New! View global litigation for patent families

WO2007089540A2 - Handheld raman body fluid analyzer - Google Patents

Handheld raman body fluid analyzer

Info

Publication number
WO2007089540A2
WO2007089540A2 PCT/US2007/002062 US2007002062W WO2007089540A2 WO 2007089540 A2 WO2007089540 A2 WO 2007089540A2 US 2007002062 W US2007002062 W US 2007002062W WO 2007089540 A2 WO2007089540 A2 WO 2007089540A2
Authority
WO
Grant status
Application
Patent type
Prior art keywords
raman
sample
body
fluid
radiation
Prior art date
Application number
PCT/US2007/002062
Other languages
French (fr)
Other versions
WO2007089540A3 (en )
Inventor
Richard H. Clarke
E. Edward Womble
Original Assignee
Prescient Medical, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65Raman scattering
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65Raman scattering
    • G01N21/658Raman scattering enhancement Raman, e.g. surface plasmons
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/84Systems specially adapted for particular applications
    • G01N21/8483Investigating reagent band
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0295Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65Raman scattering
    • G01N2021/653Coherent methods [CARS]
    • G01N2021/656Raman microprobe

Abstract

Methods and apparatus for in vitro detection of an analyte in a body fluid sample using low resolution Raman spectroscopy are disclosed. The body fluid analyzer includes a disposable strip for receiving a sample of body fluid on a target region, the target region including gold sol-gel to provide surface enhanced Raman scattering. A light source irradiates the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation that is separated into different wavelength components by a dispersion element. A detection array detects at least some of the wavelength components of the scattered light and provides data to a processor for processing the data. The results of the processed data are displayed on a screen to inform a user about an analyte within the body fluid sample.

Description

HANDHELD RAMANBODYFLUID ANALYZER

[001] This application claims priority to U.S. application serial no. 10/905,956 filed January 27, 2005, which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

[002] The present invention generally relates to methods and apparatus for testing biological samples, and in particular, to systems for in vitro testing of body fluid samples for analytcs, such as glucose.

BACKGROUND OF THE INVENTION

[003] The ability to monitor an analyte within a blood sample has greatly improved the diagnosis and treatment of diseases such as diabetes. For example, home monitors allow diabetics to test glucose levels by pricking their finger and applying a small sample of blood to a test strip. Based on the glucose reading, diet and/or insulin dosage can be adjusted.

[004] Generally, these home glucose monitor systems use an electrochemical detection technique based on glucose oxidase reactions. The system can include a disposable strip having electrodes and the glucose oxidase enzyme. When a blood drop is applied to the target area of the electrode, the glucose oxidase catalyzes the oxidation of glucose in the drop to produce gluconic acid. During the reaction, electrons are transferred by an electrochemical mediator to the electrode surface. This in turn generates a current that is measured by the sensor. The amount of current generated is proportional to the amount of glucose present in the blood drop, thus giving an accurate reading of the blood glucose concentration.

[005] While the ease of use and the low cost of these home monitor systems have proven helpful for regular blood sugar monitoring, they are limited by the amount of information that can be provided using a glucose oxidase reaction. Information on other substances within the blood is not readily available without incorporation of additional reagents and assays.

[006] Spectroscopic approaches to glucose monitoring have also been suggested. In one such approach, laser light is directed through or into a portion of a patient's skin and reflectance or scattered light is captured by a detector. A spectroscopic measurement of the blood glucose level is then obtained from the detected light. This method has met with limited success because of the cost, complexity, and difficulty of transdermal monitoring. [007] For these reasons, there continues to exist a need in this art for better devices and methods for testing blood and other body fluid samples.

SUMMARY OF THE INVENTION

[008] The present invention provides methods and apparatus for in vitro detection of analytes in a body fluid sample using Raman spectroscopy, such as low resolution Raman spectroscopy. The apparatus may, for example, be a low-resolution Raman spectroscopy system that employs a multimode laser source for radiating a sample and producing a Raman spectrum consisting of scattered electromagnetic radiation. The radiation is then separated into different wavelength components by a low resolution dispersion element and detected by a detection array. Data from the array is processed by a processor to provide information about one or more analytes.

[009] In one aspect of the invention, the handheld Raman analyzer can provide information about multiple analytes. For example, the analytes can include glucose plus at least one additional analyte selected from the group consisting of insulin, hemoglobin, cholesterol, electrolytes, antioxidants, nutrients, and other body fluid components. Other analytes that can be detected and/or monitored with the present invention include, but are not limited to, drugs such as therapeutic drugs (prescription or over-the-counter) or drugs of abuse (such as illicit drugs), metabolites of drugs (such as therapeutic drugs or drugs of abuse), alcohol, poisons, enzymes, hormones (natural or synthetic/artificial, such as, peptide hormones and steroids), cytokines, disease markers such as but not limited to tumor or cancer markers, and other body fluid components.

[0010] In another aspect, a system is disclosed including a disposable test strip that provides surface enhanced Raman Scattering (SERS). In one embodiment, the test strip can include a metallic surface or a surface that includes metallic (e.g., silver or gold) particles. One embodiment is a test strip with a sample-receiving region that includes gold nanoparticles stabilized in a porous sol-gel silicate.

[0011] In another aspect, the present invention includes a method for analyzing body fluid samples including providing a disposable strip for receiving a sample of body fluid on a target region and depositing the sample on the target region of the disposable strip. The target area is then irradiated with a laser to produce a Raman spectrum consisting of scattered electromagnetic radiation which is separated into different wavelength components using a low resolution dispersion element. At least some of the wavelength components are detected using a detection array and the resulting data is processed by a processor to assess an analyte within the body fluid sample. Results from the processor may optionally be displayed on a screen.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings:

[0013] FIG. 1 is a top view of a handheld Raman body fluid analyzer according to the present invention;

[0014] FIG. 2 is a schematic illustration of another embodiment of the present invention;

[0015] FIG. 3 is a schematic illustration of yet another embodiment of the present invention; and

[0016] FIG. 4 is a test strip of the present invention including a surface enhanced Raman spectrometry material.

DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention generally relates to a system for in vitro detection of one or more analytes in a body fluid sample, such as blood, urine or saliva, using Raman spectroscopy, such as low resolution Raman spectroscopy. The system may include a disposable strip for receiving a sample of body fluid on a target region and a laser for irradiating the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation. For low-resolution Raman spectroscopy, a low resolution dispersion element, positioned to receive the scattered radiation, preferably separates the radiation into different wavelength components, and at least some of the wavelength components are then detected by a detection array. Data from the detection array is passed to a processor for processing the data to evaluate an analyte within the body fluid sample. The system can also evaluate multiple analytes within the body fluid sample.

