Patent Grant
12072282
The technical field of the invention is the analysis of a sample, the sample being deposited on a holder comprising photonic crystals the spectral properties of which in transmission or reflection comprise a resonant wavelength, the latter undergoing a variation under the effect of the presence of an analyte.
Detection of the presence of an analyte, and determination of its concentration in a sample, are operations conventionally carried out via chemical assays or destructive biological methods. Many laboratory methods exist, among which, in the field of biology, amplification of sequences by PCR (polymerase chain reaction) or genome-sequencing techniques. These techniques are now well-established, but require expensive hardware and qualified personnel.
Analyzing methods, employing optical techniques, have been developed, these for example being based on samples placed very close to image sensors, for example via lensless imaging. In patent U.S. Pat. No. 13,905,727, a method for quantifying an analyte via detection of clusters formed in a sample is described. In WO2016151249, or in WO2018060589, use of holographic-propagation algorithms to identify particles present in a sample is described. The document US20170082975 describes a device comprising a substrate intended to be applied so as to make contact with a sample to be analyzed. The substrate comprises one- or two-dimensional photonic crystals, allowing particles present in a sample to be observed.
The publication Cetin “Handheld high-throughput plasmonic biosensor using computational on-chip imaging” describes a device for analyzing a sample that is intended to assist with medical diagnosis. The device comprises a sample holder that is able to capture analytes, and that is conducive to the generation of surface plasmon resonance. An image sensor, which is placed in a lensless imaging configuration, allows a diffraction pattern representative of the plasmonic structures formed in the holder to be acquired. Application of a holographic-reconstruction algorithm allows the analytes captured by the holder to be identified, and their concentration to be determined. Such a method requires holographic-reconstruction algorithms, which may sometimes be complex to implement, and which may be adversely affected by substantial reconstruction noise, to be applied.
Patent application WO02/059602 describes a device for analyzing a sample, comprising a nanostructured surface, which surface is configured to reflect light toward a sensor. The nanostructured surface is configured to capture an analyte. Depending on the wavelength of the reflected light, it is possible to determine the type of analyte bound to the capturing surface. A spectrometer allows the wavelength of the reflected light to be detected, this giving an indication as to whether or not the analyte is present on the capturing surface.
The publication Bougot-Robin K et al. “A multispectral resonant waveguide nanopatterned chip for robust oil quality monitoring”, Sensors and Actuators B: Chemical, vol. 216, 2015-04-15, pp 221-228, describes use of photonic crystals to analyze oil.
The document US2004/155309 describes use of metal structures that induce a plasmon resonance, to analyze samples.
The document Cheng F. et al. “Tuning asymmetry parameter of Fano resonance of spoof surface plasmons by modes coupling”, Applied Physics Letters, vol 100, n° 3, 2012-03-26 describes metal structures that induce a plasmon resonance. Each structure consists of two patterns that are offset from each other, the offset being set.
The inventors have designed an analyzing device that is easy to use, that does not require complex instrumentation, such as a spectrometer. The device allows a rapid analysis as regards the presence and an amount of analytes present in a sample.
A first subject of the invention is a method for analyzing a sample, the sample lying on a resonant holder, the resonant holder comprising a surface on which lie a plurality of photonic crystals, which are separate from one another, the photonic crystals being such that:
Two different regions of interest are optically coupled to two different photonic crystals. Each region of interest of the image corresponds to one pixel or one group of pixels of the image sensor, the group of pixels being optically coupled to one photonic crystal.
By in the absence of analyte, what is meant is in the absence of analyte in contact with the resonant holder.
According to one variant, the reference image is representative of an image acquired by the image sensor, when the resonant holder is illuminated in the spectral band of illumination, in a reference configuration, in the presence of a known amount of analyte in the sample.
