Classifications

• • 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
  • A61B5/145—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

Definitions

• the present invention relates to implantable sensors, and more specifically, to implantable sensors for monitoring levels of analytes, such as glucose.
• European patent 0 074428 describes a method and device for the quantitative determination of glucose by laser light scattering.
• the method assumes that glucose particles scatter light rays transmitted through a test solution, and that the glucose concentration can be derived from this scattering.
• the method requires measurement of the spatial angular distribution of the transmitted (i.e. forward-scattered) light emerging from a test cuvette or an investigated part of the body.
• the intensity of the transmitted light is measured in an angular region in which the change in relation to the glucose concentration is as large as possible. This intensity is then compared with the intensity measured for the central ray passing directly through the sample.
• a transmission measurement on ear lobes with laser light is exclusively recommended.
• a second method based on light scattering principles relies on the measurement of back- scattered light rather than transmitted (i.e. forward-scattered) light.
• U.S. Pat. No. 5,551,422 describes a method for determining glucose concentration in a biological matrix by performing at least two detection measurements. In each detection measurement, primary light is irradiated into the biological matrix through a boundary surface thereof at a defined radiation site. The light is propagated along a light path within the biological matrix. An intensity of the light is measured as the light emerges as secondary light through a defined detection site of the boundary surface. At least one of the detection measurements is a spatially resolved measurement of multiply scattered light.
• the detection site is located relative to the irradiation site such that light which was multiply scattered at scattering centers in the biological matrix is detected.
• the light paths of the at least two detection measurements within the biological matrix are different.
• Glucose concentration is then derived from the dependence of the intensity of the secondary light on the relative positions of the irradiation site and the detection site.
• the present invention in another form thereof, comprises an implantable optical- sensing element suitable for measuring the concentration of an analyte in a biological matrix.
• the optical-sensing element comprises a body, and a membrane mounted on the body such that the body and the membrane define a cavity for receiving the analyte.
• the membrane is substantially permeable to the analyte, and substantially impermeable to background species in the biological matrix, such as large proteins.
• a refractive element having a refractive index different from the refractive index of the analyte is disposed in the cavity.
• a light source provides light into each of the first and second cavities toward the respective first and second refractive elements, and a light detector receives light from each of the first and second cavities.
• a signal processor and computer are provided to relate the respective intensities of the provided light and the received light to the analyte concentration.
• the present invention in still another form thereof, comprises an implantable optical- sensing element suitable for measuring the concentration of an analyte in a biological matrix.
• the optical-sensing element comprises a body and a first semi-permeable membrane mounted on the body.
• the first membrane is permeable to the analyte, and impermeable to background species in the biological matrix.
• the first membrane and the body are aligned to define a first cavity, the first cavity having a first refractive element disposed therein.
• a second membrane is mounted on the body remote from the first membrane.
• the second membrane and the body are aligned to define a second cavity isolated from the first cavity, the second cavity having a second refractive element disposed therein.
• the present invention in yet another form thereof, comprises a method for measuring the concentration of an analyte in a biological matrix.
• An optical-sensing element is implanted in the biological matrix, the optical-sensing element comprising a body and a semi-permeable membrane mounted on the body, the semi-permeable membrane being permeable to the analyte and impermeable to background species in the matrix.
• the semi-permeable membrane and the body define a cavity, and a refractive element is disposed in the cavity.
• Primary light from a light-emitting source is introduced into the body of the optical-sensing element, and is directed toward the refractive element.
• the present invention in another form thereof, comprises a method for measuring the concentration of an analyte in a biological matrix.
