GB2531956A - Device and method for characterisation of biological samples - Google Patents
Device and method for characterisation of biological samples Download PDFInfo
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- GB2531956A GB2531956A GB1522844.8A GB201522844A GB2531956A GB 2531956 A GB2531956 A GB 2531956A GB 201522844 A GB201522844 A GB 201522844A GB 2531956 A GB2531956 A GB 2531956A
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- United Kingdom
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- sample
- skin
- analyte
- radiation
- reflector
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
- A61B5/1451—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid
- A61B5/14514—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14546—Measuring 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 analytes not otherwise provided for, e.g. ions, cytochromes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring 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
- A61B5/1459—Measuring 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 invasive, e.g. introduced into the body by a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B2010/0009—Testing for drug or alcohol abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B2010/008—Interstitial fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
- A61B5/683—Means for maintaining contact with the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/0404—Electrodes for external use
- A61N1/0408—Use-related aspects
- A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
Abstract
An apparatus for characterizing an analyte in a sample volume of the surface layer of the skin of a patient comprises a radiation source located outside the body and configured to irradiate the sample 12. A reflector 4 implanted beneath the surface layer of the skin 10 defines the sample volume and is configured to receive incident radiation that has passed through the sample and reflect it back through the sample to a sensor located outside the body. A mask prevents radiation from the source bypassing the reflector to damage other tissue. The analyte may be glucose. The features of the radiation measured by the sensor may be raman scattered radiation. Growth factors may be applied to the skin to promote capillary growth in the sample volume.
Description
DEVICE AND METHOD FOR CHARACTERISATION OF BIOLOGICAL SAMPLES
Background
Numerous attempts have been documented for the non-invasive measurement of s analytes in biological subjects such as humans and animals. This has been driven by the clinical need to attain finer control over chronic conditions such as diabetes, as well as for monitoring the absorption of drugs into the blood circulation. Noninvasive means are desirable as they can lead to reduced costs, reduced time, and enhanced compliance by minimizing the disturbance caused to the subject.
A wide range of examples are cited in literature to extract analyte from the skin, including sonophoresis, abrasion techniques, and reverse iontophoresis, followed by measurement of the analyte outside the skin. Measurement techniques include acoustic e.g., sonophoretic methods; optical and spectroscopic techniques such as near-infrared, and far-infrared spectroscopy, radiowave impedance (whereby non-ionic solutes such as glucose attenuates the amplitude of the radiowaves), skin impedance spectroscopy, polarimetry (or optical rotation of polarised light), and Raman spectroscopy, photo-acoustic methods, optical coherent tomography, amongst others that measure the analyte directly in the skin. Mid-infra red spectroscopy has also been applied in the measurement of glucose concentrations in samples in-vitro.
Table 1 summarises some of the main techniques and the parameters used to measure and quantify analytes.
Table 1
Technique* Definition* Parameters used (Bazaev et. al.,) Near Infra-red Spectroscopy Absorption or emission data in the 0.7 to 2.5 [tm region of the spectrum are compared to known data for glucose. Wavelength 700nm2500nm Raman Laser light is used to induce emission from transitions near the level excited. Wavelength 785nm, 532nm Spectroscopy Photoacoustic Laser excitation of fluids is used to generate an acoustic response and a spectrum as the laser is tuned. Wavelength 1550nm1850nm or 2100nm2300nm; 532nm, 1064nm Spectroscopy Scatter Changes The scattering of light can be used to indicate a change in the material being examined, e.g., Optical Coherent Tomography. Interferometer with low coherence radiation source and interferometric photodetector. Reflected radiation is superimposed on reference fiber optic bundle radiation and resulting interferometric signal detected using photodiode.
Polarization Changes The presence of glucose in a fluid is known to cause a polarization preference in the light transmitted. Wavelength 523nm, 635nm, 632.8nm Mid-Infrared Absorption or emission data in the 2.5 km -25 um region are examined and used to quantitate glucose in a fluid. Wavelength 2500nm25,000nm Spectroscopy *http://photonicssociety.org/newsletters/apr98/overview.htm Bazaev et. al., Biomedical Engineering, Volume 45, No. 6, March 2012, pp. 229-233.
