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WO2025209653A1 - Dispositif de détection optique à antenne plasmonique asymétrique - Google Patents

Dispositif de détection optique à antenne plasmonique asymétrique

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Publication number
WO2025209653A1
WO2025209653A1 PCT/EP2024/059181 EP2024059181W WO2025209653A1 WO 2025209653 A1 WO2025209653 A1 WO 2025209653A1 EP 2024059181 W EP2024059181 W EP 2024059181W WO 2025209653 A1 WO2025209653 A1 WO 2025209653A1
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WO
WIPO (PCT)
Prior art keywords
antenna elements
dielectric layer
gaps
pairs
apertures
Prior art date
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Pending
Application number
PCT/EP2024/059181
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English (en)
Inventor
Benedikt Oswald
Elias STUTZ
Peter WARNICKE
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Lspr Ag
Original Assignee
Lspr Ag
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Filing date
Publication date
Application filed by Lspr Ag filed Critical Lspr Ag
Priority to PCT/EP2024/059181 priority Critical patent/WO2025209653A1/fr
Publication of WO2025209653A1 publication Critical patent/WO2025209653A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3275—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
    • G01N27/3278—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction involving nanosized elements, e.g. nanogaps or nanoparticles

Definitions

  • the n pairs of opposite antenna elements define n respective gaps on top of the n apertures.
  • the gaps extend between opposite antenna elements of the n pairs along respective directions parallel to an average plane of the dielectric layer to define n molecular passages.
  • each gap defines a respective electromagnetic field enhancement region, in which electromagnetic radiation can be concentrated upon irradiating the respective antenna elements for optically sensing molecules passing through the gaps, in operation.
  • Each of the n molecular passages extends from the cavity through a respective one of the n apertures and a respective one of the n gaps.
  • the two antenna elements of each of the n pairs have triangular shapes in a bowtie configuration. However, one antenna element only of these two antenna elements has a slit extending from one lateral side thereof, such that the bowtie configuration is asymmetric.
  • the above design relies on plasmonic antennas, where the symmetry of the bowtie configuration is broken by introducing a slit (i.e., a slot or notch, or a strip-like cut-out) laterally in one element (call it the slit antenna element) of the two antenna elements and, this, for each of the pairs of antenna elements.
  • a slit i.e., a slot or notch, or a strip-like cut-out
  • the bowtie structure proposed above is no longer symmetrical with respect to the gap or aperture, i.e., with respect to the median plane extending perpendicular to the average plane of the antenna elements.
  • Analyte molecules can be controllably trapped in the molecular passages for sensing application, e.g., using surface-enhanced Raman spectroscopy techniques.
  • the slit extends over an entire thickness of the slit antenna element, to accentuate the asymmetry of the bowtie configuration and thus the desired effects in terms of Fano resonances and electric field enhancement.
  • the slit antenna element may further be asymmetric with respect to a transverse plane containing the line segment that passes through the apex and is perpendicular to the base (i.e., the side opposite the apex) of the slit element. That is, apices of the two antenna elements typically point towards each other (subject to fabrication tolerances, typically on the order of the nm), as a result of the bowtie configuration.
  • the slit antenna element may advantageously be asymmetric with respect to the longitudinal plane that contains the line segment passing through the apices and is perpendicular to the average plane of the dielectric layer.
  • the lateral side (or edge) from which the slit extends is preferably a lateral side joining the apex (meaning one of the two apices as defined above) of the slit antenna element.
  • this slit may extend from this lateral side to at least the longitudinal plane but preferably not up to the opposite lateral side, i.e., opposite with respect to the longitudinal plane.
  • the slit may be curved or bent along its direction of extension, or have a non-constant profile along its direction of extension. Note, this direction of extension is not necessarily straight; it is, however, parallel to the average plane of the dielectric layer.
  • an average length of the n gaps along said respective directions is between 4 nm and 20 nm.
  • the average diameter of the n apertures is equal to the average length of the gaps, subject to ⁇ 2 nm, whereby inner ends of the antenna elements of each of the n pairs are substantially flush with inner walls of the respective n apertures in the membrane. That is, the vertices of the antenna elements are brought as close as possible to the edge of the respective aperture. This allows the electromagnetic field enhancement to be further increased, all things being otherwise equal. In variants, the apices of the antenna elements even hang over the edges of the aperture underneath, which further reduces the electromagnetic field enhancement region.
  • the diameters of the apertures and the lengths of the gaps will preferably be essentially constant, subject to a dispersion (i.e., a standard deviation) of less than (or equal to) 3 nm. More preferably, an average in-plane separation distance between two closest apertures is between 1 and 10 microns, preferably between 2 and 7 microns.
