Parallel magnetic sensing of samples using solid-state spin systems

Abstract

Disclosed herein are a sensor chip for parallel magnetic sensing of multiple samples, a system for parallel magnetic sensing of multiple samples, and a method for probing multiple samples using an optically addressable solid-state spin system. The sensor chip includes an optically transparent substrate with multiple optically addressable solid-state spin systems arranged in multiple sensing regions in a surface layer below a top surface of the substrate. The sensor chip further includes multiple sample sites, each sample site disposed above a respective sensing region. The sensor chip has a light guide system configured to provide an optical path through the substrate connecting each of the sensing regions.

Description

[Technical Field]

[0001] This invention relates to the fields of chemical analysis and medical diagnosis. In particular, this invention relates to the use of an optically addressable solid spin system for multiple samples. parallel Regarding sensor chips for magnetic sensing. [Background technology]

[0002] High throughput of samples parallel Analysis is essential for many applications in chemistry, life sciences, and medicine. Such experiments can be performed, for example, with microfluidic chips containing multiple microfluidic sample wells that can provide and process a large number of samples simultaneously. However, due to the small sample volumes involved, these experiments have so far been limited to highly sensitive detection techniques such as fluorescence spectroscopy or mass spectrometry.

[0003] Nuclear magnetic resonance (NMR) spectroscopy can enable the elucidation of structure at the molecular level and molecular dynamics, as well as quantitative, non-destructive analysis of samples. However, in contrast to the methods described above, NMR spectroscopy typically requires larger samples and expensive equipment, and so far, large-scale sample analysis has been limited. parallel This is hindering the analysis.

[0004] In recent years, the use of quantum technology for various sensing applications has been rapidly advancing. A prominent example is the nitrogen vacancy (NV) center in diamond, described, for example, by R. Schirhagl et al. in Annu. Rev. Phys. Chem. 65, 83-105 (2014) and by A. Boretti et al. in Beilstein J. Nanotechnol. 10, 2128-2151 (2019). These point defects constitute a versatile quantum system exhibiting an atomic energy spectrum with electronic and spin degrees of freedom that can respond to external electric and magnetic fields and can be manipulated with light and microwaves. Therefore, NV centers can be used, for example, as nanoscale magnetometers with optical readout for detecting magnetic fields. This makes it possible to perform NMR spectroscopy in picoliter volumes, as reported, for example, in Nature 555, 351-354 (2018) by DRGlenn et al. and in international publication 2018 / 052497, and to record single-shot magnetic resonance spectra, as described, for example, in international publication 2018 / 128543.

[0005] This approach can, in principle, be extended to multiple samples using, for example, an array of selectively addressable regions, each containing a set of NV centers similar to that described by H. Zhang et al. in npj Quantum Inf.3:31 (2017). However, the laser power required to simultaneously excite NV centers at multiple regions hinders parallel measurements at more than a few regions due to limitations in the power output of available laser sources, the risk of damaging the sample and optical elements with high light intensity, and the high cost and expensive optics associated with high laser power. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] Therefore, an objective of the present invention is to enable high-throughput magnetic sensing of multiple samples using nitrogen vacancy centers while avoiding excessive laser power requirements and preventing damage to the samples. [Means for solving the problem]

[0007] The purpose of this is the plurality of samples described in claim 1 parallel Sensor chip for magnetic sensing, for multiple samples as described in claim 15 parallel The invention is further described in the dependent claims. Embodiments of the invention are described in the dependent claims.

[0008] Multiple samples according to the present invention parallel The sensor chip for magnetic sensing comprises an optically transparent substrate. Multiple optically addressable solid spin systems are arranged in multiple sensing regions within a surface layer beneath the upper surface of the substrate. The sensor chip further comprises multiple sample areas, each of which is positioned above its respective sensing region. Furthermore, the sensor chip includes a light guide system configured to provide an optical path through the substrate, connecting each of the sensing regions.

[0009] A solid spin system is a quantum system with spin degrees of freedom located or embedded within a solid host material, where these spin degrees of freedom can be read out and / or manipulated via optical transitions. A spin system can be, in particular, an object that behaves like an artificial atom or molecule, i.e., a system exhibiting an atom or molecule-like energy spectrum and having at least two distinct spin states. A spin system can be, for example, an optically active defect in a crystal structure. The energy levels of different spin states can shift in the presence of a magnetic field. Furthermore, a spin system can have, for example, spin-state dependent transition rates between different states of the spin system, such as the electronic states of the spin system. Therefore, a solid spin system can be used as a probe for a magnetic field, for example, by determining the energy difference and / or transition rates between the states of the spin system.

[0010] The solid spin system is located in a sensing region situated in the surface layer beneath the upper surface of the substrate. The surface layer can have a thickness perpendicular to the upper surface, for example, 2 μm to 1000 μm, or in one example, 10 μm to 100 μm. In some examples, the surface layer can form at least partially the upper surface of the substrate. In other examples, one or more additional layers, such as optical coatings and / or well layers detailed below, can be placed between the surface layer and the upper surface. In some examples, the spin system may be confined to the sensing region, while in other examples, as detailed below, the spin system may be dispersed throughout the entire surface layer. In one example, the sensing region may extend through the entire substrate perpendicular to the upper surface, i.e., the depth of the sensing region / surface layer perpendicular to the upper surface may be equal to the thickness of the substrate.

[0011] At least a portion of the substrate is optically transparent, particularly at wavelengths related to one or more transitions in the spin system, for example, at absorption wavelengths related to excitation from a stable or metastable state of the spin system, and / or at emission wavelengths related to decay from a metastable or short-lived state of the spin system. In some examples, the substrate may be transparent at least across the entire visible and / or near-infrared spectrum, for example, from 400 nm to 1600 nm.

[0012] Each sample area is positioned on one of the sensing regions. The sample area may be, for example, a microfluidic sample well and may be configured to receive, for example, liquid and / or solid samples, such as minute droplets of the sample fluid. The sample fluid may contain, for example, one or more substances dissolved therein. Additionally or alternatively, the sample area may be, for example, a hydrophilic region, such as a region on the surface of a sensor chip and / or a substrate having a hydrophilic coating. Preferably, the region adjacent to the sample area is hydrophobic and may include, for example, a hydrophobic coating to confine minute droplets of the sample fluid within the hydrophilic sample area. In some examples, the size of the sample area in a plane parallel to the top surface may be adapted to the size of the sensing region, for example, so that the sidewalls of the sample wells are aligned with the boundaries of the respective sensing regions. Each sample area may have a width or diameter parallel to the top surface, for example, 2 μm to 500 μm. The sample well may contain a volume of, for example, 1 picoliter to 1 microliter. In some embodiments, two or more sample wells can be connected to each other, for example, to provide and / or remove sample fluid from the sample wells, and / or the sample wells can be connected to or part of a microfluidic system. In preferred embodiments, the sample areas and sensing regions are arranged in a regular pattern, for example, in a periodic one-dimensional or two-dimensional array with constant spacing between areas, as detailed below.

[0013] The light guide system is configured to provide an optical path between sensing regions such that light propagating along the optical path passes through each sensing region sequentially at least once. In other words, all sensing regions are positioned along the optical path provided by the light guide system. The light guide system may be configured in particular to provide an optical path between sensing regions for light of one or more absorption wavelengths of a spin system. Preferably, light propagating along the optical path passes through each sensing region the same number of times, for example, once. In some examples, part of the optical path may be outside the substrate. The light guide system may include one or more optical elements that modify the propagation of light along the optical path, in particular, such as reflective structures, optical coatings, and / or waveguides.

[0014] In some embodiments, at least two segments of the optical path are not parallel to each other, for example, due to reflection from a reflective element of the optical guide system, or due to a curved or bent portion of the waveguide element of the optical guide system. Each of the non-parallel segments may be located or extend between two or more sensing regions, in particular. The non-parallel segments may be within the substrate, or at least partially outside the substrate. In some examples, the optical path may further comprise one or more sets of parallel segments. The optical path may form periodic patterns, such as zigzag patterns and / or meandering patterns, for example, in one or more planes, for example, in planes perpendicular or parallel to the upper surface of the substrate. In some examples, the optical path may form non-intersecting patterns, in particular non-intersecting periodic patterns.

[0015] By providing an optical path connecting each sensing region, the light used to address the spin system can be reused across multiple sensing regions, thereby enabling the manipulation and measurement of numerous samples without requiring excessive light output. For example, the laser pulse for exciting the spin system may be coupled to the optical path or pass through each sensing region sequentially. Typically, the proportion of light absorbed by the spin system within a given sensing region is negligible, so similar excitation probabilities can be achieved in all sensing regions. Furthermore, the light guide system may be configured to minimize overlap between the laser pulse and the sample placed at the sample site, thereby reducing the risk of damaging the sample or interfering with it in another way. In addition, the optical path provided by the light guide system may be designed such that illumination of a sensing region does not interfere with detection of an optical signal from that sensing region, and vice versa, as detailed below.

