WO2010132610A2 - Substrats thermoplastiques à surfaces métalliques ridées pour la détection de substances chimiques ou biologiques - Google Patents

Substrats thermoplastiques à surfaces métalliques ridées pour la détection de substances chimiques ou biologiques Download PDF

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WO2010132610A2
WO2010132610A2 PCT/US2010/034611 US2010034611W WO2010132610A2 WO 2010132610 A2 WO2010132610 A2 WO 2010132610A2 US 2010034611 W US2010034611 W US 2010034611W WO 2010132610 A2 WO2010132610 A2 WO 2010132610A2
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metal
wrinkle
features
substrate
film
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PCT/US2010/034611
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WO2010132610A3 (fr
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Michelle Khine
Sayantani Ghosh
Arnold D. Kim
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The Regents Of The University Of California
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/553—Metal or metal coated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection

Definitions

  • PCR polymerase chain reaction
  • molecular fluorophore readouts enables rapid nucleic acid sequencing for high-sensitivity molecular identification [4].
  • the PCR is complex, costly, and sensitive to contamination.
  • it is limited in its ability to multiplex multiple targets [5].
  • Label-free approaches are more adaptable to point-of care diagnostics, in which rapid, low-cost, low-powered, portable, and robust systems are required. This is particularly important for first responders of bio-terrorist threats as well as diagnostics for the developing world.
  • Affinity bio-sensors allow for the real-time analysis of biospecific interactions without the need for labeling molecules.
  • Various optical methods for label-free biomolecular detection have been explored. Plasmonics involves manipulating light in the subwavelength regime. Nano-structured free-electron metals can be resonantly excited using visible light to produce surface plasmon oscillations that lead to surface-bound electromagnetic fields; these fields can then be manipulated in various ways to detect bio- molecules [2,7,8]. For example, in surface plasmon resonance sensing, molecular adsorption can be detected through changes in the refractive index.
  • SERS surface-enhanced Raman spectroscopy
  • SPR Surface Plasmon Resonance
  • the sensors comprise a heat-shrunk thermoplastic substrate coated with a film of metal having a rough surface.
  • the film of metal comprises a microstructure characterized by wrinkle-like features.
  • the sensors may be used to detect chemical and biological agents, even those that are not fluorescently labeled, using backscattering spectrometry.
  • the disclosed sensors may be made using ultra-rapid processes and low cost, readily available materials.
  • the optical properties of the sensors may be tuned to correspond to the optical properties of the chemical and biological agents of interest, greatly increasing the accuracy and sensitivity of the sensors.
  • backscattering spectrometry is simple and requires only minimal instrumentation.
  • sensors are provided.
  • the sensors may include a heat-shrunk thermoplastic substrate and a film of metal disposed over the surface of the substrate, wherein the film of metal includes a microstructure characterized by wrinkle-like features.
  • the wrinkle-like features may be folded, wrinkle-like features or cracked, wrinkle-like features, both of which are further described below.
  • the orientation of the wrinkle-like features across the surface of the substrates may vary, including both random and substantially parallel orientations.
  • the dimensions, including the height and spacing, of the wrinkle-like features may vary.
  • thermoplastic substrates and the metallic film may vary.
  • thermoplastic materials including, but not limited to, polystyrene.
  • the thermoplastic substrate is heat shrunk, which means the thermoplastic substrate has been exposed to heat, resulting in a reduction of size of the substrate.
  • the metallic film may comprise a variety of metals or combinations of metals, including, but not limited to silver, gold, and copper.
  • the film may include single layers or multiple layers of metals. Similarly, the thicknesses of the metal layers may vary.
  • methods for making the sensors involve depositing a film of metal over the surface of a thermoplastic substrate and shrinking the coated substrate. Wrinkles form in the metallic film due to the stiffness incompatibility between the metallic film and the thermoplastic substrate. As further described below, the characteristics of the wrinkles may be controlled by the various parameters of the heating process and thickness of the deposited metal film.
  • methods for using the sensors to detect chemical and biological agents using backscattering spectrometry involve exposing any of the disclosed sensors to a chemical or biological agent; exposing the sensor to light, and measuring the backscattered light from the sensor to detect the chemical or biological agent.
  • Backscattering spectrometry, and the information that the technique provides, is further described below.
  • FIGS. 1A-1C show images of exemplary sensors with metallic films having folded, wrinkle-like features.
  • FIGS. 2A-2B show images of exemplary sensors metallic films have cracked, wrinkle-like features.
  • FIG. 3 illustrates the process for fabricating the nanostructured metallic substrates of the present disclosure.
  • a shape memory polymer is coated with a thin film of metal. Upon heating, the polymer retracts, but the metal does not lead to a buckling of the metal surface.
  • the final image on the right shows a scanning electron micrograph of one such nano-structured metallic substrate fabricated using this method.
  • FIG. 4 is a sketch illustrating the physical problem.
  • a wave is incident on several obstacles situated over a rough surface.
