Diffusion-based system and method for detecting and monitoring activity of biologic and chemical species

• US 20030203504A1
• Filed: 07/09/2002
• Published: 10/30/2003
• Est. Priority Date: 04/26/2002
• Status: Abandoned Application

• Current Assignee: John Hefti
• Original Assignee: John Hefti
• Inventors: Hefti, John
• Application Number:
  US10/064,392
• Publication Number:
  US 20030203504A1
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/0472 Diffusion
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 2035/00207 Handling bulk quantities of analyte
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 7/10 by allowing diffusion of components through a porous wall and measuring a pressure or volume difference
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A diffusion-based method for detecting activity of a biologic or chemical species is described. The method includes supplying the biologic or chemical species to a finite volume diffusion channel having a transport axis. The method further includes supplying a reactive constituent in fluid communication with the biologic or chemical species, whereby the reactive constituent is known or suspected of being reactive to the biologic or chemical species. The method further includes detecting the presence or absence of a diffusion gradient occurring between the biologic or chemical species and the reactive constituent. The presence or absence of the diffusion gradient can then be correlated to the presence or absence of activity of the biologic or chemical species.

Claims

1. A diffusion-based method for detecting the activity of a bio/chemical species, the method comprising:

supplying a bio/chemical species to a finite volume diffusion channel, the finite volume diffusion channel comprising a transport axis;

supplying a reactive constituent in fluid communication to the finite volume diffusion channel, wherein the reactive constituent is known, or suspected of being reactive to the bio/chemical species;

detecting the presence or absence of a diffusion gradient occurring between the bio/chemical species and the reactive constituent; and

correlating the presence or absence of the diffusion gradient to the presence or absence of activity of the bio/chemical species.

2. The method of claim 1, wherein supplying a bio/chemical species to the finite volume diffusion channel comprises supplying a first concentration of the bio/chemical species to the finite volume diffusion channel, and wherein supplying a reactive constituent comprises supplying a second concentration of the bio/chemical species to the finite volume diffusion channel.

3. The method of claim 1, wherein supplying a bio/chemical species to the diffusion channel comprises supplying a population of cells to the finite volume diffusion channel, and wherein supplying a reactive constituent comprises supplying an ionic species to the finite volume diffusion channel.

4. The method of claim 1, wherein supplying a bio/chemical species to the diffusion channel comprises supplying a population of cells to the finite volume diffusion channel, and wherein supplying a reactive constituent comprises supplying small molecules intended for therapeutic purposes to the finite volume diffusion channel.

5. The method of claim 1, wherein supplying a bio/chemical species to the finite volume diffusion channel comprises depositing the bio/chemical species within the finite volume diffusion channel.

6. The method of claim 1, wherein supplying a reactive constituent to the finite volume diffusion channel comprises depositing the reactive constituent within the finite volume diffusion channel.

7. The method of claim 1, wherein detecting a diffusion response comprises:

positioning first and second measurement probes at respective first and second locations along the finite volume diffusion channel; and

measuring an optical or electrical parameter at the first and second measurement probes; and

detecting a difference in the measured optical or electrical parameter.

8. A diffusion-based method for monitoring the activity of a bio/chemical species, the method comprising:

supplying the bio/chemical species to a finite volume diffusion channel, the finite volume diffusion channel comprising a transport axis;

supplying a reactive constituent to the finite volume diffusion channel, wherein the reactive constituent is known or suspect of being reactive to the bio/chemical species;

measuring the diffusion rate of the bio/chemical species or the reactive constituent along the transport axis; and

correlating the diffusion rate of the bio/chemical species or the reactive constituent to activity of the bio/chemical species.

9. The method of claim 8, wherein supplying a bio/chemical species to the finite volume diffusion channel comprises depositing the bio/chemical species within the finite volume diffusion channel.

10. The method of claim 8, wherein supplying a reactive constituent to the finite volume diffusion channel comprises depositing the reactive constituent within the finite volume diffusion channel.

11. The method of claim 8, wherein supplying a bio/chemical species to the diffusion channel comprises supplying a population of cells to the finite volume diffusion channel, and wherein supplying a reactive constituent comprises supplying an ionic species to the finite volume diffusion channel.

12. The method of claim 8, wherein supplying a bio/chemical species to the diffusion channel comprises supplying a population of cells to the finite volume diffusion channel, and wherein supplying a reactive constituent comprises supplying small molecules intended for therapeutic purposes to the finite volume diffusion channel.