[0016] The light guide system comprises one or more optical elements. In some embodiments, the light guide system may comprise, for example, one or more reflective coatings. The reflective coatings may be located, for example, on the top surface of the substrate, the bottom surface of the substrate opposite the top surface, and / or on one or more sides of the substrate extending between the top and bottom surfaces. The reflective coatings may be particularly reflective at one or more absorption wavelengths of the solid spin system. The reflective coatings may extend, for example, across the entire surface or a portion of each surface of the substrate. Additionally or alternatively, the reflective coatings may be located over specific areas on the surface of the substrate, for example, over a sensing area on the top surface. Preferably, the optical path is limited to the volume between the top and bottom surfaces of the substrate, or the volume between planes including at least the top and bottom surfaces. In some examples, the reflective coating on the top surface may have a magnetic susceptibility between that of the substrate and that of the sample. The reflective coating may, in particular, have a magnetic susceptibility between that of diamond and that of water.

[0017] In some embodiments, the propagation of light along the optical path may also include one or more total internal reflections on the surface of the substrate, i.e., the light guide system may be configured such that the angle of incidence of the optical path on each surface is greater than the critical angle of total internal reflection. Additionally or alternatively, the light guide system may also include one or more reflective elements located outside the substrate, e.g., micromirrors mounted on the frame of the sensor chip on which the substrate is attached. In some examples, the reflective elements outside the substrate may be adjustable, e.g., tiltable around one or two axes.

[0018] For example, illumination schemes for solid spin systems involving multiple reflected optical paths have already been used in other contexts to separate illumination and detection paths for probing a single sample having an assemblage of NV centers, as reported by DRGlenn et al. in Nature 555, 351-354 (2018) and in International Publication No. 2018 / 052497. Furthermore, such “folded” paths can also enable uniform illumination of bulk diamond substrates (see, for example, U.S. Patent Application Publication No. 2019 / 0145919 and Micromachines 9, 276 (2018) by L. Bougas et al.).

[0019] In a preferred embodiment, the light guiding system includes a dichroic reflection coating and / or a broadband reflection coating. The dichroic reflection coating is configured to reflect light at the absorption wavelength of the solid spin system and transmit light at the emission wavelength of the solid spin system. The broadband reflection coating is configured to reflect light at the absorption wavelength and the emission wavelength of the solid spin system. Preferably, the dichroic reflection coating is disposed on the bottom surface of the substrate, and the broadband reflection coating is disposed on the top surface of the substrate. In this way, the light at the absorption wavelength propagating along the optical path can be reflected, for example, at the bottom and top surfaces of the substrate, which can reduce the amount of light leaking through the top surface to the sample on the sample site and the amount of light leaking through the bottom surface to the detection path. The light emitted by the spin system in the sensing region at the emission wavelength is detected through the bottom surface while being reflected from the top surface, thereby enhancing the amount of light that can be collected for detection.

[0020] In some embodiments, the light guiding system includes one or more retroreflective structures, each of which includes two or more inclined surfaces configured to retroreflect a light beam propagating through the substrate along the optical path. The retroreflective structure may be disposed particularly on the side surface of the substrate, or may be formed by the side surface of the substrate, or may be disposed adjacent to the side surface of the substrate, for example, on the frame of the sensor chip. The light guiding system may include, for example, retroreflective structures on two opposite side surfaces of the substrate or adjacent thereto. In one example, the retroreflective structure includes two mutually orthogonal surfaces configured to displace the incident beam and retroreflect the incident beam. The orthogonal surfaces may form angles of +45° and -45°, respectively, with respect to the normal vector of the side surface of the substrate. In some examples, one or both of the inclined surfaces may be coated with a reflective coating, for example, as described above. In other examples, the orientation of one or both of the inclined surfaces with respect to the optical path may be such that light is reflected by total internal reflection.

[0021] In a preferred embodiment, the light guiding system comprises one or more focusing elements configured to refocus a light beam propagating along an optical path. The focusing elements may be arranged between sensing regions along the optical path such that light propagating between the sensing regions along the optical path passes through or is reflected from the focusing elements. The focusing elements can comprise, for example, a lens or a curved surface from which the light beam is reflected, such as a curved surface on the surface of a substrate. In one example, one or both of the inclined surfaces of the retroreflective structure may be curved. In some examples, part or all of the focusing elements may also be arranged outside the substrate, such as a microlens or a curved micromirror attached to the frame of a sensor chip to which the substrate is attached. By using the focusing elements, it may be possible to maintain a substantially constant beam diameter along the optical path. In one example, the one or more focusing elements may be configured such that the beam diameter varies by less than 50%, preferably less than 20%, in various sensing regions.

[0022] In some embodiments, the light guiding system comprises a waveguide, particularly a waveguide within a substrate, configured to guide a light beam along an optical path or a part thereof. The waveguide may be configured to confine light, for example, in one or more optical modes extending along the optical path or a part thereof. Preferably, the waveguide is a multimode waveguide capable of carrying a number of optical modes. The light guiding system may comprise, for example, a one-dimensional waveguide configured to confine light propagating along the optical path in one direction, for example perpendicular to the upper surface of the substrate. In one example, the thickness and / or refractive index of the substrate may be selected such that the upper and lower surfaces of the substrate and / or a cladding layer disposed thereon form a one-dimensional planar waveguide. For this purpose, the thickness of the substrate may be, for example, between 10 μm and 30 μm. Additionally or alternatively, the substrate may comprise one or more reflective coatings for forming the waveguide. Light propagating along the optical path can propagate simultaneously in many modes of the waveguide, for example via an "infinite" number of reflections from the bottom and top surfaces of the substrate.

[0023] In some embodiments, the light guide system comprises a two-dimensional waveguide configured to confine light propagating along the optical path in two orthogonal directions, and the waveguide can form at least a portion of the optical path. Preferably, sensing regions are formed within the waveguide, for example, at equal intervals along the waveguide. The waveguide may be formed within a substrate, for example, by appropriate structuring of the bottom and / or top surfaces of the substrate. In some examples, the substrate may be a composite substrate containing a carrier material in which the waveguide is arranged or embedded. The waveguide may include at least one bent portion and may extend along a meandering path including, for example, a plurality of parallel segments connected by the bent portion. In one example, the light guide system may comprise a plurality of two-dimensional waveguides extending parallel to each other.

[0024] In a preferred embodiment, the sensor chip further comprises a plurality of immersion lenses, which may be located, for example, on the bottom surface of the substrate. Preferably, each of the immersion lenses is located beneath its respective sensing region to collect, for example, light emitted by a spin system within its respective sensing region. In some embodiments, light propagating along the optical path may be reflected at the surface on which the immersion lenses are located, and the immersion lenses may be positioned between reflection points so as not to cover the reflection points. The immersion lenses may consist of or include a material having the same refractive index as the substrate or a higher refractive index than the substrate, and may be, for example, hemispherical or Weierstrass immersion lenses. In some embodiments, the immersion lenses are formed by the bottom surface of the substrate, which may be structured accordingly. By guiding light along the optical path through the substrate using a light guide system, the immersion lenses can be used to improve the collection efficiency of the imaging system for detecting optical signals from the sensing region without obstructing illumination of the sensing region. This may be particularly advantageous for substrates containing high refractive index materials such as diamond, where collection efficiency may be limited due to the small critical angle of total internal reflection.

[0025] In some embodiments, the sample area may be a microfluidic sample well. One or more walls of each sample well may be formed by the substrate, particularly the bottom wall of each sample well. This may be advantageous in minimizing the distance between the sample placed in the sample well and the respective sensing region in order to facilitate interaction with the spin system. In some examples, the sample well may be formed entirely on the upper surface of the substrate, i.e., a recess or notch in the upper surface. In other examples, the sample well may be formed within a well layer placed on the upper surface of the substrate. The well layer may be completely removed over the sensing region, for example, so that the upper surface of the substrate forms the bottom wall of the sample well and the well layer forms the side wall of the sample well. In other examples, the well layer may be partially removed over the sensing region, for example, so that a thin well layer remains on the upper surface of the substrate forming the bottom wall of the sample well. The thin well layer can, for example, protect the sample from evanescent light leaking from the substrate and may have a thickness of, for example, 0.1 μm to 1 μm. In some examples, the well layer may contain an opaque material, which can facilitate the separation of light emitted by adjacent sensing regions when imaging through the upper surface. Preferably, the well layer includes a material having a magnetic susceptibility that matches the magnetic susceptibility of the sample, for example, a magnetic susceptibility between that of the substrate and that of the sample. In particular, the well layer may have a magnetic susceptibility between that of diamond and that of water.

[0026] In a preferred embodiment, the sensing regions are arranged in a two-dimensional array on the surface layer of the substrate. The array may be, for example, a periodic array, and the sensing regions may form, for example, rectangles or a quadratic grid with regular spacing. In other examples, the array may be aperiodic.

[0027] Preferably, the distance between adjacent sensing regions and / or sample areas is at least twice, in one example at least five times, the width or diameter of each sensing region and / or sample area in a plane parallel to the upper surface. In one example, the distance between areas is 2 to 20 times the width of the sample area. The width of the sensing region may be the same as the width of the sample area, for example, 2 μm to 500 μm. In one example, the width of the sensing region and / or sample area is the same as the thickness of the surface layer.