  • FIG. 5 is a diagram showing the interactions between the point obstacle and the slightly rough surface given by Eq. (5.3).
  • the incident field and the incident field reflected by the rough surface excite the point obstacle.
  • that exciting field is scattered by the point obstacle and reflected by the rough surface to excite the point obstacle again.
  • This series continues to include infinitely many interactions between the point obstacle and the slightly rough surface.
  • FIG. 7 are contour plots of the image /(x,y) defined in Eq. (5.5) corresponding to a single point obstacle shown in FIG. 6 for the Dirichlet (top) and Neumann (bottom) cases.
  • FIG. 9 are contour plots of the image /(x,y) defined in Eq. (5.5) corresponding to two point obstacles shown in FIG. 8 for the Dirichlet (top) and Neumann (bottom) cases.
  • FIG. 10 illustrates the process of fabrication of nanowrinkles.
  • FIG. 11 are demonstrates characterization of nanowrinkles.
  • Bottom panel Cross- sectional SEM view, d) Wavelength distributions of uniaxial wrinkles with various thickness of gold, e) Plot of main wavelength of biaxial (black triangles) and uniaxial (red circles and blue squares) wrinkles as a function of gold layer thickness.
  • the dashed lines show anticipated slopes from the theory. Note that " 1 " and "2" in (c), (d), and (e) indicate the first and the second populations of uniaxial wrinkle wavelengths.
  • FIG. 12 shows illustrated utilities of nano wrinkles, a) Scheme of fabrication of uniaxial wrinkles inside a Shrinky-Dinks-based microchannel. b) SEM image of uniaxial wrinkles, with 45nm thick silver layer, inside a channel. Right panel: Enlarged view of outlined area, c) Wide-field epifluorescence images of dyes on a glass plate (top) and on uniaxial wrinkles (bottom), d) Top: The corresponding intensity profiles along the arrows in (c). Bottom: Fluorescence lifetime measurements of dyes on a glass plate (blue) and on wrinkles (red). The black lines show that each time trace can be well fitted with exponential decays, e) SEM image of discrete "wrinkled flowers”.
  • sensors are sensors, methods for making the sensors, and methods for using the sensors to detect and identify chemical and biological agents.
  • compositions and methods include the recited elements, but do not exclude others.
  • Consisting essentially of when used to define compositions and methods shall mean excluding other elements of any essential significance to the combination when used for the intended purpose. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants or inert carriers.
  • Consisting of shall mean excluding more than trace elements of other ingredients and substantial method steps for preparing the micro fluidic device. Embodiments defined by each of these transition terms are within the scope of this invention.
  • thermoplastic material is intended to mean a plastic material which shrinks upon heating.
  • the thermoplastic materials are those which shrink uniformly without distortion.
  • Shrinky-Dink is a commercial thermoplastic which is used a childrens toy. The shrinking can be either bi-axially (isotropic) or uni-axial (anisotropic) and can be un-iaxially or bi-axially stressed prior to further shrinkage.
  • thermoplastic materials for inclusion in the methods of this invention include, for example, high molecular weight polymers such as acrylonitrile butadiene styrene (ABS), acrylic, celluloid, cellulose acetate, ethylene-vinyl acetate (EVA), ethylene vinyl alcohol (EVAL), fluoroplastics (PTFEs, including FEP, PFA, CTFE, ECTFE, ETFE), ionomers kydex, a trademarked acrylic/PVC alloy, liquid crystal polymer (LCP), polyacetal (POM or Acetal), polyacrylates (Acrylic), polyacrylonitrile (PAN or Acrylonitrile), polyamide (PA or Nylon), polyamide-imide (PAI), polyaryletherketone (PAEK or Ketone), polybutadiene (PBD), polybutylene (PB), polybutylene terephthalate (PBT), polyethylene terephthalate (PET), Polycyclohexylene Dimethylene Terephthalate (PC
  • a "metal" for use in this invention includes but is not limited to platinum, gold, titanium, silver, copper, a dielectric substance, a paste or any other suitable metal or combination thereof.
  • suitable dielectric substances include metal oxides, such as aluminum oxide, titanium dioxide and silicon dioxide.
  • suitable pastes include conductive pastes such as silver pastes.
  • the metal can be applied to the thermoplastic material by a variety of methods known to one skilled in the art, such as printing, sputtering and evaporating.
  • the term "evaporating” is intended to mean thermal evaporation, which is a physical vapor deposition method to deposit a thin film of metal on the surface of a substrate.
  • the term "sputtering" is intended to mean a physical vapor deposition method where atoms in the target material are ejected into the gas phase by high-energy ions and then land on the substrate to create the thin film of metal. Such methods are well known in the art (Bowden et al. (1998) Nature (London) 393: 146-149; Bowden et al. (1999) Appl. Phys. Lett. 75:
  • the metal can be applied to the thermoplastic material using "pattern transfer.”
  • pattern transfer refers to the process of contacting an image-forming device, such as a mold or stamp, containing the desired pattern with an image-forming material to the thermoplastic material. After releasing the mold, the pattern is transferred to the thermoplastic material.