• An optical-sensing element is implanted in the biological matrix, the optical-sensing element comprising a body, a first semi-permeable membrane mounted on the body, and a second semi-permeable membrane mounted on the body remote from the first semi-permeable membrane.
• the body and the first membrane define a cavity having a first refractive element disposed therein, and the body and the second membrane define a second cavity isolated from the first cavity and having a second refractive element disposed therein.
• Primary light from a light-emitting source is transmitted into the body, and respective streams of the primary light are directed into the first cavity toward the first refractive element, and into the second cavity toward the second refractive element.
• Light reflected from the first refractive element is collected and transmitted to a first channel of a light-detecting device, and light from the body reflected at the second refractive element is collected and transmitted to a second channel of the light-detecting device.
• the respective intensities of light collected from each of the first and second channels is measured, and the concentration of an analyte in the biological matrix is computed by comparing the intensity of the transmitted light and the light collected from each of the first and second channels.
• the present invention in yet another form thereof, comprises an assembly for monitoring the concentration of an analyte in a biological matrix.
• the assembly includes an implantable optical-sensing element that comprises a body, a membrane mounted on the body, and a refractive element disposed in a cavity defined by the membrane and the body.
• the analyte is received in the cavity through the membrane, wherein the membrane is substantially permeable to the analyte of interest and substantially impermeable to background species in the biological matrix.
• One or more light sources provide light of a first wavelength and a second wavelength into the cavity, the refractive element in the cavity having a refractive index greater than the refractive index of the analyte at the first wavelength, and less than the refractive index of the analyte at the second wavelength.
• a detector receives from the cavity an intensity of light at each of the first and second wavelengths at a first concentration of said analyte, and receives an intensity of light at each of the first and second wavelengths at a second concentration of the analyte.
• a signal-processing and computing element is optically coupled to the detector for comparing the intensities of light received at the first wavelength to the intensities of light received at the second wavelength, and for relating the intensities to analyte concentration.
• Figure 2 shows a front cross-sectional view through the XjY plane of the optical- sensing element illustrated in Figure 1;
• Figure 3 shows a shows a top cross-sectional view through the XjZi-plane of the optical- sensing element illustrated in Figure 1;
• Figure 5 shows a front cross-sectional view through the X 2 Y 2 -plane of the optical - sensing element illustrated in Figure 4;
• Figure 6 shows a top cross-sectional view through the X 2 Z 2 -plane of the optical-sensing element illustrated in Figure 4;
• Figure 7 shows a side cross-sectional view through the Y 3 Z 3 -plane of an optical- sensing element according to a third embodiment of the present invention
• Figure 8 shows a front cross-sectional view through the X 3 Y 3 -plane of the optical- sensing element illustrated in Figure 7
• Figure 9 shows a top cross-sectional view through the X 3 Z 3 -plane of the optical-sensing element illustrated in Figure 7;
• Figure 11 shows a top cross-sectional view through the X Y -plane of the optical-sensing element illustrated in Figure 10;
• Figure 12 shows a front cross-sectional view through the X 4 Z -plane of the optical- sensing element illustrated in Figure 10;
• Figure 14 shows a side cross-sectional view through the X 5 Ys-plane of the optical- sensing element illustrated in Figure 13;
• Figure 16 shows a side cross-sectional view through the Y 6 Z 6 -plane of an optical-sensing element according to a sixth embodiment of the present invention
• Figure 19 shows a side cross-sectional view through the Y 7 Z 7 -plane of an optical-sensing element according to a seventh embodiment of the present invention
• Figure 23 shows another block diagram of the an opto-electronic detection and measurement assembly optically coupled to an optical-sensing element of the type described in embodiments 1-5;
• biological matrix denotes a body fluid or a tissue of a living organism.
• Biological matrices, to which the invention relates are optically heterogeneous, that is, they contain a large number of substances (e.g., salts, proteins, and organic acids) which can affect the refractive index.