[0028] In some embodiments, the solid spin system is arranged across the entire surface layer of the substrate. In some examples, the density of the spin system may be uniform across the entire surface layer. In other examples, the density of the spin system may be uniform in a plane parallel to the top surface of the surface layer, or it may vary as a function of depth from the top surface. In one example, the substrate may be grown, for example, by chemical vapor deposition (CVD) of carbon, and the surface layer may be formed by adding one or more additional materials, such as nitrogen, to the CVD gas mixture.

[0029] In other embodiments, the solid spin system may be limited to a portion of the surface layer, particularly the sensing region. In some examples, the density of the solid spin system in the substrate outside the sensing region is at least 100 times, preferably at least 1000 times, lower than the density of the solid spin system within the sensing region.

[0030] In embodiments where the spin system is arranged across the entire surface layer, the sensing region may be the region around the intersection between the optical path and the surface layer, i.e., the region where the spin system can be excited by light propagating along the optical path. Therefore, the optical path does not intersect the surface layer outside the sensing region. Light propagating along the optical path is reflected, for example, from the upper surface of the substrate beneath each sample area, thereby defining the corresponding sensing region. The size of the sensing region may be determined by a predetermined beam profile, for example, a predetermined beam diameter, which may be, for example, 10 μm to 100 μm.

[0031] In embodiments where the spin system is confined to the sensing region, the optical path may have a similar shape and may not intersect the surface layer outside the sensing region, for example, due to reflection from the upper surface of the substrate beneath the sample area. In other examples, the optical path or at least a portion thereof may extend parallel to the upper surface or at a small angle with respect to the upper surface, e.g., an angle of less than 5°, in one example, an angle of less than 2°. The optical path or a portion thereof may, in particular, correspond to, for example, half the thickness of the surface layer, i.e., it may extend into the surface layer between sensing regions, for example, at a certain depth below the upper surface, such that the optical path extends at least partially within the central plane of the surface layer.

[0032] In preferred embodiments, the substrate contains or consists of diamond, and the solid spin system is the color centers of the diamond, i.e., optically active point defects within the diamond crystal structure. Preferably, the spin system is nitrogen vacancy (NV) centers in the diamond, particularly negatively charged nitrogen vacancy centers.

[0033] In some embodiments, the sensing regions may form a first set of sensing regions, and the substrate may have at least a second set of sensing regions in the surface layer below the upper surface. The light guide system may be configured to provide a first optical path through the substrate connecting each sensing region in the first set, and a second optical path through the substrate connecting each sensing region in the second set. In some embodiments, at least one of the first and second optical paths may have two non-parallel segments. In some examples, the light guide system may include a beam splitter, such as a polarizing or unpolarizing beam splitter, that splits the incident optical path into the first and second optical paths. In one example, the substrate has a plurality of sets of sensing regions in the surface layer below the upper surface, and the light guide system is configured to provide a respective optical path through the substrate for each set, the optical paths connecting each of the sensing regions in each set.

[0034] The present invention further involves using a sensor chip to measure multiple samples parallelA system for magnetic sensing is provided, comprising an optically transparent substrate having multiple optically addressable solid spin systems arranged in multiple sensing regions in the surface layer below the upper surface of the substrate. The system according to the present invention comprises an illumination system and a mount configured to receive the sensor chip. The illumination system is configured to excite solid spin systems in the sensing regions by coupling a laser beam generated by a laser source to an optical illumination path through the substrate, the illumination path sequentially intersecting each of the sensing regions.

[0035] The mount may be configured to receive the sensor chip according to the present invention as described above, and the illumination path may be an optical path provided by the light guide system of the sensor chip. Thus, the illumination system may be configured to couple an incident laser beam to the optical path of the sensor chip via an incident facet or port which may be located, for example, on the side of the substrate. The mount may be configured to hold and / or adjust the sensor chip so that the incident facet of the substrate aligns with the output port of the illumination system.

[0036] Additionally or alternatively, the mount may also be configured to accept other sensor chips, for example, sensor chips without a light guide system. Such sensor chips may, for example, comprise a slab-like substrate without a reflective coating, retroreflective structure, and / or waveguide. The illumination system may be configured, for example, to couple a laser beam to the substrate such that the laser beam undergoes total internal reflection on the top, bottom, and / or sides of the substrate, thereby sequentially illuminating each sensing area. In another example, the illumination system may be configured to couple a laser beam to the substrate such that the laser beam propagates along a straight line parallel to the surface of the substrate, for example, parallel to the top surface. On the top surface of the substrate, multiple samples may be placed adjacent to the sensing area, for example, in multiple sample locations above the sensing area as described above.

[0037] The illumination system may include, for example, an alignment subsystem having one or more adjustable optical elements, particularly adjustable mirrors, for coupling a laser beam to an illumination path. In some embodiments, the illumination system may further include a beam shaper configured to adjust the beam diameter, intensity profile, phase pattern, pulse energy, and / or pulse length of the incident laser beam, as detailed below, for example.

[0038] In a preferred embodiment, the illumination path comprises at least two segments that are not parallel to each other, for example, as described above for the sensor chip according to the present invention. In particular, the light propagating along the illumination path may be sequentially reflected from the top surface of the substrate near each sensing area, i.e., the laser beam propagates through the sensing areas one after another. The laser beam may be reflected from the top surface below a sample area, such as a sample well on the top surface. In another example, the illumination path may include a single reflection from the top surface, for example, the center of the top surface. Two non-parallel segments of the illumination path connected by a single reflection may extend at a small angle with respect to the top surface so that the illumination path passes through each of the sensing areas. The angle with respect to the top surface may be, for example, 0° to 5°, or in one example, 0° to 2°. Additionally or alternatively, the laser beam propagating along the illumination path may also be reflected from a surface perpendicular to the bottom surface and / or top surface of the substrate and / or parallel to the side surface of the substrate. In some examples, the laser beam may be sequentially reflected from each surface. The laser beam may be reflected from the sides of the substrate, for example, perpendicular to the top surface or at an angle of 85° to 95° with respect to the top surface. Additionally or alternatively, the laser beam propagating along the illumination path may also be reflected by reflective elements located outside the substrate and / or outside the sensor chip. In some examples, the reflective elements outside the substrate may be adjustable, for example, tiltable around one or two axes. In some embodiments, at least one, in some examples all, of the reflections along the illumination path are due to all internal reflections at one or more surfaces of the substrate. Additionally or alternatively, the surfaces of the substrate may have reflective coatings, for example, as described above. Preferably, the illumination path is limited to the volume between the top and bottom surfaces of the substrate, or the volume between planes including the top and bottom surfaces.

[0039] In some embodiments, the illumination system is configured to couple a laser beam to a waveguide in a substrate that forms at least a portion of the illumination path, as described above. For this purpose, the illumination system may include focusing elements, such as lenses, for focusing the incident laser beam onto the incident facet of the waveguide. The waveguide may be a one-dimensional planar waveguide formed by the top and bottom surfaces of the substrate, or a two-dimensional waveguide formed within the substrate. Preferably, the waveguide is a multimode waveguide that carries a number of optical modes, and the light propagating along the illumination path can propagate simultaneously in many modes of the waveguide, for example, through an "infinite" number of reflections from the bottom and top surfaces of the substrate. The thickness of the substrate may be, for example, 10 μm to 30 μm, and may be similar to the diameter of the laser beam in the incident facet.

[0040] In some embodiments, the illumination path can form a periodic and / or non-intersecting pattern in a plane parallel to the upper surface of the substrate, as described above. The illumination path can, in particular, comprise one or more sets of parallel segments, which can form, for example, a zigzag pattern and / or a meandering pattern.

[0041] In a preferred embodiment, the illumination system comprises one or more focusing elements, such as lenses and / or curved reflective surfaces, along the illumination path, configured to refocus a laser beam propagating along the illumination path. The illumination system may, for example, be configured to maintain the diameter of the laser beam along the illumination path. The focusing elements may, in particular, be positioned between sensing regions along the illumination path. In some embodiments, the focusing elements may be located outside the substrate and / or sensor chip, for example, on a mount for the sensor chip. Additionally or alternatively, the focusing elements may be part of the sensor chip, for example, formed by or positioned on the side of the substrate, as detailed above.

[0042] In some embodiments, the illumination system includes a beam shaper configured to adjust the beam diameter, intensity profile, phase pattern, pulse energy, and / or pulse length of the incident laser beam. The beam shaper may, in particular, be configured to convert a laser beam, which may be, for example, a Gaussian beam, into a Bessel beam, i.e., a beam having an intensity profile corresponding to the square of a first type of Bessel function. This may allow the diameter of the laser beam to be maintained along the illumination path due to the non-diffraction propagation of the Bessel beam. For this purpose, the illumination system may include, for example, a reflection axis or a refraction axis.

