OPTICAL REFLECTOMETRIC DEVICE WITH INCLINED ANGULAR SCANNING OF TARGET SURFACES AND ASSOCIATED MEASUREMENT METHOD

Abstract

The present invention relates to a device for measuring (100, 101, 200) the optical response in reflection of at least one zone of interest (Z) of a target surface (F1, G1) to be analyzed, which comprises an emitting device (1) including at least one optical radiation source and producing an incident beam (2, 4) of this radiation, an optical system (SO) intended to receive the incident beam (2, 4) at input and comprising a converging lens (7) capable of deflecting the incident beam (2, 4) into an emergent beam (8) directed towards the target surface (F1, G1), the emergent beam (8) being inclined at an angle θINC with respect to the normal of the target surface (F1, G1), and a detection device (11) of an optoelectronic nature to control, after reflection on the target surface (F1, G1), the characteristics of the reflected radiation (10).According to the invention, the optical system (OS) further comprises a tiltable transparent blade (5) through which the incident beam (2, 4) passes and which is positioned upstream of the converging lens (7), to control the displacement of the beam (2, 4) passing through it in order to adjust the angle θINC of the emerging beam (8) from said converging lens (7) while maintaining the same target area (F1, G1). Figure for the abstract: Figure 1.

Description

Title of the invention: OPTICAL REFLECTOMETRIC DEVICE WITH INCLINED ANGULAR SCANNING OF TARGET SURFACES AND ASSOCIATED MEASURING METHOD Technical field of the invention

[0001] The invention relates generally to the optical reflection analysis of a surface using an inclined optical angular scanning system. More particularly, the invention relates to a device for measuring the optical reflection response of a surface to be analyzed having one or more areas of interest, as well as a method for measuring the optical response. The invention also relates to a method for optical characterization of a target surface by angular scanning reflectometry implementing such a measuring device. Technical background

[0002] Reflection analysis of optical surfaces makes it possible to achieve great sensitivity to the characteristics of the thin layers present on these surfaces, particularly if the illumination is inclined. Thus, ellipsometric measurements generally use a large illumination angle typically ranging from 40° to more than 70°, which generally makes it possible to intercept a particular angle for which a polarization component sees its reflection collapse. This component is called the p component. Around this particular angle, the reflected light has intensity and phase characteristics that are particularly sensitive to the surface state. The angle corresponding to this reflection drop is known as the Brewster angle.This angle is also known as the Kretschmann angle when the illumination is supercritical, i.e. evanescent at the surface to be analyzed, and the surface supports a surface mode at this angle, i.e. a significant optical resonance at its surface. In the latter case, the sensitivity is further increased.

[0003] For use cases, the Brewster or Kretschmann angle are typically non-zero and relatively large, so off-axis illumination is used to reach them, i.e. illumination inclined relative to the surface to be analyzed. More precisely, for off-axis illumination, the optical axis of the illumination system is not coincident with the normal to the surface to be analyzed. Excitation according to the Kretschmann angle requires not only a fairly large angle of incidence but also coupling optics, detailed later, to be in evanescent illumination conditions. The Kretschmann angle is also only reached if the surface to be analyzed can present a surface mode.

[0004] The analysis of the phase or intensity of radiation reflected from a surface of interest as a function of the angle then provides a large amount of information on possible modifications that may appear on this surface, whether it is roughness or the grafting of target molecules. In particular, we can detect the presence of a layer gradually forming at the surface level. This type of analysis is therefore particularly relevant for the analysis of biochemical species.

[0005] For the reflectometric analysis of thin layers for biodetection applications, the need for lightweight, portable and high-performance analysis devices is significant, for example for the detection of viral targets in human or animal fluids to be able to carry out decentralized analyses in care centers or outside, etc. Thus, there are a certain number of patents proposing angular scans within such reflectometric devices mainly in the context of optical molecular biodetection devices. These nevertheless present a certain complexity as we will detail later.

[0006] The quantitative detection of biochemical species using optical biosensors based on the excitation of an optical resonance of a surface makes it possible to achieve excellent sensitivity when an angular measurement is previously carried out to position oneself at the best angle, that is to say the angle for which the characteristics of the light radiation are most modified by variations at the level of the surface probed such as the Brewster or Kretschmann angles already mentioned.

[0007] Among the sensors based on this approach, we distinguish surface plasmon resonance detection systems, called SPR sensors, which generally work around the Kretschmann angle to increase their sensitivity. Physically, these devices are based on the optical excitation of a resonant surface optical wave within a thin layer, with metallic optical behavior and in immediate interaction with a superstrate constituting the medium to be analyzed. This thin layer constitutes the optical surface to be analyzed.

[0008] It is common for SPR sensors to call the physical system formed of said resonant thin layer and the substrate, on which it rests and whose dimensions are often those of a coverslip used in microscopy or biology, an optical chip.

[0009] The substrate of the optical chips used can be of various dimensions and materials. For SPR devices working in the visible or near infrared, these are often smooth and transparent glass or plastic substrates to avoid diffusion. The optically resonant layer is located on the surface of the optical chip to be sensitive to the presence of a possible analyte forming the superstrate.

[0010] Exciting the optical chip means that the optical resonance of the optical chip is excited using light radiation. This resonance, when approached angularly, results in a polarization component being an ef- melting of the reflected intensity and a significant variation of the phase.

[0011] The excitation conditions, not only angular but also spectral, of the optical chip, and more precisely of its resonant layer, are very sensitive to the immediate environment covering this layer.

[0012] Physically, in the optical chip, the surface polaritonic wave is induced by the oscillation of free carriers in sufficient concentration within the thin layer which can be a noble metal such as gold, silver, copper, etc. To achieve effective angular excitation in this more or less resonant layer, the illumination of the thin layer is typically carried out in attenuated total reflection. To obtain attenuated total reflection, an optical coupling element is used to obtain illumination in supercritical incidence of the resonant layer. The coupling optics often consists of a transparent prism whose entry surface is such that the beam enters it with a sufficiently strong angle, with respect to the normal to the target surface, to allow this type of excitation. This explains why the optical chip sometimes includes such a coupling optics.Alternatively, if the optical chip does not include coupling optics, the chip can be brought into optical contact with a coupling optic using a liquid or index gel or even with a sufficiently transparent adhesive.

[0013] Thus, in SPR devices, the substrate of the optical chip is associated with a coupling optic, such as a prism, whether the deposition of the resonant thin layer is done directly on this optic or not.

[0014] In some cases, less common in commercial devices, the coupling optics allowing total reflection to be achieved is not necessary: ​​this is the case if the coupling optics uses a grating and also for a particular category of SPR devices, called LSPR in which the resonant thin layers are typically structured to further confine the resonance at the surface. In this case, the coupling between the incident light and the resonant layer is carried out thanks to the optical properties of the structured layer itself, the illuminated structure induces the surface polaritonic excitation. In these cases, the coupling optics is no longer absolutely necessary and its role can be reduced to that of a simple mechanical support, such as an openwork support allowing the beam to pass without affecting it or a transparent support not inducing over-critical excitation.Even for LSPR devices, i.e. when the resonant layer is structured, there is typically an angular domain of optimal excitation, even if the incidence conditions allowing resonant excitation can be significantly less critical than in the absence of surface structuring.