• mMol denotes the concentration of a substance in units of millimoles per liter.
• n denotes the refractive index of a substance.
• the present invention provides an assembly comprising an implantable optical-sensing element suitable for measuring the concentration of an analyte in a biological matrix.
• the function of the optical-sensing element is to generate changes in light refraction, which changes are a function of changes in the concentration of the analyte in the biological matrix.
• the optical-sensing element includes a membrane mounted on a body, such that the membrane and the body define a cavity.
• the membrane is substantially permeable to the analyte, thereby permitting the analyte to pass through the membrane and into the cavity by means such as diffusion or osmosis, and is substantially impermeable to background species in the biological matrix.
• the optical-sensing element of the present invention is stable over extended periods of time, does not require frequent recalibration, and does not require signal amplification through enzymatic reactions.
• the optical-sensing element also minimizes or eliminates background drift in such measurements due to variations in physical parameters such as temperature and/ or changes in the concentrations of background ions, proteins, and organic acids that may be present in the biological matrix.
• an analyte suitable for monitor utilizing the assembly of the present invention is glucose. It is well known that a change in concentration of an analyte, such as glucose, in a test solution results in a change in the refractive index of the solution.
• the present invention addresses this problem by providing an optical-sensing element having a substantially impermeable body that is enclosed on at least one surface thereof by a semi-permeable membrane.
• the semi-permeable membrane is designed to exclude undesired background molecules and/ or ions from entering/exiting the interior of the body, while allowing the analyte or analytes of interest to freely diffuse through the membrane.
• the analyte of interest is glucose
• the glucose diffuses through the membrane to equilibrate with tissue glucose concentration.
• Background species cannot permeate through the membrane.
• proteins can be excluded by using membranes with adequate pore size (e.g., 30kD to exclude albumin but enable glucose diffusion), and ions can be excluded by using a polarized membrane (+/-) layer.
• Suitable bipolar membranes for use in the present invention include those produced by Tokuyama Soda (Japan) under the trade name of NeoSepta, available from Electrosynthesis Company, Lancaster, NY. These membranes are produced for bulk electrolysis and salt-splitting applications, and thus are mechanically very stable and rigid. They possess the high charge densities required for use in the high salt concentrations of biological matrices. These membranes are approximately 250 um in thickness, and maybe cut to any appropriate size. Thinner membranes of lower ionic content could also be used. Thinner membranes are advantageous because they decrease the response time of the sensor and may provide more accurate results.
• a thinner bipolar membrane is used to enable a more rapid response time, it may be desirable to combine the bipolar membrane with a third membrane layer capable of excluding macrosolutes.
• a third membrane layer may, for example, be any of the membranes typically used for dialysis applications, such as regenerated cellulose or polyamide membranes.
• the third membrane layer may be attached to the sensor body, on or around the bipolar membrane, using any of the methods suitable for attaching the bipolar membrane.
• the third membrane layer may be laminated directly to the bipolar membrane prior to application of the bipolar-membrane to the sensor body.
• the third membrane layer may be formed on the bipolar membrane by a casting process, for example, by dipping the assembled optical-sensing element with bipolar membrane attached into a solution of a membrane- forming polymer, and then drying the element under controlled conditions.
• Bipolar membranes can be formed into hollow fibers in the same way that membranes for dialysis and microdialysis are produced, and the membrane fibers slid over the sensor structure and attached with any of the above methods.
• the sensitivity of the measurement is optimized when the refractive index of a refractive element disposed within the body, and the refractive index of an analyte such as glucose are preferably within 9%, more preferably within 5%, of each other when the glucose concentration in the biological matrix is at physiological levels, i.e., between 4 and 7 mMol.
• the body 100 of the optical-sensing element has a generally "U” or “V"- shaped cross-section, and comprises a molded plastic.
• the body 100 has a base portion 101 and two opposing side walls 103. Each of the side walls 103 includes an upper edge 111.