[0043] In some embodiments, the sensing regions may form a first set of sensing regions, and the sensor chip may have at least a second set of sensing regions, and in some examples, multiple sets of sensing regions. The illumination system may be configured to couple a laser beam to each illumination path for each set of sensing regions, the illumination paths sequentially intersecting each of the sensing regions in each set. The laser beams may be generated by different laser sources or the same laser source. In a preferred embodiment, the illumination system may include a beam splitter, which may be configured to couple, for example, a laser beam generated by a laser source to a first illumination path that sequentially intersects each of the first set of sensing regions and a second illumination path that sequentially intersects each of the second set of sensing regions. In one example, the illumination system includes multiple beam splitters for coupling a laser beam generated by a laser source to multiple illumination paths. Preferably, the beam splitters are configured to evenly divide the laser beam between the illumination paths, i.e., the optical output is the same in each illumination path.

[0044] In a preferred embodiment, the system further comprises an imaging system configured to collect light emitted by a solid spin system within a sensing region. The imaging system may comprise an objective lens configured to image light emitted from the sensing region onto a detector, for example, through the top or preferably bottom surface of the substrate. Additionally or alternatively, the imaging system may comprise a detection light guide or waveguide positioned adjacent to or in contact with the substrate to collect the emitted light, for example, one detection light guide below each sensing region. Each detection light guide may comprise, for example, a fiber bundle or a large-diameter multimode fiber, for example, a multimode fiber having a core diameter greater than 200 μm. In some examples, the detection light guide may be part of the sensor chip, and the illumination system may be configured to collect light emitted from the detection light guide.

[0045] Preferably, the imaging system is configured to simultaneously determine the intensity of emitted light for each of the sensing regions. The illumination system may include a detector, for example, a multi-channel photodetector having independent channels for each of the sensing regions. The multi-channel photodetector may include, for example, a plurality of photodiodes, e.g., an array of photodiodes, and / or an extended photodetector, e.g., a CCD or CMOS camera, having a plurality of independently readable detection regions. In one example, the multi-channel photodetector may be a lock-in camera configured to determine a differential signal by subtracting the signals of two subsequent measurements, preferably before the analog-to-digital conversion of the signal. Preferably, the imaging system is configured to synchronize with one or more other elements of the system, or devices connected to the system, e.g., a laser source and / or a microwave generator. The detector may be configured, for example, to receive a trigger signal and initiate the determination of the intensity of emitted light. In some embodiments, the detector or imaging system may include one or more additional focusing elements, e.g., a respective microlens associated with each channel of the multi-channel photodetector. In one example, the multi-channel photodetector may have two or more channels for each sensing region.

[0046] The system according to the present invention may further include additional elements for, for example, performing nuclear magnetic resonance (NMR) spectroscopy. The system may include, for example, a microwave antenna, such as a wire antenna, a coil antenna or a horn antenna, or a microwave resonator for applying a microwave signal to a substrate and / or a plurality of samples. Preferably, the microwave antenna or resonator is configured to apply a microwave signal having a uniform amplitude across the entire substrate and / or in each of the samples. The microwave antenna or resonator may be configured to be connected to a microwave generator, which may also be part of the system or provided as a separate unit. The microwave generator may, in particular, be configured to generate a series of microwave pulses. Preferably, the system is configured to synchronize the microwave generator with a laser source and a detector, for example, to apply a series of microwave pulses having a predetermined time delay with respect to the laser pulse generated by the laser source and / or the detection interval of the detector. In some examples, the microwave antenna or resonator may also be configured to apply a radio frequency signal to the substrate and / or a plurality of samples. In other examples, the system may further include a radio frequency antenna or resonator configured to apply a radio frequency signal to a substrate and / or multiple samples.

[0047] The system may further include magnets for applying a bias magnetic field to the substrate and / or multiple samples. Preferably, the magnets are configured to apply a bias magnetic field having a uniform magnetic field strength across the entire substrate and / or in each of the samples. In some examples, the magnets may be configured to apply a bias magnetic field with an adjustable magnetic field strength. The magnets may include, for example, one or more coils, such as a pair of Helmholtz coils, configured to be connected to a current source for generating the bias magnetic field. In some examples, the magnets and / or mounts for the sensor chips may be configured to adjust the direction of the magnetic field relative to the substrate, for example, by aligning the direction of the magnetic field with the crystal axis of the substrate. In one example, the magnets are permanent magnets, such as rare-earth magnets such as neodymium (NdFeB) magnets.

[0048] In some examples, the system may also include a laser source configured to generate a laser beam for the lighting system. In other examples, the laser source may be provided as a separate unit. In some embodiments, the system may further include one or more sensor chips, in particular a sensor chip according to one of the embodiments described above.

[0049] The present invention further provides a method for probing multiple samples using optically addressable solid-state spin systems. The method includes (1) preparing samples on a sensor chip having an optically transparent substrate, wherein the solid-state spin systems are arranged in a plurality of sensing regions in the substrate, and each sample is arranged adjacent to each of the sensing regions; (2) simultaneously exciting the solid-state spin systems in each sensing region by illuminating the sensing regions with light propagating along an optical illumination path through the substrate connecting each sensing region; and (3) detecting the optical signal emitted by the solid-state spin system in each sensing region for each sensing region. The numbering of the above steps is for clarity only and does not imply a specific order of execution. Where technically feasible, the method may be performed in any order, and the steps may be performed at least partially simultaneously.

[0050] This method can be performed, for example, using a system according to the present invention and / or a sensor chip according to one of the embodiments described above. Therefore, the illumination path can correspond to the illumination path of the system and / or the optical path of the sensor chip described above. The sample may be a solid and / or liquid sample, for example, a microdroplet of a sample fluid. The step of preparing the sample may include the step of placing the sample on the surface of a substrate, for example, placing the sample on the upper surface above each of the sensing areas, such as the corresponding sample portion in the corresponding sample well.

[0051] The sensing region may be illuminated, for example, by coupling one or more optical pulses, particularly laser pulses, to an illumination path such that each optical pulse sequentially passes through each of the sensing regions. The wavelength of the light can be adjusted, for example, to the absorption wavelength of the spin system. The diameter of the optical pulse can be adjusted, for example, to the size of the sensing region and / or sample using the illumination system of the system according to the present invention. Illumination of the sensing region along the illumination path can be used, in particular, to optically polarize the spin system within the sensing region and / or to excite the spin system within the sensing region in order to induce a detected optical signal, i.e., for optical readout. The intensity and / or pulse duration of the optical pulses may be selected, for example, so that the spin system is prepared to a predetermined quantum state. In some examples, the intensity and / or pulse duration may be selected so that the spin system within the sensing region undergoes multiple transitions, for example, to increase the fluorescence intensity and / or for optical polarization of the spin system, i.e., to optically excite the spin system to a predetermined state. In other examples, the intensity and / or pulse duration may be selected such that the excitation probability of the spin systems within the sensing region reaches a predetermined value or exceeds a predetermined threshold, for example, at least 50% or at least 90%, and in one example, at least 99% of the spin systems transition to the excited state. In a preferred embodiment, the sensing region is illuminated multiple times, for example, a first time for optical polarization and a second time to induce the optical signal to be detected. At least one, preferably both, of the illuminations are produced by light propagating along the illumination path.

[0052] For each sensing region, an optical signal emitted by the spin system within that sensing region is detected. Preferably, the optical signals are detected simultaneously using a multi-channel photodetector, for example, as described below. The optical signal may be, for example, the intensity of light emitted by the spin system at one or more emission wavelengths, e.g., fluorescence emitted by the excited spin system, or, for example, the intensity of light transmitted through the sensing region to determine the absorption rate of light by the spin system at one or more absorption wavelengths. The detected signal can, for example, enable the extraction of information about the state of the spin system, e.g., the occupation probability of one or more spin states, which may be used, for example, to extract information about the strength and / or direction of the magnetic field in the sensing region, which may be at least partially derived from each sample. In some examples, the step of detecting the optical signal includes the step of exciting each spin system in the sensing region by illuminating the sensing region with light to induce the optical signal to be detected, in addition to, for example, prior illumination of the spin system for photoexcitation. In one example, the illumination to induce the optical signal to be detected does not have to be done via light propagating along the illumination path. Preferably, the detection is synchronized with illumination to induce a light signal, for example, using corresponding trigger signals for the light source and detector.

[0053] In some embodiments, the step of illuminating the sensing region includes reflecting the light propagating along the illumination path at least once along the illumination path so that the illumination path comprises at least two non-parallel segments, as described above, for example. In some embodiments, this may include sequentially reflecting the light propagating along the illumination path from the substrate surface near each sensing region, for example, the top surface of the substrate above the sensing region. In some examples, the light propagating along the illumination path does not need to intersect with layers in the substrate where the spin system is located outside the sensing region. In another example, the light propagating along the illumination path may be reflected once from the top surface, for example, at the center of the top surface. The two non-parallel segments of the illumination path connected by a single reflection may extend at a small angle with respect to the top surface so that the illumination path passes through each of the sensing regions. The angle with respect to the top surface may be, for example, 0° to 5°, or in one example, 0° to 2°. Additionally or alternatively, the step of illuminating the sensing area may include sequentially reflecting light propagating along the illumination path from a plane perpendicular to the plane on which the sensing area is located, particularly the side of the substrate, and / or reflecting light from a plane parallel to the plane on which the sensing area is located, particularly the bottom of the substrate. At least a portion of the reflection may be due to total internal reflection.

