WO2024099542A1

WO2024099542A1 - Integrated device for spatially offset raman spectroscopy

Info

Publication number: WO2024099542A1
Application number: PCT/EP2022/081161
Authority: WO
Inventors: Adler PEROTTE; Jens Hofrichter
Original assignee: Spiden Ag
Priority date: 2022-11-08
Filing date: 2022-11-08
Publication date: 2024-05-16

Abstract

The SORS detector device comprises a light source assembly (16) having at least one light source (18) and emitting directed from a light emission region (19) along a sampling axis (20) into a sample (22). It further has a semiconductor substrate (12) extending transversally to the sampling axis (20) and comprising a plurality of integrated light detectors (14). The light detectors (14) surround the sampling axis (20) at least in a first detection region (26-1) and in a second detection region (26-2), with the two detection regions (26-1, 26-2) having different offsets from the sampling axis (20). This allows to perform SORS measurements using a simple device design suitable for integration and mass manufacturing.

Description

Integrated Device for Spatially Offset Raman Spectroscopy

Technical Field

The invention relates to a SORS detector device, i.e., to a device adapted and structured to perform Spatially Offset Raman Spectroscopy (SORS) measurements. It also relates to a method for operating such a detector device as well as to a SORS imager having such a detector device and a control unit.

Background Art

Spatially Offset Raman Spectroscopy (SORS) is a Raman spectroscopy technique that allows a depth-resolved analysis of scattering samples. It comprises applying light at a first point of the surface of the sample and receiving Raman- scattered light at several second points of the surface, with the second points being at located at one or more known offsets from the first point, see e.g. Matousek et al., “Subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy”, Appl. Spectroscopy 59(4), 2005, pp. 393ff as well as W02006061565A1.

US9289130B2 describes using fiber bundles for feeding the light to the sample and for collecting the scattered light. The fibers need to be positioned correctly at both ends of the bundle, which makes assembling such devices cumbersome.

Disclosure of the Invention

The problem to be solved by the present invention is to provide an integrated SORS detector device that is easy to manufacture and therefore lends itself to mass manufacturing. This problem is solved by the detector device of claim 1.

Accordingly, the SORS detector device comprises at least the following elements:

- A light source assembly having at least one light source: This assembly emits light from a light emission region along a sampling axis. The light source may be located directly at the emission region, or the light source may be located at a distance from the emission region with further components that provide for the transfer of the light from the light source to the emission region.

- At least one semiconductor substrate extending transversally to the sampling axis and comprising a plurality of integrated light detectors: In other words, there is a plurality of light detectors integrated on this at least one semiconductor substrate. Advantageously, the semiconductor substrate extends perpendicularly to the sampling axis. Even though the substrate will typically be planar, it may also be curved and/or flexible.

The light detectors are arranged around the sampling axis at least in a first detection region, with the first detection region being concentric to the sampling axis.

In this context, advantageously, the sensors of a region are understood to “surround” the sampling axis if, in said region, there are several light detectors, with the largest angular distance between any two adjacent light detectors being less than 180°, in particular less than 150°.

This design is based on providing one or a few semiconductor substrates, with several light detectors integrated on each one of them, and with the light detectors surrounding the sampling axis at several distances. This is a design well- suited for SORS applications while, at the same time, allowing to easily manufacture and position the plurality of sensors in respect to the sampling axis.

In a particularly advantageous embodiment, the light detectors are arranged around the sampling axis at least in a first detection region and in a second detection region, with the two detection regions being concentric and having different offsets, in radial direction in respect to the sampling axis, from the sampling axis. In this context, advantageously.

Advantageously, in a particularly simple design, all the light sensors are integrated on the same semiconductor substrate. In this context, the term “integrated on” is to be understood such that the light sensors may be arranged at or close to a surface of the substrate and/or they may be embedded within the substrate. More specifically, “integrated” refers to the fact that the light source shall be in contact with the detector substrate, potentially through at least one interface layer, and not located remotely or coupled to free space.

Alternatively, though, the SORS detector device may comprise several semiconductor substrates adjacent to each other, with each of the semiconductor substrates having integrated several of the light detectors thereon. The light emission region is located at an interface between the semiconductor substrates. This allows using semiconductor substrates with a smaller number of light detectors. In addition, it provides more space for implementing the light source assembly or parts thereof.

At the location of the light emission region, the detector may comprise an opening extending through the substrate. In this case, the light source assembly is structured to transmit the light from the light source through said opening. This allows placing the light source “behind” or on the backside of the semiconductor substrate^) and to send the probe light through the semiconductor substrate(s). Optionally, a transparent window may be arranged in said opening may, wherein the term “transparent” advantageously indicates that the window has, at the center wavelength of the light from the light source, an optical transmission of at least 50%.

The semiconductor substrate has a front side and a back side, wherein the light detectors are integrated on said front side. In this case, the light source may be located on the back side, which allows to bring the light detectors close to the sample to be probed as there is no stand-off of the light source.

In an alternative embodiment, the light source may be located on the front side of the semiconductor substrate, advantageously mechanically and (optionally, electrically) mounted to the front side. Advantageously, the light source is connected to at least one transistor located within the same semiconductor substrate. In another embodiment, the light source may be embedded in the substrate, either by being integrated therein or by being a separate device placed at least partially in a recess or through-hole of the substrate.

The detector device may comprise one or more optical filters, in particular bandpass or high pass or low pass filters, arranged in front of the detectors for carrying out spectrally selective measurements.