[0015] Thus, the optical chip consists of a substrate covered with an optically resonant layer (structured or not) and the optical excitation of this chip depends on the angle but also the wavelength of the incident beam.

[0016] More recently, devices identical to SPR devices have been found, but in which the optical resonances are induced by atomic vibrations in polar materials. The operating principle of these devices is identical: The spectral and angular illumination conditions of the optical resonance of this thin layer are also very sensitive to the immediate environment covering this layer. These devices are sometimes called SPhR devices for surface polariton phonon resonance devices, or simply surface phonon resonance devices. These are the same family of instruments.

[0017] For many applications, the analytical medium being probed is generally fluid, whether it is saline, serum, saliva, vapors, gases, water, oils, juices, or other human or animal fluids, etc.

[0018] The optically resonant layer, the thickness of which is typically a few tens of nanometers, for operation in the visible or near infrared, can be functionalized using so-called "probe" molecules to specifically capture molecular targets of interest, such as pathogens, pollutants, biomarkers, drug molecules, etc.

[0019] Since the molecular targets of interest are generally biochemical, the surface of the optical chip is generally functionalized by biochemical probes aimed at capturing said targets. The optical chip, also called an SPR chip, is then often referred to as a biochip due to this functionalization.

[0020] The functionalization of the SPR chip makes it possible to detect a target or targets of interest. The functionalization typically consists of grafting biomolecules onto the surface of the SPR chip; these specific biomolecules can be of different types, such as DNA, aptamers, antibodies, peptides, proteins, etc. These biomolecules are typically referred to as probes. The functionalization of the surface of the biochip can also include non-stick surface agents to avoid unwanted contamination, in particular via the use of PEGs (polyethylene glycols).

[0021] For example, during functionalization, the grafting of the probes is often done using thiol or polythiol functions for SPR chips with gold surfaces.

[0022] As mentioned, the resonant layer generally comprises a noble metal such as gold and its optical resonance is obtained for a specific illumination angle Ores directly dependent on the optical index of the probed medium covering said resonant layer.

[0023] Generally, the biochip is covered with a microfluidic chamber to allow easy contact with the fluid element to be analyzed.

[0024] The assembly containing the optical coupling element such as a prism, the op biochip tically resonant on its surface, and the possible microfluidic element used to convey the fluid medium to be analyzed on the resonant biochip is here called analysis cell.

[0025] Several optical excitation configurations exist. In one configuration, the optical excitation of the surface of interest is monochromatic and the angle of the beam passing through the coupling system of the analysis cell is adjusted to be placed in the vicinity of the optical resonance of the biochip which is most strongly manifested at the angle 0RES relative to the normal to the surface of interest of the biochip, angle for which the reflected intensity of the p polarization component collapses. The s component is typically little affected unless the resonant surface of the biochip contains resonators sensitive to the s component of the incident light. The light reflected on the biochip is monitored after reflection, using a detection system comprising at least one or more optical detectors. This detection can be ensured by a point detector, when a single area of ​​the biochip is monitored without spatial resolution.But this detection can be provided by a plurality of detectors, and may even include an imaging device comprising optics and an array detector placed to image the resonant surface. Optical filters can be added to eliminate unwanted signals.

[0026] The SPR measurement may consist of monitoring, via the detection system, the variations in optical reflection occurring in the presence of the targets of interest, which tend to increase the optical index in the vicinity of the biochip as said targets are captured by the surface of the biochip. It is also possible to detect at the same time a variation in optical phase corresponding to a variation in the ellipsometric parameter, often noted A, corresponding to the phase shift between the p and s components of the reflected wave. The variations in intensity or even the relative variations in phase of the reflected p wave, in the case of an interferometric measurement, reflect the existence of a change in optical index due to the accumulation of target molecules in the immediate vicinity of the resonant layer of the optical chip.

[0027] The temporal evolution of the intensity or phase induced by the change in surface index is commonly called a sensogram. This signal makes it possible in particular to monitor, in real time, the dynamics of association or dissociation between target molecule and probe, without adding a fluorescent marker.

[0028] However, since the resonant angle 0RES depends on the surrounding optical index and therefore on the concentration of the target, it is important to be able to adjust the angle of incidence in order to be able to place oneself in favorable excitation conditions.

[0029] Optimum excitation of the resonance ideally requires a specific X wavelength. However, surface wave resonances have a fairly large spectral width, i.e. at least several tens of nanometers or more. Thus, SPR sensors can work with excellent performance with a fixed wavelength, whether it is for example a laser diode or a more spectrally extended source such as an LED, operating in particular in the red or near infrared in the case of biochips covered with an optically resonant layer of gold. On the other hand, the angle of incidence at the biochip level must typically be adjusted carefully, because the resonances can be very acute angularly, especially on phase measurements where variations of the order of a hundredth of a degree on the angle of incidence can lead to a significant variation of the resonance.

[0030] Although it is possible to work with a well-chosen fixed angle, the measurement dynamics are generally greatly reduced if this choice is made. It is therefore preferable to be able to adjust the angle of incidence.

[0031] Ideally, for the optical analysis of surfaces and in particular for SPR, it would be desirable for the angular adjustment to be able to be done simply and precisely, over a fairly wide angular range, such as around ten degrees, and fairly quickly, while having a light, compact and inexpensive device. However, depending on the level of requirement on these different points, such a combination of advantages is difficult to obtain and is not known to those skilled in the art.

[0032] For devices for analyzing the reflection of a surface of interest, particularly in ellipsometry, angular scanning, when possible, makes it possible to approach the Brewster angle. Scanning is generally carried out by tilting the lighting arm around an axis of rotation centered on the target surface to be analyzed so that the radiation beam does not deviate from the area of ​​interest located on this target surface to be analyzed.

[0033] In SPR devices also, to excite an optical resonance for biodetection purposes, it is very important to be able to adjust the angle to reach the resonance of the surface of interest. To properly excite the resonance, two approaches (a, b) each having advantages or disadvantages are possible: - The surface of interest can be excited through the coupling element with a plurality of angles, typically obtained with divergent or convergent illumination and the angular detection, in this case, is carried out statically via a matrix detector. The beam incident on the biochip therefore forms a light cone of incidence, and the optics used to produce it are typically cylindrical. Thus, in this approach, the signal is angularly dispersed around an optical axis, instead of scanning the angle (as for a spherical lens, for a cylindrical lens, the optical axis corresponds to an axis for which an incident ray is undeviated). Thus, this approach does not require a moving part to adjust the angle of incidence around the optical resonance angle of the biochip. But, This approach therefore requires, downstream of the biochip, i.e. in the detection system, the use of a matrix detector. The SPR signal of interest around the resonance is manifested by the existence of at least one dark zone within the spot measured by the matrix sensor, and in the vicinity of which sensorgrams can be obtained; - The biochip can be excited with an angular scanning system in order to determine the angular position of the resonance and thus allow it to be placed in the angular vicinity of this resonance. By positioning itself angularly in the vicinity of the resonance, it is placed in favorable excitation conditions to record the sensorgram.

