Patent Application
20150241355
In surface-enhanced Raman scattering (SERS), vibrationally excitable levels of an analyte are probed. The energy of a photon shifts by an amount equal to that of the vibrational level excited by the photon (Raman scattering). A Raman spectrum, which consists of a wavelength distribution of bands corresponding to molecular vibrations specific to the analyte being probed, may be detected to identify the analyte. In SERS, the analyte molecules are in close proximity, for instance, less than tens of nanometers, to metal nano-particles that may be or may not be coated with a dielectric, such as silicon dioxide, silicon nitride, and a polymer, that, once excited by light, set up plasmon modes, which create near fields around the metal nano-particles. These fields can couple to analyte molecules in the near field regions. As a result, concentration of the incident light occurs at close vicinity to the nano-particles, enhancing the Raman scattering from the analyte molecules.
SERS has recently been performed to probe fluids in a specimen in vivo through implantation of the metal nano-particles subcutaneously. However, because light to excite the metal nanoparticles is reflected directly from the specimen's surface, such as the specimen's skin, and the Raman scattered light is degraded by the Raman light generated from the specimen's surface, accurate results were difficult to obtain. One technique to overcome some of these issues is to detect the enhanced Raman signal as a function of spatially offset distance from the pump beam. This “offset” technique enables the deconvolution of the Raman signal from the scattered excitation light from the surface (e.g., skin) but is time-consuming and complicated to implement.
Features of the present disclosure are illustrated by way of example and not limited in the following figure(s), in which like numerals indicate like elements, in which:
For simplicity and illustrative purposes, the present disclosure is described by referring mainly to an example thereof. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present disclosure. It will be readily apparent however, that the present disclosure may be practiced without limitation to these specific details. In other instances, some methods and structures have not been described in detail so as not to unnecessarily obscure the present disclosure.
Throughout the present disclosure, the terms “a” and “an” are intended to denote at least one of a particular element. As used herein, the term “includes” means includes but not limited to, the term “including” means including but not limited to. The term “based on” means based at least in part on. In addition, the term “light” refers to electromagnetic radiation with wavelengths in the visible and non-visible portions of the electromagnetic spectrum, including infrared, near infrared, and ultra-violet portions of the electromagnetic spectrum.
Disclosed herein are an apparatus for performing spectroscopy and a method for fabricating the apparatus. The apparatus disclosed herein comprises a parabolic reflector and a plurality of surface-enhanced Raman spectroscopy (SERS) elements spaced from the parabolic reflector and positioned substantially at a focal point of the parabolic reflector. The parabolic reflector is to substantially increase the flux of the Raman signal or scattered light emitted from molecules around the SERS elements that is directed to the detector. In addition, the parabolic reflector is to be tilted with respect to the direction in which an excitation light is applied onto the SERS elements to substantially prevent specularly reflected or low-angle scattered excitation light from reaching the detector and competing with the Raman signal.
The apparatus disclosed herein may include an off-axis parabolic reflector, in which the SERS elements are positioned substantially at a focal point of the off-axis parabolic reflector. In one regard, the off-axis parabolic reflector enables the excitation light to be introduced onto the SERS elements from a direction that minimizes collection of the excitation light by the detector so that the excitation light does not substantially interfere with the Raman signals emitted from the molecules in the near fields of the SERS elements. In addition, or alternatively, the apparatus disclosed herein may include a back reflector that is positioned to reflect the Raman signals emitted from the molecules in the near fields of the SERS elements toward the parabolic reflector, to thereby further increase the flux of the Raman signals directed to the detector. According to an example, the back reflector is incorporated into the SERS element. In addition, in instances where the excitation region is small compared to the focal length of the parabolic reflector, then the back reflector may be substantially smaller than the parabolic reflector and may be flat. For instance, the back reflector may be incorporated into the substrate of a flat SERS element.