  • the dielectric layer is a first dielectric layer
  • the device further includes a second dielectric layer
  • the substrate is on top of the second dielectric layer
  • the substrate and the second dielectric layer are jointly structured to form a recess delimiting said cavity.
  • the substrate comprises silicon
  • each of the two dielectric layers comprises SislS
  • each of the antenna elements essentially comprises gold (Au).
  • the antenna elements may comprise any other metal that exhibits plasmonic behaviour in the desired wavelength region, e.g., in the range between 200 and 3000 nm, preferably between 700 and 1000 nm.
  • the thickness of each of the first and second dielectric layers is preferably between 10 and 60 nm, and more preferably between 15 and 35 nm.
  • the optical sensing device may further comprise one or more pairs of electrodes, wherein the electrodes of each of the pairs are on opposite sides of the first dielectric layer.
  • such electrodes do not form part of the device but are nevertheless brough in contact with a liquid in which the device is immersed.
  • the invention is embodied as an optical sensing apparatus.
  • the apparatus notably comprises an optical sensing device as described above. It further includes a distributed electromagnetic source (e.g., comprising a Laser), which is configured to irradiate the antenna elements of at least some of the n pairs of opposite antenna elements. This way, electromagnetic radiation can be concentrated in respective electromagnetic field enhancement regions as delimited by the n gaps, with a view to optically sensing molecules in the respective gaps.
  • the apparatus further includes a detector, which is configured to optically detect optical signals as modulated and/or generated by the molecules in said regions, in operation.
  • the detector is preferably a Raman spectrometer. It may for instance be a spatial heterodyne Raman spectrometer, a snapshot hyperspectral spectrometer or a scanning hyperspectral spectrometer.
  • the apparatus further comprises an electrical circuit comprising one or more pairs of electrodes, wherein the electrodes of each of the pairs are on opposite sides of the (first) dielectric layer.
  • the electrical circuit is notably configured to apply a voltage bias between electrodes of each of the pairs to urge molecules through the passages.
  • the optical sensing device of the apparatus may include two dielectric layers as described above, where the substrate extends on top of the second dielectric layer, so as to form a recess delimiting said cavity.
  • the dielectric layer is a first dielectric layer
  • the method further comprises depositing a second dielectric layer below the substrate, preferably while depositing the first dielectric layer.
  • the second dielectric layer is patterned (after patterning the fiducial marks but prior to patterning the n pairs of opposite antenna elements) so as for residual, peripheral portions of the second dielectric layer to delimit the recess to be formed next.
  • FIG. 5 is a 2D cross-sectional view of a variant to the optical sensing device of FIG. 1, where the antenna elements partly hang over the aperture, as in embodiments;
  • FIG. 7 shows a 3D model (top view) of a plasmonic antenna with two antenna elements in a bowtie configuration, where the lower antenna element includes a slit extending from a lateral edge, according to embodiments;
  • FIGS. 8A- 80 show top views of potential, ideal patterns of plasmonic antennas as written in negative tone electron beam resist, as involved in embodiments;
  • FIGS. 9A - 90 show top views of simulated patterns, as obtained after transferring the ideal patterns of FIGS. 8A- 80 to a metal layer, as done in embodiments;
  • FIG. 10A shows a segmented version of a scanning electron microscope (SEM) image of a plasmonic antenna pattern as written in a negative-tone electron beam resist, as in embodiments (top view, black-and-white segmented image);
  • SEM scanning electron microscope
  • FIG. 10B shows a segmented version of a SEM micrograph of the plasmonic antenna pattern of FIG. 10A, once transferred from the negative-tone e-beam resist to a gold layer, as in embodiments (top view, contour line);
  • FIG. 11 is a Surface-Enhanced Raman Scattering (SERS) spectrum obtained for thymine, showing a number of high-quality Raman peaks (after background subtraction), as obtained with a plasmonic antenna such as shown in 10B.
  • SERS Surface-Enhanced Raman Scattering
  • Such a device 1 can be used in an apparatus 100 such as shown in FIGS. 4A or 4B, in accordance with another aspect of the invention, which is described later in detail.
  • the device 1, la has a layer structure, which notably comprises a substrate 10, a dielectric layer 11, and antenna elements 17, 17a, 17b, 17c.
  • the substrate 10 is structured to laterally delimit a cavity 40.
  • the cavity 40 is typically formed by a recess defined in the substrate 10, whereby this recess laterally delimits the cavity 40.
  • the substrate 10 may for example be provided as a double-side polished silicon (Si) wafer, the thickness of which is typically equal to 275, 375, or 525 pm. This wafer then undergoes several processing steps, to define the cavity 40.
