Bio-diagnostic testing system and methods

• US 9,037,209 B2
• Filed: 12/06/2012
• Issued: 05/19/2015
• Est. Priority Date: 12/07/2011
• Status: Active Grant

• Current Assignee: California Institute of Technology, Sanofi
• Original Assignee: California Institute of Technology, Sanofi
• Inventors: Scherer, Axel, Kartalov, Emil P., Brouard, Remi III, Huang, Jingqing
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US13/706,668
• Publication Number:
  US 20130149714A1
• Time in Patent Office: 894 Days
• US Class Current: 600/342
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2560/0233 Optical standards
• CPC Class Codes: A61B 3/10 Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/14507 specially adapted for measuring characteristics of body fluids other than blood devices for taking samples of body liquids A61B10/0045
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1491 Heated applicators
• CPC Class Codes: A61B 5/20 for measuring urological functions restricted to the evaluation of the urinary system A61B5/4375 takes precedence
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 5/42 Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems A61B1/00, A61B5/4857, A61B5/486, A61B5/4866, A61B5/4869 take precedence
• CPC Class Codes: A61B 5/4337 of the vagina
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61B 5/6866 Extracorporeal blood circuits, e.g. dialysis circuits
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence

Abstract

An implantable diagnostic device in accordance with the present disclosure includes a probe assembly that can be implemented in a variety of ways. A few example implementations include: a needle inside which is located a bio-sensor chip (the needle being insertable into a human being); a compact package containing the bio-sensor chip (the compact package configured for placement inside a catheter); or a silicon-based bio-sensor package configured for insertion into a vein.

Claims

1. A bio-diagnostic system comprising:

a probe assembly configured for insertion into an animate object, the probe assembly comprising;

an optical waveguide configured for propagating a light beam;

a circular optical resonator incorporating a capture agent placed upon a binding site that is exposed to a fluid, the circular optical resonator configured to receive at least a portion of the propagated light beam and generate therefrom, a first resonant wavelength when no binding reaction is present at the binding site, and a second resonant wavelength when a binding reaction is present at the binding site, the binding reaction modifying a refractive index of the circular optical resonator;

a heating element configured for heating the binding site; and

a calorimeter for measuring a temperature of the binding site.

2. The bio-diagnostic system of claim 1, wherein the probe assembly is at least one of:

a) a needle comprising a first bio-sensor chip that includes the optical waveguide, the heating element, the calorimeter and the circular optical resonator, b) a catheter comprising a second bio-sensor chip that includes the optical waveguide, the heating element, the calorimeter and the circular optical resonator, or c) a third bio-sensor chip configured for insertion into the vein, the third bio-sensor chip comprising the optical waveguide, the heating element, the calorimeter and the circular optical resonator.

3. The bio-diagnostic system of claim 2, wherein at least one of the needle or the catheter is a part of an intravenous (IV) apparatus.

4. The bio-diagnostic system of claim 2, wherein the needle has a sub-mm diameter.

5. The bio-diagnostic system of claim 4, wherein the fluid is one of:

blood, lymphatic fluid, cerebrospinal fluid, urine, saliva, vaginal fluid, gall, digestive fluid, or ocular fluid.

6. The bio-diagnostic system of claim 4, wherein the probe assembly is configured for detecting an analyte at an in-vivo location, the in-vivo location comprising at least one of:

i) a location inside a blood vessel, ii) a location inside a lymphatic vessel, or iii) a location inside tissue.

7. The bio-diagnostic system of claim 6, wherein the analyte is detected in at least one of:

1) blood flowing in one of a vein or an artery, or

     2) lymphatic fluid in a lymphatic vessel.

8. The bio-diagnostic system of claim 4, further comprising:

a light source for injecting light at near-infrared wavelength into the optical waveguide.

9. The bio-diagnostic system of claim 8, wherein the light source is a near-infrared communications laser, and further wherein each of the first, the second and the third bio-sensor chips further includes a detector for generating a first electrical output signal upon detection of the first resonant wavelength and a second electrical output signal upon detection of the second resonant wavelength.