[0034] This second approach (b), compatible with collimated illumination, allows a spatially more uniform excitation of the resonance, facilitating imaging analysis if the system uses a matrix detector. Indeed, in this case, the detector can be entirely devoted to imaging and not to the measurement of angular dispersion. This second approach (b) is also interesting for a measurement using point detectors, since the illumination of the optical chip is more uniform, which lightens the signal processing compared to a matrix detector. Finally, the signal-to-noise ratio is very good. If the scanning is fast, approach (b) is therefore desirable if the problem of practical implementation of the angular scanning is solved. Finally, even in approach (a), a certain angular scanning can be useful to roughly center the resonance in the angular range accessible by the matrix sensor.

[0035] Several approaches have been proposed for performing angular scanning. However, several difficulties have arisen. Thus, for compact SPR sensor applications, it is desirable for the system to remain compact and energy-efficient; thus, the movement, as in certain ellipsometers or SPR devices, of the entire illumination arm, or even the detection arm, is not desirable for this type of application, in particular for reasons of robustness, stability, or speed of angular scanning. This type of assembly is, however, common, because it is acceptable for bulky devices where portability and speed are not too critical.Similarly, since the coupling element is integral or in contact with the biochip, it is not very desirable for this assembly to be mechanically moved to produce the adjustment or angular scanning, for reasons of mechanical robustness or to allow for dimensionally unconstrained analysis cell designs.

[0036] A practical difficulty also is that it is desirable for the angular scanning to occur while maintaining an unchanged analysis area at the biochip level, during the angle scanning. Thus it is generally not desirable for the scanning to produce a substantial displacement of the beam at the resonant surface of the biochip. The direct use of a beam deflector such as a rotating mirror or an acousto-optic modulator, which is faster but expensive and relatively bulky, is therefore generally not directly possible. To overcome this difficulty, the use of such angular deflectors must be coupled with a specific mechanical or optical system to allow excitation over a fixed area and possibly without angular averaging, i.e. while maintaining collimated excitation. The use of a deflector and a suitable optical system or additional moving parts increases the size and cost.

[0037] For the purposes of the present invention, the term beam deflector element means an element capable of dynamically modifying the angle of the incident beam and consisting of either an acousto-optic deflector, an electro-optic deflector or a movable mirror, such as, for example, a galvanometric mirror.

[0038] For example, US patent US 7,576,863 describes an angular scanning system with movable reflective deflectors having some of the complexity drawbacks previously cited, in that it requires a movable device additional to the use of beam deflector to maintain the beam on the analysis zone.

[0039] Similarly, Chinese patent application CN109490278 describes a complex device requiring rotation of the analysis cell comprising the surface to be analyzed itself and the coupling optics to obtain fine adjustment of the angle of incidence on the surface to be analyzed.

[0040] In order to improve the sensitivity, it is desirable that the SPR device can incorporate phase detection, which is not very widespread and often expensive. It is known that measuring the phase of the p component of the field, and not only its intensity, can provide a gain in sensitivity of the order of a factor of ten or more for sufficiently resonant optical chips, but the measurement dynamics is reduced if the SPR device allowing such phase measurement does not also allow angular scanning of the excitation beam in order to monitor the angular displacement of the resonance which occurs during detection.

[0041] Recently, a laser device for polarization interferometry has been developed by the present inventors to enable phase information to be obtained in compact SPR devices in a simple and compact manner. This laser device, which is described in international application WO2020128293, does not, however, have angular scanning solutions that overcome the aforementioned problems. Statement of the invention

[0042] An object of the invention is to provide a measuring device which does not have the in usual disadvantages of inclined scanning reflectometric devices such as the scanning SPR systems mentioned above.

[0043] In particular, an object of the invention is to enable angular scanning of a relatively rapid incident beam without having to use the mentioned beam deflecting element.

[0044] Another object of the invention is to enable angularly controlled illumination with precise and adjustable angular resolution, without angular averaging (i.e. in collimated lighting conditions).

[0045] Another aim is to allow angular control via a single moving element to maintain great simplicity of implementation, great compactness and inexpensive elements.

[0046] Another aim is that this system is compatible with phase-sensitive SPR measurement and with the use of a compact device.

[0047] More particularly, the present invention relates to a device for measuring the optical response in reflection of at least one area of ​​interest of a target surface to be analyzed, said measuring device comprising: - an emitting device comprising at least one source of optical radiation and producing an incident beam of this radiation, - an optical system intended to receive said incident beam as input and comprising a converging lens capable of bending said incident beam into an emerging beam directed towards said target surface, said emerging beam being inclined at an angle 01NC relative to the normal of said target surface and - a detection device of an optoelectronic nature for determining, after reflection on said target surface, the characteristics of the reflected radiation, said measuring device being characterized in that said optical system further comprises a transparent tilting blade crossed by said incident beam and positioned upstream of said converging lens, said transparent tilting blade being capable of being inclined so as to control the movement of said beam crossing it in order to adjust the angle 0^c of the emerging beam of said converging lens while maintaining the same target surface.

[0048] For the purposes of the present invention, the term "converging lens" means a thick converging lens or any converging optical system comparable to a thick lens, such as, for example, a converging combination of lenses.

[0049] A mechanical support makes it possible to position the target surface so as to produce illumination inclined with respect to the normal to said target surface.

[0050] Advantageously, the measuring device according to the invention may further comprise at least one additional lens upstream of the tiltable transparent blade, this additional lens being capable of adjusting the collimation of the beam. emerge.

[0051] Advantageously, the measuring device according to the invention can further comprise: - a motor capable of modifying the inclination of the tilting transparent blade, and - an electronic interface to acquire the signals from the detection device and to control the motor in order to automatically adjust the angle of incidence 01NC of the radiation from the target surface.

[0052] The present invention also relates to a method for optical characterization of a target surface comprising a substrate and / or one or more thin layers by angular scanning reflectometry, characterized in that it implements a measuring device according to the invention as defined previously, as well as the use of such a method for biomolecular detection purposes.

[0053] According to an advantageous embodiment of the device according to the invention, the target surface may be on the surface of a resonant optical chip, in particular an LSPR chip (acronym designating a localized SPR resonance, i.e. a localized surface plasmon resonance) which comprises a transparent solid substrate covered with a thin resonant layer sensitive to a fluid superstrate covering it.

[0054] In this embodiment, the device may advantageously further comprise a coupling optic having at least one input face capable of receiving the emerging beam and an output face crossed by the reflected beam, and an SPR chip optically coupled to the coupling optic will advantageously be used as the resonant optical chip. In this embodiment, the radiation passes through the optical chip and is reflected in total internal reflection conditions on the target surface to be analyzed.

[0055] Preferably, for this embodiment, a prism with a flat input surface and an additional lens for adjusting the collimation at the output of the optical system may be used as coupling optics.