[0018] While conventional glucose monitors have improved home monitoring of blood glucose levels, such electrochemical devices fail to inform the user about other important substances within the blood. Testing of other analytes can be performed in medical laboratories, but at significant time and expense. The present invention overcomes these drawbacks by using Raman spectroscopy, such as low resolution Raman spectroscopy, in a portable apparatus, such as a handheld device, to detect analytes within a body fluid sample. The handheld device of the present invention provides a cost efficient method for testing multiple analytes in a single sample.

[0019] FIG. 1 illustrates one embodiment of the handheld Raman device 10 of the present invention including a sampling area 12 containing a target area 16, on test strip 14, for receiving a body fluid sample. Spectroscopic components 18, preferably positioned within device 10, produce radiation and provide spectroscopic measurements of the body fluid sample. Results from the spectroscopic analysis can be shown on screen 20.

[0020] A more detailed example of spectroscopic components 18 is provided in FIG. 2, which shows a low-resolution Raman spectroscopy apparatus that includes a multi-mode laser source 22 and optical fiber 24 connected to the laser source for carrying laser light to the sampling site. Relay optics 26 can optionally be used with the optical fiber to focus and direct the radiation. A person skilled in the art will appreciate that optical fiber 24 may include a variety of optical fibers and light carrying materials that can collect and direct radiation.

[0021] Light is preferably directed by optical fiber 24 to the sampling area 12, and after encountering the body fluid sample, is returned in a second optical fiber 28. The returned radiation is directed through dispersion element 30 that serves to disperse the scattered light into different wavelength components. The dispersed scattered light is detected by photodetector array 32 that, in this case, consists of a photodiode array or a charged-coupled device (CCD) array. The signals generated by detector array 32 in response to the scattered light are then sent to a microprocessor 34 for analysis.

[0022] The present invention allows specific spectral bands of interest to be measured at low resolution to obtain the integrated band intensities. These bands can be narrow ones. The resolving power of the dispersion device 30 determines the position of specific wavelengths in the diode array in such a way that the signal from a particular diode in the array will typically correspond to the same (or a similar) narrow range of wavelengths. This combination of the low-resolution dispersion device 30 and the diode array photodetector 32 thus form a spectrometer. The microprocessor 34 selects a particular diode (or diodes) of the array 32 according to the property to be measured. The integrated signals lying in the two ranges can be arithmetically divided to form intensity ratios. The microprocessor 34 compares these ratios with known values or a correlating function to obtain an estimate of the chemical constituent or property of interest. In addition, the microprocessor can analyze multiple analytes within a single sample in a single test. In one embodiment, the procedure is repeated for a second analyte by choosing the appropriate diode(s) for the additional analyte. The processor can also run these calculations in series using stored information from the diodes.

[0023] The terms "radiation", "laser" and "light" are herein utilized interchangeably. In particular, the term "light" can refer to radiation having wavelength components that lie in the visible range of the electromagnetic spectrum, or outside the visible range, e.g., the infrared or ultraviolet range of the electromagnetic .spectrum. In certain embodiments of Raman spectroscopy, the preferred excitation wavelengths will range from about 700 nanometers to 2.5 micrometers. Although this portion of the electromagnetic spectrum is commonly known as infrared (IR) radiation, the term "light" will be used as a shorthand expression in describing the path of this radiation as well as the various wavelengths of radiation induced by Raman scattering and collected for analysis.

[0024] Advances in the field of solid-state lasers have introduced several important laser sources into Raman analysis. For high-resolution Raman systems the laser linewidth must be severely controlled, often adding to the cost of the excitation source and the system as a whole. For low resolution Raman spectroscopy (LRRS), however, the strategy of relinquishing resolution details in favor of emphasizing essential identifying spectral features, allows the use of a low cost, high energy multi-mode laser and a low resolution dispersion element. A multi-mode laser which can be used with a LRRS system, according to one embodiment of the present invention, is available in higher power ranges (between 50 mw and 1000 mw) than is available with a traditional single mode laser (<150 milliwatts). The higher power of a multi-mode laser increases the amount of scattered radiation available to the spectrometer system and the sensitivity of the LRRS system increases at least linearly with laser power.

[0025] A low resolution dispersion element can provide greater transmission of scattered radiation to the detector array. For example, a low resolution diffraction grating with wider slits than a typical diffraction grating can be used, providing greater transmission of incident scattered radiation to the detector array. Thus, the combination of a low cost, high energy multi-mode laser and a low loss dispersion element provides an inexpensive LRRS system with a high intensity signal.

[0026] In a typical LRRS application the need for feature separation is much like that encountered in mid-IR spectroscopy. The use of multi-mode lasers causes degradation in the resolution of the spectrometer. The resolution of the LRRS system decreases primarily because the width of the laser line used to excite the sample is much larger with multi-mode lasers than it is with a single mode laser. A multi-mode laser may have a linewidth of about 2-3 nanometers, generally on the order of one or more nanometers. In comparison, a single mode laser has a linewidth of a fraction of a nanometer. However, one rarely requires single wavenumber resolution to find a spectral fingerprint feature that allows identification and quantification of a sample under analysis. Similarly, in LRRS, since the approach uses fundamental frequencies, even if not fully resolved, in the spectral analysis, a broader band laser source may suffice for the Raman analysis. In this case inexpensive, multi-mode solid- state laser sources are both sufficient for the task and provide cost effective high power.

[0027] Since a Raman measurement is the difference in wavelength between the scattered light and the excitation line, an excitation line that has a larger spectral FWHM causes a proportional loss of resolution in the resulting Raman measurement. However, this reduction of resolution is offset by the advantages of lower cost and increased signal intensity. The increased signal intensity is a result of a higher energy laser source and wider slits in the diffraction grating allowing more light into the detector array. Since the spectrometer system resolution has been substantially reduced by the use of a multi-mode laser, the width of the slits can be increased with a negligible effect on resolution. In addition, a CCD detector array can be matched to the lower resolution laser source and the dispersion element by reducing the number of elements in the array. For example, instead of 4096 array elements, one can use 2048 larger elements.

[0028] Thus, a complete LRRS spectroscopic system can consist of an inexpensive multi- mode laser diode operating at a higher power (between 50 mw and 1000 mw output) than traditional single-mode Raman sources and a low resolution monochromator matched to a simple CCD detector, with Rayleigh filtering provided by edge or notch filters capable of removing the excitation source background. [0029] Various multi-mode laser components can be used with the device of the present invention. For example, the B&W Tck multi-mode laser BWF-OEM-785-0.5, available from B&W Tek, Inc., of Newark, DE., can be used as the multi-mode laser. The optical fibers utilized in the present invention apparatus of the invention are preferably multimode fibers, which are available from several commercial sources including, for example, Fiberguide, Inc. of Sterling, NJ. Their diameters may range from lμm to 1000 μm, preferably from about 100 μm to about 400 μm, and more preferably from about 100 μm to about 200 μm. Single fibers and fiber bundles can also be utilized in the present invention. In addition, various low resolution monochromators can be used as detector arrays. For example, Ocean Optics S- 1000 and S-2000 monochromators are commercially available from Ocean Optics of Dunedin, FIa. Optical filters can be used to eliminate the Rayleigh line.