  • image-forming device such as a mold or stamp
  • the pattern is transferred to the thermoplastic material.
  • high aspect ratio pattern and sub-nanometer patterns have been demonstrated.
  • Such methods are well known in the art (Sakurai, et al., US Patent 7,412,926; Peterman, et al., US Patent 7,382,449; Nakamura, et al., US Patent 7,362,524; Tamada, US Patent 6,869,735).
  • micro-contact printing refers to the use of the relief patterns on a PDMS stamp (also referred to as the thermoplastic material) to form patterns of self-assembled monolayers (SAMs) of an image-forming material on the surface of a thermoplastic material through conformal contact.
  • SAMs self-assembled monolayers
  • Micro-contact printing differs from other printing methods, like inkjet printing or 3D printing, in the use of self-assembly (especially, the use of SAMs) to form micro patterns and microstructures of various image-forming materials.
  • a "patterning device” is intended to be broadly interpreted as referring to a device that can be used to convey a patterned cross-section, corresponding to a pattern that is to be created in a target portion of the substrate.
  • a "pattern” is intended to mean a mark or design.
  • the sensors may include a heat-shrunk thermoplastic substrate and a film of metal disposed over the surface of the substrate.
  • the film of metal includes a microstructure characterized by wrinkle-like features.
  • microstructure it is meant a structure comprising features on the micrometer scale. However, the microstructure may also include features on the nanometer scale.
  • FIGS. 1 and 2 show images of a variety of substrates coated with wrinkled metallic surfaces. In FIG. 1, the wrinkle-like features are further characterized as folds in the metallic film, each fold having substantially rounded, smooth edges. As used herein, the types of wrinkled metallic films as shown in FIG. 1 will be referred to as a metallic films having folded, wrinkle-like features. In FIG.
  • the folds in the wrinkled metallic surface have cracked, resulting in petal-like (FIG. 2A) or ribbon-like (FIG. 2B) features.
  • petal-like FIG. 2A
  • ribbon-like FIG. 2B
  • the edges of the petal- like or ribbon- like features are relatively sharp.
  • the types of wrinkled metallic surfaces as shown in FIG. 2 will be referred to as metallic films having cracked, wrinkle-like features.
  • the wrinkled metallic films with petal-like features may also be referred to as nanopetal films.
  • the orientation of the wrinkles in the metallic film may vary.
  • the wrinkles are randomly oriented across the surface of the substrate. Such embodiments are shown in FIGS. IA, 1C, and 2A.
  • the wrinkles are oriented substantially parallel to one another across the surface of the substrate.
  • FIGS. lB and 2B By “substantially parallel,” it is meant that the wrinkles of the wrinkled metallic film are parallel to one another, but not necessarily perfectly parallel.
  • FIGS. IB and 2B although each of the wrinkles are approximately aligned with one another, many of the wrinkles are not perfectly straight so that the wrinkles are not perfectly parallel to one another.
  • the wrinkle-like features are localized to regions on the surface of the substrate and the regions are separated by areas in which the film of metal is substantially flat. Such an embodiment is shown in FIG. 1C.
  • the dimensions of the wrinkle-like features of the metallic film may vary.
  • the average height of the wrinkle-like features ranges from about 2 nm to about 100 nm. This includes average heights of about 10 nm, 25 nm, 50 nm, 75 nm, etc.
  • height it is meant the distance between a low point on the top surface of the metallic film (i.e., a valley in the wrinkled metallic film or a flat region on the metallic film) to a high point on the top surface of the metallic film (i.e., the peak of a folded wrinkle or an edge of a cracked wrinkle).
  • An average height may be obtained by averaging the heights of a plurality of wrinkles of the wrinkled metallic surface.
  • the average spacing of the wrinkle-like features ranges from about to 100 nm to about 3 ⁇ m. This includes average spacings of about 300 nm, 600 nm, 1 ⁇ m, 2 ⁇ m, etc.
  • spacing it is meant the distance between the high point on one wrinkle (i.e., the peak of a folded wrinkle or an edge of a cracked wrinkle) and the high point on another wrinkle.
  • An average spacing may be obtained similar to the average height described above.
  • the substrate of the sensor includes a thermoplastic material.
  • thermoplastic material encompasses those plastic materials that shrink upon heating.
  • suitable thermoplastic materials include, but are not limited to high molecular weight polymers such as acrylonitrile butadiene styrene (ABS), acrylic, celluloid, cellulose acetate, ethylene-vinyl acetate (EVA), ethylene vinyl alcohol (EVAL), fluoroplastics (PTFEs, including FEP, PFA, CTFE, ECTFE, ETFE), ionomers kydex, a trademarked acrylic/PVC alloy, liquid crystal polymer (LCP), polyacetal (POM or Acetal), polyacrylates (Acrylic), polyacrylonitrile (PAN or Acrylonitrile), polyamide (PA or Nylon), polyamide-imide (PAI), polyaryletherketone (PAEK or Ketone), polybutadiene (PBD), polybutylene (PB), polybutylene ter
  • thermoplastic substrates are heat shrunk.