[0054] In some examples, the step of illuminating the sensing region may include coupling light to an illumination path through the side of the substrate, for example, through an incident facet or port located on the side. In some examples, the step of illuminating the sensing region may include coupling light to a waveguide, in particular a waveguide extending between sensing regions, for example, a waveguide formed in the substrate as described above.

[0055] The step of illuminating the sensing region also preferably includes the step of refocusing the light propagating along the illumination path between the sensing regions using, for example, focusing elements positioned between the sensing regions as described above. In a preferred embodiment, the diameter of the light beam propagating along the illumination path changes by less than 50%, preferably less than 20%, in the sensing region.

[0056] In some embodiments, the sensing regions form a first set of sensing regions, and the sensor chip may have at least a second set of sensing regions. Thus, the method may also include the steps of preparing a sample on a sensor chip adjacent to each of the second set of sensing regions, illuminating the second set of sensing regions, and detecting an optical signal from each of the second set of sensing regions. The step of illuminating the sensing regions may, in particular, include illuminating the first set of sensing regions with light propagating along a first illumination path through a substrate connecting each of the first set of sensing regions, and illuminating the second set of sensing regions with light propagating along a second illumination path through a substrate connecting each of the second set of sensing regions. In some examples, this may include the step of splitting the light propagating along the incident optical path into light propagating along the first illumination path and light propagating along the second illumination path, for example, using a beam splitter. The method may further be extended accordingly to a sensor chip having multiple sets of sensing regions.

[0057] In a preferred embodiment, the illumination path and the distribution of solid spin systems within the substrate are selected such that the density of excited solid spin systems in the sensing region is at least 100 times, preferably at least 1000 times, that of adjacent regions of the substrate. In some examples, the spin systems may be limited to the sensing region, as described above. The illumination path may extend, for example, in a plane or layer in which the sensing region is located, parallel to the surface of the substrate, or at a small angle, e.g., 0° to 5°, with respect to the surface of the substrate. In other examples, the spin systems may be distributed across layers or at least a portion of them within the substrate, as described above. The illumination path does not need to intersect with this layer outside the sensing region, thereby ensuring that only spin systems within the sensing region are excited. In one example, the spin systems are arranged across the entire surface layer below the upper surface of the substrate, and light propagating along the illumination path is reflected from the upper surface only in the vicinity of the sensing region.

[0058] Preferably, the optical signal is detected along an axis perpendicular to the plane in which the sensing area is located. The sensing area may be located, for example, in a surface layer below the top surface of the substrate, as described above. Therefore, the optical signal can be detected along an axis perpendicular to the top surface, preferably through the bottom surface of the substrate. Preferably, the illumination path is limited to the volume between the top and bottom surfaces of the substrate, or the volume between the planes including the top and bottom surfaces.

[0059] In some embodiments, the step of detecting an optical signal may include, for example, using a solid immersion lens on the surface of the substrate to refract the emitted light by a spin system in a sensing region, and / or reflecting the emitted light from a reflective coating on the surface of the substrate, for example, on the top surface, and transmitting the reflected light through the opposing surface of the substrate.

[0060] In a preferred embodiment, the step of detecting an optical signal includes imaging the light emitted from a sensing region onto a multi-channel detector, where each channel of the detector is associated with one of the sensing regions. The emitted light may be imaged onto the detector using, for example, an imaging system having an objective lens, and / or the emitted light may be collected using multiple detection light guides, for example, as described above. In some examples, two or more channels may be associated with a given sensing region.

[0061] The method may further include additional steps, for example, applying a bias magnetic field, a microwave signal, a radio frequency (RF) signal, and / or light to the sensing region and / or sample. The strength of the bias magnetic field may be selected, for example, to induce a predetermined energy partition between the spin states of a spin system and / or to induce degeneracy or level crossing between the spin states of a spin system. Microwave and / or radio frequency signals may be applied, for example, to prepare the objects in the spin system and / or sample to a target state, such as a well-defined initial state before illuminating the sensing region, and / or to manipulate the state of the objects in the spin system and / or sample. Preferably, the detection of the microwave signal, RF signal, illumination of the sensing region, and / or light signal are synchronized, i.e., performed with a predetermined time delay relative to each other. In a preferred embodiment, the method includes (1) optically polarizing a spin system within a sensing region by illuminating the sensing region along an illumination path, particularly as described above; (2) manipulating the spin system by applying microwave and / or RF signals; and (3) optically exciting the spin system to induce a detected optical signal, particularly by illuminating the sensing region along an illumination path, particularly as described above. The method may also include performing an NMR spectroscopic sequence by applying a plurality of microwave, RF and / or optical pulses, wherein the illumination of the sensing region along the illumination path functions as an excitation pulse for optical polarization of the spin system and / or an optical readout pulse for determining information about the state of the spin system within the sensing region via the detected optical signal. [Brief explanation of the drawing]

[0062] The present invention and its exemplary embodiments will be described in detail below with reference to the drawings. The drawings illustrate the following schematic description. [Figure 1] This is a side view of a sensor chip having a uniform spin distribution according to an exemplary embodiment of the present invention. [Figure 2a]This is a side view of a sensor chip having a localized distribution of a spin system according to an exemplary embodiment of the present invention. [Figure 2b] Figure 2a is a top view of the sensor chip. [Figure 3] A top view of a sensor chip having a side surface with a retroreflective structure according to an exemplary embodiment of the present invention. [Figure 4] This is a top view of a sensor chip equipped with a two-dimensional waveguide according to an exemplary embodiment of the present invention. [Figure 5] This invention illustrates a system for parallel magnetic sensing of multiple samples according to an exemplary embodiment of the present invention. [Figure 6] This is a top view of a sensor chip having a frame according to an exemplary embodiment of the present invention. [Figure 7] This is a flowchart of a method for probing multiple samples using an optically addressable solid spin system, according to an exemplary embodiment of the present invention. [Figure 8] This is a flowchart of a method for probing multiple samples by nuclear magnetic resonance spectroscopy, according to an exemplary embodiment of the present invention. [Figure 9a] This is a top view of a sensor chip having multiple beam splitters according to an exemplary embodiment of the present invention. [Figure 9b] Figure 9a is a cross-sectional side view of the sensor chip. [Modes for carrying out the invention]

[0063] Figure 1 shows a plurality of samples 102 according to an exemplary embodiment of the present invention. parallel A schematic diagram of the sensor chip 100 for magnetic sensing is shown as a cross-sectional side view (not to scale).

[0064] The sensor chip 100, in this example, comprises an optically transparent substrate 104 made of diamond. The substrate 104 may be, for example, a diamond slab having a top surface 104A and a bottom surface 104B opposite the top surface 104A. The thickness of the substrate 104 from the top surface 104A to the bottom surface 104B may be, for example, between 10 μm and 1 mm, and the length and width parallel to the top surface may be, for example, between 0.5 mm and 1 cm. Preferably, the diamond crystal structure has a clear orientation with respect to the top surface 104A. For example, the crystal axes of the diamond lattice may be oriented at a predetermined angle with respect to the normal vector of the top surface 104A. In the context of this disclosure, spatially relative terms such as “top” and “bottom” are used for illustrative purposes only and are used, for example, to describe the relationship between elements or features as shown in the figures. These terms are intended to encompass different orientations of each object, such as the sensor chip 100 in use or operation, in addition to the orientations shown in the figures. The sensor chip 100 and other objects may be oriented in other directions (they may be rotated 90 degrees or in other directions), and the spatially relative terms used herein may be interpreted accordingly.

[0065] In this example, the sample 102 is placed on a plurality of sample areas 106, which are microfluidic sample wells. In other examples, the sample areas 106 may be hydrophilic regions on the upper surface 104A, for example, as detailed below with reference to Figure 9b. The microfluidic sample wells 106 are formed within a well layer 108 located on the upper surface 104A of the substrate 104. The sample wells 106 may be arranged on the upper surface 104A in a one-dimensional or two-dimensional pattern, for example, as described below with reference to Figures 2-4, 6 and 9. In some embodiments, the pattern may be periodic. The sample 102 may be a microdroplet of a sample fluid, which may be a medical sample fluid such as a patient's blood sample, a chemical sample fluid containing one or more reagents and / or products of a chemical reaction, and / or a biological sample fluid which may contain biological objects such as cells, proteins or DNA. The well layer 108 may include, or be composed of, glass, polymer materials, and / or photoresists that can be structured by photolithography, such as polymer photoresists. In the example shown in Figure 1, the well layer 108 is completely removed in the sample well 106, and the top surface 104A of the substrate 104 forms the bottom wall of the sample well 106. In other examples, for example, a thin layer of the well layer 108 may remain at the bottom of the sample well 106 to protect the sample 102 from evanescent light leaking from the substrate 104.