Advantageously, the detector device comprises a plurality of optical bandpass filters with different center wavelengths arranged in front of the detectors. This allows to carry out a spectral analysis of the scattered light. For Raman scattering, at least some of the bandpass filters having a full width at half maximum (FWHM) of less than 5 nm, in particular of less than 1 nm. In addition, the center wavelengths of at least two of these filters advantageously differ by at least 10 nm. For good resolution, on the other hand, the center wavelengths of at least two of the filters advantageously differ by less than 5nm. The wavelength bands of adjacent filters may be at least partially overlapping.

Alternatively, the detector device may comprise a single optical filter, in particular a bandpass filter, covering the light detectors in the first and the second detection region. This design is simpler to implement. It is advantageously combined with a wavelength- tunable light source as described below. The light detectors on the semiconductor substrate may be arranged in a rectangular grid, i.e., at the intersections of a first set of parallel grid lines and a second set of parallel grid lines, with lines of the first set extending perpendicularly to the lines of the second set. This geometry is easy to manufacture. Advantageously, the grid is centered on the sampling axis for performing symmetrical measurements.

In another embodiment, the light detectors may be arranged on concentric circles around the sampling axis. The detectors may be of square, rectangular or circular shape.

In an advantageous embodiment, the light source assembly comprises a wavelength-tunable light source, i.e. a light source the wavelength of which can be tuned by an electronic control signal. This allows to probe the sample at different wavelengths. This embodiment is advantageously combined with a single bandpass filter covering at least the light detectors in the first and the second detection region. Advantageously, the center wavelength of the wavelength-tunable light source is tunable over at least 20 nm. More preferably, the light source is tunable over more than 50 nm. It is preferred that the light source can be tuned over at least 75nm. Advantageously, the light source can be tuned mode-hop free over said wavelength range.

In that case, the light source assembly may further comprise a second, fixed-wavelength light source. Preferably, the second, fixed wavelength light source should be able to be operated in a pulsed mode. Preferably, said light source shall be able to emit pulses shorter than 1 nanoseconds. More preferable, the light source shall be able to emit pulses with a duration of less than 100 ps.

The light sources are structured such that the light of the wave- length-tunable light source and of the fixed-wavelength light source are both emitted along the sampling axis. This allows to perform stimulated Raman (loss and/or gain) measurements as well as any other coherent Raman methods (both stimulated Raman as well as coherent anti-Stokes Raman).

The tunable light source may also comprise a broadband source with a tunable bandpass filter.

Generally, the light source advantageously generates light at least at one wavelength in the “biological window” between 650 nm and 1000 nm where many relevant properties of biological materials can be probed.

The invention also relates to a method for operating this type of detector device. The method comprises at least the following steps:

- Emitting light from the at least one light source along the sampling axis: This light is sent into a sample to be investigated. - Detecting at least one first parameter by measuring Raman-scattered light, i.e. stokes and/or anti-Stokes Raman scattered light, returning from the sample with the light detectors in the first detection region: This parameter is descriptive of Raman scattering at a first offset.

- Deriving at least one sample parameter as a function of the first parameter and the offset of the first detection region to the sampling axis.

This method implements a SORS measurement using the detector device.

Advantageously, the method further comprises

- Detecting at least one second parameter by measuring Raman- scattered light with the light detectors in the second detection region: This parameter is descriptive of Raman scattering at a second offset.

- Deriving the at least one sample parameter as a function of the first parameter, the second parameter, the offset of the first detection region from the sampling axis, and the offset of the second detection region from the sampling axis.

Finally, the invention also relates to a SORS imager having a detector device of this type and a control unit, wherein the control unit is adapted and structured to perform the above method.

Brief Description of the Drawings

The invention will be better understood and objects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings, wherein:

Fig. 1 shows a top view of a first embodiment of a SORS detector device,

Fig. 2 is a sectional view of the detector device of Fig. 1,

Fig. 3 is a sectional view of a second embodiment of a detector device,

Fig. 4 is a sectional view of a third embodiment of a detector device,

Fig. 5 is a sectional view of a fourth embodiment of a detector de- vice, Fig. 6 shows a top view of a light source assembly having a fixed- wavelength light source and a tunable wavelength light source,

Fig. 7 shows a top view of the a SORS detector device having a single filter,

Fig. 8 shows a top view of an embodiment of a SORS detector device having a non-rectangular semiconductor substrate,

Fig. 9 shows a top view of an embodiment of a SORS detector device having two semiconductor substrates,

Fig. 10 is a sectional view of an embodiment of a detector device having a front-side light source assembly,

Fig. 11 shows a top view of a further embodiment of a SORS detector device, and

Fig. 12 is a block diagram of an embodiment of a SORS imager.

Modes for Carrying Out the Invention

Definitions

Terms of the type front, back, in front of, or behind are to be understood such that the light detectors are, by definition, located to detect light arriving from front side of the semiconductor substrate and the light source assembly emits light into the forward (front) direction.

The term angular position of a light detector is its angular position in a cylindrical coordinate system that has the sampling axis as its axial reference vector ax. More specifically, an arbitrary radial reference vector ar perpendicular to ax defines the direction attributed to a zero angle. Any light detector i is described by a radial vector vi perpendicular to ax that starts at ax and ends in the center of the light detector. The angular position of a light detector i is given by the angle between vi and ar.

The term angular distance between two light detectors i, j is the smallest angle between their radial vectors vi, vj.

Introduction

First, some general concepts of the SORS detector device 10 are described by reference to the embodiment of Figs. 1 and 2. It must be noted, though, that these concepts may apply to any embodiments of the detector device. Detector device 10 has at least one semiconductor substrate 12 with a plurality of light detectors integrated thereon. In the following, the light detectors are referred to using reference number 14, and, in addition, they are indexed using a numbering scheme of the type X.Y (see Fig. 1), with X designating the region they are attributed to and Y designating an index within region X.