• the body 100 has a proximal end 102 and a distal end 104, and is preferably less than 2 mm in length.
• a light-transmitting conduit 106 here a single optical fiber, is optically coupled to the proximal end 102 of the body.
• Optical coupling between the body and the conduit can be accomplished by any means known in the art, such as, for example, using an adhesive to secure the conduit 106 in an orifice formed in the body 100.
• the body 100 of the optical-sensing element provides a support structure for the optical-sensing element and should correspondingly be rigid or semi-rigid. Since the sensing element is designed to be implanted in living tissue, the construction material of the body 100 should also be bio-compatible.
• the distal end 104 of the body 100 preferably comprises a light absorbing material 108, although a transparent material may alternatively be utilized.
• the refractive element 114 can comprise a single structure or a plurality of structures. No particular shape is required. Examples of single structures include a porous fiber, a porous rod, a convoluted ribbon, and a convoluted fiber. The refractive element may also comprise combinations of the foregoing. Examples of pluralities of structures include regular or randomly shaped plates, particles, beads and powders, or combinations of the foregoing. Regardless of the particular embodiment, the refractive element preferably provides a plurality of reflective or refractive faces 115 that interface with the analyte to amplify the reflected light when compared to light reflected from a single surface.
• the body 200 of the optical-sensing element comprises two parallel, elongated members 203, each having an upper edge 211 and a lower edge 213.
• the body is preferably formed of molded plastic and is dimensioned in similar manner to the embodiment of Figs. 1-3.
• the body 200 also includes a proximal end 202 and a distal end 204.
• a light-transmitting conduit 206 here a single optical fiber, is sealed in an orifice in the proximal end 202.
• the distal end 204 preferably comprises a light-absorbing material 208.
• a first semi-permeable membrane 210 is attached to the top edges 211 of the elongated members 203, and a second semi-permeable membrane 209 is attached to the bottom edges 213 of the elongated members 203.
• the elongated members 203 and semi-permeable membranes 209 and 210 define a cavity 212.
• the cavity contains the analyte of interest (not shown) and a refractive element 214.
• the refractive element comprises a plurality of substantially parallel, rectangular plates, and the elongated members 203 are held together with cross-support from the rectangular plates.
• the numbers and orientation of rectangular plates 214 and faces 215 are similar to those as described in the previous embodiment.
• a fourth embodiment of the invention is illustrated in Figures 10-12.
• the body 400, base portion 401, side walls 403, light-transmitting conduit 406, light-absorbing material 408, membrane 410, edges 411, cavity 412, and respective proximal and distal ends 402 and 404 are as described in the embodiment of Figs. 1-3.
• the refractive element 414 comprises a convoluted ribbon or fiber, which provides a plurality of reflective or refractive surfaces 415.
• the composition, length, width, and - thickness of the ribbon 414 can be varied to achieve a packing arrangement which gives optimal amplification of light by multiple reflections off the surfaces 415.
• the particular composition of the ribbon or fiber is normally not important, as long as suitable reflective or refractive surfaces are provided. Glass or plastic ribbons and fibers are particularly suitable.
• the refractive elements preferably are made from the same material as the body 600 and comprise a plurality of substantially parallel, rectangular plates as before.
• the first and second light-absorbing materials, 608 and 618 respectively, preferably have the same composition.
• the second semi-permeable membrane 620 may have the same composition as its counterpart in the first cavity 612, or a different composition.
• the distal end 704 of the body 700 preferably comprises a first light- absorbing material 708 adjacent the first cavity 712.
• the first cavity 712 contains a first refractive element 714.
• the first refractive element 714 is preferably made from the same material as the body 700, and comprises a plurality of substantially parallel, rectangular plates.
• the second refractive element 724 is preferably made from the same material as the body 700, and comprises a plurality of substantially parallel, rectangular plates.
• the first and second light- absorbing materials, 708 and 718 respectively, preferably have the same composition.
• the second semi- permeable membrane 720 may independently have the same composition as its counterpart in the first cavity 712, or a different composition.