The apparatus disclosed herein may be fabricated or integrated with a housing that is to be implanted into a specimen, such as a human, an animal, an insect, a plant, a non-living item, etc. According to an example, the housing forms part of an implantable device, such as a surgically implantable stent. In one regard, the apparatus disclosed herein may be implemented to generate relatively high intensity/flux (or signal strength) and accurately detectable Raman signals in in-vivo Raman spectroscopy operations. In other words, the apparatus disclosed herein enables Raman signals having higher intensities/fluxes to be detected as compared with conventional in vivo Raman spectroscopy techniques that employ conventional spatially offset techniques to detect the Raman signals.
With reference first to
The apparatus 100 may be implemented to perform spectroscopy, which is also equivalently referred herein as surface-enhanced Raman spectroscopy (SERS), to detect a molecule in an analyte sample with a relatively high level of sensitivity. As a particular example, the apparatus 100 is to be implemented to perform spectroscopy following implantation of the apparatus 100 into a specimen, such as a human, an animal, an insect, a plant, non-living item, etc., or in any gaseous or liquid or liquid crystal environment where surface scattering degrades the signal. Examples of such environments include, for instance, chemical/food processing facilities, where surfaces and any interstitial contribution to the signal is not desirable and need to be minimized. The apparatus 100 may thus be implemented to analyze molecules in a fluid in a specimen, such as blood, lymph, saliva, interstitial fluid, an analyte carried by gas, air flow, etc. The apparatus 100 may alternatively be implemented in spectroscopy applications that do not involve implantation of the apparatus 100.
As shown, the apparatus 100 includes a parabolic reflector 102 and SERS elements 104 (a single substrate on which the SERS elements 104 are positioned is depicted in
In some examples, the SERS elements 104 may be functionalized to facilitate adsorption of analyte molecules. For example, surfaces of the SERS elements 104 may be functionalized such that a particular class of analytes is attracted and may bond or be preferentially adsorbed onto the SERS elements 104.
According to an example, when an illumination source 110 emits an excitation light 112 (or equivalently, a pump light), such as a laser beam, an LED beam, etc., onto the SERS elements 104, the SERS elements 104 create near fields around the SERS elements 104. Although the excitation light 112 has been depicted as being directly emitted from the illumination source 110 onto the SERS elements 104, it should be understood that various optical components, e.g., mirrors, prisms, lenses etc., may be positioned to direct the excitation light 112 to the SERS elements. In any regard, the near fields around the SERS elements 104 couple to analyte molecules (not shown) in the vicinities of the SERS elements 104. The metallic nanoparticles (or other plasmonic structures) of the SERS elements 104 also act to enhance the Raman emission process of the analyte molecules. As a result, Raman scattered light is emitted from the analyte molecules and the emission of the Raman scattered light is enhanced by the SERS elements 104. A portion of the Raman scattered light 114, which may be emitted in all directions from the analyte molecules near the SERS elements 104, is emitted toward the parabolic reflector 102. The Raman scattered light 114 is reflected from a reflective surface of the parabolic reflector 102 into a collimated or nearly collimated beam, as depicted in
As also depicted in
According to an example, the excitation light 112 is to be emitted through a surface layer (not shown), for instance, a skin layer, body tissue, vein walls, cover, etc., under which the apparatus 100 is implanted. In another example, the excitation light 112 is to be emitted through a gaseous or liquid environment in which the apparatus 100 has been positioned. In addition, the Raman scattered light 114 is to be emitted through the surface layer and/or the gaseous or liquid environment. According to an example, the location on the surface layer and/or the gaseous or liquid environment at which the Raman scattered light 114 is emitted is offset with respect to the location on the surface layer and/or in the gaseous or liquid environment at which the excitation light 112 is emitted. In one regard, therefore, contribution of the excitation light 112 that is scattered from the surface layer and/or the gaseous or liquid environment in the light detected by the detector 120 may substantially be minimized. In other words, the parabolic reflector 102 is tilted with respect to the direction in which the excitation light 112 is applied onto the SERS elements 104, for instance, to minimize the surface contributions of the excitation light 112 scattered (which may include spurious Raman signals from the surface and/or the interstitial gaseous or liquid environment) into the Raman scattered light 114 directed into the detector 120.