Detector device 10 further comprises a light source assembly 16 (see Fig. 2) having at least one light source 18 and being adapted to emit the light from a light emission region 19 along a sampling axis 20 into a sample 22 located in front of detector device 10.

Advantageously, light emission region 19 is defined as the region in the plane of the light detectors 14 that light passes on its way along sample axis 20.

The light detectors 14 are located at the front side 30 of semiconductor substrate 12 to receive light scattered from sample 22.

One or more optical bandpass filters 24 may be arranged in front of the light detectors 14, e.g. in order to make them sensitive for a desired wavelength band that only, which e.g. corresponds to a Raman band or fluorescence or other scattering phenomenon. Note that Fig. 1 shows only one such filter 24, but, advantageously, such filters are arranged in front of most or all of the light detectors 14.

As mentioned, the light detectors are attributed to detection regions, the innermost of which are represented by circles 26.1, 26.2, 26.3 in Fig. 1, with each detection region surrounding sampling axis 20. The regions have different offsets ol, o2, o3 from sampling axis 20.

In each detection region 26.1, 26.2, 26.3, there are advantageously at least three light detectors 14 distributed over the angular positions in such a manner that the largest angular distance between any two adjacent light detectors is less than 180°, advantageously less than 150°. If the light detectors are substantially evenly distributed along the angular positions and if there are N light detectors per region, the angular distance between any two neighboring light detectors is approximately 3607N.

Advantageously, in each region 26.1, 26.2, 26.3, the light detectors 14 have substantially the same distance from sampling axis 20, advantageously within an accuracy better than a) 10% or b) the maximum diameter of a single light detector.

Advantageously, the accuracy is better than the larger one of these two values. The light detectors 14 may be arranged, as shown in the example of Fig. 1, in a rectangular grid, which allows for a high density arrangement of light detectors having standard geometries. In the shown embodiment, the grid has the same spacing along both its main directions x and y, which makes it easier to position, in each region, a large number of sensors at substantially the same distance from sampling axis 20.

Semiconductor substrate 12 has a front side 30 and a back side 32. The light detectors 14 are integrated on front side 30 in order to face sample 22.

Back side light source arrangement

There are various possibilities to arrange and design light source assembly 16.

In the embodiment of e.g. Figs. 1 and 2, light source 18 is located at the back side 32 of semiconductor substrate 12.

An opening 34 located at emission region 19 extends through semiconductor substrate 12, coaxially to sampling axis 20, and allows the passage of light from light source 18 through the substrate to sample 22.

Light source 18 of the example of Fig. 2 is shown to be mounted to back side 32 of semiconductor substrate 12, which allows for an accurate and stable positioning in respect to opening 34.

In the shown embodiment, light source 18 is mounted to substrate 12 via solder balls 36 in a flip-chip-type mounting scheme. This type of mounting can be used to feed power to light source 18 as described in the following.

Semiconductor substrate 12 comprises e.g. two conducting vias 38a, 38b extending from front side 30 to back side 32. They are used to conduct electricity from the conducting structures at front side 30 (in particular from the BEOL structures located there) to back side 32. The solder balls 36 are used to connect light source 18 to the vias 38a, 38b. The vias 38a, 38b are used to feed electricity to light source 18.

As shown, at least one of the vias, e.g. first via 38a, may extend through opening 34. The second via 38b may e.g. extend through a separate opening.

Light source 18 may e.g. be a vertical-cavity surface-emitting laser (VCSEL) or a narrow-band LED. It may also be a broadband source; such as an LED, SLED, or supercontinous light source, filtered with a fixed-wavelength bandpass filter, a variable-wavelength bandpass filter, or a monochromator. In the shown embodiment, a lens 40 is located at the location where the light leaves light source 18. Lens 40 is adapted to collimate the light along sampling axis 20, thereby increasing the amount of light transmitted through opening 34 and providing more regular emission characteristics at light emission region 19.

Fig. 3 shows a second embodiment for mounting light source 18 to semiconductor substrate 12. Here, light source 18 has its emission side opposite to the side of its contact pads.

If this type of light source is to be mounted to back side 32 of semiconductor substrate 12, bond wires 42 may used to connect them to the vias 38a, 38b.

Die attach material 44, such as glue or DAF (Die- Attach Film), is used to mechanically mount light source 18 to semiconductor substrate 12.

Light source 18 may again be a VCSEL device.

A suitable VCSEL with integrated lens 40 is, e.g., described in US6888871.

Laser light source with horizontal waveguide

The embodiment of Fig. 4 illustrates yet another type of light source assembly 16 and light source 18 that can be used in the present invention.

This is again a laser-type light source 18 with an active region (i.e. a light amplifying region) 54 arranged between a first reflector 56 and a second reflector 58 for forming a laser cavity. A suitable laser design is e.g. described by N.A. Schilder et al in "850 nm hybrid- integrated tunable laser with Si3N4 microring resonator feedback circuits", Talk ThlE.6, OFC2022

Further, light source assembly 16 comprises a waveguide 60 and an outcoupler 62.

Waveguide 60 forms at least part of the laser cavity and extends horizontally (i.e. parallel to the front and back surfaces 30, 32 of substrate 12) from active region 54 to outcoupler 62, with second reflector 58 being arranged along waveguide 60.

Second reflector 58 as well as outcoupler 62 may e.g. be formed by gratings arranged on and/or in waveguide 60 as known to the skilled person.

In the present embodiment, a hybrid III-V/Si device design is used to implement light source assembly 16. Specifically, at least the active region 54 is arranged in a IILV semiconductor unit 64 in order to exploit the superior light amplification properties of this class of semiconductor. On the other hand, at least part of waveguide 60 is arranged in a silicon unit 66, together with second reflector 58 and outcoupler 62 because of the low-cost, high-quality manufacturing available in silicon.