According to one embodiment, a plurality of photonic crystals are aligned in a row parallel to a longitudinal axis, such that the resonant wavelength respectively associated with a photonic crystal gradually increases, or decreases, along the longitudinal axis. The resonant holder may comprise various rows of photonic crystals parallel to one another. The photonic crystals may form columns, parallel to a lateral axis, such that the photonic crystals of a given column have the same resonant wavelength.
Preferably, the photonic crystals lie in a holder plane, the illuminating light wave propagating to the resonant holder parallel to a propagation axis that is perpendicular or substantially perpendicular to the holder plane.
The method may comprise, prior to step a), a step of forming the reference image, comprising:
According to one embodiment, the reference image is an image obtained by:
The resonant holder may comprise reference photonic crystals, which are considered not to make contact with the analyte; the reference image may then be an image of the reference photonic crystals when they are illuminated in the spectral band of illumination.
The reference image and the measurement image form two distinct parts of the same image acquired by the image sensor.
Preferably, for each photonic crystal addressing the analyte, the resonant wavelength depends on a refractive index of the sample, at an interface between the sample and the photonic crystal, the refractive index varying as a function of the amount of analyte making contact with the photonic crystal.
Step e) may comprise the following sub-steps:
Step e) may comprise the following sub-steps:
Step e) may comprise estimating an amount of analyte in the sample, depending on the comparison between the measurement image and the reference image. The amount of analyte may be estimated depending on:
According to one embodiment:
Each photonic crystal may comprise:
According to one embodiment,
According to one embodiment, the photonic crystals addressing a given analyte are covered with a functionalization layer conducive to selective capture of the analyte on the photonic crystals, for example by grafting.
According to one embodiment, the resonant holder comprises:
According to one embodiment,
According to one embodiment, the resonant holder is placed between the light source and the image sensor, such that, in step b), each region of interest formed in the measurement image is representative of an intensity transmitted by the photonic crystal to which said region of interest is optically coupled.
According to one embodiment:
According to one embodiment, the resonant holder bounds a half-space, comprising the light source; the image sensor is placed in the same half-space as the light source, such that each region of interest formed in the measurement image is representative of an intensity reflected by the photonic crystal to which said region of interest is optically coupled.
A second subject of the invention is a device for analyzing a sample, comprising a light source, an image sensor and a resonant holder, which is placed between the light source and the image sensor, such that the image sensor is configured to acquire an image of the resonant holder, the resonant holder being intended to be placed in contact with a sample, the resonant holder comprising an area containing photonic crystals, which are separate from one another, the resonant holder being such that:
According to one embodiment:
According to one embodiment, each photonic crystal comprises:
According to one embodiment, the photonic crystals that are configured to make contact with the same analyte are aligned parallel to the same longitudinal axis, the resonant wavelengths respectively associated with two adjacent photonic crystals being offset by a discretization pitch comprised between 1 nm and 10 nm or between 1 nm and 50 nm.
According to one embodiment, the photonic crystals, addressing an analyte, are configured to selectively capture the same analyte. They may notably be covered with a functionalization layer of interest, conducive to a selective capture of the analyte.
According to one embodiment, the resonant holder comprises
According to one embodiment,
According to one embodiment, the photonic crystals lie in a holder plane, and the light source is configured to emit, in the spectral band of illumination, an illuminating light wave that propagates to the resonant holder along a propagation axis that is perpendicular or substantially perpendicular to the holder plane.
The holder plane may lie parallel to a detection plane defined by the image sensor.
The device may have one of the features described with reference to the first subject of the invention.
The invention will be better understood on reading the description of the examples of embodiment presented, in the remainder of the description, with reference to the figures listed below.
By analyte, what is meant is a chemical or biological species the presence, and possibly an amount, of which in the sample it is desired to determine. The analyte 21 may, for example, be a chemical molecule, a protein, a peptide, an antibody, an antigen, a fragment of a nucleotide sequence, or a particle. By particle, what is meant for example is a biological cell, a droplet that is insoluble in a medium, or a nanobead. It may also be a question of a microorganism, a bacterium for example, a yeast or a microalgae. Preferably, a particle has a diameter, or is inscribed in a diameter, smaller than 20 μm, or even than 10 μm or than 5 μm.
