Biological measurement system

• US 20040161804A1
• Filed: 04/05/2004
• Published: 08/19/2004
• Est. Priority Date: 04/11/2001
• Status: Active Grant

• Current Assignee: Rapid Biosensor Systems Ltd. (Xylem, Inc.)
• Original Assignee: Rapid Biosensor Systems Ltd. (Xylem, Inc.)
• Inventors: Storkey, Matthew Emmanuel Milton, Colby, Edward Grellier, Murray, Nicol John, McCash, Elaine Marie, Wheeler, Gavin Vashon, Stewart, James Neil, Glauser, Antony
• Granted Patent: US 7,384,793 B2
• Time in Patent Office: Days
• US Class Current: 435/7.2
• CPC Class Codes: A61B 5/097 Devices for facilitating collection of breath or for directing breath into or through measuring devices
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: G01N 2001/2244 Exhaled gas, e.g. alcohol detecting
• CPC Class Codes: G01N 2001/247 Syringes
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 2333/35 from Mycobacteriaceae (F)
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 33/5695 Mycobacteria
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

In a biological measurement system (10) for collecting one or more samples of sputum and/or mucus from a patient in the form of an aerosol and for analysing said one or more samples to detect whether or not pathogens are present therein, the one or more samples are in solution within the system (10) and detection of the pathogens is performed using a fluorescently labeled assay. The system (10) is adapted to detect bacterial pathogens using evanescent-wave spectroscopy preferably by using a single-reflective technique. The one or more samples are advantageously provided to the system (10) in aerosol form. However, the system (10) is capable of being adapted for use in analysing samples in liquid form. Methods of analysing said one or more samples in the system (10) are described.

Claims

1. A biological measurement system (10) for measuring the concentration of components included in a sample, the system (10) characterised in that it comprises:

(a) collecting means (30) adapted for collecting the sample in aerosol form;

(b) concentrating means (200, 230, 430) for mechanically collecting the sample from the inside surface of the collecting means;

(c) marking means (1530, 1540) for optically labelling the components present in the concentrated sample; and

(d) interrogating means for optically interrogating the labelled components and thereby generating a measure of the concentration of components present in the sample.

2. A system (10) according to claim 1, wherein the concentrating means further comprises a feature for scraping surfaces where the sample is deposited to spatially concentrate the sample.

3. A system. (10) according to claim 2, wherein the feature is elastically deformable for spreading the spatially concentrated sample over an optical interrogation region whereat the concentrated sample is subjected to optical interrogation.

4. A system (10) according to claim 1, wherein the marking means comprises at least one of a selective binding assay and a competitive displacement assay for optically marking presence of the components by way of fluorescent markers;

the fluorescent markers are bound to antibodies for use in at least one of the selective assay and the competitive assay;

the fluorescent markers comprise fluorophores bound to the antibodies by way of an intermediate carrier such that a plurality of fluorophores are associated with each antibody; and

the intermediate carrier is implemented in the form of latex spheres.

5. A system (10) according to claim 1, wherein the interrogating means comprises an optical evanescent detector (50, 800, 810) for detecting changes in optical response induced by the presence of the components.

6. A system (10) according to claim 5, wherein the evanescent detector includes:

(a) one or more of a diode laser and a LED as a source of interrogating radiation for interrogating the concentrated sample; and

(b) one or more of an avalanche photodiode, a photodiode array and a photomultiplier tube as an optical detector for detecting fluorescent radiation emitted from the concentrated sample in response to optical interrogation of the sample, the optical detector for generating a detection signal indicative of changes in fluorescence from the sample resulting from the presence of the components in the sample.

7. A system (10) according to claim 1, wherein the collecting means (200, 230) is arranged to enclose the sample, whereby preventing personal contact with the sample when the system is in use.

8. A system (10) according to claim 7, wherein the collection means (200, 230) can operate as a single use disposable part.

9. A system (10) according to claim 8, wherein the collecting means comprises features (1000) rendering it substantially unusable after sample collection therein.

10. A system (10) according to claim 1, wherein the collecting means (230) comprises vortex enhancing means (610, 650) for deposition of the sample within the collecting means.

11. A system (10) according to claim 1, wherein the collecting means comprising a filtering means (105;

250) for at least partially inhibiting spread of the components of the sample from the collecting means.

12. A system (10) according to claim 1, wherein the marking means includes lysing means for causing lysis of the components present in the sample, thereby enhancing measurement sensitivity of the system (10) by increasing the number of available potential optical labelling sites.

13. A method of detecting one or more pathogens in one or more samples of the sputum/mucus from a subject using a system as claimed in any one of the preceding claims, the method involving the steps of:

(a) collecting said one or more samples in aerosol form in the collecting means;

(b) spatially concentrating the one or more samples in the concentrating means by mechanically collecting the sample from the inside surface of the collecting means;

(c) optically labelling one or more pathogens present in said-one or more samples;

(d) optically interrogating the pathogens to achieve an optical response; and

(e) determining from the optical response of said one or more samples whether or not said one or more pathogens are present in said one or more samples.

14. A method according to claim 13, wherein the steps (b), (c) and (d), detection of the presence of a pathogen is performed using evanescent-wave spectroscopy.

15. A method according to either one of claims 13 and 14 adapted for the detection of bacteria associated with pulmonary and pulmonary-related infections.

16. A method according to any one of claims 13 to 15, wherein the inhalation of one or more of:

esters, eater vapour, saline vapour, expectorant and menthol is used to assist release of bacteria-containing mucus from the trachea or from the upper lung of a subject being tested.

17. A method according to any one of claims 13 to 15, wherein a partial negative pressure is employed to assist in obtaining said one or more samples in aerosol form.

18. A method according to any one of claims 13 to 17, wherein said one or more samples comprise an aerosol of blood or other bodily fluid or bodily fluid in liquid form.

19. A method according to any one of claims 13 to 18, wherein analysis of said one or more samples is performed using on or both of:

(a) an ELISA chromogenic reaction; and

(b) a surface acoustic wave (SAW) biosensor to detect an antigen in said one or more samples.