The apparatus 100 has a size, a configuration, and is fabricated of materials that make the apparatus 100 suitable for implantation into a specimen. According to an example, and as discussed in greater detail below, the apparatus 100 comprises a surgically implantable stent. The parabolic reflector 102 may comprise a polymer material that has been nanoimprinted, molded, and/or stamped to form the shape of the parabolic reflector 102. In addition, a surface of the polymer material is coated with at least one of a metal, such as gold, silver, etc., a protective coating of dielectric material, Bragg layers, etc., to be reflective. Moreover, the parabolic reflector 102 may have dimensions that range from about less than a millimeter to about a couple of centimeters. In addition, the SERS elements 104 may be positioned on a substrate that is in the range of about 100 microns wide or larger.
The SERS elements 104 comprise Raman-enhancing elements, such as plasmonic nanoparticles or nanostructures, which may comprise plasmon-supporting materials such as but not limited to, gold (Au), silver (Ag), and copper (Cu). The Raman-enhancing elements may have nanoscale surface roughness, which is generally characterized by nanoscale surface features on the surface of the layer(s) and may be produced spontaneously during deposition of the plasmon-supporting material layer(s). By definition herein, a plasmon-supporting material is a material that facilitates Raman scattering and the production or emission of the Raman signal from an analyte on or near the material during Raman spectroscopy. In addition, the Raman-enhancing elements of the SERS elements 104, e.g., plasmonic nanostructures, may be deposited onto a substrate formed, for instance, of a polymer material, a metallic material, a semiconductor material, etc., through, for instance, physical vapor deposition (PVD), chemical vapor deposition (CVD), sputtering, etc., of metallic material, or self-assembly of pre-synthesized nano-particles.
Turning now to
As shown in
The off-axis parabolic reflector 202 is to focus the excitation light 112 onto the SERS elements 104 as shown in
As shown in
The back reflector 204 is positioned and configured to reflect Raman scattered light 114 emitted from molecules near the SERS elements 104 to be directed to the parabolic reflector 102. In this regard, the back reflector 204 generally functions to increase the intensity or flux of the Raman scattered light 114 directed to the detector 120 by directing more light toward the parabolic reflector 102. The back reflector 204 may also be formed of similar materials, similar dimensions, and through similar processes as the parabolic reflector 102 discussed above.
Turning now to
Generally speaking, the apparatus 100 depicted in
The apparatus 100 may include a single set of the parabolic reflector 102 and the SERS elements 104. In this example, the remaining sections of the apparatus 100 that do not include the set of the parabolic reflector 102 and the SERS elements 104 may have a cylindrical configuration. The apparatus 100 may alternatively include multiple sets of parabolic reflectors 102 and the SERS elements 104 positioned along the housing 302. In this example, the sets of the parabolic reflectors 102 and the SERS elements 104 may be the same or may differ from each other, for instance, by including an off-axis parabolic reflector 202 in one of the sets while omitting the off-axis parabolic reflector 202 from another one of the sets. In addition, the sections of the apparatus 100 between the sets may have a cylindrical configuration.
With reference first to
Additionally, in
Turning now to
As a further alternative, in both
Turning now to
According to an example, the nano-fingers 404 are formed of a relatively flexible material to enable the nano-fingers 404 to be laterally bendable or collapsible, for instance, to enable tips of the nano-fingers 404 to move toward each other, as discussed in greater detail herein below. Examples of suitable materials for the nano-fingers 404 include polymer materials, such as, UV-curable or thermal curable imprinting resist, polyalkylacrylate, polysiloxane, polydimethylsiloxane (PDMS) elastomer, polyimide, polyethylene, polypropelene, polyurethane, fluoropolymer, etc., or any combination thereof, metallic materials, such as, gold, silver, aluminum, etc., semiconductor materials, etc., and combinations thereof.