13. The method of claim 8, wherein measuring the diffusion rate of the bio/chemical species comprises:

positioning first and second measurement probes at respective first and second locations along the finite volume diffusion channel; and

measuring an optical or electrical parameter at the first and second measurement probes; and

detecting a difference in the measured optical or electrical parameter.

14. A diffusion-based detector configured to detect or monitor the activity of a bio/chemical species, the detector comprising:

a finite volume diffusion channel operable to contain a fluid volume therein, the finite volume diffusion channel comprising a transport axis along which the fluid volume travels, wherein the fluid volume, when present, includes a source constituent comprising either (i) the bio/chemical species or (ii) a reactive constituent known or suspected of being reactive with the bio/chemical species;

a first measurement probe located at a first position along the transport axis and operable to measure the concentration of the source constituent within the fluid volume at the first position; and

a second measurement probe located at a second position along the transport axis and operable to measure the concentration of the source constituent within the fluid volume at the second position,

wherein, activity of the bio/chemical species is indicated if the concentration of the source constituent measured at the first measurement probe differs from the concentration of the source constituent measured at the second measurement probe.

15. The diffusion-based detector of claim 14, wherein the first and second measurement probes are operable to support the propagation of electrical signals.

16. The diffusion-based detector claim 14, wherein the first and second measurement probes are operable to support the propagation of RF frequency signals.

17. The diffusion-based detector claim 14, wherein the first and second measurement probes are operable to support the propagation of optical signals.

18. The diffusion-based detector of claim 14, wherein the finite volume diffusion channel comprises a microfluidic channel.

19. The diffusion-based detector of claim 15, wherein the first and second measurement probes are configured to measure the conductance of the fluid volume at the first and second positions, respectively.

20. A diffusion-based detector configured to detect or monitor the activity of a bio/chemical species, the detector comprising:

a first finite volume diffusion channel operable to contain a fluid volume therein, the finite volume diffusion channel comprising;

a transport axis along which the fluid volume travels, wherein the fluid volume, when present, includes a source constituent comprising either (i) the bio/chemical species or (ii) a reactive constituent known or suspected of being reactive with the bio/chemical species; and

an interaction region disposed within the first finite volume diffusion channel and comprising a sink constituent which is known or suspected of being reactive to the source constituent;

a first measurement probe located at a first position along the transport axis, the first measurement probe operable to measure the concentration of the source constituent within the fluid volume before flow to the interaction region; and

a second measurement probe located at a second position along the transport axis, the second measurement probe operable to measure the concentration of the source constituent within the fluid volume after flow to the interaction region.

21. The diffusion-based detector of claim 20, wherein the first and second measurement probes are operable to support the propagation of electrical signals.

22. The diffusion-based detector claim 20, wherein the first and second measurement probes are operable to support the propagation of RF frequency signals.

23. The diffusion-based detector claim 20, wherein the first and second measurement probes are operable to support the propagation of optical signals.

24. The diffusion-based detector of claim 20, wherein the finite volume diffusion channel comprises a microfluidic channel.

25. The diffusion-based detector of claim 20, wherein the first and second measurement probes are configured to measure an electrical or optical parameter of the fluid volume at the first and second positions, respectively.

26. The diffusion-based detector of claim 20, further comprising a second finite volume diffusion channel intersecting the first finite volume diffusion channel.

27. A multi-cell detector configured to monitor the activity of a bio/chemical species, the multi-cell detector comprising:

a finite volume diffusion channel operable to contain a fluid volume therein, the finite volume diffusion channel comprising a transport axis along which the fluid volume travels, wherein the fluid volume, when present, includes a source constituent comprising either (i) the bio/chemical species or (ii) a reactive constituent known or suspected of being reactive with the bio/chemical species;

a first detector cell formed along a first portion of the finite volume diffusion channel, the first detector cell comprising;

a first interaction region disposed within the first portion of the finite volume diffusion channel and comprising a first sink constituent which is known or suspected of being reactive to the source constituent;

a first measurement probe located at a first position and operable to measure the concentration of the source constituent within the fluid volume before flow to the first interaction region; and

a second measurement probe located at a second position and operable to measure the concentration of the source constituent within the fluid volume after flow to the first interaction region; and

a second detector cell formed along a second portion of the finite volume diffusion channel, the second detector cell comprising;

a second interaction region disposed within the second portion of the finite volume diffusion channel and comprising a second sink constituent which is known or suspected of being reactive to the source constituent;

a first measurement probe located at a first position and operable to measure the concentration of the source constituent within the fluid volume before flow to the second interaction region; and

a second measurement probe located at a second position and operable to measure the concentration of the source constituent within the fluid volume after flow to the second interaction region.