[0056] Advantageously, for this embodiment, the resonant optical chip may be, according to a variant of this embodiment, functionalized in at least one zone in order to detect biomolecular targets circulating in the fluid superstrate.

[0057] Advantageously, according to a first variant of this embodiment, the device according to the invention may comprise, as emitting device, a laser device for polarization interferometry, with an analysis polarizer arranged at the level of said detection device.

[0058] The present invention also relates to a method for measuring the optical response in reflection of a target surface to be analyzed, implementing this advantageous embodiment of the device according to the invention as defined above (and in particular the first variant), and in which the phase shift of the p component of said radiation after reflection on the target surface is determined with respect to the phase of the s component of said radiation after reflection on the target surface.

[0059] Advantageously, according to a second variant of this embodiment, the device according to the invention may have the following characteristics: the target surface to be analyzed comprises multiple functionalized areas of interest for detecting biochemical targets; the illumination within the coupling optics is collimated, and the detection device comprises a plurality of detectors. Brief descriptions of the figures

[0060] Other advantages and particularities of the present invention will result from the description which follows, given by way of non-limiting example and made with reference to the appended figures and to the examples: - [fig.l]: [fig.l] schematically represents an example of a measuring device according to the present invention; - [fig.2]: [fig.2] represents the measuring device of [fig.l] with an increased angle of incidence; - [fig.3]: [fig.3] represents the measuring device of [fig.l] with a reduced angle of incidence; - [fig.4]: [fig.4] schematically represents a detection cell C intended to be arranged in the embodiments of the measuring device shown in figures 1 and 5 (see below) - [fig.5]: [fig.5] schematically represents an embodiment of the measuring device according to the invention adapted to SPR measurement; - [fig.6]: [fig.6] represents an angular scanning reflectometric measurement in intensity carried out with the device according to [fig.5], this figure being commented on in the example of realization n°1; - [fig.7] represents an angular scanning reflectometric measurement in intensity and phase carried out with the device according to [fig.5], this figure being commented on in embodiment example no. 2; - [fig.8] schematically represents an embodiment of the measuring device according to the invention adapted to the ellipsometric characterization of thin layers Detailed description of the figures

[0061] [fig.l] represents an angle scanning reflectometric device 100 according to an embodiment adapted to SPR measurement. This device 100 comprises an emitting device 1 producing a beam 2 represented in the figure by two of its emerging rays. A converging optical system comparable to a thick lens 3 makes it possible to create an image of the radiation source in the vicinity of the object plane PO of a second optical system comparable to a thick lens 7 of effective focal length f in order to produce a collimated or approximately collimated illumination beam within the detection cell C, which includes the optical surface to be analyzed.

[0062] The detection cell C typically includes a coupling optic Cl provided with an input surface SI crossed by the illumination beam. The main role of Cl is to allow illumination of the optical surface to be analyzed under total internal reflection conditions. The surface to be analyzed is therefore here placed on the upper surface of CL. The presence of Cl is necessary to excite the majority of SPR surfaces; which in fact require a supercritical incidence, that is to say an incidence under total internal reflection conditions, around a particular angle.For some surfaces, illumination in attenuated total reflection is not necessary, nor is the presence of Cl. This is the case for certain nanostructured surfaces with localized SPR resonances, called LSPR, but also for SPR surfaces that may include a network or if the user wishes to work off-resonance, for example, to characterize the surface of interest independently of any analyte, for example for ellipsometric measurements. Thus, Cl is advantageously retractable.

[0063] The entrance surface S can be likened to a diopter which, with appropriate curvature, can play the role of the lens 7, but this is undesirable because it places greater dimensional constraints on the coupling optics CL. Thus, it is preferred that the lens 7 forms a separate element of the device, i.e. dissociated from CL.

[0064] Advantageously, the orientation of the input surface SI is such that the angle between its normal and the beam passing through it and causing the resonance is small. Indeed, it is known that working with small angles with respect to the normal to a diopter promotes stigmatism and minimizes any possible angular averaging by this diopter, which would be linked to its aberrations.

[0065] The average angle of incidence 01NC of the beam 8 emerging from the optics 7 in the direction of the detection cell C is adjusted by tilting the angle a of a movable transparent blade 5 whose role is to shift the propagation axis of the beam 4 emerging from the optics 3. Thus, the beam 6 emerging from the transparent blade 5 will be shifted if the transparent blade is tilted. As a result, the image produced by the thick lens 3 is also shifted, producing a beam 8 of average tilt adjustable by this means and advantageously passing through a fixed point centered on the area of ​​interest on the surface of the optical chip present within the detection cell C.

[0066] The beam emerging from the detection cell with an angle Oref is collected by a detection device 11 comprising at least one optical detector.

[0067] The detection system is of the optoelectronic type and its role is to collect the optical signal coming from the area of ​​interest. It may include elements likely to facilitate the analysis of the optical signal such as collection optics, a optical filter to minimize unwanted radiation, etc.

[0068] [Fig. 2] represents the SPR device with angle scanning 100 where the movable transparent blade, initially attacked at normal incidence in [Fig. 1], has been inclined so as to increase the angle of incidence 0INC compared to its initial value, as it was schematically represented in [Fig. 1].

[0069] [Fig. 3] represents the SPR device with angle scanning 100 where the movable transparent blade has been inclined so as to reduce the angle of incidence 0INC compared to its initial value, as it was schematically represented in [Fig. 1].

[0070] In practice, the movable transparent blade 5 may be a simple parallel blade of thickness e and index n and may consist of a simple glass blade. Advantageously, the blade may be treated to avoid multiple reflections.

[0071] Compared to the case where there is no beam shift induced by the moving blade 5, the shift D of the beam 4 induced by the moving blade 5 creates a variation of angle A0 iNc=D / f' of the angle O^c, where f' is the effective focal length of the optical system formed by the optical system 7.

[0072] If we denote f” the effective focal length of the thick optical system formed by the optical system 7 and the possible coupling optics, the variation in the angle of incidence induced by the shift D of the beam 4 induced by the moving blade 5 at the level of the optical chip is A0PR=D / f”.

[0073] Furthermore, the offset D is a known function of the index n, the angle of inclination a of the blade and the thickness of the blade e. By choosing the angular origin of a for a normal incidence of the beam 4 with respect to the surface of the blade 5, we have: D=e*sin a (l-cos(a) / g0'5) with g=(n2-sin2a).

[0074] We note that the variation of D of the beam 4 induced by a rotation of the angle a of the blade is maximum for low values ​​of a, and in this case, D is proportional to a and is simply D« a*e*sin(a) ~ a*e*a, with a = (nl) / n.

[0075] If the precision or uncertainty on the control of the inclination a of said optics 5 is u(a), then the device 100 makes it possible to obtain a precision on the angle of incidence u(0INC) which, with respect to the value of u(a), is divided by a minimal factor coeffmin=f' / (a*e) easily ranging from 10 to more than 100 depending on the form factor e / f' allowed. Representative improvement coefficients are given in table 1 below for n=1.5: [Tables 1] coeffmin f (mm) 10 20 50 e (mm) 0.6 50 100 250 1 30 60 150 2 15 30 75 3 10 20 50 4 7.5 15 37.5 5 6 12 30

[0076] Thus the device 100 is advantageous because it offers in particular two independent ways of improving the angular resolution compared to the resolution u(a) of the system used to tilt the blade, either by reducing the thickness e of the blade, or by increasing the focal distance f.