Patent literature contains numerous examples of methods of enhancing the signal strength generated from these types of non-invasive measurement techniques: WO 2013/173237 (A1) -describes a focusing element for focusing an incident light from a laser light source, and an optical element for collecting a signal from the io sample with a reflected light sensor situated on the inner housing of the spectrophotometer.
US 2013/266258 (Al) -describes a means of converting an optical input to a differently shaped optical output, using stacked waveguides.
WO 2012/173686 (Al) -describes an apparatus for stabilizing an optical, thermal, s and mechanical interface between a spectroscopic and/or imaging system and biological sample, using a window retainer which does not obstruct light travelling back from the sample to the imaging or spectroscopic system.
US 2011/194183 (A1) -describes an optical window for re-directing scattered io radiation. It further describes an aperture of the optical window fabricated from a reflective material such that light emerging from the sample outside the area of the aperture is redirected back to the sample.
WO 2010/141258 (Al) -describes an apparatus for emitting optical radiation onto is a sample and for collecting in-elastically scattered radiation from a sample, and comprises an off-axis reflector and filter to transmit the in-elastically scattered radiation; the reflective optics are used to both deliver the excitation beam and collect the scattered radiation.
WO 2007/127909 (A2) -describes the use of optical fiber bundles positioned to receive the scattered light collected by the optics.
All of the above inventions relate to the use of optical radiation for the purpose of detecting scattered light from the sample containing the analyte, which is generally described as being human skin. It follows that the pathway between incident radiation and the sample containing the analyte of interest must be optically transparent to allow the radiation to reach its target. Furthermore the incident light source is essentially unidirectional towards the sample containing the analyte, i.e., the skin, on the assumption the surface being irradiated, e.g., the skin is a substantially thick three-dimensional substrate.
Reverse iontophoresis is widely documented in literature to be able to effectively extract a number of charged and uncharged analytes from the interstitial fluid of the skin. The major benefit is that the sensing process is unaffected by the numerous other molecules that constitute the chemical and biological environment s within the skin, from which the analytes are essentially filtered out to the surface of the skin, and whilst there is still a mixture of analytes that is extracted, the process of detection or sensing is significantly simplified in that the volume or quantity of interfering species is reduced, in particular macromolecules such as proteins present in the skin that would interfere with the sensing are generally not io extracted from the skin using reverse iontophoresis due to the size of the protein molecules. Optical methods involving the exposure of the skin to a light source, followed by measurement of the scattered signal suffer from a number of impediments: is noise generated from the complex skin composition - differences in light absorption due to skin colour and skin thickness - minimal distance of penetration by the light source heating of exposed tissue leading to burns and tissue damage - presence of moisture/sweat on the skin leading to variability overlapping spectral signals from tissue composition Acoustic methods of measuring the desired analyte in vivo suffer from analogous problems.
The above has lead to efforts to refine the signals generated, using physical means such as improved optics, and mathematical means such as complex algorithms, but with limited success. Indeed several commercial entities have ceased to operate due to lack of precision and accuracy of their optical non-invasive systems, initially developed for glucose monitoring. An improved non-invasive method would therefore provide a tool for monitoring chronic conditions, with meaningful clinical outcomes.
Summary
The invention provides an apparatus for characterisation of an analyte in a sample volume of the surface layer of the skin of a patient, as defined in claim 1.
s The invention further provides a method of characterisation of an analyte in a sample volume of the surface layer of the skin of a patient, as defined in claim 4 Preferred but non-essential features of the invention are defined in the dependent claims.
In this specification, the term "radiation" is used to encompass acoustic waves as well as electromagnetic and other forms of radiation.
Providing a reflective surface behind the sample to be illuminated causes the is radiation to pass twice through the sample and enhances the extent of irradiation of the analyte, with a concurrent increase in scattered light returning to the collection/detector optics and increased signal strength. It also permits the radiation source and the sensor to be conveniently packaged together on the same side of the sample.
