Patent Application
20130060106
Embodiments of the present invention relate generally to sensor technology, including sensors used for sensing a variety of physiological parameters, e.g., glucose concentration. More particularly, embodiments of the invention relate to optical sensors, to methods of making and using such sensors, to optical and optoelectronic systems for interrogating optical sensors, and to methods of making and using such optical/optoelectronic systems. More particularly still, embodiments of the invention relate to optical fiber sensors including a fluorophore-labeled assay, to stacked planar optical integrated systems for interrogating such optical fiber sensors, and to methods of making and using such optical fiber sensors and optical integrated systems.
Epifluorescence microscopy is a method of fluorescence microscopy that is becoming increasingly used in the biological and medical fields. An epifluorescence microscope is used primarily to excite a specimen by passing a source light through an objective lens and then onto the specimen. The fluorescence in the specimen generates emitted (fluorescent) light which is focused onto a detector by the same objective lens that is used for the excitation. Since most of the source light is generally transmitted through the specimen, only reflected source light reaches the objective lens together with the fluorescent light. An additional filter between the objective lens and the detector can filter out the remaining source light from fluorescent light.
The underlying principles of epifluorescence microscopy may be used in optical, or optoelectrical, systems for interrogating assay-based glucose sensors. The assay in such sensors may be interrogated using a variety of methods, such as Streak Camera recording, single photon counting, frequency domain lifetime measurement, and steady state fluorescence measurement. In both the frequency domain lifetime and steady state fluorescence interrogation, the function of the optical interrogation system is to excite the assay fluorophore(s) and prevent the excitation light from reaching the detector(s) while, at the same time, transmitting the emitted fluorescence. It is understood that the fluorescence emitted from fluorophore-labeled assays is generally weak. Therefore, it is important to excite the assay as efficiently as possible and to gather as much of the isotropically emitted fluorescence as possible.
In the context of a continuous glucose monitor based on frequency domain lifetime interrogation and steady state fluorescence interrogation, it is important not only to minimize the cost, size, and weight of the (optical system) instrumentation and of the optical sensor, but also to optimize manufacturability of both the instrumentation and the sensor. In this regard, the currently-used optical systems are in general fairly large and expensive, and require precision assembly as they include a number of different optical components. Thus, improved optical systems and optical glucose sensors, including sensors for use with such optical systems, are needed that address the above-mentioned requirements.
In accordance with one embodiment of the invention, an optical glucose sensor includes an optical fiber with a glucose-permeable membrane joined to its distal end. The membrane may be, e.g., tube-shaped, such that its hollow interior defines a compartment for holding an assay. In one aspect of the invention, the assay is a competitive glucose binding affinity assay that includes a glucose receptor, a glucose analog, a first (donor) fluorophore labeled onto the glucose receptor, and an acceptor dye labeled onto the glucose analog. In a variation of this aspect of the invention, the assay may include a reference fluorophore in addition to the first fluorophore.
In accordance with another embodiment of the invention, the optical fiber of the optical glucose sensor includes a compound parabolic concentrator (CPC)-shaped tip that is in direct contact with the assay. In yet another aspect, a reflector may be disposed within the compartment, opposite the CPC-shaped tip, to reflect fluorescence that is emitted from the assay towards the CPC-shaped tip.
Embodiments of the invention are also directed to optical systems for lifetime and/or intensity interrogation of the assay. Thus, in one aspect, a fluorophore-labeled assay may be interrogated by an optical interrogating system including a light source and a filter substrate having one or more coatings to effect, e.g., an excitation filter and/or an emission filter. In another aspect, the interrogating system may be manufactured as a wafer-scale stacked planar integrated optical system (SPIOS) and diced into smaller units.
Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings which illustrate, by way of example, various features of embodiments of the invention.
In the following description, reference is made to the accompanying drawings which form a part hereof and which illustrate several embodiments of the present invention. It is understood that other embodiments may be utilized and structural and operational changes may be made without departing from the scope of the present invention.