  • heat shrunk it is meant that the thermoplastic substrate has been exposed to heat, which reduces the size of the substrate as compared to the size of the substrate prior to exposure to heat.
  • the size of the heat shrunk substrate may be reduced by a variety of amounts as compared to the size of the substrate prior to exposure to heat. In some embodiments, the size of the heat shrunk substrate is about 60%, 70%, 80%, or 90% the size of the substrate prior to exposure to heat. Heat shrinking is further described below.
  • the composition of the metallic film may vary.
  • metals may be used, including, but not limited to platinum, gold, titanium, silver, copper, a dielectric substance, a paste or any other suitable metal or combination thereof.
  • suitable dielectric substances include metal oxides, such as aluminum oxide, titanium dioxide and silicon dioxide.
  • suitable pastes include conductive pastes such as silver pastes.
  • the metallic film includes a single layer of any of these metals or combinations of these metals.
  • the metallic film may include two or more adjacent layers of metal.
  • a multi-layer metallic film may include a first layer of metal disposed over the substrate and a second layer of metal disposed over the first layer of metal.
  • the thickness of the metallic film may vary.
  • thickness of the metallic film it is meant the thickness of the film prior to the heating of the substrate which leads to the formation of the wrinkle-like features, as further described below.
  • the thickness of the metallic film may vary from about 1 nm to about 100 nm. This includes embodiments in which the thickness is about 10 nm, 25 nm, 50 nm, 75 nm, etc.
  • the thickness of each layer of metal may be the same or different.
  • the multi-layer film comprises two layers of different metals, wherein the first layer of the first metal has a thickness of about 30 nm to about 50 nm and the second layer of the second metal has a thickness of about 30 nm to about 50 nm.
  • Such multi-layer films at these thicknesses are particularly suitable for forming metallic films have cracked, wrinkle-like features.
  • the methods for making the disclosed sensors involve depositing a film of metal over the surface of a thermoplastic substrate and shrinking the coated substrate. Wrinkles form in the metallic film due to the stiffness incompatibility between the metallic film and the thermoplastic substrate. As further described below, the characteristics of the wrinkles may be controlled by the various parameters of the heating process and thickness of the deposited metal film.
  • PVD physical vapor deposition
  • CVD chemical vapor deposition
  • Micronking of the coated thermoplastic substrates may be accomplished by exposing the coated thermoplastic substrates to heat.
  • a variety of heat sources may be used, including, but not limited to an oven, such as a conventional oven or toaster oven.
  • the temperature of the heating process may vary. In some embodiments, the temperature ranges from about 100 0 C to about 200 0 C. This includes a temperature of about 16O 0 C, although other temperatures are possible.
  • the length of heating may also vary. In some embodiments, the length of heating may be from about 1 minute, 5 minutes, 10 minutes, or even more. Longer heating times increase the amount of shrinkage of the thermoplastic substrate.
  • the coated thermoplastic substrates may be biaxially or uniaxially shrunk.
  • shrinking of the thermoplastic material is isotropic.
  • uniaxially shrunk it is meant that the shrinking of the thermoplastic material is anisotropic. Uniaxially shrinking may be accomplished by constraining a thermoplastic substrate at two edges during the heating process, resulting in shrinking along only one axis of the material.
  • Various parameters of the heating process may be adjusted to control the characteristics of the metallic wrinkles.
  • the length of heating which determines the degree of shrinkage, affects the wrinkle height and wrinkle spacing.
  • the orientation of the wrinkles may be controlled through biaxial or uniaxial shrinking. As shown in FIGS. IA, 1C, and 2A, biaxially shrinking leads to the formation of wrinkles that are randomly oriented across the surface of the substrate. Uniaxially shrinking leads to the formation of wrinkles that are oriented substantially parallel across the surface of the substrate, as shown in FIGS. IB and 2B.
  • the thickness of the metallic film affects the characteristics of the metallic wrinkles.
  • the thickness of the metallic film affects the wrinkle spacing and the wrinkle height.
  • the thickness of the metallic film also affects whether the metallic film will include folded wrinkle-like features or cracked wrinkle-like features. Thinner metallic films (i.e., those less than about 80 nm) tend to produce folded wrinkle-like features while thicker metallic films (i.e., those greater than about 80 nm) cracked wrinkle-like features.
  • the disclosed sensors may also be incorporated into a variety of devices, including, but not limited to micro fluidic devices.
  • Micro fluidic devices may include micrometer-sized channels etched into the surface of a substrate. Exemplary microfluidic devices and methods for making the devices are described in International Application No. PCT/US2008/083283, which is hereby incorporated by reference in its entirety.
  • the incorporation of sensors into such micro fluidic devices may be accomplished in a variety of ways.
  • channels etched into a thermoplastic substrate may be coated with a film of metal and the coated thermoplastic substrate heated to provide channels having any of the wrinkled metallic surfaces described above. Integration with microfluidics will serve to reduce the target-probe reaction time based on reduced diffusion distance, enhanced mass transport and increases in the probability of collisions.