  • the membrane 11 includes n apertures 30 to the cavity 40. These apertures are defined as through holes through the membrane 11. There is at least one aperture (n > 1). A single aperture already makes it possible to sense molecules, one at a time. In typical applications, however, the device 1, la includes several apertures (n > 2). For applications such as sequencing applications, one will typically seek to fabricate a device with hundreds to thousands to millions of apertures (n > 100). Such apertures are also referred to as nanopores herein, because of their preferred dimensions, as discussed later.
  • the apertures can for instance be arranged according to a 2D lattice, e.g., a hexagonal, square or rectangular lattice, as assumed in FIG. 3.
  • the average, in-plane separation distance between the apertures will typically be between 1 and 100 microns, as measured centre-to-centre.
  • the average lattice step is between 1 and 10 microns, preferably between 2 and 7 microns. More preferably, it is between 3 and 6 microns.
  • the average distance between apertures can be of 5 microns.
  • the areal density of the apertures 30 is between 0.0001 and 1 pm' 2 , though preferably between 0.01 and 1 pm' 2 .
  • a chip of, e.g., 5 x 5 mm 2 .
  • the device 1, 1a further includes n pairs of opposite antenna elements 17, 17a, 17b, 17c (i.e., plasmonic structures), where each pair of antenna elements form a plasmonic antenna.
  • a plasmonic antenna includes two antenna elements. These antenna elements are patterned on top of the dielectric layer 11.
  • the antenna elements 17, 17a, 17b, 17c preferably have a form factor. That is, their largest dimension preferably extends parallel to the plane (x, y). They are ideally made as sharp as possible toward the centre to enhance the electromagnetic hot spot, although they will likely exhibit rounded edges due to the reality of the fabrication steps.
  • the antenna elements 17, 17a, 17b, 17c of each pair are on arranged on opposite lateral sides of the respective apertures 30. In each pair, the antenna elements are separated by a respective gap g. There are n gaps g in total. Such gaps extend between opposite antenna elements 17, 17a (or 17b, 17c) of respective ones of the n pairs. The gaps extend along respective directions, which are all parallel to an average plane (x, y) of the substrate 10.
  • the pairs of antenna elements 17, 17a will typically be all aligned along parallel directions, as assumed in FIG. 3, where all pairs extend along an axis parallel to direction x. In general, the relative orientation of the bowties will be consistent with the orientation of the polarization of the incident light.
  • the bowties are typically designed to be excited by light with a linear polarization along the long axis of the bowties. Orienting one or many bowties away from this preferred orientation reduces the field enhancement, and thus the efficiency of the sensing apparatus.
  • maximal efficiency is obtained if all the bowties are aligned in the same direction and parallel to the polarization direction of incident light.
  • n gaps g define, together with the respective apertures, n molecular passages.
  • Each passage extends from the cavity 40, i.e., across the membrane 11, along a direction z that is transverse to the main plane or the average plane (x, y) of the substrate 10. That is, each molecular passage extends through a respective aperture 30 and a respective gap g.
  • the average length of the n gaps is preferably between 4 nm and 20 nm. More preferably, this dimension is between 4 nm and 15 nm, and even more preferably between 5 nm and 12 nm.
  • the gaps separating each antenna element pair are ideally constant, subject to fabrication tolerances, which can be as low as ⁇ 1 to ⁇ 2 nm, owing to preferred fabrication methods as discussed herein. In fact, both the diameters of the apertures and the gap lengths may essentially be constant, subject to a dispersion of less than 2 nm.
  • SEM scanning electron microscopy
  • TEM transmission electron microscopy
  • the high resolution permitted by TEM allows the variability (dispersion) of the dimensions of the nanostructures to be accurately estimated. Note, the variability (or dispersion) is measured as a standard deviation, actually an uncorrected sample standard deviation.
  • the n gaps define (i.e., laterally delimit) respective electromagnetic field enhancement regions, also referred to as hot spot regions. That is, electromagnetic radiation can be concentrated in such regions upon irradiating the antenna elements 17, 17a, 17b, 17c, with a view to optically sensing analytes (molecules), in operation.
  • the antenna elements enable an electromagnetic field enhancement mechanism, which can generate a field-enhanced hot spot, wherein electromagnetic radiation can be concentrated. This, in turn, can be exploited to sense an analyte (e.g., a DNA molecule, by surface-enhanced Raman spectrometry), by irradiating the antenna elements.
  • an analyte e.g., a DNA molecule, by surface-enhanced Raman spectrometry
  • the resulting electromagnetic field enhancement region is essentially confined to the gap in-between (as illustrated in FIG. 4B), above the apertures 30.
  • the antenna elements generally have a bowtie configuration. They can be regarded as flat prisms, pointing at each other. I.e., seen from above, they essentially have triangular shapes pointing at each other. Now, the symmetry of antenna elements can be altered to further improve the electromagnetic field enhancement.