[0066] The substrate 104 comprises multiple optically addressable solid spin systems, in this example, nitrogen vacancy (NV) centers embedded in a diamond crystal structure. The NV centers may, in particular, be in a negatively charged state exhibiting a triplet electronic ground state with spin S=1. The spin states of the NV centers can be manipulated using microwaves and read out and / or initialized via optical transitions to excited triplet states, for example, via spin-dependent fluorescence of the excited state. This makes it possible to use the NV centers as nanoscale magnetometers for measuring magnetic fields, for example, via optically detected magnetic resonance (ODMR).

[0067] NV centers are located in multiple sensing regions 110 within the surface layer 104-I beneath the upper surface 104A of the substrate 104. In the example shown in Figure 1, the NV centers are uniformly distributed throughout the surface layer 104-I. The surface layer 104-I may extend, for example, from the upper surface 104A into the substrate 104 to a depth of 2 μm to 500 μm, or in one example, 10 μm to 20 μm. The density of NV centers in the surface layer 104-I is, for example, 10 15 cm -3 ~10 18 cm -3 For example, in one example, 10 16 cm -3 ~10 17 cm -3 This may also be the case. In some examples, the NV centers may be distributed throughout the entire substrate 104, that is, the depth of the surface layer 104-I may be equal to the thickness of the substrate 104.

[0068] The sensor chip 100 further comprises a light guide system configured to provide an optical path 112 through the substrate 104, the optical path 112 comprising at least two segments that connect each of the sensing regions 112 and are not parallel to each other. In the example of Figure 1, the light guide system comprises two reflective coatings: a reflective coating 114 on the top surface 104A and a reflective coating 116 on the bottom surface 104B. The optical path 112 extends within the substrate 104 from a first side surface 104C to the opposite second side surface 104D, forming a zigzag pattern between the top surface 104A and the bottom surface 104B, in which reflection occurs at the respective coatings 114 and 116 in this zigzag pattern. The angle of incidence α of the optical path 114 with respect to the normal vector of the top surface 104A and / or bottom surface 104B is selected such that light propagating along the optical path 114 is reflected by the coating 114 on the top surface 104A at the center of each sample well 106, thereby defining a corresponding sensing region 110 within the surface layer 114-I. In other words, each of the sensing regions 110 is located beneath each of the sample wells 106. The first side surface 104C is provided with an angled incidence facet for coupling the light beam to the optical path 112, which may be, for example, perpendicular to the optical path 112, i.e., form an angle with the top surface 104A and / or bottom surface 104B equal to the angle of incidence α. In some embodiments, the entire first side surface 104C may be inclined. Preferably, the angled incident facet covers only a portion of the first side surface 104C, and the angled incident facet may be inclined with respect to the rest of the first side surface 104, for example, around one or two axes, for example, around the field of view direction in Figure 1, and / or around the Z-axis in Figure 1. This may allow the light beam to be coupled to the optical path 112 through an incident facet inclined at, for example, 90°, while reflecting the light beam propagating along the optical path 112 from the first side surface 104C at different points on the first side surface 104C, for example, by total internal reflection.

[0069] In the example in Figure 1, the reflective coating 114 on the top surface 104A is a broadband reflective coating, and the reflective coating 116 on the bottom surface 104B is a dichroic reflective coating. The broadband reflective coating 114 may be configured to reflect light in the range of 400 nm to 1100 nm, for example. Thus, the broadband reflective coating 114 reflects light at an absorption wavelength that can be used to excite the NV center to an excited electronic state, and the excitation may include the emission of one or more phonons in the substrate 104, i.e., the absorption wavelength may be shorter than the intrinsic wavelength of the electronic transition of the NV center. The absorption wavelength may be, for example, 500 nm to 600 nm, preferably 532 nm. The broadband reflective coating 114 further reflects light at an emission wavelength that can cause the NV center to fluoresce as it decays from the excited electronic state to the electronic ground state, and the emission wavelength may be longer than the absorption wavelength due to the emission of phonons and / or other transitions involved in the decay from the excited electronic state, particularly non-emission transitions. The emission wavelength may be, for example, 635 nm to 800 nm and / or 1000 nm to 1100 nm. The dichroic reflective coating 116 may be, for example, a long-pass coating that transmits light at emission wavelengths, e.g., wavelengths greater than 630 nm or greater than 650 nm, and reflects light at absorption wavelengths, e.g., wavelengths less than 630 nm or less than 650 nm.

[0070] In other embodiments, the sensor chip 100 may not include the reflective coatings 114 and / or 116. Instead, the optical path 112 may be formed such that light propagating along the optical path 112 is reflected from the top surface 104A and / or bottom surface 104B by total internal reflection. Thus, the incident angle α of the optical path with respect to the normal vector of the top surface 104A and / or bottom surface 104B can be selected to be greater than the critical angle of total internal reflection at each surface, for example, greater than the critical angle at the diamond-air interface (24.5°), the diamond-water interface (33.4°), or the diamond-glass interface (38.5°). In one example, the incident angle α is 35° to 60°.

[0071] Figures 2a and 2b show a sensor chip 200 according to another exemplary embodiment of the present invention. FIG. 2a shows a cross-sectional side view (not to scale) of the sensor chip 200, and FIG. 2b shows a top view (not to scale) of the sensor chip 200. The sensor chip 200 is similar to the sensor chip 100 of FIG. 1 and also includes a diamond substrate 104 in which NV centers are embedded in the surface layer 104-I. In contrast to the sensor chip 100, the NV centers are limited to the sensing region 110 within the substrate 104 of the sensor chip 200. The concentration of NV centers within the substrate 104 outside the sensing region 110 may be, for example, at least 100 times, preferably at least 1000 times less than that within the sensing region 110. In one example, the density of NV centers in the sensing region 110 is 10 16 cm -3 ~10 18 cm -3 , but the density of NV centers in the remaining part of the substrate is less than 10 15 cm -3 , preferably less than 10 14 cm -3 .

[0072] In the example shown in Figure 2a, the optical path 112 extends parallel to the surface layer 104-I between the sensing regions 110 and does not intersect with the top surface 104A and bottom surface 104B of the substrate 104. The light guide system has reflective coatings 202 and 204 on opposing side surfaces 104C and 104D perpendicular to the top surface 104A and bottom surface 104B. The optical path 112 enters the substrate 104 through side surface 104C at an incident angle β with respect to the normal vector of side surface 104C, and the incident angle β is measured in a plane parallel to the top surface 104A of the substrate 104 (in other words, the incident angles α and β are the polar angle and azimuthal angle with respect to the normal vector of the top surface 104A, respectively). The incident angle β is selected so that the optical path 112 forms a zigzag pattern in the surface layer 104-I between the sides 104C and 104D, and sequentially passes through each sensing region 110 located beneath the sample well 106. In some examples, the side 104C may have an inclined incident facet for coupling the light beam to the optical path 112, as described above for, for example, the sensor chip 100. The inclined incident facet may be inclined with respect to the side 104C around the Y axis and / or the Z axis in Figures 2a and 2b.

[0073] In other embodiments, the substrate 104 may not have one or both of the reflective coatings 202, 204, and the incident angle β may be selected so that all internal reflections occur on the sides 104C, 104D, respectively. In some embodiments, the optical path 112 may also include reflections from the top surface 104A and / or bottom surface 104B of the substrate 104, for example, as in the sensor chip 100 of Figure 1. In one embodiment, the optical path 112 may not extend parallel to the surface layer 104-I, for example, but may include a coating layer located between each pair of subsequent reflections from the top surface 104A or from the sides 104C, 104D, preferably centered on the top surface 104A between the sides 104C, 104D. The segments of the optical path 112 may extend at a small angle with respect to the top surface 104A, for example, the angle may be, for example, ±0.5° to ±5°, that is, the incident angle α with respect to the normal vector of the top surface 104A (see Figure 1) may be, for example, 85° to 89.5°. Preferably, the sides 104C and 104D are inclined by the same angle with respect to the normal vector of the top surface 104A, for example, so that the segments of the optical path 112 are perpendicular to the sides 104C and 104D in the xz plane of Figure 2a, so that the optical path 112 maintains an angle with respect to the top surface 104A when reflected from the sides 104C and 104D. In other embodiments, the thickness of the substrate 104 may be selected so that the top surface 104A and bottom surface 104B of the substrate 104 are small enough to form a planar waveguide, for example, as will be detailed below with reference to Figure 9b.

[0074] Each sensing region 110 is positioned beneath each sample well 106. Preferably, the sample well 106 is slightly larger than the sensing region 110 in a plane parallel to the top surface. The width or diameter of the sample well 106 may be, for example, 5% to 25% larger than the width of the diameter of the sensing region 110. In other examples, the sidewalls of the sample well 106 may be aligned with the boundary of the sensing region 110. In the examples of Figures 2a and 2b, both the sample well 106 and the sensing region 110 have a circular shape with a diameter d1, which may be, for example, 2 μm to 500 μm, or in one example, 10 μm to 100 μm. In other examples, the sample well 106 and / or the sensing region 110 may have a rectangular or quadratic shape, which may be advantageous for, for example, NMR applications. The sample well 106 can contain a volume of, for example, 1 picoliter to 1 microliter, or in one example, 50 picoliters to 10 nanoliters. The sensing regions 110 are arranged in a periodic pattern in a plane parallel to the upper surface 104A, and the distance d2 between adjacent sensing regions 110 is at least twice, preferably at least five times, the diameter d1 of the sensing region 110 in order to prevent crosstalk between adjacent sensing regions 110 and / or the sample 102 and to facilitate independent detection of optical signals from adjacent sensing regions 110.