First reflector 56 may be arranged in III-V semiconductor unit 64 or external to semiconductor unit 64.

In the shown embodiment, III-V semiconductor unit 64 is shown to be located at an edge of silicon unit 66 and use edge-side coupling into waveguide 60. Alternatively, it may e.g. also be integrated on top of silicon unit 66 and use vertical coupling into waveguide 60.

As shown, outcoupler 62 is advantageously arranged on sampling axis 20 beneath opening 34.

Tunable light source

Fig. 5 shows a light source assembly 16 having a wavelength-tunable light source 18.

As mentioned, this type of light source is advantageous for various reasons:

- It can be used to reduce the effort of spectrum analysis on the detector side. Instead of using a comparatively large number of bandpass filters 24 with different center wavelengths in order to analyze the Raman spectrum, the excitation wavelength may be tuned while the detectors are sensitive at one or a few wavelengths only.

- It can be used in combination with a second light source of e.g. fixed wavelength for “Stimulated Raman Gain” (SRG) or “Stimulated Raman Loss” (SRL) measurements as described in more detail in the next section.

In the embodiment of Fig. 5, the wavelength-tunable light source is implemented using a laser similar to the one of Fig. 4. In this case, however, a tuning element 68 is arranged in the laser cavity, advantageously along waveguide 60 between active region 54 and second reflector 58.

Tuning element 68 may e.g. be a Mach-Zehnder or Cascaded Mach- Zehnder or ring resonator or any other phase tuning element suitable to tune the cavity over the desired wavelength range. The tuning mechanism may e.g. be based on thermally- induced refractive- index change or the electro-optic effect, e.g. the Pockels effect.

A laser of the type shown in Fig. 5 is e.g. shown by Schilder et al. in “850 nm hybrid-integrated tunable laser with Si3N4 micro-ring resonator feedback circuits”, ThlE.6, OFC, Optica Publishing Group 2022. The wavelength-tunable light source may advantageously be used in combination with a detector array as shown in Fig. 7, where the same bandpass filter 24 extends over all the detectors. This filter should have a sufficiently narrow full width at half maximum (FWHM) to resolve the Raman spectrum. As above, the FWHM should advantageously be less than 5 nm, in particular of less than 1 nm.

Hence, in one embodiment, the detector device advantageously comprises a single optical bandpass filter 24 extending over at least all the light detectors in the first and second detection regions.

In yet another embodiment, the detector device may comprise two optical bandpass filters, with one of them having a center wavelength above the wavelength range of the tunable light source(s) and the other one below said range. This enables collecting both the Stokes and well as the anti-Stokes spectrum at the same time.

It must be noted that the current device may comprise any number of tunable light sources, i.e. it may e.g. comprise two or more tunable light sources.

Further, the tunable light sources based on tunably filtered broadband light with e.g. acousto-optic tunable filter or liquid crystal tunable filter

Stimulated Raman spectroscopy

Fig. 6 shows the top view of a light source assembly 16 comprising two light sources 18a, 18b, with at least one of the light sources being a wavelength- tunable light source.

In the shown embodiment, light source 18a is a wavelength-tunable light source of the type shown in Fig. 5 while light source 18b is a fixed-wavelength light source of the type shown in Fig. 4.

In the embodiment of Fig. 6 (left part of figure), each light source 18a, 18b has its own outcoupler 62a, 62b, which are arranged adjacent to each other beneath opening 34.

Alternatively, and as also shown in Fig. 6 (right part of figure), the two outcouplers may overlap, e.g. by being arranged behind each other along probing direction 20 or by being formed by two superimposed gratings (as shown), with each grating being oriented to couple out the light from the respective light source. In yet another embodiment (not shown), the light from the waveguides 60a, 60b is combined in a light combiner and subsequently fed to outcoupler 62. A pair of light sources 18a, 18b, with at least one of them being wavelength-tunable, can be used for Stimulated Raman Spectroscopy (SRS) techniques as known to the skilled person, see e.g. https://en.wikipedia.org/wiki/Stimu- lated_Raman_spectroscopy.

In SRS, two light beams with slightly different optical frequencies (i.e. slightly different wavelengths) are sent into the sample. If the energy difference between the photons at the two frequencies corresponds to a vibrational or rotational transition of molecules in the sample, photons at the higher frequency (pump frequency) are absorbed (corresponding to a loss at the respective wavelength) and photons at the lower frequency (Stokes frequency) are generated (corresponding to a gain at the respective wavelength) in a stimulated process of high efficiency.

The method is typically implemented in two variants:

- In Stimulated Raman Gain (SRG) spectroscopy, the light intensity at the lower energy (Stokes wavelength) is detected. To do so, filters 24 at the Stokes wavelength are located in front of at least some of the light detectors 14. These filters are spectrally selective to block the pump wavelength and to only measure Raman scattering in a narrow band. In this case, the intensity of the light source at the pump wavelength is typically amplitude-modulated at an RF frequency, and the signal of the detectors is filtered to only said RF frequency in order to remove the DC signal from the Stokes light source. Alternatively, the light source at the lower wavelength may be scanned (tuned), and the light source at the higher wavelength may be fixed. In that scenario, only a single filter is required as well (at the higher wavelength).

- In Stimulated Raman Loss (SRL) spectroscopy, the light intensity at the higher energy (pump wavelength) is detected. To do so, filters 24 at the pump wavelength are located in front of at least some of the light detectors 14. These filters are spectrally selective to block the Stokes wavelength and to only measure light at the pump wavelength in a narrow band. In this case, the intensity of the light source at the Stokes wavelength is typically amplitude-modulated at an RF frequency, and the signal of the detectors is filtered to only said RF frequency in order to remove the DC signal from the pump light source.