  • one antenna element only of the two antenna elements of each plasmonic antenna is pattern so as to have a slit 18 (i.e., a slot or notch, or a strip-like cut-out) extending from one lateral side thereof.
  • the antenna element 17a, 17c with the slit is referred to as a slit antenna element in the following.
  • the bowtie configuration is asymmetric.
  • the symmetry of the antenna elements is broken by introducing a lateral slit 18 in one of the two antenna elements, which effectively results in an asymmetric bowtie configuration.
  • the antenna structure proposed herein is no longer symmetrical with respect to the gap or aperture, i.e., with respect to the median plane IE. parallel to the plane (y, z), i.e., the plane extending perpendicular to the average plane of the antenna elements, the average plane of the substrate 10, or the average plane of the dielectric layer 11. This makes it possible to obtain Fano resonances and increase the electric field enhancement.
  • FIG. 7 An example of the modification of the geometrical layout of the plasmonic bowtie antenna is shown in FIG. 7.
  • the proposed geometry breaks the symmetry of the bowtie configuration by introducing a strip-like cut-out 18 from the lower antenna element. The dimensions and the position of the cut-out determine the wavelength position and strength of the desired resonance. The maximum field enhancement will normally occur at the position of the resonance.
  • the slit 18 may extends over an entire thickness of the slit antenna element, as assumed in FIGS. 2, 3, 5, 6, and 7. This accentuates the asymmetry of the bowtie configuration and thus the desired effects in terms of Fano resonances and electric field enhancement.
  • the slit extends only partly, albeit substantially, though the thickness of the antenna element, which already results in an asymmetry. It is worth noting, in that respect, that preferred fabrication methods as discussed herein rely on grayscale lithography, such that the slit does not necessarily need to extend through the entire depth of the slit antenna element 17a, 17c. However, given the aspect ratio typically intended for the antenna elements, the slit 18 preferably extends over the entire thickness of the slit antenna element 17a, 17c.
  • the slit antenna element 17a, 17c may further be asymmetric with respect to the longitudinal transverse plane H._-, parallel to (x, z), as assumed in the accompanying drawings.
  • This plane contains the line segment passing through the apices 19, 19a of the antenna elements and is perpendicular to the average plane of the dielectric layer 11.
  • a bowtie configuration implies that the apices 19, 19a are located inwardly and point towards each other, subject to slight deformations that may result from fabrication tolerances, typically on the order of the nm.
  • the antenna elements generally evoke perfect geometrical shapes (e.g., triangles or prisms having apices and edges), one keeps in mind that apices 19, 19a of such antenna elements will actually show a certain radius of curvature (or osculating radius) resulting from actual fabrication steps, as illustrated in FIG. 7.
  • this radius will preferably be less than 30 nm, preferably less than 20 nm, and more preferably on the order of 5 nm, thanks to fabrication methods as discussed herein. This radius is assumed to be approximately equal to 8 nm in FIG. 7.
  • any gap g extends between respective antenna elements along a respective direction parallel to the plane (x, y). This direction passes through the apices pointing towards each other.
  • the slit 18 may extend from one lateral side SI joining the apex 19a of the slit antenna element up to the plane H x , z , or beyond said plane n v . z , but preferably not up to the opposite side S2.
  • the slit may extend from the base S3, but then it should typically be sufficiently wide, or preferably bent, to create a substantial asymmetry. Best is for the slit 18 to extend laterally from SI (or equivalently S2).
  • the slit 18 should be sufficiently pronounced to enable a sufficient asymmetry and, in turn, a meaningful improvement to the field enhancement.
  • the slit 18 cannot be too large either as this would amount to making the slit element 17a, 17c disappear, hence a necessary trade-off.
  • the apparent area of the slit 18 can normally be characterized using a suitable characterization method, such as SEM or TEM.
  • SEM or TEM a suitable characterization method
  • the relative importance of the slit can be appreciated thanks to the ratio of the apparent area (call it the slit area) of the slit 18 to the area of the triangle 17a, 17c (call it the reference area).
  • the reference area corresponds to the actual prism (with the slit) and not the ideal prism (without the slit).
  • This ratio should normally be less than 0.5; it is typically between 0.05 and 0.25. In embodiments, however, this ratio is between 0.10 and 0.20, which gives rise to optimal field enhancements according to estimations by the inventors.
  • Each of the slit area and the reference area is measured in a plane parallel to the plane (x, y), or in projection in the plane (x, y), which can for instance be taken as corresponding to the top surface of the dielectric layer 11.
  • the slit can possibly be curved (or bent) along its direction of extension.
  • the slit may have a non-constant profile along its direction of extension, parallel to the plane (x, y), see FIGS. 9H, 91, 9 J, 9K, 9L, and 90.