By resonant holder, what is meant is a holder one portion of which is able to resonate, so as to transmit or to reflect a maximum light intensity at a resonant wavelength. The structure of the resonant holder is described below.
The sample 20 may take the form of a drop deposited on the resonant holder 15. It may also be a question of a fluid confined in a fluidic chamber 18 associated with the resonant holder 15. The resonant holder may for example consist of a wall of the fluidic chamber 18 in which the sample lies.
The device 1 also comprises an image sensor 30. The image sensor is preferably a pixelated sensor, comprising pixels 31 arranged in a matrix array. The pixels of the image sensor 30 define a detection plane P30.
Preferably, the detection plane P30 is placed perpendicular to the propagation axis Z, or substantially perpendicular to the latter. By substantially perpendicular, what is meant is perpendicular to within an angular tolerance of ±20°, or preferably ±10°, or even ±5°. Thus, the illuminating wave 11 emitted by the light source 10 reaches the holder at a normal incidence, to within the angular tolerance.
Preferably, the resonant holder 15 defines a capture plane P15. The capture plane P15 lies perpendicular to the propagation axis Z, or substantially perpendicular to the latter. The resonant holder extends along a longitudinal axis X and a lateral axis Y. The axes X and Y are coplanar with the capture plane. They are secant, and preferably perpendicular.
The light source 10 may be monochromatic or polychromatic. The illuminating wave 11 lies in a spectral band of illumination Δλ, the width of which is preferably smaller than 200 nm, or even smaller than 100 nm or than 10 nm. The spectral band of illumination preferably lies in the visible domain, or in the near UV or in the infrared. Thus, the spectral band of illumination lies below 1500 nm. Preferably, the light source 10 is placed at a distance Δ from the resonant holder 15, such that the light wave 11 reaches the latter in the form of a plane wave. A collimating optical element, known to those skilled in the art, may be placed between the light source 10 and the sample 20, so as to form a plane light wave 11.
Preferably, the detection plane P30 extends parallel to the capture plane P15.
An important aspect of the invention is that the resonant holder 15 comprises nanostructured elementary zones that are separate from one another, each elementary zone forming one photonic crystal 16. Thus, the resonant holder comprises photonic crystals 16k, which are different from one another, and which are spaced from one another. The index k is an integer strictly comprised between 1 and K, K corresponding to the number of photonic crystals formed on the resonant holder 15.
Each photonic crystal 16k has a resonant wavelength λk that is specific thereto. At the resonant wavelength λk that is associated with it, each photonic crystal 16k exhibits a peak in light transmission or reflection. Each crystal thus has a resonant wavelength in reflection and a resonant wavelength in transmission.
The image sensor 30 is configured such that the pixels 31 are divided into groups of pixels 32k, the pixels 31 belonging to the same group of pixels 32k being optically coupled to the same photonic crystal 16k. The image sensor 30 is for example a CMOS matrix-array sensor.
By group of pixels, what is meant is a pixel or a set of pixels that are adjacent to one another and optically coupled to the same photonic crystal.
By optically coupled, what is meant is that the pixels 31 of the same group of pixels 32k collect light the intensity of which is at least 80% or 90% due to light propagating through the photonic crystal 16k.
In the example shown in
Alternatively, as shown in
The light source is placed at a distance Δ from the resonant holder, such that a plurality of photonic crystals are simultaneously illuminated by the light source. Thus, at least 3, and preferably at least 5 or 10 photonic crystals are simultaneously illuminated by the light source. The illumination of the resonant holder is preferably extensive, in the sense that the illuminated area is preferably larger than 1 mm2, or even 1 cm2. The illuminated area may correspond to the field of observation of the image sensor 30. In the lens-less configuration described with reference to
The device 1 also comprises a processing unit 40, for example a microprocessor, configured to process and/or display images acquired by the image sensor 30. The processing unit may be connected to a memory 41, comprising instructions for implementing image-processing algorithms. The processing unit 40 is preferably connected to a screen 42.