[0030] The microprocessor used with the device of the present invention can include any computer with sufficient storage capacity and processing capability to house a library of body fluid components for matching and quantifying. An exemplary microprocessor is the Compaq iPAQ from the Hewlett-Packard Company.

[0031] The device of the present invention can include a number of other features that can assist with analyzing samples in the sampling area. In one embodiment, sampling area 12 includes an optical assembly 40 as illustrated schematically in FIG. 3. Optical assembly 40 directs the light received from spectroscopic components 18 into position for contacting the sample, collects the scattered radiation, and returns the collected radiation for analysis.

[0032] Excitation radiation enters optical assembly 40 via optical fiber 24. The beam from the input fiber is passed through lens 42, which serves to collimate or otherwise project the incoming radiation along beam path 44 with minimal dispersion. The radiation from lens 42 then passes through an optional safety switch including chamber 46 and through one or more optional filters 48, e.g., a low-pass filter.

[0033] The filtered incoming light is then reflected by dichroic beam-splitter 50 (which is designed to reflect nearly all of the excitation light) and directed toward target area 16. A second lens 52 can be disposed to focus the excitation radiation to a particular point or region within a sample 54. Preferably, lens 52 focuses the light on target area 16.

[0034] Returning radiation 56 passes through lens 52, which now serves to collimate the scattered radiation and convey it to collection fiber 28. From lens 52, the collected radiation travels along beam path 58, passing through dichroic beam-splitter 50 and, optionally, a mid- pass or long-pass filter 60 and lens 62. Lens 62 serves to focus the collected radiation into output fiber 28. (It should be appreciated that the lens elements of the present invention can be simple or compound lens assemblies and that the functions that these optical elements perform — directing excitation radiation into a sample and collecting scattered radiation for analysis — can be achieved by various equivalent structures, such as those known to ones skilled in the art.)

[0035] Optical assembly 40 can further include a "beam dump" 64 to capture and absorb incoming radiation that is not reflected by dichroic beam-splitter 50. Beam dump 64 can comprise a chamber that has been coated with suitable radiation absorbing material or otherwise formed or shaped to ensure that the radiation that is not directed into the sampling tube is captured and dissipated as heat.

[0036] Safety switch 66 is formed by a protective shutter, as shown in FIG. 3, that is disposed in chamber 46. Chamber 46 intersects incoming beam path 44. Plunger 68 is disposed within chamber 46 and operatively connected to spring 70 and solenoid 72. In an activated state, solenoid 72 pulls plunger 68 out of light beam path 44, thereby allowing the multimode radiation to pass through optical assembly 40 and to sample 54. In a deactivated state, ("laser blocking" position), the solenoid releases plunger 68, which moves into light beam path 44 and prevents the multimode radiation from passing to the outside environment. Thus, safety switch 66 ensures that the probe remains in a "normally-off ' state should a malfunction or power loss occur.

[0037] A handheld Raman device of the present invention can additionally include a disposable test strip 14. Test strip 14, pictured in FIG. 1, preferably provides an area to deposit a body fluid sample onto which the laser radiation is directed, and even more preferably, includes features to enhance spectroscopy. In one embodiment, the test strip can include a substance for surface enhanced Raman spectroscopy (SERS), such as a roughened metallic surface and/or SERS-active metallic particles. The SERS-active metallic particles may, for example, be solid metallic particles or particles that are at least partially coated with a SERS-active metal.

[0038] SERS techniques enhance Raman spectroscopic signals and allow more effective differentiation of spectroscopic signatures by placing the sample to be analyzed in contact with SERS material (usually an appropriately prepared metal surface). Two mechanisms are considered responsible for the improvement. The primary contribution is an enlargement of the local electromagnetic field, due to the excitation of a localized surface plasmon, while the other mechanism results from a charge transfer-state between the surface complex of the adsorbed molecule and the metal surface.

[0039] Preferably, a SERS test strip includes SERS-active material, such as, for example silver, gold, nickel, copper and/or cadmium. FIG. 4 illustrates one exemplary embodiment of SERS active test strip 80 including a support substrate 82 and a roughened metal surface layer 84 having a degree of roughness sufficient to induce the SERS effect. Layer 84 may include a microparticle or microstructure layer 86 on the upper surface of support substrate 82 and a metal layer 88 containing silver, gold, nickel, copper and/or cadmium.

[0040] In one embodiment, a coating 90 can be applied to roughened surface layer 84 to adsorb analytes which are not easily adsorbed by the roughened surface and which are capable of either penetrating into the coating or being attached to the coating. The analytes are thereby "adsorbed" and become positioned in the vicinity of the roughened surface and exhibit the SERS effect.

[0041] In one embodiment, the SERS active material is positioned only in target area 16 of the test strip. In use, a sample is deposited on the SERS-active material in the target area and light is directed toward the sample for spectroscopic analysis. A person of skill in the art will appreciate that the choice of SERS-active material will depend on the desired analyte and the chosen radiation spectrum. In one embodiment, the SERS-active materials include a porous sol-gel containing gold microcolloid particles where the laser radiation is about 785 nm. SERS techniques and materials are described in U.S. Patent Nos. 5,400,136 and 5,864,397 to Vo-Dinh, which are incorporated herein by reference in their entirety.

[0042] In one embodiment, the device of the present invention additionally includes a lancet, which can puncture a user's skin, typically on the user's finger, to draw a blood sample. The lancet preferably includes a sharpened tip and a mechanism for propelling the metal tip into a user's skin. An exemplary lancet is the BD Ultra-Fine™ Lancet available from BD Consumer Healthcare, Ontario, Canada.

[0043] Where the device of the present invention investigates multiple analytes within a single sample during a single analysis it may be particularly advantageous to test analytes related to a single condition of interest. For example, when a patient arrives for a check-up, instead of running two diagnostic tests related to one condition, e.g., one for blood sugar, one for hemoglobin AIc, the present invention allows simultaneous testing. The result is a cost effective and almost immediate analysis. Thus, one embodiment of the invention provides for the analysis of multiple analytes that are related to a single preselected condition or to the health status of a preselected organ or tissue system.

[0044] Other groups of analytes can include a blood chemistry profile (a test for levels of two or more of: urea, creatinine, uric acid, bilirubin, phosphorous, alkaline P-Tase, total protein, albumin, globulin, glucose, calcium, calcium ionized, magnesium, iron, sodium, potassium, chloride, carbon dioxide, T-3 uptake, T-4 RIA, free thyroxine index, TSH-ultra sensitive cholesterol, triglycerides, HDL, LDL, VLDL, iron, iron saturation and ferritin).

[0045] In another embodiment, mineral and heavy metal assessments may be desirable to reveal the levels of beneficial elements and toxic elements that commonly occur in humans as the result of lifestyle and toxic exposures. Preferred analytes include mercury, iron, calcium, phosphorous, magnesium, and lead. Such a test may be desirable for persons concerned with health hazards in their living or work space.