The nano-fingers 404 are attached to the surface of the substrate 402 through any suitable attachment mechanism. For instance, the nano-fingers 404 are grown directly on the substrate 402 surface through use of various suitable nano-structure growing techniques. As another example, the nano-fingers 404 are integrally formed with the substrate 402. In this example, for instance, a portion of the material from which the substrate 402 is fabricated is etched or otherwise processed to form the nano-fingers 404. In a further example, a separate layer of material is adhered to the substrate 402 surface and the separate layer of material is etched or otherwise processed to form the nano-fingers 404. In various examples, the nano-fingers 404 are fabricated through a nanoimprinting or embossing process in which a template of relatively rigid pillars is employed in a multi-step imprinting process on a polymer matrix to form the nano-fingers 404. In these examples, a template may be formed through photolithography or other advanced lithography with the desired patterning to arrange the nano-fingers 404 in the predetermined arrangement. More particularly, for instance, the desired patterns may be designed on a mold by any of E-beam lithography, photolithography, laser interference lithography, Focused Ion Beam (FIB), self-assembly of spheres, etc. In addition, the pattern may be transferred onto another substrate, for instance, a silicon, glass, or polymer substrate (PDMS, polyimide, polycarbonate, etc.). Various other processes, such as, etching, and various techniques used in the fabrication of micro-electromechanical systems (MEMS) and nano-electromechanical systems (NEMS) may also be used to fabricate the nano-fingers 404.
A nano-finger 404 is defined, for instance, as an elongated, nanoscale structure having a length (or height) that exceeds by more than several times a nanoscale cross sectional dimension (for instance, width) taken in a plane perpendicular to the length (for instance, length>3×width). In general, the length is much greater than the width or cross sectional dimension to facilitate bending of the nano-finger 404 laterally toward one or more neighboring nano-fingers 404. In some examples, the length exceeds the cross sectional dimension (or width) by more than a factor of about 5 or 10. For example, the width may be about 100 nanometers (nm) and the height may be about 500 nm. In another example, the width at the bases of the nano-fingers 404 may range between about 10 nm and about 1 micrometer (μm) and the length may range between about 50 nm and 2 μm. In other examples, the nano-fingers 404 are sized based upon the types of materials used to form the nano-fingers 404. Thus, for instance, the more rigid the material(s) used to form the nano-fingers 404, the less the width of the nano-fingers 404 may be to enable the nano-fingers 404 to be laterally collapsible. In further examples, the nano-fingers 404 may form ridges in which two of three dimensions (for instance, length and height) exceed by more than several times a nanoscale cross sectional dimension (for instance, width).
The nano-fingers 404 have been depicted as having substantially cylindrical cross-sections. It should, however, be understood that the nano-fingers 404 may have other shaped cross-sections, such as, for instance, rectangular, square, triangular, etc. In addition, or alternatively, the nano-fingers 404 may be formed with one or more features, such as, notches, bulges, etc., to substantially cause the nano-fingers 404 to be inclined to collapse in particular directions. Thus, for instance, two or more adjacent nano-fingers 404 may include the one or more features to increase the likelihood that the nano-fingers 404 collapse toward each other. Various manners in which the nano-fingers 404 may be collapsed are described in greater detail herein below.
The array 400 includes a substantially random distribution of nano-fingers 404 or a predetermined configuration of nano-fingers 404. In any regard, according to an example, the nano-fingers 404 are arranged with respect to each other such that the tips of at least two neighboring nano-fingers 404 are able to be brought into close proximity with each other when the nano-fingers 404 are in a collapsed state, for instance, less than about 10 nanometers apart from each other. By way of particular example, the neighboring nano-fingers 404 are positioned less than about 100 nanometers apart from each other. According to a particular example, the nano-fingers 404 are patterned on the substrate 402 such that neighboring ones of the nano-fingers 404 preferentially collapse into predefined geometries, for instance, triangles, squares, pentagons, etc.
In addition, although
The Raman-enhancing elements 406 comprise a plasmonic material such as, but not limited to, gold, silver, copper, platinum, aluminum, etc., or a combination of these metals in the form of alloys, or other suitable material that is able to support surface plasmons for field enhancement for Raman scattering. In addition, the Raman-enhancing elements 406 may be multilayer structures, for example, 10 to 100 nm silver layer with 1 to 50 nm gold over-coating, or vice versa. By definition herein, a plasmonic material is a material that supports plasmons.