[0077] Furthermore, the inclination of the blade 5 can be easily achieved by placing it on the axis of a servomotor or even a stepper motor. Lightweight and compact stepper motors can ensure a rotation step of the order of u(a)=0.05° or better. Thus the typical angular resolution on 01NC can be of the order of u(01NC )-0.001° or better depending on the value of coeffmin obtained by design, that is to say depending on the choice of the thickness e of the focal length f'.

[0078] For a given blade thickness e, the maximum scanning angular range for 01NC can be optimized by adjusting the position and dimensions of the blade as well as the dimensions of the beam 4. This analysis can be done by ray tracing by considering the extreme inclinations of the blade 5 making it possible to ensure that the beam 6 is correctly intercepted by the lens 7, i.e. ideally in its entirety so as not to diffuse the beam and to maintain a luminous flux favorable to obtaining a good signal-to-noise ratio. Without simulation, a rapid analytical analysis shows that the maximum algebraic shift D induced by a blade of thickness e is equal to ±e at grazing incidence, which gives a maximum theoretical angular range of ±e / f'. Table 2 below gives the maximum accessible ranges (in °) for the angle 01NC for representative values ​​of e and f'. [Tables 2] 0 INC f (mm) 10 20 50 e (mm) 0,6 ± 3,44° ± 1,72° ± 0,69° 1 ± 5,73° ±2,86° ± 1,15° 2 ± 11,46° ±5,73° ± 2,29° 3 ± 17,19° ± 8,59° ± 3,44° 4 ± 22,92° ± 11,46° ± 4,58° 5 ± 28,65° ± 14,32° ± 5,73°

[0079] In practice these limit values ​​for 01NC are not reached due to the non-zero extension of the beam which is not limited to a single ray, and the fact that the blade is also of finite dimension. Thus the finite lateral dimension of the blade leads to a reduction in the maximum accessible offset value D, because the extreme values ​​of D ±e can only be reached asymptotically for a beam 4 resembling a single thin ray and a blade with a lateral dimension greater than e / (n2-l)0'5 at least. The consequence is that, in practice, beyond a certain angle for a, the optical signal is scattered by the edges of the blade 5 and the signal detected in the collection arm, that is to say in the detection device 11, decreases quite rapidly. The value of this limit angle for a is more or less high depending on the diameter of the beam and the lateral dimensions of the blade with respect to its thickness.For example, experimentally, a significant part of the signal disappears beyond an lcd angle of about 77° for a blade with a lateral dimension equal to three and a half times the blade thickness e, illuminated with a beam of width e / 2. Nevertheless, the maximum theoretical 01NC angle values ​​shown in Table 2 can be approached to more than 70% with shape factors e / f' of the order of one fifth and a beam of width e / 2.

[0080] Advantageously, the lateral dimension of the lens 7 is greater than twice the maximum offset, accessible in practice, plus the diameter of the beam at the level of the lens 7, in order to avoid unnecessarily diaphragming the beam.

[0081] According to a preferred embodiment of the invention, the input surface SI of the coupling optics C1 is spaced from the lens 7, that is to say that it is not integral, as is possible, with the optical system 7.

[0082] Advantageously, for reasons of cost and ease of obtaining the coupling optics C, the input surface SI of the coupling optics is flat. It is then preferable for the angle at the top of the prism APR to be close to the angle of the rays 0PR allowing to excite the optical resonance in the biochip. Under these conditions, the planar SI input surface acts as an approximately stigmatic optic ensuring that the area of ​​interest in the vicinity of the optical axis and the PI plane always remains targeted during scanning. For a planar SI input surface, the beam 8 undergoes a refraction reducing the angular range accessible for 0PR, compared to the range of O^c, by a factor approximately equal to n^ / n^c, where nPR is the index of the coupling optics and n1NC the index of the medium between the lens 7 and the SI input surface typically approximately equal to one. Under these conditions, the variations on the angle 0PR within the coupling optics are controlled with a precision u(0PR) further improved, compared to u(01NC) given previously, by a factor typically worth nPR« 1.5 for a glass prism in the visible and more generally worth u(0PR)= u(01NC)* n1NC / nPR.The angular range for the 0PR angle is also reduced by the same factor compared to the theoretical maximum values ​​given in Table 2. An example of an accessible range realized practically is given in particular in the first detailed example which will follow. EXAMPLES

[0083] EXAMPLE 1: production of a reflectometric analysis device with angular scanning of a target surface of the SPR type in intensity.

[0084] An angular scanning reflectometric device 200 illustrated in the diagram of [fig.5] is produced, suitable for SPR biodetection and making it possible to detect the reflection response of a target surface here located within a detection cell C shown in the detailed diagram of [fig.4]. The device 200 comprises the following elements fixed on a flat surface T2 parallel to the plane of incidence: - an emitting device 1, here composed of a collimated laser source of the VCSEL type referenced “VC670M-TO46GL” emitting at approximately 670 nm; - an additional lens 3 (thick lens 3), of cylindrical plano-convex shape referenced LJ1402L2 at Thorlabs Inc; - a movable blade 5 consisting of a glass blade 5.0mm thick and with square lateral dimensions of 15mm, mounted on the axis of a stepper motor; - a converging lens 7 (thick lens) referenced LJ1810L2 at Thorlabs Inc., with focal length H'F'=24.88 mm, separated from the additional lens 3 by a distance of 66.6 mm along the optical axis; - The detection cell C has as optical coupling element a prism with flat faces made of N-BK7 glass, with an apex angle APR = 67.5°. The input surface SI is flat and polished. The upper face of the prism, also flat and polished, is coupled via an index oil to an optical chip C2 comprising on the surface an optically resonant layer of 47 nm of FL-functionalized gold

[0085] In this practical embodiment, the functionalized gold resonant layer Fl, shown in [fig.4], constitutes the surface of interest to be analyzed on which the radiation is reflected in total internal reflection at the level of a target zone Z. The surface of interest to be analyzed is in contact with a microfluidic circuit C3 comprising channels closed by a glass cover C4 provided with inlets C41 and outlets C42, arranged to be able to convey a fluid on the surface to be analyzed of the optical chip.

[0086] The detection cell comprising the surface to be analyzed is inserted into a mechanical support Tl (see [fig.5]). This mechanical support Tl makes it possible to position the target surface so as to produce illumination inclined with respect to the normal to the target surface FL. The mechanical support here consists of a perforated plastic plate Tl to accommodate the detection cell C. Tl is here perpendicular to the plane of incidence and the surface of the optical chip is parallel to the plate TL. In this example, for an initial position a=0° of the mobile transparent blade, the optical surface to be analyzed is inclined by approximately 67.5° with respect to the incident radiation. This angle corresponds to the angle between the optical axis of the thick lens 7 and the normal to the surface of interest, which corresponds to off-axis illumination. It is also the angle between the normal to the surface of interest and the normal to the input surface SL.