As shown in the drawings for purposes of illustration, embodiments of the invention are directed to optical sensors that may be interrogated by optical, or optoelectronic, systems. Optical sensors may be introduced and/or lodged transdermally, or may be implanted in and/or through subcutaneous, dermal, sub-dermal, inter-peritoneal, or peritoneal tissue. In the discussion herein, preferred embodiments of the devices, systems, and methods of the invention are described with reference to glucose as the analyte whose level/concentration in the blood and/or bodily fluids of the user is to be determined. However, this is by way of illustration and not limitation, as the principles, devices, systems, and methods of the present invention may be used for sensing and/or determining the level of a variety of other physiological parameters, agents, characteristics, and/or compositions.
As will be described in more detail below, an optical glucose sensor having an assay compartment may be formed, e.g., by including a glucose permeable membrane containing the assay at the distal end of an optical fiber. The optical fiber may then be inserted transdermally into the user's body, thereby situating the assay compartment in the user's tissue, while leaving at least a part of the optical fiber outside the body such that it can be accessed by an interrogating system. Alternatively, the optical sensor may be implantable, e.g., as part of an implantable glucose monitor including an interrogating optoelectronic system and a power source. The assay compartment may be formed between a glucose permeable membrane and an optical interface to the optoelectronic system. The optical sensor may preferably be biodegradable.
As shown in
Several molecules may serve as the glucose receptor in the glucose assay. Examples include, but are not limited to, Concanavalin A, periplasmic glucose/galactose-binding receptor, antibodies raised against glucose-like molecules, Boronic Acids, and Mannan Binding Lectin (MBL). Mannan Binding Lectin is human protein, which is a part of the innate immune system. Thus, the assay may include MBL as the glucose receptor and dextran as the glucose analog.
The binding between MBL and glucose-like molecules (e.g., dextran) is reversible. When no glucose is present, MBL and dextran will predominantly be bound together. When glucose is added to the assay, it will compete off a part of the dextran population, such that the assay enters a new equilibrium state. The equilibrium state at all times corresponds to the glucose concentration. In order to determine this equilibrium state, MBL is labeled with a fluorophore (e.g., Alexa Fluor 594, or AF594), and the dextran is labeled with a dye (e.g., hexamethoxy crystalviolet-1 (HMCV1)—a proprietary crystal violet derivative, Medtronic, Inc.). The donor fluorophore and the acceptor dye together form a Förster Resonance Energy Transfer (FRET) pair—i.e., the emission spectrum of the fluorophore and the absorption spectrum of the dye overlap.
The occurrence of FRET affects the lifetime of the excited state and the intensity of the emitted fluorescence and can only occur when the fluorophore and the corresponding dye are in close proximity (i.e., in the range of about 50Å). Thus, the FRET mechanism permits interrogation of the equilibrium state optically by illuminating the assay and measuring either the lifetime of the excited state, and/or the intensity of the emitted fluorescence from the donor fluorophore. It is noted that the donor fluorophore and the acceptor dye are preferably water soluble, as they are to function in an aqueous environment.
f
opt=1/(2*π*τ) Eq. (1)
Thus, for a lifetime of 3 ns, e.g., the optimum modulation frequency (fopt) is in the range of about 50 MHz to about 60 MHz.
With reference to
The emitted fluorescence 103 and the reflected excitation light 123 are picked up and collimated by the lens 150. The dichroic beam splitter 140 transmits the fluorescence 103. However, it reflects the majority of the back-reflected excitation light 123. An emission filter 160 with a distinct wavelength region red shifted with respect to, and not overlapping, the pass band of the excitation filter blocks the remaining part of the excitation light 123 and transmits the fluorescence 103. Thus, in effect, only the fluorescence carrying the modulated and phase shifted fluorescence is focused onto a photodetector 180 using a lens 170. The phase lag between the detected fluorescence and the excitation light correlates with the glucose concentration in the assay.