• the sixth and seventh embodiments of this invention are particularly useful for simultaneously measuring the concentration of two different analytes in a biological matrix. This maybe accomplished by choosing respective semi-permeable membranes that are permeable to different species.
• the first semi-permeable membrane could be permeable to analyte A but impermeable to analyte B, while the second semi-permeable membrane could be permeable to analyte B but impermeable to analyte A.
• the first cavity would then be used to monitor the concentration of analyte A, while the second cavity would be used to monitor the concentration of analyte B.
• the sixth and seventh embodiments of this invention may also be useful for correcting for background changes in the refractive index of a biological matrix resulting from variations in physical parameters like temperature.
• the first semi- permeable membrane could be permeable to only analyte A, while the second semi- permeable membrane could be impermeable to all of the components (analytes) of the biological matrix.
• the first cavity would then constitute a sample cell, while the second cavity would constitute a reference cell.
• the sample cell could be used to monitor changes in light resulting from changes in the concentration of analyte A and physical changes in the environment of the sensing element.
• the reference cell could be used to monitor changes in light intensity resulting solely from physical changes in the environment of the biological matrix. The differences in light intensity between the sample and reference cells would then correlate to the change in refractive index of the biological matrix due solely to a change in concentration of analyte A.
• the first semi-permeable membrane could be permeable to analyte A and background species in the biological matrix, while the second semi-permeable membrane could be permeable to the background species but impermeable to analyte A.
• the first cavity would still constitute a sample cell, while the second cavity would constitute a reference cell.
• the sample cell would now be used to monitor changes in light intensity resulting from changes in the concentration of analyte A, physical changes in the environment of the sensing element, and changes in the concentration of the background species.
• the reference cell would be used to monitor changes in light intensity resulting from physical changes in the environment of the sensing element and changes in the concentration of the background species.
• the implantable analyte sensor of the present invention is designed to optically couple with an opto-electronic detection and measurement assembly.
• the opto-electronic detection and measurement assembly may include the light source for transmitting light from the light source to the sensing element, or alternatively, the light source may comprise a separate assembly.
• the opto-electronic detection and measurement assembly includes a detector for receiving light that has been returned or otherwise reflected from the sensing element.
• a signal-processing and computing element is optically coupled to the detector to compare the intensity of the received light to that of the transmitted light. By using previously measured reference values, the signal- processing and computing element converts the differences in light intensity to a signal relating to analyte concentration. The signal can then be displayed on a readout device.
• LEDs laser diodes, xenon and metal halide lamps, can be used as the light source.
• FIG. 22 A block diagram of an opto-electronic detection and measurement assembly optically coupled to an optical-sensing element of the type described in embodiments 1-5 is shown in Figure 22.
• the first end 802 of a first light-transmitting conduit 800 is optically coupled to the proximal end 806 of the body of the optical-sensing element
• the second end 804 of the first light-transmitting conduit 800 is optically coupled to both a light- emitting source and a light-detecting device.
• optical coupling is provided by a beam-splitter 810.
• the beam-splitter is preferably tilted such that the angle of incoming light is equal to the angle of reflected light, and is oriented such that secondary light emitted from the second end 804 of the first light-emitting conduit 800 is directed into a second light-transmitting conduit 814 connected to a light-detecting device.
• the light- detecting device can be, for example, a photomultiplier tube or a photodiode.
• the beam-splitter 810 is also oriented such that primary light emitted from a third light-transmitting conduit 812 connected to the light- emitting source is directed into the second end 804 of the light- transmitting conduit 800.
• the source can emit light either continuously or in a pulsed mode. Suitable light sources and detectors can be purchased from Hamamatsu Corporation, Bridgewater NJ.