[0075] In contrast to the sensor chip 100, the sensor chip 200 does not have a well layer. Instead, the sample well 106 is formed in the substrate 104 itself as a recess or notch in the top surface 104A. Multiple immersion lenses 206 are arranged on the opposing bottom surface 104B, and each of the immersion lenses 206 is aligned with the respective sensing region 110 to facilitate the collection of light emitted from the respective sensing region 110. The immersion lenses 206 may be, for example, hemispherical or Weierstrass immersion lenses, and may contain an optically transparent material having the same refractive index as the substrate 104 or a higher refractive index, i.e., a refractive index higher than that of diamond. Preferably, the immersion lenses 206 also contain or consist of diamond, formed, for example, by appropriate structuring of the bottom surface 104B.

[0076] Figure 3 shows a schematic top view (not to scale) of a sensor chip 300 according to another exemplary embodiment of the present invention. The sensor chip 300 is similar to the sensor chip 200 described above and also comprises a diamond substrate 104, with the NV center located in a sensing region below the sample area 106 on the upper surface of the substrate 104, where the sample area 106 may be, for example, a microfluidic sample well as described above or a hydrophilic region of the upper surface 104A of the substrate 104.

[0077] Instead of reflective coatings 202, 204 on the sides 104C, 104D of the substrate 104, the light guide system of the sensor chip 300 comprises a plurality of retroreflective structures 302 on the sides 104C, 104D. Each of the retroreflective structures 302 comprises a pair of inclined surfaces 302A, 302B that are orthogonal to each other and extend at angles of +45° and -45°, respectively, with respect to the normal vector of each side, where the normal vector of each side is the normal vector of the plane connecting the corners of the substrate 104 connected by the sides. Preferably, the retroreflective structures 302 are formed by the sides 104C, 104D, which may be structured accordingly, for example. In other embodiments, the retroreflective structures 302 may be attached to the sides 104C, 104D, or located outside the substrate 104, as detailed below with reference to Figure 6, for example. The retroreflective structures 302 may be arranged at equidistant intervals, and the retroreflective structures 302 on one side surface 104C, 104D are displaced by half the period relative to the retroreflective structures 302 on the other side surface 104C, 104D.

[0078] The pair of mutually orthogonal surfaces 302A and 302B reflect the incident beam back with a finite displacement relative to the incident beam, for example, by total internal reflection or by a reflective coating on surfaces 302A and 302B, as shown in Figure 3. In this way, the optical path 112 can pass through each of the sensing regions 110 below the sample portion 106 and form a meandering pattern comprising multiple parallel segments connected by orthogonal segments between the inclined surfaces 302A and 302B of the retroreflective structure 302.

[0079] In the example shown in Figure 3, the inclined surfaces 302A and 302B are curved surfaces, and in particular, convex surfaces that act as focusing elements for light propagating along the optical path reflected from each of the inclined surfaces 302A and 302B. In one example, the curvature of the surfaces 302A and 302B may be selected such that the effective focal length of the retroreflective structure 302 is equal to half the path length between the opposing retroreflective structures 302, that is, adjacent retroreflective structures 302 along the optical path 112 form a 4f telescope configured to image the intensity distribution at a first center point between sides 104C and 104D along the optical path 114 to a second center point between sides 104C and 104D along the optical path 114. In another example, each retroreflective structure 302 may be configured to image the intensity distribution at the nearest center point in front of each retroreflective structure to the nearest center point after each retroreflective structure. In one example, each of the inclined surfaces 302A and 302B may have a focal length equal to half the distance between adjacent inclined surfaces 302A and 302B on opposing sides of the substrate 104.

[0080] Figure 4 shows a schematic top view (not to scale) of a sensor chip 400 according to another exemplary embodiment of the present invention. In this example, the light guide system comprises a two-dimensional waveguide 402 that provides optical paths 112 connecting each of the sensing regions 110 formed within the substrate 104 and located beneath the sample area 106. In one example, the substrate 104 is made of diamond, and the waveguide 402 corresponds to rib-shaped or fin-shaped protrusions on the top and / or bottom surface of the substrate 104, as described, for example, in Diamond and Related Materials 20, 564-567 (2011) by Y. Zhang et al. Preferably, the sensing region 110 is formed in the waveguide 402 itself. A well layer can be placed on the top surface of the substrate 104 to form a sample well 106 on the waveguide 402, as described above with reference to Figure 1, for example. In other embodiments, the substrate 104 may be a composite substrate 104 comprising a carrier material, such as glass or a polymer material, on which the waveguide 402 is formed or embedded, the waveguide 402 preferably comprising diamond, and including a sensing region 110.

[0081] Figure 5 shows multiple samples 102 according to an exemplary embodiment of the present invention. parallel A schematic diagram of the system 500 for magnetic sensing is shown (not to scale). The system 500 is configured to be used with a sensor chip 502 having an optically transparent substrate 104 having multiple optically addressable solid spin systems (not shown), for example, a diamond substrate with NV centers. The spin systems are arranged in multiple sensing regions (not shown) in the surface layer below the upper surface 104A of the substrate 104, and the sample 102 may be placed, for example, on the upper surface 104A adjacent to each of the sensing regions. In some embodiments, the sensor chip 502 may be, for example, one of the sensor chips 100, 200, 300, 400 described above, or similar to the sensor chips 600 or 900 described later. In other examples, the sensor chip 502 may not have a light guide system, but may be, for example, a diamond slab without a reflective coating, retroreflective structure and / or waveguide.

[0082] The system 500 includes a mount 504 configured to receive a sensor chip 502. The mount 504 may include, for example, a frame configured to mount the sensor chip 502 and one or more fasteners (not shown), such as clips and / or screws, for attaching the sensor chip 502 to the frame. In some embodiments, the frame may include a recess or notch in which the sensor chip can be positioned, as detailed below with reference to, for example, Figures 6, 9a, and 9b. In some examples, the mount 504 may be adjustable, allowing the sensor chip 502 to be moved and / or tilted along one or more directions.

[0083] System 500 further comprises an illumination system 506 configured to couple a laser beam generated by a laser source 508 to an optical illumination path 112 passing through the substrate 104 to excite NV centers in the sensing region 110. The illumination path 112 sequentially intersects each sensing region and can correspond, for example, to the optical path of one of the sensor chips 100, 200, 300, 400 described above, or to one of the sensor chips 600, 900 described later. In cases where the sensor chip 502 does not have an optical guide system, the illumination path 112 may have one or more reflection points where the laser beam is reflected from the surface of the substrate by total internal reflection, for example, as shown in Figure 1 and / or Figures 2a, 2b, or it may be a straight line extending parallel to the upper surface 104A of the substrate 104. In some embodiments, the lighting system 506 may also include one or more reflective elements, such as micromirrors and / or one or more beam splitters, to define the lighting path 112, as detailed below with reference to, for example, Figures 6, 9a, and 9b.

[0084] The illumination system 506 includes an alignment subsystem configured to align the incident optical path 510, along which a laser beam emitted by the laser source 508 travels, with the illumination path 112. The alignment subsystem includes one or more adjustable optical elements, such as an adjustable mirror 506A, for coupling the laser beam to the illumination path 112. The adjustable mirror 506A may, in particular, be an operating mirror, such as a piezoelectric operating mirror.

[0085] The illumination system 506 further comprises a beam shaper 506B, simply symbolically represented by double-headed arrows in Figure 5, which may be configured to adjust, for example, the beam diameter, intensity profile, phase pattern, pulse energy, and / or pulse length of the laser beam emitted by the laser source 508. For this purpose, the beam shaper 506B may comprise, for example, one or more lenses, an acousto-optic modulator, an electro-optic modulator, and / or a spatial light modulator. The beam shaper 506B may be configured to generate laser pulses from a continuous wave laser beam emitted by the laser source 508 and adjust the beam diameter of the laser beam to the size of the sensing area of ​​the sensor chip 502. In a preferred embodiment, the beam shaper 506B is configured to convert the laser beam generated by the laser source 508 into a Bessel beam, which may comprise, for example, a reflection axis or a refraction axis. In some examples, the beam shaper 506B may be configured to change the intensity profile of the laser beam generated by the laser source 508 into a flat-top profile and / or an elongated profile, such as an elliptical profile, in particular an optical sheet. The optical sheet may have an aspect ratio of, for example, 1:10 to 1:50. The width of the optical sheet may be selected so that the laser pulse instantaneously illuminates the sensing areas of two or more adjacent sensing areas in a row, i.e., the width may be, for example, greater than twice the distance between adjacent sensing areas, and in one example, greater than five times the distance between adjacent sensing areas.

[0086] The laser source 508 may be part of the system 500 or it may be provided as an independent unit. The laser source 508 emits light at an NV-center absorption wavelength, for example, 500 nm to 600 nm, preferably 532 nm. In one example, the laser source 508 is a diode-pumped solid-state laser.