In addition to the lifetime of the excited state, the intensity of the emitted fluorescence also correlates to the glucose concentration. In contrast to a lifetime measurement, the measured intensity of the emitted fluorescence is affected by the intensity of the light source and the coupling between the assay and the optical system. Therefore, the intensity measurement requires an internal reference fluorophore to be incorporated into the assay, as shown in
The reference fluorophore must differ from the assay fluorophore in a way that the emitted fluorescence from the assay and that from the reference may be separated from one another, e.g., by having different absorption spectra or emission spectra. The reference fluorophore may be, e.g., Alexa Fluor 700 (AF700) labeled onto Human Serum Albumin (HSA) or another macro molecule, which largely does not bind to the glucose receptor. See
The excitation, as well as the detection, of the emitted fluorescence for the assay and the reference follow the same optical path from the optical system to the assay. As such, the detected signal from the reference serves as a measure for the optical coupling between the optical interrogating system and the assay. Any effect originating from changes in the optical coupling such as alignment may be cancelled out.
The assay and the reference emit fluorescence. The emitted fluorescence 301 and the reflected excitation light 323 are picked up and collimated by the lens 350. The first dichroic beam splitter 340 transmits the fluorescence 301. However, it reflects the majority of the back reflected excitation light 323. A second beam splitter 344 reflects the reference fluorescence at a 90° angle 307, but it transmits the assay fluorescence 309. An assay emission filter 360 with a distinct wavelength region red shifted with respect to, and not overlapping, the pass band of the excitation filter and matching the desired part of the assay fluorescence spectrum then blocks the remaining part of the excitation light and transmits the assay fluorescence.
Similarly, a reference emission filter 364 with a distinct wavelength region red shifted with respect to, and not overlapping, the pass band of the excitation filter and matching the desired part of the reference fluorescence blocks the remaining part of the excitation light and transmits the reference fluorescence 307. Thus, in effect, only the fluorescence from the assay and the fluorescence from the reference are focused onto their respective photo detectors 380, 384 using respective lenses 370, 374. The ratio between the detected assay fluorescence and the detected reference fluorescence correlates with the glucose concentration in the assay. As mentioned previously, any changes in light-source intensity or optical coupling will be cancelled out as they scale the assay and reference fluorescence equally.
As described in connection with
Similarly, an assay emission filter 360 with a distinct wavelength region red shifted with respect to, and not overlapping, the pass band of the excitation filter and matching the desired part of the assay fluorescence blocks the remaining part of the excitation light and transmits the assay fluorescence 309. Thus, in effect, only the fluorescence from the assay and the fluorescence from the reference are focused onto their respective photo detectors 380, 384 using respective lenses 370, 374. The ratio between the detected assay fluorescence and the detected reference fluorescence correlates with the glucose concentration in the assay. Again, as mentioned previously, any changes in light-source intensity or optical coupling will be cancelled out as they scale the assay and reference fluorescence equally.
With the above configuration, the assay may now be excited through the optical fiber 410, and the resulting fluorescence collected by the optical fiber. As the fluorescence from the assay radiates isotropically, the amount of the emitted fluorescence, which can be picked up by the optical fiber 410, is set by the numerical aperture of the fiber.
The numerical aperture (NA) of the optical fiber is a function of the refractive index of the fiber core (n1) and the refractive index of the cladding (n2):
NA=√{square root over (n1−n22)} Eq. (2)
Generally, light entering the optical fiber at an angle less than a critical angle will be transmitted through the optical fiber due to total internal reflection in the core/cladding boundary, whereas light entering at an angle larger than the critical angle will simply exit the fiber through the cladding. Commercially available optical fibers have a high refractive index core and a low refractive index cladding. Typical refractive indices for the core and the cladding for a plastic optical fiber are about 1.49 and about 1.40, respectively, which, based on Eq. (2), results in a numerical aperture of about 0.51. Per Eq. (3) below, this corresponds to a critical angle (θ) of about 30.6° , or a solid angle of about 0.88sr:
NA=n sinθmax Eq. (3)
For the ideal case, this translates into about a 7% pickup of the total emitted fluorescence—where isotropic radiation is 4πsr, and 0.88sr/4πsr≈7%. The maximum fluorescence pickup is thus set by the optical fiber.