  • the profile of the slit may even be dotted or dashed, see FIGS. 9D or 9M, i.e., formed of several segments.
  • the slit may even extend (in a curved or bent manner) from one side SI back to the same side SI, see FIG. 9N.
  • the slit is preferably “blind,” i.e., it forms a blind slit, similar to a blind hole, to accentuate the asymmetry.
  • the slit 18 may possibly be filled with a distinct material. That is, while the antenna elements are normally made of a same material (call it first material), preferably a metal such as gold, the slit 18 may advantageously be filled by a second material, i.e., a solid material (not air) that is distinct from the first material, therefore having a distinct permittivity.
  • the second material is preferably a dielectric material, e.g., with a relatively high permittivity. Note, this second material optionally fills the slit 18 only, i.e., the second material stops at the edge (along SI in FIG. 7). In variants, the second material makes up another layer, on top of the dielectric layer 11, which notably fills the slit 18.
  • a voltage bias (transmembrane bias) is applied through the electrodes, so as to urge DNA molecules towards the passages and trap them at the gaps, thanks to the combined action of the voltage bias applied and the antenna element irradiation. Meanwhile, the field enhancement enabled by the antenna irradiation allows the trapped or translocating molecules to be sensed.
  • other applications may rely on water or oil, for example.
  • a substrate 10 is provided and a dielectric layer 11 is deposited on top of the substrate 10.
  • Fiducial marks are then patterned on both the dielectric layer 11 and the substrate 10.
  • Such fiducial marks are preferably patterned using both EBL and a dry etching procedure.
  • the fiducial marks may for instance be patterned as slits extending through the dielectric layer 11 and partly in the substrate 10 (such slits are unrelated to the slit 18).
  • n pairs of laterally opposite antenna elements are patterned on top of the dielectric layer 11, preferably using EBL, to form asymmetric plasmonic antennas 17 - 17c as described earlier. I.e., one antenna element has a slit extending from a lateral side thereof.
  • the dielectric layer 11 is etched (using a dry etching technique, preferably using reactiveion etching, or RIE), at locations defined according to the fiducial marks. This is done so as to open n apertures 30 through the dielectric layer 11, between opposite antenna elements of respective pairs. As a result, opposite antenna elements are on opposite lateral sides of respective apertures 30.
  • RIE reactiveion etching
  • a fabrication method as defined above makes it possible to obtain an optical sensing device 1, la in which the n gaps define respective electromagnetic field enhancement regions.
  • the control and precision offered by this approach allow clean nanostructures to be obtained, in which the average diameter d of the n apertures 30 may be larger than or equal to the average length of the gaps along their respective directions.
  • the dimension of the cavity (recess) on the backside is approximately the same as the membrane. This, in turn, allows the number of membranes on the front side to be increased, since space requirements caused by the KOH etch are reduced significantly.
  • Using DRIE requires an etch stop layer on the front side, between the silicon and the silicon-nitride layer. Additional aspects of such fabrication methods can be found in WO2023117078A1.
  • the following addresses a modified geometrical layout of a bowtie plasmonic nanoantenna that leads to significantly higher electric field enhancement ⁇ E ⁇ in the plasmonic hotspot, as discussed in section 1.
  • the geometrical modification results from a cut-out of a metallic strip from one of the two antenna elements composing a plasmonic bowtie antenna, in order to break the symmetry of the usual bowtie layout. This results in Fano resonances, which, in turn, result in higher field enhancements and thus increase the Raman signal S.
  • the following embodiments address improvements to plasmonic nanostructures.
  • the underlying idea is to increase the signal level of the surface enhanced Raman (SERS) signal that originates from nucleotides (adenine, guanine, thymine, cytosine) arranged along the DNA helical structure.
  • SERS surface enhanced Raman
  • Raman spectroscopy is widely known spectroscopic technique that allows to identify molecules through a spectrum that is unique for every molecule.
  • SERS Surface enhanced Raman spectroscopy
  • the SERS signal level scales as S oc IE) 4 , such that even a slight increase of the electric field enhancement significantly improves SERS efficiency.
  • plasmonic nanopore single molecule DNA sequencing As described in WO2023117078 Al, a practical implementation of plasmonic, solid-state nanopore sequencing requires fabricating the necessary nanostructures in the sequencing chip, arranging the chip in a measurement setup to be able to read nucleotides and DNA sequence information from the chip, and implementing software to extract nucleotide information from measurements. This approach increases the throughput of DNA sequencing to unprecedented levels.
  • the present invention makes it possible to improve the signal level measured from SERS signal, something that benefits the data quality, starting with the signal-to-noise ratio and counts in Raman peaks.
  • Such improvements result from the modification of the geometrical layout of the plasmonic bowtie nanoantennas and a specific modification of the nanofabrication process to fabricate the sequencing chip.