• the light-detecting device is electrically coupled to a signal-processing and computing element which converts the secondary light to an electronic signal that can be read in conventional fashion, such as by visual display on a conventional readout device.
• the signal-processing and computing element may comprise, for example, a conventional controller such as a software-driven computer.
• each of the first, second, and third light-transmitting conduits, 800, 814, and 812 respectively, comprises one or more optical fibers.
• Suitable optical fibers and optical fiber bundles can be purchased from Polymicro Technologies, LLC of Phoenix, AZ.
• Suitable beamsplitters for optical fibers can be purchased from Oz Optics LTD. of Carp, Ontario, Canada.
• first end 912 of a second light-transmitting conduit 910 which is optically coupled to the proximal end 906 of the body of the optical-sensing element.
• the second end of the conduit 914 is optically coupled to a light-detecting device, for example using an SMA connector.
• the light-detecting device can be, for example, a photomultiplier tube or a photodiode.
• each of the first and second light- transmitting conduits, 900 and 910 respectively, comprises one or more optical fibers.
• the light-detecting device is electrically coupled to a signal-processing and computing element, which converts the secondary light to an electronic signal, which can be displayed on a readout device.
• FIG. 24 A block diagram of an opto-electronic detection and measurement assembly optically coupled to an optical-sensing element of the type described in embodiments 6-7 is shown in Figure 24.
• Primary light is emitted from a light- emitting source.
• the light- emitting source is optically coupled to the first end 922 of a first light- transmitting conduit 920.
• the second end 924 of the first light- transmitting conduit 920 is optically coupled to the proximal end 926 of the body of the optical-sensing element adjacent the first cavity, in an alignment such that the primary light is directed into the first cavity toward the first refractive element.
• Secondary light resulting from reflection or refraction at the first refractive element is collected in the first end 942 of a second light- transmitting conduit 940.
• the first end 942 of the second light-transmitting conduit 940 is optically coupled to the proximal end 926 of the body of the optical-sensing element adjacent the first cavity, while the second end 944 is optically coupled to a channel of a light-detecting device.
• the light-detecting device can be, for example, a photomultiplier tube or a photodiode.
• the light-emitting source is optically coupled to the first end 932 of a third light- transmitting conduit 930.
• the second end 934 of the third light- transmitting conduit 930 is optically coupled to the proximal end 926 of the body of the optical- sensing element adjacent the second cavity, in an alignment such that the primary light is directed into the second cavity toward the second refractive element. Secondary light resulting from reflection or refraction at the second refractive element is collected in the first end 952 of a fourth light-transmitting conduit 950.
• the invention further contemplates a method of measuring the concentration of an analyte in a biological matrix.
• an optical-sensing element is inserted in the matrix.
• the optical-sensing element includes a body, a semi-permeable membrane and a refractive element as described previously.
• primary light is transmitted from a light- emitting source to the body of the optical-sensing element, and directed into the cavity to the refractive element.
• secondary light resulting from the reflection or refraction of the light at the refractive element is collected and read by a light- detecting device.
• the difference in intensity between the transmitted light and the reflected light is measured by a standard computing device, and the analyte concentration in the biological matrix is determined by the computing device using, for example, an algorithm and calibration procedure.
• algorithm and calibration procedure are well known to those of ordinary skill in the art.
• changes in light intensity returned from the optical sensing component can be related to changes in the concentration of a specified analyte, such as glucose, in the biological matrix without the necessity of spectroscopic measurement at multiple wavelengths.
• a specified analyte such as glucose
• the principle relied on is light reflection, not optical absorption.
• the wavelength is preferably chosen in a region of the spectrum where absorption of the analyte is relatively low.
• the wavelength is between 400 nm and 1300 nm. Other wavelengths outside of this range may be utilized in suitable cases, provided that interfering species are not substantially present in the matrix, or if present, are compensated for by the use of proper reference test samples.