Furthermore, some of the excitation light will spill out of the assay compartment through the glucose permeable membrane as the excitation light is coupled into the assay at angles corresponding to the fiber numerical aperture.
The Optical Invariant theorem states that the product of the source area (A) multiplied by the solid angle (Ω) is constant:
A1Ω1=A2Ω2 Eq. (4)
In Eq. (4), A1 is equal to the cross sectional area of the optical fiber, Ω1 equals the solid angle corresponding to the numerical aperture of the optical fiber, and A2 and AΩ2 are set according to a trade-off between the maximum fiber tip length, saturation intensity for the assay, and manufacturable tip geometry.
Applied to the fiber sensor 400, this means that, with the right optical component and fiber tip design, the excitation light transmitted through the optical fiber 410 may be focused down to a smaller area moving the excitation away from the glucose permeable membrane 430 and thereby reduce the spillage of excitation light out of the sensor. In addition, the numerical aperture of the fiber tip may be increased resulting in an increased fluorescence pickup from the assay.
The Compound Parabolic Concentrator (CPC) is a non-imaging component, which has an entrance aperture, a parabolic shaped reflective surface, and an exit aperture. The CPC may be formed as an air filled void or an optical material with a parabolic mirror surface, or it may be formed by an optical material with a refractive index which is higher than that of the surrounding material. The parabolic shaped part of the CPC is formed as a parabola which ensures total internal reflection due to the high-low refractive index transition.
The radial coordinate of points on the CPC as a function of the z coordinate along the axis is given by the positive real root of the following quadratic equation:
C
2
r
2+2(CSz+aP2)r+(z2S2−2aCQz−a2PT)=0 Eq. (5)
Where C=cosθ, S=sinθ, P=1+S, Q=1+P, and T=1+Q
Shaping the tip of the optical fiber 410 as a CPC with the right dimensions will lead to the desired properties. As an example, a CPC shape applied to the tip of a 250 μm optical fiber reduces tip diameter to 125 μm. Area is thus reduced four times, leading to a theoretical four-fold increase in numerical aperture, which corresponds to a four-fold increase in fluorescence pickup.
An embodiment of the present invention employing a CPC tip geometry is shown in
It is noted that the theoretical four-fold increase in fluorescence pickup is based on the assumption that the fluorophore(s) of the assay are excited at the tip-assay transition, i.e., the CPC-assay optical interface 415. However, since the fluorescence occurs in a volume in front of the fiber tip 414, the increase in fluorescence pickup may be significantly less than the four-fold increase predicted by crude theoretical calculations.
Thus, even though, theoretically, the numerical aperture of the CPC fiber tip 414 will be increased dramatically compared to the conventional straight cut fiber tip 412, in operation, the CPC design generally cannot pick up more than about 50% of the emitted fluorescence. Nevertheless, in an embodiment of the invention, the fluorescence pick-up percentage may be increased by placing a concave mirror 417 in front of the fiber tip 414 to reflect fluorescence emitted in a direction that is opposite to the fiber tip and focus it into the fiber.
As shown in
The straight cut fiber tip 412, the CPC shaped fiber tip 414, and the CPC shaped fiber tip in combination with a reflector 414, 417 have been modeled using Zemax optical design software. For each of the three designs, the model included the following: (1) an excitation light source at the proximal (free) end of the fiber sensor, coupling light into the optical fiber and exciting the assay at the (distal, in-situ) tip of the optical fiber; (2) an optical fiber with the selected fiber tip geometry; (3) an assay-filled compartment including assay absorption and assay fluorescence processes; and (4) a detector with a fluorescence filter only selecting the fluorescence picked up and transmitted back through the optical fiber.
For all three designs, the ratio between the excitation and the detected fluorescence was calculated. As can be seen from the results shown in Table 1 below, the Zemax simulations shows significantly lower fluorescence pickup from the CPC designs than the Optical Invariant theorem predicts. As stated, this is due to the fact that the excitation and resulting fluorescence emission occur in a volume in front of the fiber tip rather than directly at the fiber tip/assay boundary.