  • the disclosed sensors may be used to detect chemical and biological agents via backscattering spectrometry and enhanced backscattering spectrometry. These are known techniques. See, e.g., A. Ishimaru, Wave Propagation and Scattering in Random Media (IEEE Press, New York, 1996); L. Tsang, J. A. Kong and K. -H. Ding, Scattering of Electromagnetic Waves: Theories and Applications (John Wiley & Sons, Inc., New York, 2000); L. Tsang, J. A. Kong, K. -H. Ding and C. O.
  • backscattering enhancement a phenomenon in which a well-defined peak in the backscattered direction off randomly rough surfaces is apparent, is the result of multiple scattering effects as well as surface plasmon interactions.
  • a chemical or biological agent is adsorbed to such a surface, interactions of light scattered by the agent and the surface as well as any self-interactions that might occur are encoded in the optical characteristics of the measured scattered light, such as wavelength, angle, spatial and polarization diversity. Both direct and inverse scattering measurements may be used.
  • unlabeled chemical and biological agents may be detected by comparing the optical characteristics of backscattered light from a surface having adsorbed agents to the optical characteristics of backscattered light from a bare surface.
  • plasmon resonance interactions with the chemical and biological agents of interest can provide additional information about adsorbed agents, thereby aiding in molecular identification. This may be accomplished by identifying spectral signatures of plasmatic resonances and their polarization dependent reflectance through extinction spectra studies. As described in International Application No. PCT/US2008/083283, which is hereby incorporated by reference in its entirety, it has been observed that wrinkled metallic surfaces having wrinkles that are oriented substantially parallel across the surface of a thermoplastic substrate exhibit a polarization-dependent shift in the surface plasmon resonance. Finally, to increase accuracy and sensitivity of the sensors, any of the disclosed sensors can be made to have overlapping extinction spectra with the extinction spectra of the chemical and biological agent of interest.
  • the disclosed methods involve exposing any of the disclosed sensors to a chemical or biological agent; exposing the sensor to light, and measuring the backscattered light from the sensor to detect the chemical or biological agent. Any chemical and biological agents may be detected using the disclosed sensors. A variety of light sources and a variety of wavelengths of light may be used. Techniques for measuring the backscattered light are known. Similarly, experimental set-ups for backscattering spectrometry are known.
  • kits comprising, or alternatively consisting essentially of, or yet further consisting of the materials necessary to perform the methods described above.
  • the kit comprises, or alternatively consists essentially of, or yet further consists of a thermoplastic material and instructions for carrying out the method.
  • the kits further comprise one or more metals for forming wrinkles and instructions.
  • the kit provides instructions for making and using the apparatus described above and incorporated herein by reference.
  • this invention provides a method for assaying or screening for new materials and methods having the same function of the inventions as described herein.
  • the new materials and/or methods are used in the methods as described herein and compared to the performance of the devices of this invention.
  • Example 1 Scattering of light by molecules over a rough surface
  • This example demonstrates that rough surfaces provided by the metal wrinkles of the present technology are useful in application in biological and chemical sensing. A theory for multiple scattering of light by obstacles situated over a rough surface is also provided.
  • This example further presents a systematic method for studying the multiple scattering due to an obstacle situated over a rough surface.
  • This theory requires knowledge of the scattering properties of the obstacle and the rough surface separately.
  • This example combines these two operations in a self-consistent way.
  • This theory is simply an extension to the Foldy-Lax theory for multiple scattering [20-23].
  • This example shows explicitly that this theory takes into account infinitely many interactions between an obstacle and the rough surface.
  • this theory provides a foundation for studying carefully the multiple scattering by obstacles over rough surfaces provided that scattering by the obstacle and the rough surface themselves is sufficiently accurate.
  • the rough surface here is not considered a random rough surface. Although one may not know the exact spatial properties of the surface for these applications, the surface is fixed. Thus, one may perform several calibration steps, if necessary. In particular, this example works under the assumption that one can first measure the light scattered by the rough surface without the presence of the obstacles. Then this example measures the light scattered by the obstacles over the rough surface. For this reason, this examples does not compute any statistical quantities. One may consider computing statistical quantities using this method to make statements about an ensemble of sensors.
  • This example seeks to develop a theoretical framework to study the interactions of light scattered by obstacles over a rough surface.
  • this example studies time-harmonic (monochromatic light), scalar wave propagation, and scattering.
  • this example considers a wave incident on several obstacles situated over a rough surface.
  • This example considers time-harmonic wave propagation with time dependence e ⁇ t and circular frequency ⁇ .
  • this example needs to solve the following reduced wave or Helmholtz equation:
  • this example develops a self-consistent theory for the multiple scattering of light by M obstacles situated over a rough surface. This theory requires knowledge of the scattering operator or the t-matrix for each of the obstacles and the reflection operator for the rough surface. Once those operators are established, this example combines them in a self-consistent manner to obtain a multiple scattering theory.