For spectroscopy purposes, at least one of the light sources (pump or Stokes) must be wavelength-tunable.

The light detectors 14 may be adapted to detect the light at the wavelength of the wavelength-tunable light source 18a or at wavelength of the fixed- wavelength light source 18b:

- If the light detectors 14 are to detect the light at the wavelength of the wavelength-tunable light source 18a, there should be several bandpass filters 24 for a plurality of center wavelengths extending over the tuned range of the light source in order to selectively measure the radiation at the wavelength of the wave- length-tunable light source. For example, an array of individual filters as shown in Fig. 2 can be used.

- If the light detectors 14 are to detect the light at the fixed-wave- length light source 18b, a single bandpass filter 24 as shown in Fig. 7 can be used.

In order to perform SRS measurements, the light sources 18a, 18b are advantageously structured to emit light at wavelengths close to each other, namely at wavelengths whose photon energy difference is in the typical range of the rotational and/or vibrational transitions of the molecules to be probed. Advantageously, the wavelength difference between the two light sources 18a, 18b can e.g., be tuned over a range of at least 5 nm to 50 nm. More preferably, the light source can be tuned over a wavelength range of larger than 75 nm. In terms of wave numbers, tuning may extend advantageously over the frequency difference (e.g. Raman shift) of 0 and 1900 wavenumbers (cm ¹), in particular to a frequency difference of at least 3800 cm’ ¹ to include a range of typically important bond types.

For example, wavelength-tunable light source 18a may be adapted emit the Stokes radiation over a tunable range of 800 to 900 nm while fixed-wave- length light source 18b may be adapted to emit pump light at a wavelength of 785 nm.

In another embodiment, there may be more than one tunable source to cover a larger range, and the gap between the two is better characterized by the frequency difference (e.g. Raman shift) of preferably between 0 and 1900 wavenumbers (cm-1) and even better up to 3800 to include a few more important bond types of in- ter-est

Coherent anti-Stokes Raman spectroscopy

The present device can also be used for coherent anti-Stokes Raman spectroscopy (CARS). In this techniques, light of three different wavelengths are sent into the sample, namely at a pump frequency fl, at a Stokes frequency fl, and at a probe frequency f3. Photons at the three frequencies interact with the sample and generate a coherent optical signal at the anti-Stokes frequency fl + f3 - f2, see e.g. https://en.wikipedia.org/wiki/Coherent_anti-Stokes_Raman_spectroscopy.

In this case, advantageously, light source assembly comprises at least two tunable light sources as well as a third (tunable or non-tunable light source).

Similarly, such a device can also be used for Coherent Stimulated Raman spectroscopy (SRS) measurements. Semiconductor substrate design

In the embodiments shown so far, all the light detectors 14 of at least the first and second detection region 26-1, 26-2... are arranged on the same semiconductor substrate 12, and this substrate 12 is shown to be rectangular.

Fig. 8 shows a more compact design of semiconductor substrate 12. Here, the corners of the substrate are cut off and the detectors extend over a smaller area.

In the embodiment of Fig. 8, semiconductor substrate 12 is octagonal. It may, for example, also be hexagonal or circular. In more general terms, the ratio of its maximum diameter Dmax to its minimum diameter Dmin should be less than the one for a square, i.e. Dmax/Dmin < [2, advantageously by at least 10%.

Fig. 9 shows yet another embodiment of detector device 10 having several semiconductor substrates 12a, 12b arranged in coplanar configuration. In this embodiment, there are two such substrates. Optionally (and less advantageous), there may also be e.g. three or four such substrates.

Several light detectors 14 are integrated on each substrate 12a, 12b. The light emission region 19 is located at the interface 70 between the two substrates 12a, 12b.

This design makes it easier to form the opening 34.

Advantageously, the substrates 12a, 12b are arranged edge-by-edge and adjacent to each other in order to form a substantially continuous field of light detectors 14.

At emission region 19, at least one of the semiconductor substrates 12a, 12b comprises a set back edge region for forming opening 34 to extend from the front side to the back side of the substrates 12a, 12b. In the embodiment of Fig. 9, each semiconductor substrate 12a, 12b comprises such a set back edge region 72a, 72b.

It must be noted that the embodiments of Figs. 8 and 9 may also be combined as indicated by dotted lines 74 in Fig. 9. In such an embodiment, Dmax is defined as the maximum diameter of the arrangement of all the semiconductor substrates and Dmin is defined as the minimum diameter of all the semiconductor substrates, with Dmax/Dmin < 2, advantageously by at least 10%. Front-side light source

In the embodiments shown so far, light source 18 is located behind the substrate(s) 12, and opening 34 is provided for the passage of the light towards sample 22.

Alternatively, though, and as shown in Fig. 10, light source 18 may be located at front side 30 of semiconductor substrate 12.

Advantageously, and as shown, light source 18 may be mechanically mounted to front side 30. Such mounting may be implemented by means of solder balls 36, which also allows to electrically connect light source 18 to feed lines integrated in semiconductor substrate 12.

Filter arrangements

As mentioned, in some embodiments, several bandpass filters 24 with different center wavelengths are arranged in front of the light detectors 14.

In order to carry out spectral analysis in each detection region 26-1, 26-2..., each detection region should comprise at least three filters 24 with different center wavelengths. In other words:

- in first detection region 26-1, the filters 24 have at least Mi > 3 different center wavelengths XI 1, X12,... XlMi,

- in second detection region 26-2, the filters 24 have at least M2 > 3 different center wavelengths X21, X22,... X2M2, etc.