Turning now to
Although the nano-fingers 404 have been depicted in
As shown in
Turning now to
In any event, and in one regard, the tips 408 of the nano-fingers 404 are caused to be drawn toward each other as shown in
According to an example, the nano-fingers 404 are positioned into the collapsed state depicted in
Turning now to
At block 502, a parabolic reflector 102 is obtained. The parabolic reflector 102 may be obtained through fabrication of the parabolic reflector 102 in any of the manners discussed above. Alternatively, the parabolic reflector 102 may comprise a pre-fabricated component and may thus be obtained from a manufacturer or supplier of the parabolic reflector 102.
At block 502, a plurality of SERS elements 104 are obtained. The SERS elements 104 may be obtained through fabrication of the SERS elements 104 fabricated in any of the manners discussed above. Alternatively, the SERS elements 104 may be pre-fabricated on a substrate and may thus be obtained from a manufacturer or supplier of the SERS elements 104. According to a particular example, the SERS elements 104 comprise the Raman-enhancing elements 406 provided on the tips 408 of nano-fingers 406, as shown in
At block 506, an off-set parabolic reflector 202 and/or a back reflector 204 are optionally obtained. The obtaining of the off-set parabolic reflector 202 and/or the back reflector 204 is considered optional because the apparatus 100 may be fabricated without either of these reflectors. In the instance that either or both of these reflectors are obtained, the off-set parabolic reflector 202 and/or a back reflector 204 may be obtained through fabrication of these reflectors in any of the manners discussed above or obtained from a manufacturer or supplier of these reflectors. According to a particular example, the off-set parabolic reflector 202 is integrally formed with the parabolic reflector 102 as discussed above with respect to
At block 508, the plurality of SERS elements 104 is positioned substantially at the focal point of the parabolic reflector 102. According to an example, the positioning of the SERS elements 104 with respect to the parabolic reflector 102 may occur during the obtaining of the parabolic reflector 102 and the SERS elements 104. Thus, for instance, the SERS elements 104 may be fabricated at block 504 to be positioned substantially at the focal point of the parabolic reflector 102. In any regard, the SERS elements 104 may be supported substantially at the focal point of the parabolic reflector 102 through use of any suitable mechanism, such as the supporting membrane 304 depicted in
In addition, at block 508, if the off-set parabolic reflector 202 is to be included in the apparatus 100, the SERS elements 104 may also be positioned substantially at the focal point of the off-set parabolic reflector 202. Moreover, if the back reflector 204 is to be included in the apparatus 100, the back reflector 204 may be positioned to direct light emitted from the SERS elements 104 toward the parabolic reflector 102. Furthermore, the SERS elements 104 may be positioned substantially at the focal point of the back reflector 204.
At block 510, the parabolic reflector 102 and the SERS elements 104 are integrated into a housing 302. The parabolic reflector 102 and the SERS elements 104 may be integrated into the housing 302 in any of the manners discussed above with respect to
According to an example, the parabolic reflector 102 and the SERS elements 104 are formed and then positioned into the housing 302. In another example, the parabolic reflector 102 and the SERS elements 104 are formed directly in the housing 302. The off-axis parabolic reflector 202 and the back reflector 204 may also be fabricated in either of these manners.
Although described specifically throughout the entirety of the instant disclosure, representative examples of the present disclosure have utility over a wide range of applications, and the above discussion is not intended and should not be construed to be limiting, but is offered as an illustrative discussion of aspects of the disclosure.
What has been described and illustrated herein is an example along with some of its variations. The terms, descriptions and figures used herein are set forth by way of illustration only and are not meant as limitations. Many variations are possible within the spirit and scope of the subject matter, which is intended to be defined by the following claims—and their equivalents—in which all terms are meant in their broadest reasonable sense unless otherwise indicated.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US2012/049031 | 7/31/2012 | WO | 00 | 12/9/2014 |