The configurations schematically shown in
Thus, the thin layer 22 comprises a plurality of resonant photonic crystals 16k that are separate from one another, and that each have a resonant wavelength λk in transmission or in reflection. The thickness of the thin layer 22 is preferably comprised between 20 and 500 nm, or between 20 nm and 1 μm. The holes 23 extend through the thin layer 22, about an axis perpendicular to the plane of the holder. The holes 23 may in particular extend about an axis parallel to the propagation axis Z.
In the holder plane P15, the photonic crystals 16k have a diagonal or a diameter comprised between 10 μm and 500 μm, of 100 μm for example. Each photonic crystal is borne by a transparent or translucent membrane, formed by a layer 24. Fabrication of the photonic crystals is described below, with reference to
The spectral properties of the photonic crystals with respect to transmission and reflection of light may be determined using simulations performed via computer codes. Specifically, the properties of propagation of light in the photonic crystals stem from their specific periodic arrangement. These propagation properties may easily be modeled, by a person skilled in the art, on the basis of Maxwell's equations. In the remainder of this description, the modelling was carried out using the software package Rsoft and a method of RCWA type.
By photonic crystal, what is meant is a structure the refractive index of which varies periodically, on the wavelength scale, in one or more directions. In the examples described in this description, the photonic crystals are two-dimensional, this being a preferred configuration. The invention therefore takes advantage of the development of techniques for micro-structuring dielectrics, semiconductors or metals, allowing control of the interaction of electromagnetic waves in three-dimensional structures based on the arrangement of materials of various indices.
Each photonic crystal 16k transmits (or reflects) light according to a spectral transmission (or reflection) function describing a variation in a light intensity transmitted (or reflected) by the photonic crystal, as a function of wavelength. The exploitation of Fano resonance makes it possible to design compact resonant photonic crystals, which may be illuminated collectively by one illuminating light wave, at a normal incidence. This makes it possible to simultaneously illuminate, in a simple manner, photonic crystals distributed in one or two dimensions. The spectral transmission function of each photonic crystal exhibits a maximum, at a resonant wavelength in transmission. Analogously, the spectral reflection function exhibits a maximum, at a resonant length in reflection.
The spectral transmission or reflection function, and in particular the resonant wavelengths in transmission or in reflection, depend first of all on the structure of each photonic crystal, i.e. on the size and on the spatial arrangement of the holes 23 produced in the thin layer 22, to form the photonic crystal 16k. In reflection or in transmission, the resonant wavelength λk also depends on the refractive-index contrast between the thin layer 22 and the sample, in the holes 23. The resonant wavelength also depends on the thickness of the thin layer 22. It also depends on the refractive index and on the thickness of the transparent layer 24.
Before it is brought into contact with the sample, the resonant holder 15 will have undergone a surface functionalization, in the holder plane P15, such that each photonic crystal is able to capture a predetermined analyte. Surface functionalization is a concept known to those skilled in the art. It consists in adding a specific function to the surface to be functionalized, by nanostructuring, or by depositing a coating, or by adsorbing or grafting molecules with specific properties. In the present case, the surface functionalization confers, on each photonic crystal, a property enabling selective capture of an analyte. The analyte may be captured via formation of a covalent, hydrogen or electrostatic bond with the analyte and/or via grafting of the analyte with a ligand placed on the functionalized capturing surface. Following the functionalization, the holder plane P15 is also a functionalized capture plane, i.e. one that has been functionalized to capture one or more analytes.
When the resonant holder is placed in contact with the sample, the sample fills the holes 23 of each photonic crystal 16k. The spectral properties of each photonic crystal 16k with respect to transmission (or reflection) of the light are then governed by the structure of each photonic crystal (in particular the size and distribution of the holes 23) and the respective refractive indices of the sample 20 and of the thin layer 22.