Further, in order to carry out spatially offset Raman spectroscopy for the same rotational/vibrational transitions, it should be possible to measure at least some of the same bands in the different detection regions. In the formalism used above, this means that at least three wavelengths of the set of XI 1, X12,... XlMi are equal to wavelengths in the set of X21, X22,... X2M2.

In another, more general, embodiment, at least two of the wavelengths of XI 1, X12,... XlMi are between a pair of wavelengths of X21, X22,... X2M2, and at least two of the wavelengths of X21, X22,... X2M2 are between a pair of wavelengths of XI 1, X12,... XlMi.

Typically, there is more room for light detectors 14 in the outer detection regions 26 than in the centermost detection regions 26. This can be exploited in two ways:

- There may be more light detectors 14 attributed to at least one common center wavelength Xij (i.e. located behind a filter for that center wavelength) in an outer detection region 26 than in an inner detection region 26. This allows to increase the sensitivity at said center wavelength in the outer regions. This is particularly advantageous because outer regions tend to receive less photons than inner regions.

- The number Mi of filters with different center wavelengths may be larger for an outer detection region than for an inner detection region. In other words, if first detection region 26-1 is located closer to sampling axis 20 than second detection region 26-2, then M2 > Mi. This allows to increase the spectral resolution of the outer detection region(s).

The bandpass filters 24 may, as shown in Figs. 1 and 2, be each attributed to one light detector 14 only. Alternatively, at least some of the bandpass filters 24 may extend over several of the light detectors 14. This is illustrated in Fig. 11 .

In this figure, there is a first type of filters 24al... 24a8, each of which extends e.g. over one detector in each of the shown three detection regions 26- 1... 26-3. At least some of this first type of filters may have different center wavelengths.

Then, there is a second type of filters, 24bl... 24b8, each of which extends e.g. over one detector in detection region 26-2 and over two detectors in detection region 26-3. Again, at least some of this second type of filters may have different center wavelengths.

In more general terms, at least some of the bandpass filters 24 may extend over several of the light detectors 14.

Advantageously, at least some of the bandpass filters 24 may extend over light detectors in the first as well as the second detection region. In particular, at least some of the bandpass filters 24 may extend over more light detectors in an outer detection region (e.g. the second detection region) than in an inner detection region (e.g. the first detection region).

It must be noted that the filters may also comprise polarization filters, advantageously overlapping with — or being integrated in — the spectral filters mentioned above. As known to the skilled person, Raman scattering is polarization dependent and a polarization- selective detection can provide information on the symmetry of the involved Raman-active modes, thereby providing additional information on the molecular structure of the probe.

Arrangement of light detectors

Fig. 11 illustrates yet another aspect of the invention. While, in the embodiments of Figs. 1 - 10, the light detectors 14 are arranged on a rectangular grid, the light detectors 14 may also be arranged on circles (corresponding to the circles 26-1... 26-3) as shown in Fig. 11.

In this case, all the detectors in a given detection region 26-1... 26-3 have the same distance from the sampling axis 20, which can provide better spatial resolution when carrying out a SORS measurement.

Spatially offset Raman spectroscopy

As mentioned, the present detector device is adapted to carry out spatially offset Raman spectroscopy (SORS) measurements. To do so, Raman scattering needs to be detected at different offsets from emission region 19, i.e. at different offsets from sampling axis 20. This allows to detect the structure of sample 22 in a direction along sampling axis 20. Techniques for doing so are known to the skilled person and e.g. described by Matousek et al, “Subsurface probing in diffusely scattering media using spatially offset Raman spectroscopy”, Appl. Spectroscopy 59(4), 2005, pp. 393ff as well as on https://en.wikipedia.org/wiki/Spatially_offset_Raman_spec- troscopy and the references cited there.

Fig. 12 shows the block diagram of a SORS imager suited to carry out such a measurement. It comprises a control unit 76, such as a microprocessor, adapted to control the measurement in automated manner by means of e.g. suitable software stored in a memory 78. It is connected to at least one SORS detector device 10 as described above, controls the operation of light source assembly 16 and reads out the signals from the light detectors 14.

In particular, it operates light source assembly 16 to emit light from light source 18 along sampling axis 20 into sample 22. There, the light causes transitions between different vibrational and/or rotational states of the molecules, thereby generating Raman spectra of scattered photons that are indicative of the substances present in sample 22.

The Raman scattering is detected by means of the light detectors 14 in the different detection regions 26-1, 26-2, 26-3.... In particular, a first measurement parameter can be derived by measuring Raman- scattered light returning from sample 22 by means of the light detectors 14 in the first detection region 26-1, and at least a second measurement parameter can be derived by measuring Raman- scattered light returning from sample 22 by means of the light detectors 14 in the second detection region 26-2

Using the signals from the detection regions at the different offsets, control unit 76 can derive at least one sample parameter descriptive of the sample structure. This sample parameter is a function of the measurement parameters as well as of the offsets of the detection regions 26-1, 26-2, 26-3... from sampling axis 30. In particular, the sample parameter may be a function of the first measurement parameter from first detection region 26-1, the second measurement parameter from second detection region 26-2, the offset of first detection region 26-1 from sampling axis 20, and the offset of second detection region 26-2 from sampling axis 20.

In a particularly interesting embodiment, the present invention combines, as described, a SORS measurement with a stimulated Raman spectroscopy (SRS) measurement. In this case, two light sources 18a, 18b are provided to emit light along sampling axis 20, with at least one of the light sources 18a, 18b being wave- length-tunable. In addition, the light detectors 14 are arranged around the sampling axis 20 at least in a first detection region and in a second detection region, with the two regions being concentric and having different offsets from the sampling axis.