[0046] In yet another embodiment, analytes may be chosen which focus on a certain preselected health condition. For example, testing for analytes related to cardiac health may be desirable during a regular check-up or as part of a heart health screening. Such analytes may, for example, include two or more of cholesterol (e.g., total, LDL, HDL)5 triglycerides, C-reactive protein and homocysteine.

[0047] In an additional embodiment, it may be desirable to screen for a group of drugs, and in particular illegal drugs or drags of abuse, such as but not limited to narcotics, amphetamines and hallucinogens. As an example, analytes could include two or more of marijuana (including but not limited to active substance THC)5 amphetamines, barbiturates, methamphetamines, opioids (such as but not limited to morphine, heroin and synthetic opioids), and PCP.

[0048] The Raman methods and apparatuses of the invention may be used to monitor pharmacotherapy in human or animal subjects. The quantification of a preselected drug and/or its metabolites in a sample obtained from a patient may be used to determine whether the active species of the drug is/are present at a desired concentration in the patient, and if not, the cause of the problem. The activity of many therapeutic drugs is at least partially dependent on their metabolism to one or more active forms within the body. For example, buproprion (Zyban™, Wellbutrin™) is extensively metabolized into three active metabolites. Activity of the antihypertensive angiotensin I-converting enzyme (ACE) inhibitors benazepril, enalapril, moexipril, and quinapril is due to the active metabolites benazeprilat, enalaprilat, moexiprilat, and quinaprilat, respectively. The antihistamine terfenadine is metabolized to an active metabolite fexofenadine. Determining the relative concentration of parent drug to active metabolite(s) in a patient, according to the invention, provides an indication of whether drug metabolism is normal and/or whether an abnormality in metabolism that interferes with the pharmacotherapy may be present, for example due to a metabolic insufficiency in the patient. Determining the concentration(s) of parent drug and/or metabolites thereof in a patient can provide information as to whether there is a problem in drug absorption/administration or a patient's compliance therewith, if the desired level of drug or metabolites is not achieved.

[0049] One embodiment of the invention provides a method for monitoring pharmacotherapy of a subject that includes the steps of: obtaining a sample of a body fluid, such as blood, urine or saliva, from a subject; irradiating at least a portion of the sample with monochromatic light to produce a Raman spectrum consisting of scattered electromagnetic radiation; detecting at least some of the wavelength components of the Raman spectrum that are associated with a preselected drug, such as a therapeutic drug, and/or one or more metabolites of the drug; and determining the concentration of the drug and/or one or more metabolites in the body fluid based on the detected wavelength components. In one variation, the subject has previously received the drug via a route of administration at least once. Another variation of the embodiment includes the further steps of: detecting at least some of the wavelength components of the Raman spectrum for one or more analytes that are associated with the state of a condition treated by the drug; and determining the concentration of the one or more analytes in the body fluid based on the detected wavelength components of the Raman spectrum for the one or more analytes. A test strip apparatus as described herein may, for example, be used to implement the embodiment and its variations.

[0050] The present invention provides the ability to monitor a variety of analytes using a test simple enough for use at home and sophisticated enough to provide valuable information about selected analytes. [0051] The results determined by the processor can be displayed on screen 20. Depending on the particulars of the analyte and the user's needs, the displayed results can be provided in a variety of forms. For example, where glucose is tested, the results can be displayed quantitively (120 mg/dl) or relatively (Normal). With other analytes, it may be desirable to display results indicating only the presence (or absence) of an analyte (e.g., the presence of poisons).

[0052] The term "body fluid" as used herein includes, but is not limited to, blood, urine and saliva. Other body fluids include, for example, lymph and cerebrospinal fluid.

[0053] General background information on Raman spectral analysis can be found in U.S. Patent No. 5,139,334, issued to Clarke and incorporated herein by reference in its entirety, which teaches a low resolution Raman analysis system for determining certain properties related to hydrocarbon content of fluids. The system utilizes a Raman spectroscopic measurement of the hydrocarbon bands and relates specific band patters to the property of interest. See also, U.S. Patent No. 6,208,887 also issued to Clarke and incorporated herein by reference in its entirety, which teaches a low-resolution Raman spectral analysis system for determining properties related to in vivo detection of samples based on a change in the Raman scattered radiation produced in the presence or absence of a lesion in a lumen of a subject. Additionally, U.S. Application Serial No. 10/ 367,238 (U.S. Pub. No. 20040160601) entitled "Probe Assemblies for Raman Spectroscopy" describes devices for analyzing samples with Raman spectroscopy and is incorporated herein by reference in its entirety.

U.S. Pub. No. 20040174520 entitled "Low resolution surface enhanced Raman spectroscopy on sol-gel substrates," U.S. Pub. No. 20040204634 titled "Raman spectroscopic monitoring of hemodialysis," and U.S. Pub. No. 20050171436 titled "Raman spectroscopy for monitoring drug-eluting medical devices" are each also incorporated by reference herein in their entireties.

[0054] One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.