The implantation depth of the reflector should be sufficient to permit the build-up of micro-circulation of capillaries between the reflective surface and the outer surface of the skin, creating a fixed focal point where optical, acoustic or impedance or other physical techniques may be applied to measure the signal generated by the sample. Furthermore enhanced (micro) vascular growth may be achieved by application of appropriate growth factors to the skin in that region as is known in the current state of the art, or as is taught by Yuan Liu et al., (BioMed Research International, Volume 2013 (2013), Article ID 561410). Alternatively the implantation depth of the reflector may be sufficient to ensure a (rich) supply of interstitial fluid which would form the sample volume to be measured.
This differs from existing implanted sensors in two fundamental ways: implanted sensors, for example those used for glucose measurement, using glucose oxidase, or fluorescent technologies, suffer from bio-fouling, i.e., the build-up of cells and micro-vasculature around the implanted device which leads to drifting of the s signals that are generated, thus requiring multiple calibrations using blood glucose values determined by finger-prick in order to re-calibrate the system. In this invention however the build-up of cellular and micro-vascular network over the reflector is preferred to ensure a sufficiently large and representative quantity of the analyte within the sample volume.
Secondly, current implanted sensors are required to be removed and replaced after a period of time, which varies from 5 to14 days for glucose oxidase based sensors and is up to 6 months for optical based sensors. The implant described in this invention may be retained in the skin on a permanent or long term basis as it is an is entirely inert material that does not react chemically, and provides a physical surface from which to reflect optical or acoustic waves. This has important ramifications in that optical or acoustic measurements taken from different locations can lead to wide variations in the accuracy of the data generated, thus the ability to select and maintain a specific area that would reduce that variability is beneficial. The type of material that would be used for such implant would have the general characteristics of being a solid, non-porous material with smooth surfaces. This can be created from metals, ceramics and plastics/polymers, or a composite thereof, which are bio-compatible, and suitable for long term implantation, such as materials used in bone graft surgery, hip replacements etc. In combination with the invention, the sensor that detects the radiation emitted from the sample may transmit measurement signals to a remote location for analysis and presentation to the user. The apparatus may incorporate a control module interfaced to the patch, containing a power source and programmable micro-chip to determine the sequence of the analyte extraction mechanism, as well as any input or output communications.
Previous reverse iontophoretic systems discuss means of determining the concentration of an analyte such as glucose by extracting the glucose and then depleting the extracted glucose by reaction with an enzyme to determine the amount extracted (e.g., the former Glucowatch® developed by Cygnus, Inc).
However, optical methods would not necessarily deplete any or all of the extracted analyte as part of the detection process. Optical sensors would likely lead to a cumulative build-up of analyte extracted into the collection chamber, other than where the collection chamber is replaced after each extraction/measurement; the latter is possible, but not necessary. UK patent application GB 2502287 A, entitled "Cumulative measurement of an analyte", teaches a means of detecting the concentration of analyte based on cumulative build-up of substantially most of the extracted analyte; this principle may be applied here.
A patch, as described in patent application GB 2461355 A entitled "Patches for reverse iontophoresis", may be used to extract and collect the analyte from the skin, containing a skin attachment means, such as an adhesive or mechanical attachment means such as peripheral vacuum seal, or pressure applied using a belt of some form around the patch, a chamber containing an analyte diffusion or conducting medium, and a means of inducing withdrawal or extraction of the analyte from the skin. Techniques to extract analyte from the skin may include active methods and passive methods. Active methods are defined herein as methods that are continually or intermittently applied to enable sample extraction. These may include reverse iontophoresis (whereby electrodes would be present in electrical communication with the sample collection chamber, via a conductive medium), and thermal inducement of forced perspiration. Passive methods are defined here as methods whereby the skin is 'treated' at the outset to remove its barrier properties sufficiently to cause the analyte to flow out of the skin. These methods may include skin poration using microneedles or laser skin poration; skin ablation or abrasion using mechanical, physical or chemical means, or a combination of these methods, to continuously extract glucose and/or interstitial fluid, or analytes from the skin containing the analyte of interest. The latter of these methods would rely on the skin intervention method to lead to the continuous and passive diffusion of the analyte out of the skin thus not requiring an electrically conductive medium in which to collect the analyte, and instead any medium, liquid or gelatinous, such as polymeric, hydrogel, glycerine based, oil based, or water based (depending on the hydrophilicity/lipophilicity of the s analyte), for example could be employed to allow the analyte to either diffuse evenly throughout the medium, or diffuse into a region from which the analyte is to be measured, such that a representative concentration of the analyte can be determined using the non-invasive measurement means.