In
Because of the surface functionalization, when the desired analyte is present in the sample, the concentration of analyte captured by the holder increases after the latter has been brought into contact with the sample. This results in a local variation in the index of the sample, at the interface between the sample and the functionalized holder. Under the effect of such a variation in index, the spectral transmission (or reflection) properties of each functionalized photonic crystal change—in particular the resonant wavelength of the photonic crystals changes.
A noteworthy aspect of the invention is that the photonic crystals are dimensioned such that:
All the resonant wavelengths of photonic crystals addressing the same analyte lie between a minimum resonant wavelength λr,min and a maximum resonant wavelength λr,max. The latter bound a spectral band of resonance Δλr. It is necessary for the spectral band of illumination Δλ of the light source to be, at least partially, included in the spectral band of resonance αλr. The spectral band of illumination Δλ may be the same as the spectral band of resonance αλr. It may be wider or narrower than the spectral band of resonance Δλr.
In the spectral band of resonance αλr, which is defined by the photonic crystals of the holder, the intensity of the light wave 11 emitted by the light source 10 is not constant. In the spectral band of resonance αλr, the intensity of the light wave 11 is variable, and follows a spectral illumination function ƒ. The spectral illumination function ƒ defines the intensity of the incident light wave 11 at various wavelengths of the spectral band of resonance, such that:
I(λ)=ƒ(λ)
where:
It is important that the illumination function ƒ not be constant, i.e. that the intensity of the illuminating wave not be uniform in the spectral band of resonance αλr. The illumination function ƒ may thus be monotonic in the spectral band of illumination, and for example an increasing or decreasing function. It may also increase (decrease, respectively) to an extremum and then decrease (increase, respectively) from the extremum. When the light source is monochromatic, the illumination function forms a peak in the spectral band of resonance αλr.
In the preferred embodiment, two adjacent photonic crystals 16k, 16k+1 have resonant wavelengths that are offset by a known spectral offset dλk. The spectral resolution of the method is dependent on the spectral offset dλk. In absolute value, the spectral offset dλk is preferably smaller than 10 nm, and more preferably smaller than 5 nm, or even than 2 nm. It corresponds to a spectral discretization pitch, with which the illuminating light wave 11 is discretized, as described with reference to
On capture of the analyte, the resonant wavelength of each photonic crystal changes, passing from a value λref,k, in the absence of analyte, to a value λk in the presence of analyte, with λk=λref,k+δλ (1). It will be noted that the variation in resonant wavelength δλ is the same for all the photonic crystals addressing a given analyte. In other words, the sensitivity of the resonant wavelength to variations in index is the same for all the various photonic crystals.
The change in resonant wavelength δλ is consecutive to the capture of the analyte, which generally results in an increase in the index at the interface between the resonant holder and the sample. The increase in index causes a variation in the resonant wavelength of each photonic crystal.
Thus, the invention is based on a measurement of a variation in resonant wavelength δλ under the effect of capture of the analyte by photonic crystals addressing the same analyte.
The variation δλ in resonant wavelength is observed by taking into account a reference configuration, in which the captured amount of analyte is known. Preferably, in the reference configuration, the amount of analyte captured by each photonic crystal is zero. This is the case that will be considered in the remainder of the description. Alternatively, provision may be made for an embodiment in which in the reference configuration corresponds to a known captured amount of analyte.
The precision with which the variation δλ in resonant wavelength is estimated depends on the spectral offset dλk between two adjacent photonic crystals. The smaller the spectral offset dλk, the better the resolution with which the variation δλ is estimated.
The variation in resonant wavelength δλ is determined by comparing a reference image Iref of the resonant holder, in the reference configuration, with an image I of the resonant holder taken after capture of the analyte. The image I of the holder, after capture, is called the measurement image.
