the second aperture, across the optical filter, to the third aperture;
a light source configured to emit a light beam into the first aperture; and
a photosensor configured to detect the light beam transmitted out of the third aperture and to generate a current or voltage output from the detected transmission light; and
wherein the system is configured to conduct a fluid flow from the enzyme reaction module, through the sequestration-liberation module, to the detection module.

15. The system of claim 14 , further comprising a biological sample obtained from a subject, cystathionine synthase, cystathionine lyase, wash or exchange buffer, and detection reagent.

16. The system, comprising according to claim 14 wherein the light source is a spectrometer configured to emit a light beam into the first aperture and detect the transmission light intensity out of the third aperture.

17. A method, comprising:
providing a system of claim 1 ;
supplying a biological sample obtained from a subject, cystathionine synthase, cystathionine lyase, wash or exchange buffer, and detection reagent into the system;
operating the system to generate a current or voltage output; and
using the generated current or voltage output to calculate a cysteine and/or methionine metabolite level in the biological sample.

18. The method of claim 17 , further comprising diagnosing or prognosticating a cancer based on the detected cysteine and/or methionine metabolite level.

19. A method, comprising: providing a system of claim 14 ;
supplying a biological sample obtained from a subject, cystathionine synthase, cystathionine lyase, wash or exchange buffer, and detection reagent into the system; operating the system;
detecting a transmission light intensity out of the third aperture; and using the detected transmission light intensity to calculate a cysteine and/or methionine metabolite level in the biological sample.

20. The method of claim 19 , further comprising diagnosing or prognosticating a cancer based on the detected cysteine and/or methionine metabolite level.

Assignees

• Cedars Sinai Medical Center

Inventors

• Bhowmick Neil A
• Choudhury Diptiman
• Baker Michael J
• Drlik Mark Sasha
• Hansen Bjarne
• Bhowmick Ayon

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• G01N33/575

  for cancer · CPC title

• C12Q1/527 Primary

  involving lyase · CPC title

• G01N2021/7763

  Sample through flow · CPC title

• G01N21/78

  producing a change of colour · CPC title