In embodiments of the invention employing the CPC tip geometry described above, the assay, including the reference dye, can be carried or contained by a hydrogel in order to ease production and stabilize the assay. Specifically, the glucose assay is first dissolved in a hydrogel. Next, the CPC-shaped fiber tip may be dipped into the hydrogel containing the assay, and a droplet may be left in front of the CPC-shaped fiber tip. Finally, the hydrogel may be cross-linked so as to provide a glucose sensor. Suitable cross-linking hydrogels may include, e.g., Poly acryl based hydrogels (such as poly-Hydroxy-Ethyl-Methacrylate (pHEMA), PMMA-pHEMA co-polymers, etc.), Polyurethanes, Polyesters, Polyethers, etc.
Where the hydrogel containing the assay is not cross-linked, the entire embodiment could be coated by any of the polymers suitable for glucose sensors, i.e., polymers that allow glucose diffusion through the polymer. Suitable non-crosslinking hydrogels may include, e.g., poly-vinyl alcohol (PVA), Poly-ethylene glycol (PEG), poly-propylene glycol (PPG), poly-Hydroxy-Ethyl-Methacrylate (pHEMA), etc., and co-polymers thereof.
Two cuts are made on opposite sides of the fiber and displaced from each other sufficiently to maintain the structural strength of the fiber. For the first side cut cavity 1420a, the surface 1421 a parallel to the fiber axis is preferably optical quality. As the refractive index of the assay is significantly lower than the fiber core, this will provide total internal reflection for excitation light 1423 traveling from the proximal end of the fiber sensor to the second assay compartment 1420b and furthermore provide total internal reflection for fluorescence emitted from the second assay compartment 1420b and back to the proximal end of the fiber. The above-described configuration provides structural strength to the fiber sensor, which is advantageous, especially for fiber sensors where a soft glucose permeable membrane in itself does not provide sufficient structural strength to ensure the stability of the assay compartment.
It is noted that, in embodiments of the invention, fewer or more assay compartments may be included. For example, with reference to
It is noted that the CPC configuration applied to the fiber sensor in the above description is illustrative, and other geometries, e.g., a CPC with a rectangular cross sectional area, as well as other imaging or non-imaging geometries that also change the numerical aperture of the fiber tip may also be applied.
Embodiments of the invention are also directed to improved optical systems for interrogating fluorophore-labeled assays contained within optical sensors and, in particular, fiber optical sensors of the types described above.
As noted previously, in typical interrogation systems (e.g., epifluorescence microscopy), fluorescence applications commonly operate with fairly intense excitation of the fluorophore in the absorption band of the fluorophore and detection of the weak fluorescence emitted by the fluorophore. In such applications, the dichroic beam splitter serves as a crude filtering of the light, whereas the heavy filtering occurs in the excitation filter and the emission filter, which are used in transmission mode and depend on 106 times attenuation of wavelengths outside the pass band in a single pass. Such filters are normally based on dielectric multilayer filters consisting of a substrate with optical coatings on both sides consisting of up to 100 layers with alternating refractive indices. In the pass band, the filters have up to 99% transmittance, which is most probably caused by reflection losses in the air-coating transition on both sides of the filter in spite of the fact that filter stacks on both sides of the substrate generally include an anti-reflective coating.
In accordance with embodiments of the present invention, an optical system may be used for interrogating a fluorophore-labeled assay either with, or without, an internal reference. The inventive optical system is based on a filter substrate with one or multiple optical coatings separated in location on the surfaces of the substrate. The coatings may be dielectrical multilayer coatings forming short wave pass, longwave pass, band pass filters, and anti-reflection coatings. Furthermore, coatings may be metallic reflective coatings.
More specifically, embodiments of the present invention utilize the fact that a dielectrical multilayer filter reflects what is not transmitted. Therefore, a filter in accordance with embodiments of the present invention may include a first coating on the filter substrate which transmits a certain wavelength range of the excitation, but reflects wavelengths outside the pass band. This enables the emitted fluorescence to be reflected once or multiple times by the coating, while allowing reflected excitation light to be transmitted out of the optical system. The filtered fluorescence then exits the filter substrate when it reaches a part of the substrate that is not coated with the first coating, and is picked up by one or more detectors.