Claims

1. A system for in vitro detection of an analyte in a body fluid sample using low resolution Raman spectroscopy comprising: a disposable strip for receiving a sample of body fluid on the target region; a light source for irradiating the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation; a low resolution dispersion element positioned to receive and separate the scattered radiation into different wavelength components; a detection array, optically aligned with the dispersion element for detecting at least some of the wavelength components of the scattered light, and a processor for processing data from the detector array and calculating information about an analyte within the body fluid sample.
2. The system of claim 1, wherein the processor calculates information about multiple analytes within the body fluid sample.
3. The system of claim 2, wherein the multiple analytes further comprise at least one body fluid component.
4. The system of claim 2, wherein the multiple analytes further comprise at least one drug.
5. The system of claim 2, wherein the multiple analytes further comprise at least one disease marker.
6. The system of claim 2, wherein the multiple analytes further comprise at least one poison.
7. The system of claim 1, wherein the concentration of the analyte within the body fluid sample is calculated.
8. The system of claim 1, wherein the disposable strip comprises a SERS-active material.
9. The system of claim 8, wherein the disposable strip comprises a gold sol-gel strip to provide surface-enhanced Raman scattering.
Attorney Docket No. 022720.0125C1WO 3670439
10. The system of claim 1, wherein the light source is a multi-mode laser.
1 1. The system of claim 1, wherein the processor includes a library of spectral properties of analytes for comparing with spectral information obtained from the body fluid sample.
12. The system of claim 1, including a screen for displaying information related to the analyte detected within the body fluid sample.
13. The system of claim 1, wherein the analyte is selected from the group consisting of urea- based compounds, ammonium-based compounds, uric acid based compounds, nitrogen-based compounds, and combinations thereof.
14. The system of claim 1, wherein the detected analyte in the body fluid sample is selected from the group consisting of cardiac enzymes, cardiovascular stent coatings, poisons, therapeutic drugs, drugs of abuse, hormones, steroids, and combinations thereof.
15. The system of claim 1, including a lancet to puncture a patient's skin.
16. A system for in vitro detection of an analyte in a body fluid sample using low resolution Raman spectroscopy comprising: a strip for receiving a sample of body fluid on a target region, the target region including a material to provide surface enhanced Raman scattering; a laser for irradiating the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation; a low resolution dispersion element positioned to receive and separate the scattered radiation into different wavelength components; a detection array, optically aligned with the dispersion element for detecting at least some of the wavelength components of the scattered light; and a processor for processing data from the detector array and calculating glucose concentration and information about at least one other analyte within the body fluid sample.
17. The system of claim 12, wherein the at least one other analyte includes hemoglobin A Ic.
18. The system of claim 11, wherein the test strip target region includes gold.
Attorney Docket No. 022720.0125Cl WO 3670439
19. The system of claim 11, wherein the test strip target region includes a sol-gel.
20. A method for in vitro detection of an analyte in a body fluid sample using low resolution Raman spectroscopy comprising: providing a disposable strip for receiving a sample of body fluid on a target region; depositing a sample of body fluid on the target region of the disposable strip; irradiating the target region with a laser to produce a Raman spectrum consisting of scattered electromagnetic radiation; receiving and separating the scattered radiation into different wavelength components using a low resolution dispersion element; detecting at least some of the wavelength components of the scattered light using a detection array; processing data from the detector array and calculating information about an analyte within the body fluid sample with a processor; and displaying information related to the analyte detected within the body fluid sample on a screen.
21. The system of claim 2, wherein the multiple analytes comprise at least two analytes related to a single preselected condition.
22. The system of claim 21, wherein the single preselected condition is a single preselected health condition.
23. The system of claim 2, wherein the multiple analytes comprise at least two analytes related to cardiac health.
24. The system of claim 1, wherein the analyte is a therapeutic drug.
25. The system of claim 1, wherein the analyte is a metabolite of a therapeutic drug.
26. The system of claim 2, wherein the multiple analytes comprise a therapeutic drug and one or more metabolites of the drug.
27. A method for monitoring pharmacotherapy of a subject, comprising the steps of:
Attorney Docket No. 022720.0125C1WO 3670439 obtaining a sample of a body fluid from a subject;
irradiating at least a portion of the sample with monochromatic light to produce a Raman spectrum consisting of scattered electromagnetic radiation;
detecting at least some of the wavelength components of the Raman spectrum that are associated with a therapeutic drug and/or one or more metabolites of the drug; and
determining the concentration of the drug and/or one or more metabolites in the body fluid based on the detected wavelength components.
28. The method of claim 27, wherein the subject has previously received the drug via a route of administration at least once.
29. The method of claim 27, further comprising the steps of:
detecting at least some of the wavelength components of the Raman spectrum for one or more analytes that are associated with the state of a condition treated by the drug; and
determining the concentration of the one or more analytes in the body fluid based on the detected wavelength components of the Raman spectrum for the one or more analytes.
30. The method of claim 27, wherein
the step of detecting comprises detecting at least some of the wavelength components of the Raman spectrum that are associated with the therapeutic drug and at least one of the metabolites of the drug; and
the step of determining comprises determining the concentration of the drug and at least one of the metabolites of the drug in the body fluid based on the detected wavelength components.
Attorney Docket No. 022720.0125C IWO 3670439
PCT/US2007/002062 2005-01-27 2007-01-24 Handheld raman body fluid analyzer WO2007089540A3 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US11340712 US7651851B2 (en) 2005-01-27 2006-01-27 Handheld Raman body fluid analyzer
US11/340,712 2006-01-27

Publications (2)

Publication Number Publication Date
WO2007089540A2 true true WO2007089540A2 (en) 2007-08-09
WO2007089540A3 true WO2007089540A3 (en) 2007-11-15

Family

ID=38327888

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/002062 WO2007089540A3 (en) 2005-01-27 2007-01-24 Handheld raman body fluid analyzer

Country Status (2)

Country Link
US (1) US7651851B2 (en)
WO (1) WO2007089540A3 (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050171436A1 (en) * 2004-01-09 2005-08-04 Clarke Richard H. Raman spectroscopy for monitoring drug-eluting medical devices
US7651851B2 (en) 2005-01-27 2010-01-26 Prescient Medical, Inc. Handheld Raman body fluid analyzer
US7688440B2 (en) * 2005-01-27 2010-03-30 Prescient Medical, Inc. Raman spectroscopic test strip systems
WO2006116637A3 (en) * 2005-04-27 2007-03-01 Massachusetts Inst Technology Raman spectroscopy for non-invasive glucose measurements
WO2007014173A3 (en) * 2005-07-22 2007-06-21 Massachusetts Inst Technology Intrinsic raman spectroscopy
WO2007092173A3 (en) * 2006-02-06 2008-01-24 Prescient Medical Inc Raman spectroscopic lateral flow test strip assays
US8211048B2 (en) * 2006-02-22 2012-07-03 Henry Ford Health System System and method for delivery of regional citrate anticoagulation to extracorporeal blood circuits
US8133194B2 (en) 2006-02-22 2012-03-13 Henry Ford Health System System and method for delivery of regional citrate anticoagulation to extracorporeal blood circuits
US8677650B2 (en) * 2007-06-15 2014-03-25 Abbott Cardiovascular Systems Inc. Methods and devices for drying coated stents
US8003157B2 (en) 2007-06-15 2011-08-23 Abbott Cardiovascular Systems Inc. System and method for coating a stent
WO2009149072A3 (en) * 2008-06-03 2010-03-04 The Research Foundation Of State University Of New York At Albany Identification of body fluids using raman spectroscopy
US9877672B2 (en) 2010-01-28 2018-01-30 Ellume Pty Ltd Sampling and testing device for the human or animal body
CN101806740B (en) * 2010-04-19 2011-12-21 加拿大Bc癌研究中心 Detection method of human plasma surface enhanced raman spectroscopy by integrating main component analysis
JP5640592B2 (en) 2010-09-14 2014-12-17 セイコーエプソン株式会社 The optical device unit and the detection device
JP5545144B2 (en) 2010-09-14 2014-07-09 セイコーエプソン株式会社 The optical device unit and the detection device
CN102419320A (en) 2010-09-14 2012-04-18 精工爱普生株式会社 Detection apparatus
US9581552B2 (en) * 2011-04-06 2017-02-28 Klein Medical Limited Spectroscopic analyser
EP2992826A4 (en) * 2013-05-02 2017-01-04 Atonarp Inc Monitor and system for monitoring living organisms
CN103512874A (en) * 2013-09-22 2014-01-15 福建师范大学 Ultrasonic perforation-laser tweezer cell surface enhanced Raman spectroscopy method
DE102014005101A1 (en) 2014-04-08 2015-10-08 Bodo Köhler The portable apparatus and method for determining a characteristic variable insulindeterminierenden
USD748510S1 (en) * 2015-02-03 2016-02-02 Bwt Property, Inc. Handheld raman spectrometer