io The surface of the patch contains an optically and/or acoustically transparent window for the transmission of the light or sound radiation, and collection of returned radiation to detect and provide a qualitative or quantitative indication of the concentration of the analyte. The analyte may be an innate/internal component, e.g., physiological component of the subject, or an externally introduced component is such as a drug or other foreign molecule or entity. The transparent window may be composed of glass, ceramic, polymer or other material known in the prior art, or an absorbent material that is softer in nature, for acoustic transmission.
In the invention the reflector protects the skin below from potential injury caused by the incident energy source. A mask is provided to prevent the radiation bypassing the reflector to contact neighbouring areas of the skin. There is also a region above the reflective substrate, between it and the optical window or optically/acoustically transparent film, sufficient to allow the representative concentration of the analyte to be determined from the reflected radiation. The analyte may diffuse to this region via the periphery of the reflective film or through perforations within the film. In the event that perforations are created within the film, a mask of optically or acoustically opaque regions may be coated or applied to corresponding regions on the optically/acoustically transparent window.
The term characterisation is used here to define qualitative or quantitative analysis of molecules and chemical entities within the skin or extracted from the skin, including the determination of the concentration of said analyte. Qualitative analysis may involve merely determining the relative levels of two or more analytes. Characterisation may also involve the determination of structural properties of the analyte.
It will be understood to the person skilled in the art that the reflector described above is a substrate that is able to enhance the signal generated by the sample. There may be one or more reflectors or there may be a single reflector with perforations. The reflector may be planar, or it may be three-dimensional with io curved or angular surfaces, for example in the form of spherical beads, or particles, of the requisite surface properties.
Furthermore whilst glucose has been used as a prime example of an analyte to be measured, it will also be appreciated that the technique will also apply to other is analytes such as sodium, potassium, lithium, lactate, urea, and drugs. Whilst the analyte may be extracted adjacent to the skin, it will be also appreciated that for purposes of practicality the sample may be characterised away from the immediate vicinity of the area where the sample has been extracted, and this region is broadly defined as the 'collection chamber'. The term 'adjacent' to the skin is used to define a region in proximity to the region where the sample is extracted from the skin.
Drawings Figures 1 to 6 illustrate apparatus for characterisation of an analyte in a sample that has been extracted from the skin of a patient to a collection chamber adjacent to the surface. They are useful for understanding the present invention but do not fall within its scope.
Figure 1 -Cross section schematic showing the patch consisting of a skin attachment means 1, optically transparent window 2, analyte collection chamber 3, and reflective substrate 4 in contact with the skin 10.
Figure 2 -Cross section schematic similar to Fig. 1 but showing a reflective substrate 4A anchored within the adhesive layer 1 so as to be spaced a small distance from the surface of the skin 10, and conductive medium 8 shown around the underside and above the reflective substrate 4A.
Figure 3 -Cross section schematic similar to Fig. 1 but showing the reflective substrate 413 in a concave configuration, which may help to redirect the incident radiation back towards a focus at the sensor.
io Figure 4 -Exploded diagram schematically depicting an optical light source 7 transmitting radiation or acoustic waves through the optically transparent window 2 and a detector 11 for sensing the radiation received through the window 2 from the sample. The detected radiation may be radiation from the source 7 that has been reflected directly from the reflector 4, in which case changes in the radiation is due to its passage through the sample, such as the absorption or scattering of certain frequencies, will leave a signature characteristic of the presence and concentration of the analyte. Alternatively, the detected radiation may be that scattered or re-emitted by the analyte itself, which will have a recognizable characteristic.
In Fig. 4 the detector 11 is shown schematically as concentrically surrounding the source 7 but the positions could be exchanged, or the source 7 and detector 11 could simply be placed side by side or in any other convenient arrangement.