  • FIG. 10A shows a segmented SEM image of the patterned nano-antenna as written in a negative tone e-beam resist
  • FIG. 10B is a segmented SEM micrograph of a Fano-resonant plasmonic nanostrucure written in gold.
  • the slit in the lower structure can still be seen. Still, the resolution limit of the SEM is close to being reached in this case, making it difficult to acquire clear and detailed images of the slit shape and topography.
  • FIG. 11 shows a Raman spectrum acquired from a pure thymine single-stranded DNA oligomer, using a Fano-resonant plasmonic bowtie as shown in FIG. 10B. The background signal is subtracted. The spectrum shows high-quality Raman peaks.
  • the Raman signal power PRaman obtained from a sample is given by
  • K is the fraction of photons emitted from the molecules, which are both collected and converted into electrons by the detector.
  • the fraction K depends on a number of detector parameters, starting with the quantum efficiency (QE), which is a function of the wavelength.
  • QE quantum efficiency
  • the apparatus may operate in the near-infrared (NIR) region of the electromagnetic spectrum and, thus, QE in the band 800 - 900 nm is most relevant.
  • nk-i, nk, nk+i respectively correspond to the nucleotide that was previously, is currently, and will next be in the centre of the hotspot. It may well be needed to consider more nucleotides before and after entering the hotspot, thus contributing to the Raman spectrum measured for nucleotide nk. Such behaviour is expected, considered normal, and a consequence of the realities of experimental life.
  • Deconvolution is the means to extract the ‘true’ Raman signal for nucleotide nk from the weighted superposition of spectra of nucleotides nk-i, nk, and nk+i. Then, ⁇ Jk (in cm 2 /molecule) is the Raman scattering cross section for mode k, integrated over its relevant bandwidth and over the complete spatial emission angle. I denotes the intensity of laser incident onto the molecule(s).
  • Raman scattering is intrinsically a very weak phenomenon. While it is straightforward to measure Raman spectra from powders, acquiring a high-quality Raman spectrum from a few molecules, or even a single molecule, in solution is extremely difficult, hence the advantage of SERS.
  • SERS requires the presence of appropriately structured nanoparticles or nanostructures, usually made from noble metals, e.g., gold (Au), silver (Ag), platinum (Pt), or even aluminium (Al), to generate the necessary localized electromagnetic field. In such a situation, the Raman power P S ERS measured from a few molecules or a single molecule is amplified through the presence of the nanostructured surface.
  • G SERS is the total SERS enhancement factor formed from the product of the electromagnetic enhancement factor GsTM RS and the chemical enhancement factor G ER TM.
  • the chemical enhancement factor G( ⁇ ” l originates from a change in the polarizability of the molecule, and thus from a change in its Raman scattering cross section oe through the quantummechanical interactions between the Raman photon emitting molecule and its immediate neighbourhood. This mechanism is short ranged, i.e., at most a few A or even less.
  • the chemical enhancement is a function of the molecule and its neighbourhood.
  • the electromagnetic enhancement ⁇ E ⁇ has two main contributions, namely local (i.e., near-field) and reradiation enhancement.
  • the near-field enhancement of the electric field amplitude ⁇ E ⁇ is a consequence of surface plasmons that are excited when a metallic nanostructured surface is illuminated by laser light. The following focuses on metallic surfaces, which are most often used, although non-metallic surfaces may also work. Localized surface plasmons associated with nanometre sized and structured metallic particles create tiny electromagnetic hotspots where the electric field amplitude is significantly higher, compared with situations without the presence of nanoparticles.
  • the molecule that emits Raman photon radiates like a Hertzian dipole.
  • the presence of metallic structures in the immediate vicinity of a Hertzian dipole modifies the way in which electromagnetic power is radiated by this Hertzian dipole. Therefore, reradiation enhancement is a consequence of the presence of metallic structures in the immediate vicinity of the Raman photon emitting molecule.
  • the electromagnetic SERS enhancement can, in the
  • Eq. (4) simplifies as where Eq. (5) is known as the zero Stokes shift limit of the
  • the functional behaviour of M 0C (m L ) in the immediate plasm onic vicinity of the Raman photon emitting molecule may deviate rapidly, particularly if the Raman peak wavenumber C R moves farther and farther away from the exciting laser wavelength COL.
  • 4 approximation scales as IE] 4 such that even a relatively small increment in ⁇ E ⁇ will significantly increase the SERS signal.
  • Such increments may well mark the difference between detection of SERS signals and no detection, according to evidence originating from pre- and post-measurement SEM investigations of plasmonic structures.
  • the first and foremost priority when optimizing the SERS signal level is to increase the electric field enhancement in the nanostructured plasmonic hotspot.