Subsequent filtering may also be achieved by applying a second coating which transmits a desired wavelength range originating from a first fluorophore, but reflects wavelengths outside the transmission band—in particular, remains of the excitation light. In this way, the desired wavelength range will be transmitted out of the substrate where it may be picked up by one or more suitable detectors. In addition, anti-reflective coatings may be applied to areas of the substrate where light is coupled into, or out of, the substrate to reduce reflection losses.
In an intensity interrogation configuration, where both a first fluorophore and a second fluorophore are used, the above-mentioned second coating may transmit the desired wavelength range associated with the first fluorophore and reflect wavelengths outside the transmission band—in particular remains of the excitation light and fluorescence related to the second fluorophore. The filtered fluorescence originating from the second fluorophore then exits the filter substrate when it reaches a part of the substrate that is not coated with the first or second coating, such that it can be picked up by a suitable detector(s). Subsequent filtering of fluorescence originating from the second fluorophore may be achieved by applying a second coating which transmits the desired wavelength range associated with the second fluorophore and reflects wavelengths outside the transmission band—in particular, remains of the excitation light. In this way, the desired wavelength range may be transmitted out of the substrate where it may be picked up by a suitable detector(s). In other embodiments, the system may be expanded to include multiple light sources and/or multiple wavelength ranges to be detected.
Implementation of the above-described filter configurations requires imaging optical elements such as lenses, mirrors or diffractive optical elements to focus, pick up, and collimate light. Furthermore, apertures and light traps may be required to control light path and to absorb undesired wavelengths that are transmitted out of the filter substrate, such as, e.g., the excitation light to be blocked. In this embodiment, the above-mentioned optical elements and light traps are shown with an air gap between the elements and the (glass) substrate. However, the optical elements and light traps may also be formed in an optically transparent material with mirror coating and absorbing coating on the surface facing away from the filter substrate. Such a configuration is generally more advantageous, as the optical elements and light traps are better index matched to the filter substrate/filter coating than is the case when an air gap is present.
The above-mentioned elements may be individually aligned and fitted onto both sides of the coated filter substrate as discrete units. Similarly, one or more light sources and one or more detectors may be aligned and fitted onto the filter substrate as packaged units, as raw dies laminated directly onto the coated filter substrate, or mounted as raw dies onto a printed circuit board and mounted as a unit onto the coated filter substrate.
Suitable light sources may include, e.g., light emitting diodes (LEDs) and laser diodes, and suitable detectors may include, e.g., photodiodes, avalanche photodiodes, silicon photomultipliers, photomultipliers, and phototransistors. In addition, the assembled optical system may be coated or placed in an enclosure to block out ambient light.
A stacked planar integrated optical system (SPIOS) for interrogating a single fluorophore in accordance with an embodiment of the invention is shown in
Traveling through the sensor 590, the excitation light 591 reaches the assay compartment 595, where it excites the fluorophore in the assay such that the fluorophore emits fluorescence 593. Furthermore, excitation light is reflected and back scattered from the optical window and sensor. The fluorescence 593 and reflected/back scattered excitation light are picked up and collimated by the second mirror 540 and enter the filter substrate 500 through an uncoated or anti-reflection coated area 503 on the filter substrate. The emitted fluorescence is reflected between the two coated surfaces (i.e., the excitation filters 520) while the excitation light is transmitted through the coatings 520 and absorbed by the light traps 560. The filtered fluorescence exits the filter substrate 500 where the coated area ends 507 and is focused by a third mirror 570 onto a detector 580 through an uncoated, or anti-reflection coated, region of the filter substrate.
In an alternative embodiment, a stacked planar integrated optical system (SPIOS) for interrogating a sensor with an assay fluorophore and a reference fluorophore is shown in
Traveling through the sensor 590, the excitation light 591 reaches the assay compartment 595, where it excites the fluorophore in the assay such that the fluorophore emits fluorescence 593. Furthermore, excitation light is reflected and back scattered from the optical window and sensor. The fluorescence 593 and reflected/back scattered excitation light are picked up and collimated by the second mirror 540 to enter the filter substrate 500 through an uncoated or anti-reflection coated area 503 on the filter substrate. The emitted fluorescence is reflected between the two excitation filter coatings 520 while the excitation light is transmitted through the coatings and absorbed by the light traps 560.