[0087] Advantageously, mirrors can be added to the beam path to fold the optical path in order to minimize the total size of the device 200. Thus in the example given, a mirror M1 is placed between the thick lens 3 and the tilting blade 5 to minimize the size of the device according to the initial direction of the beam 2. Similarly, a second mirror, M2 is added here to minimize the size of the device according to the direction of the beam 6 having passed through the blade 5.

[0088] The entire device produced, shown schematically in [fig.5], here occupies a surface area of ​​less than 16 cm by 8 cm.

[0089] In this example, the VCSEL laser is relatively linearly polarized and is oriented so that the p-polarization component is predominant in order to increase the signal-to-noise ratio. The detection system simply consists of a point detector referenced Hamamatsu S6967.

[0090] The electronic signal acquisition system to which the detector is connected, not shown in [fig.5], is located behind the surface T2. This system therefore serves as an electronic interface to recover the detected optical signal and also allows the orientation of the blade to be controlled. In practice, this interfacing is achieved using an electronic card comprising digital inputs / outputs within a microcontroller referenced STM32 G474. This card is connected to a display and power supply device by a USB cable. In this example, the electronic card is thus connected to a laptop which allows the angular scanning parameters to be adjusted via the electronic card. For convenience, this electronic card also powers the laser source and it also controls the blade tilt 5 via a NEMA14 stepper motor referenced at Stepperonline with 400 steps per rotation, which is connected to the electronics by an A4988 driver from Alegro Microsystems. Thus the SPR system produced is entirely powered by USB and does not require other power or communication cables.

[0091] The program embedded in the microcontroller, usually called "firmware", allows the motor, the VCSEL and the acquisition of signals to be controlled. It is written here in C, and is loaded into the microcontroller using the STM32CubeIDE software development environment.

[0092] The firmware accepts input variables to define the desired angular scanning range and acquisition time for each motor position. These inputs are defined here from a user interface implemented in Python3 programming language on the PC, allowing this information to be sent to the microcontroller via the USB port. The firmware also sends the detected signal to the user interface for display.

[0093] Thus the angle of incidence at the biochip can be freely adjusted or scanned.

[0094] [Fig.6] represents the SPR signal detected as a function of the angle of incidence defined and scanned from the user interface. The signal thus represents the intensity reflected on the biochip at the level of a microfluidic channel in which a saline solution (PBS Buffer) circulates, with an index slightly higher than 1.333. Although the angle can possibly be determined using optical control, here it is known precisely in absolute value because the angle of the motor a is controlled by the electronics.

[0095] Indeed, the angle obtained upstream of the detection cell is given by 01NC =atan(D / H'F'), where the optical shift is D=e*sin a (l-cos(a) / g0'5) and g=(n2-sin2a). In our case H'F'=24.88mm, the thickness of the blade e is 5mm and its index is approximately n=1.515. The angle a of the blade is controlled to within a constant by the motor. The angle 01NC of incidence on the detection cell makes it easy to find the incident angle on the biochip which is 0PR=asin(01NC / 1.515). A complete rotation of the blade makes it possible to find the angular limits of detection which here corresponds to approximately 10° within the coupling optics, i.e. for 0PR. For this device the angular resolution is u(0PR)« 0.0025°. This resolution is improvable by design as discussed previously.

[0096] The angular scan shown in [fig.6] is obtained here in about 5 seconds. Once the surface to be analyzed is optically positioned, the SPR measurement method of the reflected signal as a function of the angle of incidence leading to this type of curve simply consists of recording the intensity of the reflected signal for a series of angular positions defined via the electronic interface. Depending on the resolution desired angular frequency and the desired acquisition time, the scan can be performed more quickly, for example in less than one second if no time averaging is performed.

[0097] In this example, the optical chip consisted of a BK7 glass coverslip coated with a monolayer of mercapto-silane bonding metallized with approximately 47 nm of gold.

[0098] In the optical system SO composed of the thick lens 3, the tilting transparent plate 5 and the thick lens 7, the additional lens 3 can also be removed. In this case where the additional lens 3 is absent, the optical system SO still allows the average emerging angle of the optical system composed of the tilting plate 5 and the converging lens 7 to be adjusted. However, without the additional lens 3, the collimation of the emerging beam of the optical system cannot be adjusted to obtain a parallel beam, thus tables 1 and 2 are still valid but refer in this case to the average emerging angle of the optical system, whether it is the resolution improvement factor (table 1) or the angle range (table 2).The thick lens 3 therefore makes it possible to avoid angular averaging, it is therefore very preferable to put it to improve the sensitivity of the SPR device, unless the detection device 11 comprises a large plurality of detectors making it possible to discriminate the reflected angles, in particular if the detection device comprises a CCD or a CMOS sensor. However, in this case, that is to say without the thick lens 3 but with a CCD or a CMOS sensor in the detection device 11, these sensors cannot be fully used for imaging because then a direction of the sensor is used to discriminate the angle. Thus the addition of the additional lens 3 is advantageous in this respect by avoiding this drawback. It makes it possible in particular to adjust the collimation of the beam emerging from the optical system.

[0099] For this first detailed example, the chosen angular range corresponds approximately to an angle range for the emerging angle of the SO system of 01NC of approximately 15° centered on 67.5°. Taking into account the index of the prism, this range corresponds for 0PR to a range of 10° beyond 62°. This range makes it possible to excite the optical chip at the resonance angle which is typically located a little beyond the critical angle. Indeed, the critical angle depends on the index of the substrate of the optical chip, here close to nSUB=i.5i for the BK7 glass making up the substrate, as well as the index of the superstrate covering it, typically close to nSUp=1.33 for an aqueous medium. For these index values, the critical angle for 0PR is close to 62°.This critical angle value is given by the formula asin(nSup / nSUB)- As it is appropriate to be above, the chosen range between 62° and 72° is suitable for 0PR, knowing that the resonance angle, greater than the critical angle, increases as the target of interest is grafted to the surface of the optical chip. For some applications, it may be interesting to go beyond 01NC=75°, . if the medium being probed has a higher index. The design can be easily adapted to increase the angle, which in all cases remains less than 90°, either by increasing the angular range by choosing a thick lens 7 with a shorter focal length or by increasing the inclination of the optical axis defined by the optical system SO.

[0100] If the analysis is done dry (analysis of vapor or gas or after drying), which is less common, nSUp is approximately one and the critical angle is greatly reduced. In this case, a range leading to an angle 0PR ranging from 42° to 52°, depending on the index of the coupling optics, is satisfactory. The design elements given previously make it easy to adjust the angle range and the average angle to ensure the excitation of the resonance. SPR devices do not usually work below 01NC=40° because the resonance of optical chips is typically obtained at higher angles. Similarly for ellipsometric measurements of thin films, the analysis angle is generally high enough to be able to approach the Brewster angle, so it is preferable to work beyond 0 inc=40°.In the infrared, near phononic frequencies or plasma resonances of certain target surfaces, the Brewster angle can be lower, but this remains exceptional. For reasons of space, it is also preferable to work above approximately 01NC=30°.