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5991653A (en) * 1995-03-14 1999-11-23 Board Of Regents, The University Of Texas System Near-infrared raman spectroscopy for in vitro and in vivo detection of cervical precancers
US6770488B1 (en) * 1999-03-19 2004-08-03 The University Of Wyoming Practical method and apparatus for analyte detection with colloidal particles
US20040160601A1 (en) * 2003-02-14 2004-08-19 Womble M. Edward Probe assemblies for Raman spectroscopy
US20040174520A1 (en) * 2001-07-17 2004-09-09 W Ranjith Premasiri Low resolution surface enhanced raman spectroscopy on sol-gel substrates
US20040204634A1 (en) * 2003-04-09 2004-10-14 Womble M. Edward Raman spectroscopic monitoring of hemodialysis
US20050171436A1 (en) * 2004-01-09 2005-08-04 Clarke Richard H. Raman spectroscopy for monitoring drug-eluting medical devices

Family Cites Families (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3598727A (en) * 1969-04-07 1971-08-10 Charles B Willock Artificial kidney
US4370983A (en) * 1971-01-20 1983-02-01 Lichtenstein Eric Stefan Computer-control medical care system
US3900396A (en) * 1974-03-22 1975-08-19 Baxter Laboratories Inc Blood leak detector
US4172033A (en) * 1974-12-23 1979-10-23 DWS, Inc. Artificial kidney proportioning system
US4127033A (en) 1976-08-23 1978-11-28 The United States Of America As Represented By The Secretary Of The Navy Ultrasonic scanner system for cast explosive billets
US5993378A (en) 1980-10-28 1999-11-30 Lemelson; Jerome H. Electro-optical instruments and methods for treating disease
DE2838414C2 (en) * 1978-09-02 1984-10-31 Fresenius Ag, 6380 Bad Homburg, De
US4329986A (en) * 1979-06-14 1982-05-18 Biomedics, Inc. Treatment of an extracorporeal stream of blood with a dialyzable chemotherapeutic and a fluorescable tracer
US4573761A (en) * 1983-09-14 1986-03-04 The Dow Chemical Company Fiber-optic probe for sensitive Raman analysis
US5318024A (en) * 1985-03-22 1994-06-07 Massachusetts Institute Of Technology Laser endoscope for spectroscopic imaging
US4913142A (en) * 1985-03-22 1990-04-03 Massachusetts Institute Of Technology Catheter for laser angiosurgery
DE3650688T2 (en) * 1985-03-22 1999-03-25 Massachusetts Inst Technology The fiber optic probe system for the spectral diagnosis of tissue
US5199431A (en) * 1985-03-22 1993-04-06 Massachusetts Institute Of Technology Optical needle for spectroscopic diagnosis
US5693043A (en) 1985-03-22 1997-12-02 Massachusetts Institute Of Technology Catheter for laser angiosurgery
US4769134A (en) * 1985-11-20 1988-09-06 C D Medical Open patient fluid management method and system
US4733253A (en) * 1986-07-03 1988-03-22 Xerox Corporation Apparatus and method for detecting and eliminating diode laser mode hopping
US4781458A (en) 1987-11-30 1988-11-01 The United States Of America As Represented By The United States Department Of Energy Fiber optic apparatus for detecting molecular species by surface enhanced Raman spectroscopy
DE68925586D1 (en) * 1988-12-21 1996-03-14 Massachusetts Inst Technology A method for laser induced fluorescence of tissue
US5376556A (en) * 1989-10-27 1994-12-27 Abbott Laboratories Surface-enhanced Raman spectroscopy immunoassay
US5266498A (en) * 1989-10-27 1993-11-30 Abbott Laboratories Ligand binding assay for an analyte using surface-enhanced scattering (SERS) signal
US5112127A (en) * 1989-11-28 1992-05-12 Eic Laboratories, Inc. Apparatus for measuring Raman spectra over optical fibers
US5011284A (en) * 1990-03-22 1991-04-30 Kaiser Optical Systems Detection system for Raman scattering employing holographic diffraction
US5139334A (en) * 1990-09-17 1992-08-18 Boston Advanced Technologies, Inc. Hydrocarbon analysis based on low resolution raman spectral analysis
US5280788A (en) * 1991-02-26 1994-01-25 Massachusetts Institute Of Technology Devices and methods for optical diagnosis of tissue
CA2104960C (en) * 1991-02-26 2005-04-05 Richard P. Rava Systems and methods of molecular spectroscopy to provide for the diagnosis of tissue
US5486286A (en) * 1991-04-19 1996-01-23 Althin Medical, Inc. Apparatus for performing a self-test of kidney dialysis membrane
WO1993012712A1 (en) 1991-12-31 1993-07-08 Vivascan Corporation Blood constituent determination based on differential spectral analysis
US5400136A (en) * 1992-01-16 1995-03-21 Martin Marietta Energy Systems, Inc. Surface-enhanced Raman scattering (SERS) dosimeter and probe
US5452723A (en) * 1992-07-24 1995-09-26 Massachusetts Institute Of Technology Calibrated spectrographic imaging
US5849179A (en) 1992-10-13 1998-12-15 Baxter International Inc. Automatic apparatus for obtaining equilibration samples of dialysate
ES2102187T3 (en) * 1992-11-18 1997-07-16 Spectrascience Inc Apparatus for imaging diagnosis.
DK88893D0 (en) * 1993-07-30 1993-07-30 Radiometer As A method and an apparatus for Determining the content of a constituent of blood of an individual
US5381237A (en) * 1993-08-18 1995-01-10 Petrometrix Ltd. Multi-purpose optical head probe
US5685988A (en) 1993-09-15 1997-11-11 Malchesky; Paul Dialysis process and system
US5377004A (en) 1993-10-15 1994-12-27 Kaiser Optical Systems Remote optical measurement probe
US5553616A (en) 1993-11-30 1996-09-10 Florida Institute Of Technology Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator
US5455673A (en) * 1994-05-27 1995-10-03 Eastman Chemical Company Apparatus and method for measuring and applying a convolution function to produce a standard Raman spectrum
US5485481A (en) * 1994-06-28 1996-01-16 Seastar Optics Inc. Fibre-grating-stabilized diode laser
DE9414467U1 (en) * 1994-07-15 1994-11-10 Bruker Analytische Messtechnik Raman spectrometer with a measuring probe
DE4433305A1 (en) 1994-09-28 1996-04-04 O K Tec Optik Keramik Technolo Fibre-optic probe for measuring e.g. fluorescence, scattering or Raman effect in solid, liquid and gaseous material
US5697373A (en) * 1995-03-14 1997-12-16 Board Of Regents, The University Of Texas System Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies
US5615673A (en) * 1995-03-27 1997-04-01 Massachusetts Institute Of Technology Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes
US5621522A (en) * 1995-04-05 1997-04-15 The United States Of America As Represented By The Secretary Of The Navy Fiber optic probe for determination of trace levels of organic pollutants using Raman spectroscopy
US5657404A (en) * 1995-05-25 1997-08-12 Eastman Chemical Company Robust spectroscopic optical probe
DE69636967D1 (en) * 1995-09-20 2007-04-26 Arkray Inc A method for analysis by light scattering
DE69635819T2 (en) * 1995-10-18 2006-12-21 Arkray, Inc. An apparatus for urinalysis
US6580935B1 (en) * 1999-03-12 2003-06-17 Cirrex Corp. Method and system for stabilizing reflected light
USH2002H1 (en) 1995-12-19 2001-11-06 The Dow Chemical Company Apparatus for conducting Raman spectroscopy using fiber optics
US5862273A (en) * 1996-02-23 1999-01-19 Kaiser Optical Systems, Inc. Fiber optic probe with integral optical filtering
US5902246A (en) * 1996-03-26 1999-05-11 Lifespex, Incorporated Method and apparatus for calibrating an optical probe
US5751415A (en) * 1996-05-13 1998-05-12 Process Instruments, Inc. Raman spectroscopy apparatus and method for continuous chemical analysis of fluid streams
US5773835A (en) * 1996-06-07 1998-06-30 Rare Earth Medical, Inc. Fiber optic spectroscopy
US5842995A (en) 1996-06-28 1998-12-01 Board Of Regents, The Univerisity Of Texas System Spectroscopic probe for in vivo measurement of raman signals
US6018389A (en) * 1996-07-22 2000-01-25 The Regents Of The University Of California Cone penetrometer fiber optic raman spectroscopy probe assembly