  • the scattering operator S m gives the field scattered by the mth obstacle due to an exciting field.
  • SmuE the scattered field produced by the field uE exciting the obstacle.
  • Sm the scattering operator Sm (otherwise known as the t-matrix or transition operator) with kernel t m (r,r') for the mth obstacle is given by
  • X 1n corresponds to the support of the mth obstacle.
  • the reflection operator R gives the field reflected by the rough surface due to an exciting field.
  • the reflected field produced by the field u E exciting the rough surface is given by Ru E .
  • R is defined by the solution of a surface integral equation derived from the Kirchhoff theory [22-24]. For the special case of a slightly rough surface, this example obtains an asymptotic result for R which will be used later.
  • This example represents the exciting fields as
  • Equations (3.3) and (3.4) comprise a self-consistent system for the exciting fields ⁇ m and ⁇ .
  • This self-consistent system is an extension of the so-called Foldy-Lax theory for multiple scattering [20-23]. This extension incorporates scattering by the rough surface.
  • the Foldy-Lax theory includes infinitely many interactions, Eqs. (3.3) and (3.4) include infinitely many interactions between the obstacles and the rough surface.
  • Eq. (3.3) reduces to
  • Ru 1 The field reflected by the slightly rough surface, Ru 1 can then be represented as
  • Equations (4.11) and (4.12) correspond to the free-space Green's function rather than Eq. (4.2) since the example is not evaluating them near the singularity. Now, the example introduces the quantities
  • U ⁇ r RUi(T) + 2 ⁇ m [G 0 ⁇ r;r m ) + -RG 0 ⁇ r;r m )] ⁇ & ⁇ j .
  • this example considers two particular examples. The first one is for a single point obstacle situated over a slightly rough surface. The second one is for two point obstacles situated over a slightly rough surface. These two examples are relevant for applications of optical sensors for point-of-care diagnostics.
  • the ability to detect extremely low concentrations of analytes in a solution is important for this application, but remains a persistent challenge.
  • the limit of detection for the ELISA the gold standard, is typically in the picomolar range. To be able to detect molecules at much more dilute concentrations would enable earlier stage detection with a less invasive sampling.
  • this example assumes only a few obstacles in a site specific region to test the ability to detect extremely low concentrations.
  • this example is able to obtain analytical results that the example interprets physically. Using those analytical results, this example computes asymptotic results for the scattered field u s (r) evaluated in the far- field.
  • the first term corresponds to the incident field ui and the incident field reflected by the slightly rough surface, Ru 1 , exciting the point obstacle.
  • the next term corresponds to the scattering of that exciting field down to the slightly rough surface and reflected back up to excite the point scatterer, and so on.
  • a diagram showing these interactions appears in FIG. 5.
  • Eq. (5.3) shows that this theory takes into account infinitely many interactions between the point obstacle and the slightly rough surface.
  • Figure 7 shows contour plots of the image /(x,y) defined as for both the Dirichlet (top) and Neumann (bottom) cases.
  • This difference image /(x,y) corresponds to the subtraction of the direct image without the point obstacles taken at the detector plane from the direct image with the point obstacles taken at the detector plane.
  • This example has computed numerically the results given by Eq. (5.13).
  • the example uses the same rough surface that this example used for the numerical example above.
  • the two point obstacles are two wavelengths apart from one another.
  • the location of the two point obstacles in relation to this rough surface is shown in FIG. 8.
  • FIG. 9 the example plots the image I(x,y) defined in Eq. (5.5) for both the Dirichlet (top) and Neumann (bottom) cases.
  • This example has developed a theoretical framework to study obstacle scattering over a rough surface. This theory involves combining each of the scattering operators for each of the obstacles and the reflection operator for the rough surface in a self-consistent way. For the simple case of point obstacles over a slightly rough Dirichlet or Neumann surface, this example is able to obtain analytical results. The example has shown analytical and numerical results for the cases involving one and two point obstacles.
  • This theoretical framework provides, to the applicants' knowledge, a critical first step in studying the multiple scattering of light by nano -structured metallic substrates for sensor applications. It takes into account the interactions made between a single molecule and a rough surface. Here, the example has addressed this problem in an idealized setting.
  • the obstacles are point scatterers and the rough surface is a small perturbation from a plane. Moreover, the surface is assumed to be a perfect electric conductor.
  • Example 2 Scattering of light by molecules over a rough surface [0103] This example shows preparation of tunable nano wrinkles suitable for detection of biological or chemical agents.
  • the sample was then coated with 45 nm of silver by sputter deposition. After coating, the tape was removed from the surface of the chip; what remained was only the silver that was deposited on the surface of the channel. The sample was then shrunk, without being constrained, at 150 0 C to create uniaxial wrinkles inside the channel.