10. A bio-diagnostic system comprising:

a probe assembly configured for detecting at least one target molecule in a fluid that makes flowing contact with the probe assembly, the probe assembly comprising;

an optical waveguide configured for propagating a light beam;

a circular optical resonator incorporating a capture agent placed upon a binding site that is exposed to the at least one target molecule, the circular optical resonator configured to receive at least a portion of the propagated light beam and generate therefrom, a first resonant wavelength when no binding reaction is present at the binding site, and a second resonant wavelength when a binding reaction is present at the binding site, the binding reaction modifying a refractive index of the circular optical resonator;

a heating element configured for heating the binding site; and

a calorimeter for measuring a temperature of the binding site.

11. The bio-diagnostic system of claim 10, wherein the probe assembly includes at least one of:

a) a needle comprising a first bio-sensor chip that includes the optical waveguide, the heating element, the calorimeter and the circular optical resonator, b) a catheter comprising a second bio-sensor chip that includes the optical waveguide, the heating element, the calorimeter and the circular optical resonator, or c) a silicon-based probe assembly configured for insertion into the vein, the silicon-based probe assembly comprising the optical waveguide, the heating element, the calorimeter and the circular optical resonator.

12. The bio-diagnostic system of claim 10, further comprising:

a light source for injecting light at near-infrared wavelength into the optical waveguide.

13. The bio-diagnostic system of claim 12, wherein the at least one molecule is a short-lived molecule present in at least one of:

a) blood, or b) a dialysate.

14. The bio-diagnostic system of claim 13, wherein the probe assembly is incorporated into a catheter that is a part of at least one of:

a) an intravenous (IV) system, or b) a dialysis apparatus.

15. The bio-diagnostic system of claim 12, wherein the probe assembly is configured as one of:

a) a needle, b) a catheter, or c) an object that is insertable onto a tube transporting the fluid.

16. A method of using a bio-diagnostic system, comprising:

inserting a first probe assembly into at least one of;

a) a first conduit that is propagating a fluid containing at least one target molecule, or b) an animate object, the first probe assembly comprising a bio-sensor chip incorporating an optical waveguide and a circular optical resonator containing a capture agent placed at a binding site in the circular optical resonator;

heating the binding site;

deriving thermal characteristics of the at least one target molecule;

propagating light through the optical waveguide;

coupling at least a portion of the light from the optical waveguide into the circular optical resonator;

generating in the circular optical resonator, a first resonant wavelength when no binding reaction is present at the binding site;

generating in the circular optical resonator, a second resonant wavelength when a refractive index of the circular optical resonator is modified as a result of a first binding reaction at the binding site, the first binding reaction characterized by the at least one target molecule binding to the capture agent; and

deriving information pertaining to the at least one target molecule upon detecting the change from the first resonant wavelength to the second resonant wavelength.

17. The method of claim 16, wherein the first conduit is a first tube of a dialysis apparatus, and further comprising:

inserting a second probe assembly into a second tube of the dialysis apparatus;

deriving information pertaining to another at least one target molecule propagating through the second tube; and

analyzing the fluid by using at least one of a) the derived information pertaining to the at least one target molecule, or b) the derived information pertaining to the another at least one target molecule.

18. The method of claim 16, wherein the first probe assembly is incorporated into a catheter, and inserting the first probe assembly into the animate object comprises inserting a portion of the catheter into at least one of:

a) a peritoneal cavity of an animal, or b) a rectouterine pouch of the animal.

19. The method of claim 18, further comprising:

retaining the portion of the catheter in the one of the peritoneal cavity or the rectouterine pouch for over a day.

20. The method of claim 19 wherein the portion of the catheter is retained in the one of the peritoneal cavity or the rectouterine pouch for at least one year.

21. The method of claim 16, wherein the first conduit is one of a) a vein propagating blood or b) a tube propagating an intravenous (IV) fluid.

22. The method of claim 21, wherein deriving information pertaining to the at least one target molecule comprises deriving information pertaining to a plurality of different types of target molecules.

23. The method of claim 21, wherein deriving information pertaining to the at least one target molecule comprises information pertaining to only a first type of target molecule.

24. The method of claim 21, further comprising:

heating the binding site to desorb the at least one target molecule from the capture agent and prepare the binding site for a second binding reaction.

25. The method of claim 16, wherein heating the binding site and deriving thermal characteristics comprise heating the binding site over a period of time for deriving thermal characteristics over the period of time.