• these spectral regions need not normally be further narrowed to avoid interferences due to absorption by other components in the biological matrix (e.g., hemoglobin), since the semi-permeable membrane excludes such components from the sensing volume.
• other components in the biological matrix e.g., hemoglobin
• the semi-permeable membrane excludes such components from the sensing volume.
• there is no particular preference for relatively short wavelengths because the method does not depend on the depth of penetration of light into the biological matrix.
• absorption-based methods for noninvasive analytical determination of the glucose concentration in a biological matrix in the present invention it is generally not necessary to use narrow-band measurement, due to the minimal dependence on the measurement wavelength.
• relatively broad-banded light sources (with half- widths larger than 20 nm), such as light-emitting diodes (LED's) and other semi-conductor light sources, can be used without the need for subsequent spectral selection on the primary side or secondary side. This considerably reduces the cost of the apparatus.
• This feature makes the apparatus especially suitable for the continuous monitoring of the glucose concentration of a diabetic. Even though it is generally not necessary to use a laser as a primary light source, in some situations, such as with planar refractive surfaces, laser light may be utilized if desired. Similarly, it is generally not necessary to use coherent or polarized light.
• An alternative arrangement to that described above utilizes one or more light sources that emit light into the cavity at defined wavelengths in order to exploit the dispersion (i.e., wavelength-dependence) of the refractive indices of the refractive material and/or the analyte.
• a light source emits light having a wavelength ⁇ i at which the refractive index of the refractive element ⁇ e i ement is always greater than the refractive index of the analyte n ana i y te-
• Another light source emits light having a wavelength ⁇ 2 at which the refractive index of the refractive element n e i ement is always less than the refractive index of the analyte ⁇ ana i yte .
• a single light source that emits light at multiple wavelengths may be used in combination with a (dichroic) beam splitter to split the light into separate beams at the desired wavelengths.
• n ana i yte increases and therefore n ⁇ increases for both ⁇ i and ⁇ 2 .
• this arrangement can be used to improve the sensitivity and/or the specificity of the method.
• either a single detector or multiple detectors can be used. For example, when two wavelengths ⁇ j . and ⁇ 2 are used as described above, two separate detectors can be utilized to receive the signals. One detector would receive the " ⁇ i -light" and the other would receive the " ⁇ 2 - light".
• a wavelength-dependent dicroic beam splitter can be used to isolate the proper wavelength from the reflected light.
• a controller could then be utilized to analyze the signals by means such as signal subtraction to yield an analyte-dependent result.
• a single detector may also be utilized, however in this instance, the signals are generally received alternating in time.
• Suitable light sources for use in this multiple wavelength approach include multiple independent single light sources each having a different wavelength.
• a beam splitter may be utilized with a single, multichromatic light source to split the light into separate beams at different, well-defined wavelengths.
• the sensor could be designed as a transcutaneous sensor, which uses a light guide to transmit light to and from the optical-sensing element.
• the sensor could be an integrated device.
• the implanted device would incorporate the light- emitting and optical-sensing elements in a single element.
• a fully compatible sensor unit can also include RF data transmission means and a battery charge.

Priority Applications (4)

Applications Claiming Priority (2)

Publications (2)

Family

ID=25204303

Family Applications (1)

Country Status (6)

Cited By (5)

Families Citing this family (220)

Citations (5)

Family Cites Families (20)

• 2001
  • 2001-03-16 US US09/810,635 patent/US6952603B2/en not_active Expired - Fee Related
• 2002
  • 2002-03-18 EP EP02703638A patent/EP1372466A2/en not_active Withdrawn
  • 2002-03-18 WO PCT/EP2002/002960 patent/WO2002074161A2/en active Application Filing
  • 2002-03-18 AU AU2002237332A patent/AU2002237332A1/en not_active Abandoned
  • 2002-03-18 CA CA 2440854 patent/CA2440854C/en not_active Expired - Fee Related
  • 2002-03-18 JP JP2002572876A patent/JP3692116B2/ja not_active Expired - Lifetime
• 2005
  • 2005-04-27 US US11/116,099 patent/US20050271547A1/en not_active Abandoned
  • 2005-04-27 US US11/115,889 patent/US7499738B2/en not_active Expired - Fee Related

Patent Citations (5)

Also Published As

Similar Documents

Legal Events