The regions of interest ROIk are distinct from one another, and aligned parallel to the photonic crystals 16k. In
Comparison of the measurement image I shown in
On the basis of the measurement image and of the reference image, it is possible to form an intensity profile representative of a spatial distribution of the intensity of each region of interest ROIk along the longitudinal axis X.
On account of the alignment of the photonic crystals along the same axis X, and of the small spectral offset dλk between two adjacent photonic crystals, each profile has approximately the same shape as the spectral illumination function. Thus, the resonant holder 15 allows spectral information to be converted into spatial information. It acts in the same way as a spectrometer. The spatial information corresponds to a position, along the axis X, of each region of interest ROIk. A spectral variation δλ, in the present case the variation in resonant wavelength affecting each photonic crystal, results in a spatial variation Δx in the profile, between the reference image and the measurement image. As the spectral offset dλk between two adjacent photonic crystals is set, the variation in resonant wavelength δλ may be estimated, using the expression:
where:
Preferably, the spectral offset dλk between two adjacent photonic crystals may be considered to be constant and equal to dλ. In this case, the preceding expression becomes:
δλ=Δk×dλ (3)
The advantage of using a non-uniform spectral illumination function ƒ will now be understood. It facilitates a comparison of the intensity profiles in the reference configuration and in the measurement configuration, respectively, so as to allow the number Δk of regions of interest ROIk by which the intensity profile shifts between the reference configuration and the measurement configuration to be estimated. In the example shown in
In contrast to certain prior-art devices that require a spectrometer to be used, the invention transfers the spectral splitting function to the resonant holder 15. This allows the use of a simple image sensor, which is clearly less expensive and complex to implement.
According to one embodiment, the light source is monochromatic. The spectral band of illumination may then be narrower than or equal to the spectral resonant-wavelength offset dλk between two adjacent photonic crystals. In order to be able to estimate the variation δλ in resonant wavelength under the effect of the capture of the analyte, the spectral band of illumination then corresponds to a resonant wavelength of a single photonic crystal in the reference configuration, i.e. in the absence of analyte capture, and in the measurement configuration.
The light source may be monochromatic and tunable, so that the spectral band of illumination may be modified.
The reference image may be an image, of the sample, acquired before the capture. In this case, the reference image is taken at an initial time, at which the capture of the analyte by the holder is considered to be negligible. It may for example be a time close to the time at which the holder and the sample are brought into contact. The measurement image is then acquired after the reference image.
Alternatively, the reference image is an image obtained with a reference holder that is considered to be representative of the holder brought into contact with the sample. The reference holder is then brought into contact with a reference sample that is considered to be representative of the analyzed sample. The reference image is stored in memory. Such an embodiment assumes a good reproducibility in the fabrication of the holders.
Thus, the reference image, taken into account to estimate the variation in resonant wavelength, may be:
Regardless of the embodiment, the reference image is formed by illuminating the holder or the reference holder, in a spectral band of illumination αλ and according to a spectral illumination function ƒ equal to those employed to acquire the measurement image. In other words, the reference image and measurement image of the employed holder(s) are obtained under the same illumination conditions.
The method makes it possible to detect a presence of the analyte in the sample, this corresponding to the observation of a non-zero variation δλ in resonant wavelength. It also makes it possible to estimate an amount of analyte captured by the resonant holder, with an precision depending on the number of photonic crystals and on the spectral offset dλk between the resonant wavelength of two adjacent photonic crystals.
On the basis of the amount of analyte captured by the holder, it is then possible to estimate an amount of analyte in the sample, said amount possibly for example being expressed in the form of a concentration. A calibration, using samples the analyte concentration of which is known, allows a calibration function, relating the amount of analyte captured by the holder to the analyte concentration initially present in the sample, to be obtained.
Step 100: bringing the sample into contact with the resonant holder.
Step 110: illuminating the sample in the spectral band of illumination Δλ, according to the spectral illumination function ƒ.
Step 120: acquiring a measurement image I of the resonant holder.
Step 130: taking into account of a reference image Iref, the reference image possibly being an image of the holder acquired just after step 110, prior to the acquisition of the measurement image, this forming the optional step 115.