EP0942759B1 (en) * 1996-11-28 2005-06-29 Gambro Lundia AB System for preventing intradialytic symptomatology
US5858186A (en) * 1996-12-20 1999-01-12 The Regents Of The University Of California Urea biosensor for hemodialysis monitoring
US6924153B1 (en) * 1997-03-06 2005-08-02 Quidel Corporation Quantitative lateral flow assays and devices
DE69834034D1 (en) * 1997-06-02 2006-05-18 Gambro Lundia Ab Lund Means for calculating dialysis efficiency
JP2002510395A (en) * 1997-07-02 2002-04-02 スペクトラ コード インコーポレイテッド Fast identification Raman system
US5902247A (en) * 1997-09-09 1999-05-11 Bioenterics Corporation Transilluminating catheter
US5864397A (en) * 1997-09-15 1999-01-26 Lockheed Martin Energy Research Corporation Surface-enhanced raman medical probes and system for disease diagnosis and drug testing
US5951482A (en) * 1997-10-03 1999-09-14 Intraluminal Therapeutics, Inc. Assemblies and methods for advancing a guide wire through body tissue
DE19747360B8 (en) 1997-10-27 2007-05-16 Fresenius Medical Care De Gmbh Method for measuring performance parameters of material and energy exchange modules
ES2281143T3 (en) * 1997-11-12 2007-09-16 Lightouch Medical, Inc. Method for non-invasive measurement of an analyte.
GB9804083D0 (en) * 1998-02-26 1998-04-22 Univ Strathclyde Immunoassays
US5982484A (en) 1998-02-26 1999-11-09 Clarke; Richard H. Sample analysis using low resolution Raman spectroscopy
US6174291B1 (en) * 1998-03-09 2001-01-16 Spectrascience, Inc. Optical biopsy system and methods for tissue diagnosis
US6560478B1 (en) * 1998-03-16 2003-05-06 The Research Foundation Of City University Of New York Method and system for examining biological materials using low power CW excitation Raman spectroscopy
US6151522A (en) 1998-03-16 2000-11-21 The Research Foundation Of Cuny Method and system for examining biological materials using low power CW excitation raman spectroscopy
US6154596A (en) 1998-03-26 2000-11-28 Hughes Electronics Corporation Front end preparation procedure for efficient coupling and improved power handling of light into a multi-mode fiber
US6064897A (en) * 1998-06-01 2000-05-16 Abbott Laboratories Sensor utilizing Raman spectroscopy for non-invasive monitoring of analytes in biological fluid and method of use
DE69916053D1 (en) 1998-06-04 2004-05-06 Althin Medical Ab Ronneby Procedures and specifications of waste products in dialysis fluids during dialysis treatment
US6281971B1 (en) * 1999-05-18 2001-08-28 New Chromex, Inc. Method for adjusting spectral measurements to produce a standard Raman spectrum
US6226082B1 (en) * 1998-06-25 2001-05-01 Amira Medical Method and apparatus for the quantitative analysis of a liquid sample with surface enhanced spectroscopy
US6574501B2 (en) * 1998-07-13 2003-06-03 Childrens Hospital Los Angeles Assessing blood brain barrier dynamics or identifying or measuring selected substances or toxins in a subject by analyzing Raman spectrum signals of selected regions in the eye
US6038887A (en) * 1998-08-19 2000-03-21 Glasstech, Inc. Apparatus and method for forming glass sheets
US6087182A (en) * 1998-08-27 2000-07-11 Abbott Laboratories Reagentless analysis of biological samples
US6212424B1 (en) * 1998-10-29 2001-04-03 Rio Grande Medical Technologies, Inc. Apparatus and method for determination of the adequacy of dialysis by non-invasive near-infrared spectroscopy
US6144444A (en) 1998-11-06 2000-11-07 Medtronic Avecor Cardiovascular, Inc. Apparatus and method to determine blood parameters
US6721583B1 (en) * 1998-11-19 2004-04-13 The United States Of America Method for non-invasive identification of individuals at risk for diabetes
US6507747B1 (en) * 1998-12-02 2003-01-14 Board Of Regents, The University Of Texas System Method and apparatus for concomitant structural and biochemical characterization of tissue
US6219137B1 (en) * 1998-12-03 2001-04-17 Lockheed Martin Energy Research Corporation Nanoprobe for surface-enhanced Raman spectroscopy in medical diagnostic and drug screening
US6297020B1 (en) * 1999-03-01 2001-10-02 Bayer Corporation Device for carrying out lateral-flow assays involving more than one analyte
US6511814B1 (en) * 1999-03-26 2003-01-28 Idexx Laboratories, Inc. Method and device for detecting analytes in fluids
US6208887B1 (en) * 1999-06-24 2001-03-27 Richard H. Clarke Catheter-delivered low resolution Raman scattering analyzing system for detecting lesions
US6486948B1 (en) 1999-09-14 2002-11-26 Haishan Zeng Apparatus and methods relating to high speed Raman spectroscopy
US6514767B1 (en) * 1999-10-06 2003-02-04 Surromed, Inc. Surface enhanced spectroscopy-active composite nanoparticles
US6373567B1 (en) * 1999-12-17 2002-04-16 Micron Optical Systems Dispersive near-IR Raman spectrometer
US6621574B1 (en) * 2000-05-25 2003-09-16 Inphotonics, Inc. Dual function safety and calibration accessory for raman and other spectroscopic sampling
US6643012B2 (en) 2001-02-23 2003-11-04 National University Of Singapore Apertureless near-field scanning raman microscopy using reflection scattering geometry
JP2004532251A (en) * 2001-05-31 2004-10-21 ミラヴァント ファーマシューティカルズ インコーポレイテッド Metallo tetrapyrrole-based photosensitizers used in photodynamic therapy
CA2450114A1 (en) * 2001-06-08 2002-12-19 F. Hoffmann-La Roche Ag Sampling devices and methods utilizing a horizontal capillary test strip
US6841159B2 (en) * 2002-01-30 2005-01-11 The United States Of America As Represented By The Secretary Of The Navy Rapid lateral flow assay for determining exposure to Mycobacterium tuberculosis and other mycobacteria
US6750963B2 (en) * 2002-05-21 2004-06-15 Agilent Technologies, Inc. Imaging systems for signals on a surface
EP1430835B1 (en) * 2002-12-17 2011-11-16 Kabushiki Kaisha Toshiba System for peripheral X-ray angiography
EP1581115B1 (en) * 2002-12-30 2009-10-14 Roche Diagnostics GmbH Blood acquisition suspension system
US7374546B2 (en) * 2003-01-29 2008-05-20 Roche Diagnostics Operations, Inc. Integrated lancing test strip
US20040191921A1 (en) * 2003-02-21 2004-09-30 Stuart Farquharson Simultaneous chemical separation and surface-enhanced raman spectral detection
US20050059894A1 (en) * 2003-09-16 2005-03-17 Haishan Zeng Automated endoscopy device, diagnostic method, and uses
EP1676123A2 (en) 2003-10-17 2006-07-05 Axsun Technologies, Inc. Multi channel raman spectroscopy system and method
US7245369B2 (en) * 2003-11-13 2007-07-17 B & W Tek, Inc. Spectroscopic apparatus using spectrum narrowed and stabilized laser with Bragg grating
US7102746B2 (en) * 2003-12-16 2006-09-05 New Chromex, Inc. Raman spectroscope
WO2006071247A3 (en) 2004-03-30 2007-08-16 California Inst Of Techn Diagnostic assays including multiplexed lateral flow immunoassays with quantum dots
USH2202H1 (en) 2004-04-28 2007-09-04 Symantec Corporation Method and apparatus to dynamically hook runtime processes without interrupting the flow of execution
US7688440B2 (en) * 2005-01-27 2010-03-30 Prescient Medical, Inc. Raman spectroscopic test strip systems
US7524671B2 (en) * 2005-01-27 2009-04-28 Prescient Medical, Inc. Handheld raman blood analyzer
US7651851B2 (en) 2005-01-27 2010-01-26 Prescient Medical, Inc. Handheld Raman body fluid analyzer
US20060176478A1 (en) * 2005-02-09 2006-08-10 Raman Systems, Inc. Raman spectroscopy with stabilized multi-mode lasers
US7518721B2 (en) * 2005-09-09 2009-04-14 Ge Homeland Protection, Inc. Raman-active lateral flow device and methods of detection
WO2007092173A3 (en) * 2006-02-06 2008-01-24 Prescient Medical Inc Raman spectroscopic lateral flow test strip assays