  • CellTracker; Invitrogen with absorption peaking at 577 nm and emission peaking at 602 nm, were used. They were first dissolved in dimethylsulfoxide (Sigma) to a concentration of 10 niM and then diluted with poly( vinyl alcohol) solution (PVA, 1 wt% in water, MW ca. 13000-23000; Sigma) to ca. 10 ⁇ M. Sample (10 ⁇ L) was dropped onto the uniaxial wrinkles (50nm thick gold) and a glass plate and then spin-coated at 3000 rpm for 2 min to form a sample layer with tens of nanometers thickness [51].
  • PVA poly( vinyl alcohol) solution
  • PVA polymers are used to form a buffer layer between the metal surface and fluorophores to avoid metal-induced quenching by direct contact [51].
  • the fluorescence images were acquired using a wide-field epifluorescence microscope (TE 2000-U; Nikon) equipped with a illumination system (X- Cite Series 120; EXFO) and a green color excitation filter (D540/25X; Chroma Tech).
  • the emission was collected by a 40 ⁇ , numerical aperture (NA) 0.75 objective (Plan Fluor;
  • Emission passing through a 410 nm notch filter (CVI) and a 590-650 nm band-pass filter (D620/60 M; Chroma Tech) was detected by an avalanche photodiode (PDM 50ct; MPD).
  • PDM 50ct avalanche photodiode
  • the corresponding fluorescence decays were measured with a time-correlated single-photon counting module (PH300; Picoquant).
  • the prevailing wavelengths peak near 400 nm and range from ca. 200 nm to ca. 1 ⁇ m. This range is smaller but more heterogeneous than those reported from other approaches, where the wrinkles had periodicities ranging from 20 ⁇ m to 50 ⁇ m. [37] As discussed below, one can adjust this broader range to its advantage for sensing applications.
  • Uniaxial wrinkles can be easily created as well (FIG. 10a, right).
  • This example modifies the fabrication process by introducing boundary conditions by clamping two edges of a gold-coated PS sheet during the heating process. This gives rise to constrained shrinking along one direction. Large areas of well-aligned linear wrinkles can be produced (FIG. 10c). For the 10 nm thick sample, these wrinkles exhibit two distinct populations with peaks at 300 nm and 800 nm (FIGS. 1 lc,d). Their cross-sectional SEM image (FIG. l ie, bottom) demonstrates that the two populations correspond to two hierarchical generations of wrinkles.
  • the peak wavelengths of both populations are proportional to the thickness of deposited gold and can thus be controllably tuned by adjusting the thickness of deposited gold (FIG. l id).
  • the scaling of the dominant wavelengths with film thickness for both first and second generations is linear, with slopes of 2.1 and 2.4, respectively (blue squares and red circles of FIG. l ie).
  • the consistency between experimental results and the anticipated value for the bare metal film indicates that the loss of coherence is not the dominant issue, allowing the sample to clearly see features of the underlying wrinkle distribution.
  • the first population small wrinkles
  • the second population larger wrinkles
  • the second population arises from the saturation of the previous generation of wrinkles (first population), leading to the formation of an effective skin, which can still be regarded as having a modulus comparable to the bare metal but with a thickness that is about 300 nm greater than the metal film thickness.
  • hierarchical wrinkling is a nonlinear process, it is difficult a priori to predict the effective skin thicknesses of successive generations. As a rough approximation, one can take the wrinkle amplitude (ca.
  • the effective thicknesses for the first and second populations above are then consistent with second- and third-generation wrinkles for an overall strain of order unity.
  • the stresses are then of the order of Y go i d ⁇ h/ ⁇ , which yields values ranging from several hundred magapascals to IGPa over the range of thicknesses.
  • the ability to achieve nanometer-scale wrinkles enables us to use these self-organized structures for surface plasmon resonance (SPR)-based sensing applications, such as metal-enhanced fluorescence (MEF).
  • SPR surface plasmon resonance
  • MEF metal-enhanced fluorescence
  • This technique utilizes metallic nanostructures in which the plasmons resonate with the fluorophores to reduce their excited state lifetimes and simultaneously increase their fluorescence emission intensities.
  • Silver island films are often used to meet such a requirement, and the typically ca. 10-fold enhancement has been applied to improve detection of DNA hybridization [56] and immunoassay.
  • detrimental chemical properties of silver such as low stability and easy oxidization, inevitably restrict its potential in biomedical applications.
  • Figures 12c and d show fluorescence images along with the corresponding intensity profiles of dyes, dissolved in polymer solution and then spin-coated on either a bare glass plate or uniaxial gold wrinkles.
  • the average fluorescence intensity increased approximately threefold over a relatively large area when the dyes were deposited on the wrinkles rather than the glass. Many bright lines parallel to the direction of the wrinkles indicates that there are many continuous hotspots along the wrinkles, with 5- to 7-fold enhancements.
  • the approach can create tunable nano wrinkles with broad yet tunable wavelength distributions.
  • Such flexibility and heterogeneity hold a number of advantages over single, homogeneous, wavelength wrinkles.
  • these properties make it possible to adjust broad SPR bands to overlap well with various absorption bands of fluorophores.