Step 140: comparing the measurement image I with the reference image Iref, so as to estimate a variation in the resonant wavelength δλ of the photonic crystals. It is notably a question of determining the number of photonic crystals (or the number of regions of interest) corresponding to the variation in resonant wavelength δλ. Knowing the spectral offset dλk between the resonant wavelengths of the photonic crystals, it is thus possible to determine the variation in resonant wavelength δλ.
Step 150: on the basis of the comparison, determining whether the analyte addressed by the photonic crystals is present in the sample, and possibly estimating an amount of analyte in the sample.
In the example shown in
As described with reference to the first embodiment, the photonic crystals are distributed in columns Y1, Y2, Yk, YK, such that the photonic crystals belonging to two adjacent columns Yk have, in the reference configuration, the same resonant wavelength λk,ref.
This configuration, which is referred to as the two-dimensional configuration, corresponds to the addition of one dimension to the embodiment described with reference to
It will be noted that the device allows a plurality of photonic crystals to be illuminated simultaneously, this making it possible to obtain exploitable information relating to various analytes from a single image acquired using a simple image sensor.
According to this embodiment, steps 100 to 150, which were described with reference to
In the reference image (
According to one such embodiment, the device allows the presence of various analytes in the sample to be detected simultaneously, and the concentration thereof to be estimated.
Reflectivity quantifies the aptitude of a photonic crystal to reflect light that is incident thereon. It is a question of a standardized value, varying between 0 and 1, the value of 1 corresponding to complete reflection. It may be seen that each spectral reflectivity function has a minimum, which corresponds to a maximum transmission, at a very precise resonant wavelength. When the sample is water (n=1.328), the resonant wavelength is equal to 950 nm.
These simulations were carried out considering one particular embodiment, in which each photonic crystal has a structure as shown in
In this example the first periodic pattern P1 and the second periodic pattern P2 define a rectangular mesh, of period a along X and 2a along Y, the rectangular mesh being reproduced in two orthogonal directions of translation. In this example, the two directions of translation correspond to the longitudinal axis X and to the lateral axis Y, respectively. The first periodic pattern P1 and the second periodic pattern P2 are interlaced in the sense that, in one direction of translation, in the present case the Y-direction, an alternation is observed between rows of first holes 231, parallel to the longitudinal axis X, and rows of second holes 232, also parallel to the longitudinal axis X. In this example, the period a1 (along X) of the first periodic pattern P1 is equal to the period a2 (along X) of the second periodic pattern P2, the common period of the two patterns being denoted a. The value of the period is typically between 100 nm and 1 μm or even 2 μm. In this example, the period a is equal to 300 nm. Generally, if λ is a wavelength belonging to the spectral band of illumination Δλ, the period a is comprised between λ/4 and λ.
One advantage of a double-period resonant structure is the ability to adjust a spatial offset δ between the first pattern and the second pattern. The spatial offset corresponds to a distance between the respective rows of first and second holes.
On the basis of the spectral functions shown in
The modeled curves in
The quality factor depends on the ratio R2/R1. When R2/R1 is of the order of 0.6 to 0.8, the quality factor is equal to a few tens. When R2/R1 tends toward 1, the quality factor rapidly increases. The quality factor may then exceed a several thousand.
Generally speaking, the first radius R1 is smaller than a/2. The ratio R2/R1 is preferably higher than 0.6, or even higher than 0.8. The period a may vary between 100 nm and 1 or 2 μm, as indicated above.
Thus, another advantage of the double-period structure such as described above is to allow the resonant wavelength to be adjusted:
The quantitative values given in the previous paragraph were obtained by modeling.