  • Fano type resonances can lead to higher field enhancement in a plasmonic hotspot, which can, in turn, increase the SERS signal significantly.
  • Several methods can be contemplated to excite Fano resonances in plasmonic nanostructures.
  • both symmetric and non- symmetric geometrical antenna arrangements can exhibit Fano resonances, depending on the material, shape, and size, of the antenna elements. The decision as to which type of structure to use, symmetrical or not, may depend on the intended application.
  • FIG. 7 illustrates a possible modification of the geometrical layout of the original plasmonic bowtie antenna, which breaks the symmetry of the bowtie antenna by introducing a strip-like cut-out from the metallic layer of one of the two prisms that form the bowtie antenna. The dimensions and the position of the cut-out determine the wavelength position and strength of the desired resonance.
  • the maximum field enhancement will occur at the position of the resonance.
  • the cut-out 18 is in the lower prism 17a, 17c.
  • the size of the cut-out 18 is given by its length, its width, and its distance, from the baseline S3 of the (lower) prism 17a, 17c.
  • the cut-out may also be obtained in the upper prism 17, 17b as this does not alter the physics.
  • the cut-out may also be curved or bent, thus further modifying the way the electromagnetic modes of the bowtie structure are changed, see FIGS. 8C, 8G, 81, 8J, 8L, 8N, and, correspondingly, FIGS. 9C, 9G, 91, 9J, 9L, 9N.
  • the corners of the bowtie antenna layout have a finite radius of curvature. While it would be desirable to have sharp corners and edges, such ideal geometric shapes cannot be fabricated in reality. Rather, corners and edges always have a finite radius of curvature; it is the objective and task of the process engineer to minimize this radius of curvature. The smaller the radius of curvature, the higher the field enhancement in the gap g of the plasmonic bowtie antenna.
  • the nanofabrication process is carried out in a cleanroom. This process description represents one way of preparing the Fano plasm onic nanoantenna. Multiple variants can be contemplated, as exemplified in the following.
  • a preferred fabrication method revolves around patterning the antenna elements (e.g., using EBL) using an alignment protocol exploiting previously patterned fiducial marks, prior to etching the apertures. More precisely, the apertures are etched only after having patterned the asymmetric antenna element and optionally after having protected the inner ends (i.e., the apices) of the antenna elements thanks to a protective layer.
  • the following focuses especially on process steps to pattern asymmetric antenna elements. The reader is otherwise referred to WO2023117078A1 for more details.
  • a substrate is selected, preferably a monocrystalline wafer of silicon, e.g., a 380 pm-thick, double-side-polished (DSP) silicon wafer.
  • DSP double-side-polished
  • Other substrates could be used, which should ideally be flat, chemically, and structurally compatible with the fabrication systems used in the following steps, e.g., not so soft as to bend significantly under its own weight, but thin enough and small enough to fit in the machines.
  • the substrate is then cleaned to improve the structural quality of the following metal layers, and preferably coated with a material having different dielectric properties.
  • the plasmon resonances occurring in the metallic plasmonic nanoantenna are influenced by the interface between the metal and the substrate and are especially impacted by the complex index of refraction of the substrate. So, preferred is to clean and coat the wafer, whereby the wafer undergoes a standard set of cleaning steps (“RCA Standard Clean”) before being coated on both sides with two layers.
  • RCA Standard Clean a standard set of cleaning steps
  • LPCVD Low Pressure Chemical Vapor Deposition
  • the metal lies on a silicon nitride layer.
  • the HADES3D/DGFD solver described in 2.3. 1.4 takes into account the refractive index of this substrate
  • the prepared substrate is coated with a metallic layer that will later make up the plasmonic nanostructures.
  • a metallic layer that will later make up the plasmonic nanostructures.
  • the choice of metals suitable for this layer includes (but is not limited to) gold, silver, and platinum. Preferred is to use gold as the main medium for the plasmonic nanostructure.
  • thin layers of chromium are deposited, on the one hand, between the substrate and the gold layer and, on the other hand, on top of the gold layer.
  • the chromium layers serve as adhesion-promoting layers, one for the gold layer to the wafer, the other for future resist layers on top of the metals.
  • the layer stack (e.g., 2 nm of chromium, 34 nm of gold, and 2 nm of chromium) is obtained thanks to an evaporator system.
  • the lower layer of chromium is covered with gold without breaking vacuum and is not exposed to oxygen.
  • the second chromium layer starts oxidizing immediately upon removing the wafer from the vacuum system and likely becomes fully oxidized shortly thereafter.
  • a layer of e-beam lithographic resist is deposited on the topmost metal layer.
  • the process spincoats a 40 nm layer of 2% hydrogen silsesquioxane (HSQ) in methyl isobutyl ketone (MIBK) and toluene (CAS# 108-88-3) negative-tone e-beam resist.