  • this approach is considerably faster and significantly less expensive and more robust than other means of achieving such size-controllable nanometer-scale structures (including nanosphere lithography, focused ion beam lithography, and electron-beam lithography).

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Abstract

L'invention concerne des capteurs servant à détecter des substances chimiques ou biologiques. Le capteurs comprennent un substrat thermoplastique thermorétracté et un film métallique disposé à la surface du substrat. Le film métallique comprend une microstructure caractérisée par des éléments ridés. L'invention concerne également des procédés de fabrication des capteurs, et des procédés de détection de substances chimiques ou biologiques avec les capteurs, par spectrométrie de rétrodiffusion.
PCT/US2010/034611 2009-05-13 2010-05-12 Substrats thermoplastiques à surfaces métalliques ridées pour la détection de substances chimiques ou biologiques WO2010132610A2 (fr)

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US8828302B2 (en) 2011-02-07 2014-09-09 The Regents Of The University Of California Preparation and use of nanowrinkles
US20150037802A1 (en) * 2013-08-05 2015-02-05 The Johns Hopkins University Fabrication of hierarchical silica nanomembranes and uses thereof for solid phase extraction of nucleic acids
US9452564B2 (en) 2011-02-07 2016-09-27 The Regents Of The University Of California Multi-scale wrinkles for functional alignment of stem cells and cardiac derivatives
US9522820B2 (en) 2007-11-13 2016-12-20 The Regents Of The University Of California Processes for rapid microfabrication using thermoplastics and devices thereof
US9625819B2 (en) 2011-05-27 2017-04-18 The Regents Of The University Of California Photolithography on shrink film
CN107328764A (zh) * 2017-07-24 2017-11-07 济南大学 化学发光驱动光致电化学纸基传感器的制备与应用
US20180001325A1 (en) * 2015-01-27 2018-01-04 Circulomics Inc. Hierarchical silica lamella for magnetic nucleic acid extraction
CN111398248A (zh) * 2020-04-22 2020-07-10 南通大学 一种基于多形貌银修饰的纳米金膜sers基底制备方法
CN111572983A (zh) * 2020-04-26 2020-08-25 浙江天益塑业有限公司 一种高强可降解型纸塑复合袋及其制备方法

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WO2007011331A2 (fr) * 2005-07-14 2007-01-25 3M Innovative Properties Company Substrat polymere hydrosoluble presentant un revetement de nanoparticules metalliques
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* Cited by examiner, † Cited by third party
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US9522820B2 (en) 2007-11-13 2016-12-20 The Regents Of The University Of California Processes for rapid microfabrication using thermoplastics and devices thereof
US9452564B2 (en) 2011-02-07 2016-09-27 The Regents Of The University Of California Multi-scale wrinkles for functional alignment of stem cells and cardiac derivatives
US8828302B2 (en) 2011-02-07 2014-09-09 The Regents Of The University Of California Preparation and use of nanowrinkles
US9625819B2 (en) 2011-05-27 2017-04-18 The Regents Of The University Of California Photolithography on shrink film
US10023859B2 (en) 2013-08-05 2018-07-17 The Johns Hopkins University Fabrication of hierarchical silica nanomembranes and uses thereof for solid phase extraction of nucleic acids
US20150037802A1 (en) * 2013-08-05 2015-02-05 The Johns Hopkins University Fabrication of hierarchical silica nanomembranes and uses thereof for solid phase extraction of nucleic acids
EP3030644A4 (fr) * 2013-08-05 2017-03-01 The Johns Hopkins University Fabrication de nanomembranes hiérarchiques en silice et leurs utilisations pour l'extraction sur phase solide d'acides nucléiques
US9765325B2 (en) * 2013-08-05 2017-09-19 The Johns Hopkins University Fabrication of hierarchical silica nanomembranes and uses thereof for solid phase extraction of nucleic acids
EP3587551A1 (fr) * 2013-08-05 2020-01-01 The Johns Hopkins University Fabrication de nanomembranes de silice hiérarchiques
CN105518120B (zh) * 2013-08-05 2018-05-15 约翰霍普金斯大学 分层硅石纳米膜的制造和其用于核酸的固相提取的用途
US20180001325A1 (en) * 2015-01-27 2018-01-04 Circulomics Inc. Hierarchical silica lamella for magnetic nucleic acid extraction
US10737276B2 (en) * 2015-01-27 2020-08-11 Circulomics Inc. Hierarchical silica lamella for magnetic nucleic acid extraction
US11198135B2 (en) 2015-01-27 2021-12-14 Pacific Biosciences Of California, Inc. Hierarchical silica lamella for magnetic nucleic acid extraction
CN107328764A (zh) * 2017-07-24 2017-11-07 济南大学 化学发光驱动光致电化学纸基传感器的制备与应用
CN111398248A (zh) * 2020-04-22 2020-07-10 南通大学 一种基于多形貌银修饰的纳米金膜sers基底制备方法
CN111572983A (zh) * 2020-04-26 2020-08-25 浙江天益塑业有限公司 一种高强可降解型纸塑复合袋及其制备方法

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