The inventors have fabricated a resonant holder so as to carry out experimental tests. The characteristics of the resonant holder were as follows:
The main steps of fabrication of the photonic crystals are described below, with reference to
In order to obtain an upper layer 22 of Si having the desired thickness, said layer undergoes a thermal oxidation, then a chemical etch in hydrofluoric acid to remove the resulting SiO2 so as to obtain a layer 22 of Si of 58 nm thickness and a layer 22′ of SiO2 of 80 nm thickness on the upper layer 22. This step is schematically shown in
The steps shown in
The steps shown in
In the fabricating process described above, the holes 23 are formed by photolithography then etching, this allowing wafer-level fabrication of photonic crystals on the holder. Such a process makes it possible to simultaneously obtain a high number of photonic crystals, this being advantageous from an economic point of view. Alternatively, the holes may be formed by scanning with an electronic beam (e-beam), this making it possible to obtain more precise geometries, to the detriment of the cost and rate of fabrication.
Trials have been carried out to characterize the resonant holder 15 thus formed, and more precisely the photonic crystals 16k. To this end, a drop of water was placed on a resonant holder 15, and a glass slide of 17 μm thickness applied to confine the drop of water. A light-emitting diode centered on 940 nm was used as light source, the spectral band of illumination extending to ±40 nm with respect to the central wavelength of 940 nm. The transmission of the photonic crystals was then characterized via transmission spectrometry tests.
For various fabricated photonic crystals 16k, other tests, in fact reflectometry tests, made it possible to establish a resonant wavelength.
A resonant holder comprising such photonic crystals allows a resonant wavelength to be identified in a relatively wide spectral band, of spectral width typically larger than 50 nm, and in this example of spectral width equal to 60 nm. When the photonic crystals are aligned, as shown in
A holder, produced using the process described above, was integrated into a fluidic chamber 18 and subjected to use. More precisely, a removable cover made of PDMS (polydimethylsiloxane), which could be placed on the holder so as to form a fluidic chamber 18, was formed. Various liquids, notably water and ethanol, were introduced in succession into the fluidic chamber, into contact with the holder. Reflectometry trials were carried out.
In one advantageous configuration (shown in
Provision may be made to use a cross polarization, combining an upstream polarizer, upstream of the sample, and a downstream polarizer, downstream of the sample, in the embodiments shown in
A holder such as described with reference to
Because of the variation in index between water and ethanol, the wavelength of each photonic crystal undergoes a spectral variation δλ, in the present case a decrease, this resulting in a slight shift, to the left in the image, of the discretized spectral illumination function.
The invention will possibly be used to detect and quantify an analyte in samples, for example in the field of biological analysis or to assist with medical diagnosis. The invention may also be employed to monitor industrial processes, for example in the food industry, or even to monitor the environment.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1906132 | Jun 2019 | FR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/065484 | 6/4/2020 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2020/245272 | 12/10/2020 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 20040155309 | Sorin et al. | Aug 2004 | A1 |
| 20080278722 | Cunningham | Nov 2008 | A1 |
| 20170082975 | Gliere et al. | Mar 2017 | A1 |
| Number | Date | Country |
|---|---|---|
| 3 147 646 | Mar 2017 | EP |
| Entry |
|---|
| International Search Report issued on Sep. 3, 2020 in PCT/EP2020/065484 filed on Jun. 4, 2020, 3 pages. |
| Bougot-Robin, K. et al., “A multispectral resonant waveguide nanopatterned chip for robust oil quality monitoring,” Sensors and Actuators B: Chemical, vol. 216, 2015, pp. 221-228, XP029243348. |
| Cheng, F. et al., “Tuning asymmetry parameter of Fano resonance of spoof surface plasmons by modes coupling,” Applied Physics Letters, vol. 100, 131110, 2012, pp. 131110-1-131110-4, XP012155359. |
| Nazirizadeh, Y. et al., “Low-cost label-free biosensors using photonic crystals embedded between crossed polarizers,” Optics Express, vol. 18, No. 18, 2010, pp. 19120-19128, XP002635685. |
| Number | Date | Country | |
|---|---|---|---|
| 20220317028 A1 | Oct 2022 | US |