  • HSQ hydrogen silsesquioxane
  • MIBK methyl isobutyl ketone
  • MIBK methyl isobutyl ketone
  • CAS# 108-88-3 toluene
  • the Fano plasmonic nanostructures are written to the resist- and metal-coated substrate with an e-beam lithography system, e.g., a Raith EBPG5000+ electron beam lithography system.
  • an e-beam lithography system e.g., a Raith EBPG5000+ electron beam lithography system.
  • the nanostructures are revealed by developing the sample.
  • the patterns written in the resist are transferred to the underlying metal layers by ionbeam milling.
  • Argon ions hit the top of the sample and eject tiny amounts of material away, thinning the sample from the top.
  • the resist nanostructures shield the metal below them, thinning instead of the gold. Any uncovered gold is also thinned.
  • SIMS secondary ion mass spectrometry
  • any remaining polymerized HSQ is mostly or completely etched away. Remaining process steps are described in WO2023117078A1.
  • the present approach makes it possible to tune the position and amplitude of individual resonances, thus providing a way to place each resonance in the spectral region of highest relevance.
  • the underlying principle is based on Fano resonances, an effect originating from the coupling between a background mode and local excitation mode.
  • Numerical simulations performed by the present Inventors have confirmed the resonant properties of Fano bowties as described in section 1.
  • the electric field enhancement observed can be more than twice the enhancement obtained with the corresponding, symmetrical antenna layout.
  • Such tunable resonance properties can be useful for bio-sensing applications.
  • Structured Substrate e.g., Si, forming a recess
  • First dielectric layer (membrane, e.g., SisN ⁇
  • Second dielectric layer e.g., SisN ⁇
  • Liquid droplet e.g., KC1 solution containing DNA molecules
  • Detector e.g., Raman spectrometer

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Abstract

L'invention concerne notamment un dispositif de détection optique (1, 1a) ayant une structure de couche comprenant : un substrat (10) structuré pour délimiter latéralement une cavité (40) ; une couche diélectrique (11), qui s'étend au-dessus du substrat (10) et forme une membrane (11) recouvrant la cavité (40), la membrane (11) comprenant n ouvertures (30) à la cavité (40), où n ≥ 1, de préférence n ≥ 100, et de préférence n ≥ 400 ; et des antennes plasmoniques comprenant n paires d'éléments d'antenne opposés (17, 17a) modelés au-dessus de la couche diélectrique (11) sur des côtés latéraux opposés des ouvertures respectives des ouvertures n (30), de manière à définir n espaces respectifs (g) au-dessus des ouvertures n , les espaces s'étendant entre des éléments d'antenne opposés (17, 17a) des paires n le long de directions respectives parallèles à un plan moyen ( x, y ) de la couche diélectrique (11) pour définir n passages moléculaires, s'étendant chacun à partir de la cavité (40) à travers l'une respective des ouvertures n (30) et l'un respectif des n intervalles, et les deux éléments d'antenne de chacune des n paires ont des formes triangulaires dans une configuration papillon, mais un élément d'antenne seulement desdits deux éléments d'antenne a une fente s'étendant d'un côté latéral de celui-ci, de telle sorte que ladite configuration papillon est asymétrique. L'invention concerne en outre des appareils associés, des procédés de fabrication et des procédés de détection optique d'analytes.
PCT/EP2024/059181 2024-04-04 2024-04-04 Dispositif de détection optique à antenne plasmonique asymétrique Pending WO2025209653A1 (fr)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023117078A1 (fr) 2021-12-22 2023-06-29 Lspr Ag Dispositifs de séquençage nanofabriqués avec des ouvertures de membrane déterministes bordées par des antennes d'amélioration du champ électromagnétique

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023117078A1 (fr) 2021-12-22 2023-06-29 Lspr Ag Dispositifs de séquençage nanofabriqués avec des ouvertures de membrane déterministes bordées par des antennes d'amélioration du champ électromagnétique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEN JI ET AL: "Bowtie nanoantennas with symmetry breaking", JOURNAL OF NANOPHOTONICS, SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 1000 20TH ST. BELLINGHAM WA 98225-6705 USA, vol. 9, no. 1, 1 January 2015 (2015-01-01), pages 93798, XP060053812, DOI: 10.1117/1.JNP.9.093798 *
USTUN E ET AL: "Investigation of nanoantenna geometries for maximum field enhancements at optical frequencies", 2017 PROGRESS IN ELECTROMAGNETICS RESEARCH SYMPOSIUM - SPRING (PIERS), IEEE, 22 May 2017 (2017-05-22), pages 3673 - 3680, XP033302331, DOI: 10.1109/PIERS.2017.8262396 *

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