In Fig. 4 the reflector is shown to be perforated by apertures 6, through which the sample containing the analyte can diffuse from the skin below, thus ensuring that no part of the upper surface of the reflector 4 is so far from an edge that it cannot be reached by a representative concentration of the analyte. In order that the incident radiation from the source 7 should not pass through the apertures 6 and damage the skin below, the transparent window 2 is provided with a mask containing light opaque regions 5 aligned with the positions of the apertures 6 in the reflector 4.
Figure 5 -Cross section schematic showing electrodes/thermal device/analyte extraction mechanism 9 to induce the extraction of the analyte from the skin 10, positioned within the analyte collection chamber 3.
Figure 6 -Plan view of a convoluted electrode 9, which also serves as the reflector 4. By providing a long edge and a narrow width of the reflector 4, this is an alternative way of ensuring that no part of the upper surface of the reflector 4 is so far from an edge that it cannot be reached by a representative concentration of the io analyte diffusing around the edges of the reflector 4 under the influence of the electrode 9.
Figure 7 -Cross section schematic showing the reflective substrate 4 implanted below the surface of the skin 10 according to the invention. The sample 12 to be is analysed in accordance with the invention is the volume of the skin located between the reflector 4 and the outer surface, as indicated by stippling.
Claims (7)
- CLAIMS1. An apparatus for characterisation of an analyte in a sample volume of the surface layer of the skin of a patient, the apparatus comprising: a radiation source located outside the body and configured to irradiate the s sample; a reflector implanted beneath the surface layer of the skin to define the sample volume, the reflector being configured to receive incident radiation that has passed through the sample and reflect it back through the sample; a sensor located outside the body and configured to measure features of the io radiation emitted from the sample from which characterisation information about the analyte can be derived; and a mask to prevent radiation from the source bypassing the reflector.
- 2. An apparatus according to claim 1, wherein the analyte is glucose.
- 3. An apparatus according to claim 1 or claim 2, wherein the features of the radiation measured by the sensor include Raman scattered radiation.
- 4. A method of characterisation of an analyte in a sample volume of the surface layer of the skin of a patient, the method comprising: irradiating the sample; using a reflector that has been previously implanted beneath the sample volume of the surface layer of skin to receive radiation that has passed through the sample and reflect it back through the sample; using a mask to prevent radiation from bypassing the reflector; and measuring features of the radiation emitted from the sample from which characterisation information about the analyte can be derived.
- 5. A method according to claim 4, further comprising the step of applying 30 growth factors to the skin to promote capillary growth in the sample volume.
- 6. A method according to claim 4 or claim 5, wherein the analyte is glucose.
- 7. An apparatus substantially as described herein with reference to Figure 7 of the drawings.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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GB1522844.8A GB2531956A (en) | 2013-12-23 | 2013-12-23 | Device and method for characterisation of biological samples |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB1322953.9A GB2521627A (en) | 2013-12-23 | 2013-12-23 | Device and method for characterisation of biological samples |
GB1522844.8A GB2531956A (en) | 2013-12-23 | 2013-12-23 | Device and method for characterisation of biological samples |
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GB201522844D0 GB201522844D0 (en) | 2016-02-03 |
GB2531956A true GB2531956A (en) | 2016-05-04 |
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GB1322953.9A Withdrawn GB2521627A (en) | 2013-12-23 | 2013-12-23 | Device and method for characterisation of biological samples |
GB1522844.8A Withdrawn GB2531956A (en) | 2013-12-23 | 2013-12-23 | Device and method for characterisation of biological samples |
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GB (2) | GB2521627A (en) |
WO (1) | WO2015097190A2 (en) |
Cited By (1)
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WO2020152380A1 (en) | 2019-01-22 | 2020-07-30 | Universidad De Sevilla | Portable device and method for non-invasive blood glucose level estimation |
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2014
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WO2020152380A1 (en) | 2019-01-22 | 2020-07-30 | Universidad De Sevilla | Portable device and method for non-invasive blood glucose level estimation |
Also Published As
Publication number | Publication date |
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GB2521627A (en) | 2015-07-01 |
WO2015097190A2 (en) | 2015-07-02 |
GB201322953D0 (en) | 2014-02-12 |
GB201522844D0 (en) | 2016-02-03 |
WO2015097190A3 (en) | 2016-05-26 |
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