In this case, the method comprises the steps of simultaneously sending light from the two light sources 18a, 18b into sample 20 and detecting the first and second parameters for different wavelengths of the wavelength-tunable light source 18a, i.e. while operating the wavelength-tunable light source 18 at these different wavelengths.

It must be noted that, for Raman measurements with good spectral resolution, the light source 18 or the light sources 18a, 18b, respectively, should be narrow-band. Advantageously, the light source(s) has/have a full width at half maximum (FWHM) of less than 5 nm, in particular of less than 1 nm. More preferably, the light source has a spectral bandwidth of less than 100 pm.

The offsets of the various detection regions 26-1, 26-2, 26-3 from sampling axis 20, the diameter of emission region 19, and the diameters of the light detectors 14 define the resolution and range of the measurement within the probe along sampling axis 20.

Advantageously, opening 34 and therefore emission region 19 should have a diameter of less than 1 mm, in particular of less than 100 pm. Typically, the resolution along sampling axis 20 is, at best, about half the diameter of emission region 19.

In order to measure over a range of e.g. 2.5 mm, the offset of the outermost detection region 26 from sampling axis 20 should be at least 5 mm.

The number of differently offset detection regions 26 also affects the spatial resolution along sampling axis 20. Advantageously, the light detectors 14 are arranged around sampling axis 20 at least in three detection regions 26-1, 26-2, 26-3, advantageously more than three such regions, concentric to sampling axis 20 and at different offsets from the sampling axis 20. Having a spatial resolution of 50 p.m or better combined with a range of at least 2.5 mm is advantageous for probing many structures, in particular for probing many biological structures, e.g. in transdermal configuration. Hence, advantageously, the combination of following parameters is used:

- The diameter of emission region 19 should be 100 m or less.

- The offset of the innermost detection region 26 from sampling axis 30 should be less than 500 pm.

- The offset of the outermost detection region 26 from sampling axis 30 should be more than 2.5 mm.

- There should be at least three detection regions 26 at different offsets from sampling axis 20.

The diameters of the individual light detectors 14 should be small enough for good spatial resolution. Advantageously, the light detectors 14 have diameters of less than 75 pm, in particular of less than 15 pm.

Notes

The present invention can be used in a large number of applications where the inner structure of sample 20 is to be explored. Sample 22 may, e.g., be a biologic tissue.

As shown in the above embodiments, sampling axis 20 is advantageously located in the center of the area occupied by the light detectors 14 for obtaining a similar amount of SORS data from all angular positions.

In the embodiments above, the device comprises at least two detection regions 26-1 and 26-2. However, there may also be only a single detection region at a known offset from the sampling axis 20. In that case, at least the “first parameter” can be measured and the sample parameter is derived therefrom, optionally by combining it with further parameters measured in different manner and/or under different conditions.

The technique is particularly suited for non-invasively measuring a parameter of body tissue, such as for detecting the presence and/or amount of a given substance at a given depth beneath the skin. In particular, this technique is suitable of measuring a multitude of biomarkers at depths of the human skin.

While there are shown and described presently preferred embodiments of the invention, it is to be distinctly understood that the invention is not limited thereto but may be otherwise variously embodied and practiced within the scope of the following claims.

Claims

1. A SORS detector device comprising a light source assembly (16) having at least one light source (18) and emitting directed from a light emission region (19) along a sampling axis (20), at least one semiconductor substrate (12) extending transversally to said sampling axis (20) and comprising a plurality of integrated light detectors (14), wherein said light detectors (14) are arranged around the sampling axis (20) at least in a first detection region (26-1), wherein the first detection region (26-2) is concentric to the sampling axis (20).

2. The detector of claim 1 wherein said light detectors (14) are arranged around the sampling axis (20) at least in the first detection region (26-1) and in a second detection region (26-2), wherein the second detection region (26-2) is concentric to the sampling axis (20), and wherein the first detection region (26-1) and the second detection region (26-2) have different offsets from the sampling axis (20).

3. The detector device of any of the preceding claims wherein all the light detectors (14) are integrated on the same semiconductor substrate (12).

4. The detector device of any of the claims 1 or 2 comprising several semiconductor substrates (12a, 12b) adjacent to each other, with each of the semiconductor substrates (12a, 12b) having integrated several of the light detectors (14) thereon and with the light emission region (19) being located at an interface (70) between the semiconductor substrates (12a, 12b).

5. The detector device of claim 4 comprising exactly two semiconductor substrates (12a, 12b) adjacent to each other.

6. The detector device of any of the claims 4 or 5 wherein, at said light emission region (19), at least one of the semiconductor substrates (12a, 12b) comprises a set back edge region (72a, 72b) for forming an opening (34) extending from a front side (30) to a back side (32) of said semiconductor substrates (12a, 12b).

7. The detector device of any of the preceding claims Dmax/Dmin < 2, with Dmax being a maximum diameter of all the semiconductor substrate(s) (12) and Dmin being a minimum diameter of all the semiconductor substrate(s) (12).

8. The detector device of any of the preceding claims further comprising an opening (34) extending through said semiconductor substrate (12) at the light emission region (19), wherein the light source assembly (16) is structured to transmit the light from the light source (18) through said opening (34).

9. The detector device of any of the claims 7 or 8 further comprising at least a first conducting via (38a) extending through the opening (34), wherein the light source (18) is electrically connected to the first via (38a).

10. The detector device of claim 9 further comprising at least a second conducting via (38b) extending through the semiconductor substrate (12), wherein the light source (18) is electrically connected to both the first and the second conducting vias (38a, 38b).