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5991653A (en) * 1995-03-14 1999-11-23 Board Of Regents, The University Of Texas System Near-infrared raman spectroscopy for in vitro and in vivo detection of cervical precancers
US6770488B1 (en) * 1999-03-19 2004-08-03 The University Of Wyoming Practical method and apparatus for analyte detection with colloidal particles
US20040174520A1 (en) * 2001-07-17 2004-09-09 W Ranjith Premasiri Low resolution surface enhanced raman spectroscopy on sol-gel substrates
US20040160601A1 (en) * 2003-02-14 2004-08-19 Womble M. Edward Probe assemblies for Raman spectroscopy
US20040204634A1 (en) * 2003-04-09 2004-10-14 Womble M. Edward Raman spectroscopic monitoring of hemodialysis
US20050171436A1 (en) * 2004-01-09 2005-08-04 Clarke Richard H. Raman spectroscopy for monitoring drug-eluting medical devices

Also Published As

Publication number Publication date Type
WO2007089540A3 (en) 2007-11-15 application
US20060240401A1 (en) 2006-10-26 application
US7651851B2 (en) 2010-01-26 grant

Similar Documents

Publication Publication Date Title
Choo‐Smith et al. Medical applications of Raman spectroscopy: from proof of principle to clinical implementation
Kong et al. Raman spectroscopy for medical diagnostics—From in-vitro biofluid assays to in-vivo cancer detection
Yuen et al. Transcutaneous glucose sensing by surface-enhanced spatially offset Raman spectroscopy in a rat model
US6208887B1 (en) Catheter-delivered low resolution Raman scattering analyzing system for detecting lesions
US6377828B1 (en) Method for non-invasive measurement of an analyte
Berger et al. Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy
Feng et al. Gastric cancer detection based on blood plasma surface-enhanced Raman spectroscopy excited by polarized laser light
US20050106713A1 (en) Personal diagnostic devices and related methods
US6928311B1 (en) Compact device for measuring, tissue analytes
US20030060693A1 (en) Apparatus and method for quantification of tissue hydration using diffuse reflectance spectroscopy
US6741875B1 (en) Method for determination of analytes using near infrared, adjacent visible spectrum and an array of longer near infrared wavelengths
US5460177A (en) Method for non-invasive measurement of concentration of analytes in blood using continuous spectrum radiation
Maruo et al. In vivo noninvasive measurement of blood glucose by near-infrared diffuse-reflectance spectroscopy
US5383452A (en) Method, apparatus and procedure for non-invasive monitoring blood glucose by measuring the polarization ratio of blood luminescence
Virkler et al. Raman spectroscopic signature of blood and its potential application to forensic body fluid identification
US20140330098A1 (en) Reflectance calibration of fluorescence-based glucose measurements
US20050007582A1 (en) Methods and apparatus for collection of optical reference measurements for monolithic sensors
US5348003A (en) Method and apparatus for chemical analysis
US20110184260A1 (en) Methods and Apparatuses for Noninvasive Determinations of Analytes
EP1424040A1 (en) Body fluid testing device
US20050201897A1 (en) Body fluid testing device
US5864397A (en) Surface-enhanced raman medical probes and system for disease diagnosis and drug testing
US20040015060A1 (en) Measurement of body compounds
US20120203086A1 (en) Apparatus and method for non-invasively detecting diseases that affect structural properties in biological tissues
Pappas et al. Raman spectroscopy in bioanalysis

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07709870

Country of ref document: EP

Kind code of ref document: A2