The filtered fluorescence exits the filter substrate 500 where the excitation filter coatings end 507, and an emission filter 525 transmits a wavelength range relating to a first fluorophore (the assay fluorophore). The filtered fluorescence from the first fluorophore is focused by a third mirror 570 onto a first detector 580, while the fluorescence associated with the second fluorophore (the reference fluorophore) is reflected between the emission filter 525 on the two sides of the filter substrate 500. The filtered fluorescence from the second fluorophore exits the filter substrate 500 where the coated area ends 509 or is replaced with an anti-reflection coating, and is focused by a fourth mirror 575 onto a second detector 585 through an uncoated, or anti-reflection coated, region of the filter substrate.
As noted previously, the optical elements, apertures, and light traps of the SPIOS for interrogating a sensor with an assay fluorophore and a reference fluorophore may be disposed with an air gap between the elements and the (glass) substrate. See
It is noted that the light emitting area of a LED chip has an area, which is comparable to a 500 μm multimode fiber. Furthermore, the LED chip emits in a large angular space. For a SPIOS equipped with a LED interrogating a fiber sensor, the fluorescence output gradually becomes limited by the ability to focus light from the LED onto the fiber when the fiber diameter is reduced. Also the positioning of the proximal end of the fiber relative to the optical system becomes more critical.
As shown in
The CPC may be an integral part of the SPIOS, as shown, e.g., in
In yet another embodiment shown in
One or more optical layers 620 may include mirrors and absorbers laid out on a wafer-sized injection molded disk. Mold inserts defining optical surfaces are made by a diamond turning/milling company (e.g., Kaleido Technology in Denmark). Gold or protected silver is applied to mirror surfaces, e.g., by sputtering, while any absorbers are masked off during the process.
The optical filter layer 630 includes a wafer-sized glass substrate with optional coatings. Specifically, multilayer optical coatings may be applied on both sides of the glass substrate using ion-assisted sputtering to form durable coatings. The technique is similar to that used in manufacturing fluorescence filters by, e.g., Semrock in the United States and Delta in Denmark.
As shown in
The above-described system may be made small and is suitable for large-scale production. The system may be used for interrogating a sensor in a light scattering environment, such as a sensor implanted into the skin, as well as a fiber sensor. Coating or packaging may be used to block out ambient light.
While the description above refers to particular embodiments of the present invention, it will be understood that many modifications may be made without departing from the spirit thereof. The accompanying claims are intended to cover such modifications as would fall within the true scope and spirit of the present invention.
The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
This application claims priority from U.S. Provisional Application Ser. No. 61/531,449, filed Sep. 6, 2011, and U.S. Provisional Application Ser. No. 61/531,451, filed Sep. 6, 2011, and U.S. Provisional Application Ser. No. 61/531,456, filed Sep. 6, 2011, and U.S. Provisional Application Ser. No. 61/554,057, filed Nov. 1, 2011, and U.S. Provisional Application Ser. No. 61/561,146, filed Nov. 17, 2011, and U.S. Provisional Application Ser. No. 61/587,819, filed Jan. 18, 2012, and U.S. Provisional Application Ser. No. 61/620,563, filed Apr. 5, 2012, and is related to the U.S. Patent Application entitled “Orthogonally Redundant Sensor Systems and Methods”, Attorney Docket No. 040088-0405699, which is being filed concurrently herewith, all of which are incorporated herein by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 61531449 | Sep 2011 | US | |
| 61531451 | Sep 2011 | US | |
| 61531456 | Sep 2011 | US | |
| 61554057 | Nov 2011 | US | |
| 61561146 | Nov 2011 | US | |
| 61587819 | Jan 2012 | US | |
| 61620563 | Apr 2012 | US |