[0101] EXAMPLE 2: production of an SPR device with interferometric scanning and multiple detection.

[0102] Advantageously, the emitting device 1 can produce a beam composed of several parallel beams. In this second detailed example of implementation, the principle diagram 200 is similar to the previous one with regard to the angular scanning whose range and angular resolution are identical. However, the emitting device 1 produces two beams of similar intensity, only separated in a direction perpendicular to the plane of incidence. Indeed, the beam coming from the VCSEL is here separated into two parallel beams separated by an approximate distance of 3 mm. The two beams being parallel at the output of the emitting device 1, these can also be perceived as forming a single beam of radiation having a particular intensity profile, composed of two maxima. This separation is carried out using a first semi-reflecting surface then a second reflecting surface recovering the semi-reflected beam.These surfaces, spaced about 6 mm apart, are inclined by 30° to produce a separation of about 3 mm. This duplication of the beam, which must be carried out before the optical chip, is here carried out within the emitting device 1, at the output of the latter, but this duplication could have been carried out downstream of this device without additional difficulty. These two beams undergo simultaneous angular scanning using the same device detailed in the first detailed example of embodiment, that is to say by tilting the tilting blade 5. The two . beams are reflected in total internal reflection on the resonant surface of an optical chip at two fixed zones located at the center of two microfluidic channels. The reflected beams are detected through the polished output surface S2 of the prism using two detectors, referenced Hamamatsu S6967, present in the detection device 1.

[0103] Advantageously also, the transmitter device 1 here includes a laser device for polarization interferometry to enable detection of not only the intensity but also the phase of the SPR optical signal conveyed by the beam 10 using the detection system 11.

[0104] Thus, in this second embodiment also, the emitting device 1 consists of a laser device for polarization interferometry similar to that detailed in the international application WO2020128293Al and shown schematically in the first figure of this application. This device is used to generate a laser beam whose polarization components are temporally phase modulated with respect to each other.

[0105] In this laser device for polarization interferometry, the source is here composed of the same VCSEL as in the first detailed example, but its electric injection current is here temporally modulated using control electronics included in the electronic interface, i.e. implemented in the microcontroller program. In the emitting device 1, the VCSEL is followed by a birefringent YV04 crystal whose main axis is oriented so that said temporal modulation induces a modulated phase difference between the p and s components of the beam 2 emerging from the emitting device 1. The length of the crystal is here approximately 14 mm and its square section is 5 mm. The injection current modulation of the VCSEL is of the order of 2 mA.

[0106] A fixed polarizer, called an analysis polarizer, is added to the detection system 11 to allow observation of the interferometric beat induced by the injection current modulation. The two detectors, referenced Hamamatsu S6967, are therefore placed just after this analysis polarizer to detect these beats. Here, two detectors are used, so that there is one for each analyzed area. Thus, the beat between the polarization components is obtained independently on each of the two detectors. These signals acquired by the acquisition electronics provide access not only to amplitude or intensity information on the SPR signal reflected on the optical chip but also to the optical phase information of the p polarization component.Indeed, the analysis of the interferometric beat between the two components of the field makes it possible to recover the amplitude and phase of the p component, with respect to the s component, considered as constant.

[0107] In this second detailed example of implementation, we therefore have two sensorgrams which can be recorded for each of the two beams: an amplitude sensorgram, or an intensity sensorgram if this signal is squared, and a phase sensorgram. Similarly, during an angular scan the device provides access to two signals depending on the angle of incidence 0PR for each zone analyzed: a phase signal and an amplitude or intensity signal if this is squared.

[0108] As an example, [fig.7] represents the intensity signals, i.e. the amplitude squared, and the phase signals recorded on one of the two detectors present in the detection arm 11, obtained after analysis of the interferometric beats acquired by the electronic acquisition device. These signals are obtained as a function of the angle, i.e. the intensity and the phase of the SPR signal coming from a channel are obtained for a series of angles.

[0109] In this example, the optical chip consisted of a coverslip made of N-BK7 glass metallized with approximately 47nm of gold without a bonding layer. The fluid superstrate consisted of a saline solution (PBS buffer solution) with an index close to 1.334.

[0110] Thus, once the surface to be analyzed is optically positioned, the SPR measurement method in amplitude and phase of the reflected signal as a function of the angle of incidence leading to this type of curve represented in [fig.7] simply consists of analyzing the interferometric beats generated by the device and recorded via the electronic interface for each angle defined via the electronic interface.

[0111] EXAMPLE 3: Reflectometric measurement method using the SPR angular scanning device used in Examples 1 and 2.

[0112] In the two detailed examples of embodiments, measurements were carried out and represented in Figures 6 and 7 respectively. Thanks to this type of curve, sen-sorgrams, i.e. measurements in reflection at a fixed but well-chosen angle, can also be recorded by placing oneself angularly at the maximum sensitivity. Obtaining the best angle in terms of sensitivity is therefore done here thanks to the angular scanning carried out as in Figures 6 and 7. The angular position corresponding to the maximum sensitivity typically corresponds to the angle for which the variation of signal, in intensity or in phase, is maximum. Thus, molecular detection tests in intensity and in phase were carried out for a fixed angle close to 70° determined using [fig.7] (angle for which the intensity is close to 0).For the optical chip described, the choice of this angle made it possible to detect DNA in nanomolar concentration in around ten minutes using complementary DNA fixed to the gold surface of the functionalized optical chip. The same type of measurement can be carried out on a quantity of molecular targets by varying the nature of the functionalized probes on the surface of the biochips.

[0113] Depending on the resonance quality of the biochips used, detection limits of the order of a few micro-RIUs were obtained using the second example device. detailed 200. This evaluation of the detection limit is obtained by circulating liquids of known indices in the microfluidic channels.

[0114] The same approach can be followed to detect various biochemical targets, such as viruses, bacteria, drugs, biomarkers, etc. This detection can be coupled with amplification mechanisms such as cultures in the case of bacteria or gene amplification in the case of DNA or ANR detection.

[0115] The optical properties of the surface to be analyzed within the detection cell, if this surface includes layers of unknown indices and thicknesses, can also be analyzed using the type of curve shown in [fig.7]. For example, the analysis of [fig.7] can lead to the determination of the characteristics of the gold layer such as its thickness and roughness as well as the characteristics of a possible addendum which is useful for characterizing the optical chip before and after interaction with the fluid medium containing the targets of interest. For example, in the case of [fig.7] which also provides a phase measurement informing us about the ellipsometric parameters of the reflected beam, an analysis of this type of curve using a multilayer code adapted to ellipsometry makes it possible to estimate the thickness of the gold layer, which in this case is determined to be equal to approximately 46.5nm as well as the presence on the surface of a rough gold layer of Inm thickness filled to 50%. This type of measurement is then similar to an ellipsometric measurement, that is to say a sensitive measurement of the phase of the p component with respect to the s component, by angular scanning reflectometry. The SPR resonance of the layer makes it possible to amplify the sensitivity of the reflectometric measurement and to characterize very thin layers such as the rough layer mentioned.