11. The detector device of any of the preceding claims wherein the semiconductor substrate (12) has a front side (30) and a back side (32), wherein the light detectors (14) are integrated on said front side (30) and the light source (18) is located on said back side (32).

12. The detector device of any of the claims 1 to 10 wherein the semiconductor substrate (12) has a front side (30) and a back side (32), wherein the light detectors (14) are integrated on said front side (30) and the light source (18) is located on said front side (30) and/or embedded in the substrate (12).

13. The detector of claim 12 wherein the light source (18) is mounted to the front side (30) of the semiconductor substrate (12).

14. The detector device of any of the preceding claims further comprising at least one optical filter (24) arranged in front of said light detectors (14).

15. The detector device of any of the preceding claims further comprising at least one optical bandpass filter (24) arranged in front of said light detectors (14).

16. The detector device of claim 15 comprising a plurality of optical bandpass filters (24) with different center wavelengths arranged in front of said light detectors (14).

17. The detector device of the claims 2 and 16 wherein, in said first detection region (26-1), the bandpass filters (24) have at least Mi > 3 different center wavelengths XI 1, X12,... XlMi, in said second detection region (26-2), the bandpass filters (24) have at least M2 > 3 different center wavelengths X21, X22,... X2M2, wherein

- at least three wavelengths of XI 1, X12,... XlMi are equal to wavelengths in X21, X22,... X2M2 and/or

- at least two of the wavelengths of XI 1, X12,... XlMi are between a pair of wavelengths of X21, X22,... X2M2 and at least two of the wavelengths of X21, X22,... X2M2 are between a pair of wavelengths of XI 1, X12,... XlMi.

18. The detector of claim 17 wherein, for at least one center wavelength Xij, there are more light detectors (14) attributed to said center wavelength Xij in an outer detection region (26-2) than in an inner detection region (26-1).

19. The detector of any of the claims 17 or 18 wherein said first detection region (26-1) is located closer to the sampling axis (20) than said second detection region (26-2) and wherein M2 > Mi.

20. The detector device of any of the claims 14 to 19 wherein at least some of said filters (24) extend over several of said light detectors (14).

21. The detector device of claim 20 wherein at least some of the filters (24) extend over light detectors (14) in the first as well as in the second detection region (26-1, 26-2).

22. The detector device of the claims 2 and 14 comprising a single bandpass filter (24) covering the light detectors (14) in the first and the second detection region (26-1, 26-2).

23. The detector device of any of the claims 14 to 22 wherein said at least one filter (24) comprises at least one polarizing filter.

24. The detector device of any of the preceding claims wherein said light detectors (14) are arranged in a rectangular grid.

25. The detector device of any of the claims 1 to 23 wherein said light detectors (14) are arranged on concentric circles around the sampling axis (20).

26. The detector device of any of the preceding claims wherein said light source (18) comprises a lens (40) collimating the light along the sampling axis (20).

27. The detector device of any of the preceding claims wherein the light source assembly (16) comprises a light source (18) having a laser having an active region (54), a first reflector (56), a second reflector (58), and an outcoupler (62), a waveguide (60) extending from the active region (54) to the outcoupler (62), wherein the second reflector (58) is arranged along the waveguide (60), a III-V semiconductor unit (64), wherein the active section (54) is arranged in the III-V semiconductor unit (64), and a silicon unit (66), wherein at the second reflector (58), the outcoupler (62), and least part of the waveguide (60) are arranged in the silicon unit (66), wherein the outcoupler (62) is arranged on said sampling axis (20).

28. The detector device of any of the preceding claims wherein the light source assembly (16) comprises a vertical-cavity surface emitting laser.

29. The detector device of any of the preceding claims wherein said light source assembly (16) comprises a first, wavelength-tunable light source (18a).

30. The detector device of claim 29 wherein said light source assembly (16) further comprises a second light source (18b), and in particular wherein the second light source (18b) has a fixed wavelength.

31. The detector device of claim 2 and of any of the claims 29 or 30 further comprising a single optical bandpass filter (24) extending over the light detectors (14) in the first and second detection regions (26-1, 26-2).

32. The detector of any of the preceding claims wherein said light detectors (14) are arranged around the sampling axis (20) at least in three detection regions (26-1, 26-2, 26-3) concentric to the sampling axis (20) and at different offsets from the sampling axis (20).

33. The detector of any of the preceding claims wherein the sampling axis (20) is arranged in a center of an area occupied by the light detectors (14).

34. A method for operating the detector device of any of the preceding claims comprising the steps of emitting light from the at least one light source (18) along the sampling axis (20) into a sample (22), detecting at least one first parameter by measuring Raman- scattered light returning from the sample (22) with the light detectors (14) in the first detection region (26-1) and deriving at least one sample parameter as a function of the first parameter and an offset of the first detection region (26-1) from the sampling axis (20).

35. The method of claim 34 comprising the steps of detecting at least one second parameter by measuring Raman-scattered light returning from the sample (22) with the light detectors (14) in the second detection region (26-2) and deriving the at least one sample parameter as a function of the first parameter, the second parameter, the offset of the first detection region (26-1) from the sampling axis (20), and an offset of the second detection region (26-2) from the sampling axis (20).

36. The method of any of the claims 34 or 35 for operating the detector device of claim 30 further comprising the steps of simultaneously sending light from the first and second light sources (18a, 18b) into the sample (20) and detecting the first and second parameters for different wavelengths of the first, wavelength-tunable light source (18a).

37. A SORS imager having a detector device (10) of any of the claims 2 to 33 and a control unit (76), wherein the control unit (76) is adapted and structured to perform the method of any of the claims 35 or 36.