[0116] EXAMPLE 4: other examples of embodiment of a scanning SPR device.

[0117] From the examples given above, it follows that the detection system 11 can include a larger plurality of detectors such as a CMOS type matrix detector in order to detect the SPR signal coming from a significantly larger number of functionalized zones within the illumination spot, i.e. within the illuminated zone on the surface of the biochip.

[0118] Also, the incident beam 2 may consist of more parallel incident beams, typically generated within the laser device. In other words, the intensity profile of the beam 2 may have several maxima in order to excite in a preferential manner specific zones in the excitation spot. As indicated, in this case a plurality of detectors may be employed within the detection arm 11 to selectively monitor these different zones.

[0119] According to another embodiment, the thick optic 3 can form an intermediate image located outside the plane Po so as to illuminate the resonant surface with a plurality of angles simultaneously. In this case, the rays propagated according to different angles are collected by a matrix detector within 11. In this case again, the role of the tilting blade 5 is to adjust the average characteristic angle of this plurality of angles

[0120] Also the detection arm 11 may include an imaging system for mapping the resonant optical surface.

[0121] EXAMPLE 5: production of a reflectometric device according to the invention for the ellipsometric characterization of thin layers.

[0122] [Fig. 8] schematically represents a device 101 similar to the device 200, but which does not contain a mirror capable of reducing the size of the device. The device is simpler because it also does not include coupling optics, which have been removed. However, it contains the same emitting device 1 as in the second detailed example, i.e. a laser device for polarization interferometry, the same thick lens 3, the same tilting transparent plate and thick lens 7 and the same detection system as in the second detailed example, i.e. a detector provided with an analysis polarizer. These elements are fixed to a support T22 parallel to the plane of incidence.

[0123] In this example, the target surface is here that of a silicon sample whose surface to be analyzed, here noted Gl, is covered with an oxide layer of initially unknown thickness. This target surface to be analyzed rests on a mechanical support T21, perpendicular to the support T22. The sample being homogeneous, the area of ​​interest is here the location targeted by the beam at the level of the surface GL. This area is therefore here the size of the beam at the level of the surface, i.e. approximately 6mm2. As previously, the targeted area is always the same during the angular scanning. The mechanical support T21 is perforated to allow the radiation beam to pass through and makes it possible to present the surface to be analyzed at an angle close to 71° for an initial position of the transparent blade a=0°. The device thus constitutes a device for a reflectometric measurement in off-axis lighting conditions, adjustable in angle over a range of about ten degrees centered around 71°.The device made it possible to determine the Brewster angle around 75.4° by locating the minimum intensity in the detection system as a function of the angle of incidence. The analysis of the ellipsometric parameter A also made it possible to measure the thickness of the thin oxide layer of approximately 2 nm for an index close to 1.46. The second ellipsometric parameter tanW, very close to zero at the Brewster angle, was also determined in order to constitute a complete variable angle ellipsometer, by incorporating an adjustable polarizer in the emitting device 1 in order to measure the reflected intensity for the two polarization components successively. Other implementations based on the same angular scanning device can be implemented for the same purpose of determining the physical characteristics of thin layers, for example in . separating the polarization components within the detection device.

Claims

Claims

1. A device (100, 101, 200) for measuring the optical response in reflection of at least one area of ​​interest (Z) of a target surface (Fl, Gl) to be analyzed, said measuring device (100, 101, 200) comprising: - an emitting device (1) comprising at least one source of optical radiation and producing an incident beam (2) of this radiation, - an optical system (SO) intended to receive at input said incident beam (2, 4) and comprising a converging lens (7) capable of bending said incident beam (2, 4) into an emergent beam (8) directed towards said target surface (Fl, Gl), said emergent beam (8) being inclined at an angle 0^c relative to the normal of said target surface (Fl, Gl) and - a detection device (11) of an optoelectronic nature for determining, after reflection on said target surface (Fl, Gl), the characteristics of the reflected radiation (10), said device measure (100, 101,200) being characterized in that said optical system (SO) further comprises a tiltable transparent blade (5) crossed by said incident beam (2, 4) and positioned upstream of said converging lens (7), said tiltable transparent blade (5) being capable of being tilted so as to control the movement of said beam (2, 4) crossing it in order to adjust the angle 01NC of the emerging beam (8) of said converging lens (7) while maintaining the same target surface (Fl, Gl).,

2. Measuring device (100, 101, 200) according to claim 1, further comprising at least one additional lens (3) upstream of said tiltable transparent blade (5), said additional lens (3) being capable of adjusting the collimation of the emerging beam (8).

3. Measuring device (100, 101, 200) according to any one of claims 1 and 2, further comprising: - a motor capable of modifying the inclination of said tiltable transparent blade (5), and - an electronic interface making it possible to acquire the signals from said detection device (11) and to control said motor in order to automatically adjust the angle of incidence O^c of the radiation of said target surface (Fl, Gl).

4. Measuring device (100, 200) according to any one of claims 1 to 3, wherein said target surface (F1) is on the surface of a resonant optical chip (C2), which comprises a transparent solid substrate covered with a resonant thin layer sensitive to a fluid superstrate covering it.

5. Measuring device (100, 200) according to claim 4, - which further comprises a coupling optic (Cl) having at least one input face (SI) capable of receiving said emerging beam (8) and an output face (S2) crossed by the reflected beam (10), and - in which said resonant optical chip (C2) is an SPR chip optically coupled to the coupling optic (Cl).

6. Measuring device (100, 200) according to claim 5, in which - the coupling optics (Cl) is a prism of which said entry surface (SI) is planar, and - said converging lens (7), and where appropriate said additional lens (3), are cylindrical.

7. A measuring device (100, 200) according to any one of claims 4 to 6, wherein said resonant optical chip (C2) is functionalized in at least one area in order to detect biomolecular targets circulating in said fluid superstrate.

8. A measuring device (100, 200, 201) according to any one of claims 4 to 7, wherein said emitting device (1) is a laser device for polarization interferometry and wherein an analysis polarizer is arranged at said detection device (11).

9. Method for measuring the optical response in reflection of a target surface to be analyzed, characterized in that it implements the device (100, 101, 200) as defined according to any one of claims 4 to 8, and in that the phase shift of the p component of said radiation after reflection on the target surface (Fl, Gl) is determined relative to the phase of the s component of said radiation after reflection on the target surface.

10. A measuring device (100, 200) according to any one of claims 4 to 7, wherein: said target surface (Fl) to be analyzed comprises multiple areas of interest (Zl, Z2) functionalized to detect biochemical targets; the illumination within the coupling optics (Cl) is collimated, and the detection device (11) comprises a plurality of detectors.

11. Method for optical characterization of a target surface (Gl) comprising a substrate and / or one or more thin layers by angular scanning reflectometry, characterized in that it implements a measuring device (101) as defined according to any one of claims 1 to 2

12. d 3. Use of the method as defined according to claim 11, for biomolecular detection purposes.

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