[0087] The system 500 further comprises magnets for applying a bias magnetic field to the substrate 104 and the sample 102. In the example of Figure 5, the magnets are formed by a pair of coils 512A, 512B, which are positioned adjacent to the sensor chip 502 and configured to be connected to a current source (not shown) for applying the bias magnetic field. In some examples, the system 500 may also include a current source. The system 500 may be configured to apply a bias magnetic field with a variable magnetic field strength that can be adjusted, for example, in the range of 0mT to 1T, and in one example, in the range of 0T to 5T. In one example, the coils 512A, 512B may be superconducting coils.

[0088] System 500 also includes a microwave antenna 514 configured to be connected to a microwave generator (not shown) for applying a microwave signal, for example, a series of microwave pulses schematically shown in Figure 5, to the substrate 104 and sample 102. The microwave antenna 514 may be, for example, a wire, coil, or horn antenna. The microwave antenna 514 may be configured to emit a microwave signal having a frequency matched to the strength of the bias magnetic field. Typical microwave frequencies may be, for example, several hundred MHz for a bias magnetic field of 0.1 T, about 25 GHz for a bias magnetic field of 1 T, and about 125 GHz for a bias magnetic field of 5 T. The microwave antenna 514 may be configured to emit a microwave signal in a frequency range of at least 10 GHz to 50 GHz, in one example at least down to a frequency of 300 MHz and in another example at least up to a frequency of 125 GHz. In some examples, System 500 may also include a microwave generator, which may be, for example, an arbitrary waveform generator. In some embodiments, the system 500 may include a microwave resonator (not shown) instead of, or in addition to, the microwave antenna 514.

[0089] The system 500 further comprises an imaging system 516 configured to collect light emitted by a solid spin system in a sensing region within the substrate 104. The imaging system is configured, in particular, to simultaneously determine the intensity of the emitted light for each of the sensing regions. For this purpose, the imaging system 516 comprises an objective lens 518 facing the bottom surface of the substrate 104, the objective lens 518 configured to collect light emitted from the sensing region. The imaging system 516 is configured to image the emitted light onto a detector 522 along an imaging path 520. In this example, the detector 522 is a multi-channel photodetector comprising a plurality of light-receiving elements or channels 524, each channel 524 associated with each of the sensing regions and configured to measure the intensity of light incident on the channel 524. The channels 524 may be, for example, photodiodes, i.e., the detector 522 may comprise an array of photodiodes. Each of the channels 524 may comprise a single photodiode or a plurality of photodiodes. Alternatively, a channel may be an area on an extended photodetector, such as a CCD or CMOS chip, and each channel may comprise, for example, multiple pixels of the photodetector. In one example, the detector may be a lock-in camera configured to determine a differential signal by subtracting the signals of two subsequent measurements, preferably before the analog-to-digital conversion of the signal. In some embodiments, the detector 522 or imaging system 516 may include one or more additional focusing elements, such as each microlens associated with each channel 524 of the detector 522 or each microlens associated with each photodiode or pixel of the detector 522. The imaging system 516 is configured to image the light emitted from each sensing area onto each channel 524.

[0090] In other embodiments, the imaging system 516 may include one or more detection light guides (not shown) configured to collect light emitted from each of the sensing regions. The incident facets of the light guides may be located, for example, adjacent to or in contact with the bottom surface of the substrate 104, for example, beneath each sensing region. The output facets of the light guides may be directly coupled, for example, to each photodetector, for example, a photodiode.

[0091] In some examples, the system 500 may further include a controller (not shown) configured to control a mount 504, an illumination system 506, a laser source 508, a current source connected to coils 512A and 512B, a microwave generator connected to a microwave antenna 514, and / or a detector 522. The controller may be implemented in hardware, software, or a combination thereof, and may be configured to perform at least partially one of methods 700 and 800 described later, for example.

[0092] Figure 6 schematically shows a sensor chip 600 according to an exemplary embodiment of the present invention in a top view (not to scale). Sensor chip 600 is similar to sensor chips 200 and 300 described above. Sensor chip 600 also comprises a diamond substrate 104 on which NV centers are positioned in sensing regions beneath a plurality of sample portions 106 on the upper surface of the substrate 104, and a light guide system configured to provide an optical path 112 through the substrate 104 connecting each sensing region 110.

[0093] The sensor chip 600 further comprises a frame 602 on which the substrate 104 is placed. The frame 602 may consist of or be constructed of, for example, metal, glass, plastic, or a combination thereof, and may include a notch or hole in the center, where the substrate 104 can be placed so that its top and bottom surfaces are accessible. The frame 602 further comprises a microwave antenna or resonator 514 formed by or comprising wires surrounding the substrate 104. The wires 514 may, for example, be placed on or embedded in the frame 602, and may include a connector for connecting the wires 514 to a microwave generator. In other examples, the wires 514 may additionally or alternatively be used to apply a magnetic field to the substrate 104 and the sample, and may be connected to, for example, a current source. In some examples, the sensor chip 600 may not have a frame 602, but the frame 602 and the elements placed thereon are according to the present invention. parallel The sensor chip mount for the system for magnetic sensing may be part of, for example, mount 504 of system 500.

[0094] The light guide system includes a lateral opening 604 in a frame 602 that provides optical access to an incident facet on the side surface of the substrate 104 to couple light to the optical path 112. The light guide system further includes a plurality of retroreflective structures 606 for reflecting light propagating along the optical path 112. The retroreflective structures 606 are similar to the retroreflective structures 302 of the sensor chip 300 in Figure 3, but are located on the frame 602 instead of being part of the substrate 104. Each of the retroreflective structures 606 may comprise a pair of micromirrors, for example, oriented at a 90° angle to each other and which may be curved as shown in Figure 6. In some embodiments, the retroreflective structures 606 also comprise the present invention parallel The lighting system for the magnetic sensing system may be part of, for example, the lighting system 516 of system 500.

[0095] Figure 7 shows a flowchart of Method 700 for probing multiple samples using an optically addressable solid spin system, according to an exemplary embodiment of the present invention. Method 700 can be carried out, for example, with one of sensor chips 100, 200, 300, 400, 600, 900 and / or System 500, and will be described below using sensor chip 100 and System 500 as examples. Method 700 is not limited to the execution order shown in the flowchart of Figure 7. Method 700 may be carried out in any order as long as it is technically feasible, and its steps, for example steps 704 and 706 described below, may be carried out at least partially concurrently.

[0096] Method 700 includes the step of preparing a sample 102 on the sensor chip 100 in step 702. The sample 102 may be, for example, a chemical sample fluid, a solution containing reagents and / or products of a chemical reaction. In some embodiments, each of the samples 102 may be different, for example, containing different concentrations and / or substances than the other samples 102. The samples 102 may be prepared on the sensor chip 100 by, for example, placing microdroplets of each sample 102 into each of the sample wells 106 on the upper surface 104A of the substrate 104 on the sensing region 110. The microdroplets may have a volume of, for example, 10 picoliters to 1 nanoliter.

[0097] In step 704, the sensing regions 110 are simultaneously illuminated to optically excite the solid spin systems within each sensing region 110, i.e., the NV centers within the sensor chip 100. For this purpose, laser pulses may be generated using a laser source 508 and an illumination system 506, the wavelength of which is selected to match the excitation wavelength of the NV centers, for example, 532 nm. The laser pulses are coupled to the optical path or illumination path 112 using the illumination system 506, for example, through the side surface 104C of the substrate 104, or by coupling to a waveguide such as the two-dimensional waveguide 402 in Figure 4 or a planar waveguide such as that in Figure 9b. Subsequently, the laser pulses propagate sequentially through each sensing region, exciting the NV centers within the sensing regions from the electronic ground state to the electronically excited state. The sensing regions 110 may be illuminated, for example, to optically polarize the spin systems within them, or for optical readout of the spin system states, for example, as detailed below. In some examples, the sensing region 110 may be illuminated multiple times, for example, for optical polarization at the start of an experimental sequence and for optical readout at the end of the optical sequence. The pulse energy and / or pulse length of the laser pulse may be selected to achieve a predetermined transition probability to a particular state of NV centers in the sensing region, for example, as detailed below. This may include selecting the pulse energy and / or pulse length such that the spin system receives multiple excitations, for example, for the optical polarization of the spin system.

[0098] As detailed above, the propagation of laser pulses along the illumination path 112 may include, for example, one or more reflections from the upper surface 104A of the substrate 104 near each sensing region 110, as shown in Figures 1 and 5, and / or from one or more surfaces perpendicular to the plane in which the sensing region 110 is located, as shown in Figures 2, 3 and 6. The illumination path 112 can be adapted to the distribution of NV centers in the substrate 104, for example, by adjusting the incident angle α and / or β of the illumination path 112. Additionally or alternatively, the diameter of the laser pulse may be adapted to the distribution of NV centers. In particular, the illumination path 112 and / or pulse diameter may be adapted so that only NV centers in the sensing region 110 are excited, for example, by selecting the incident angle α and diameter such that the pulse propagating along the illumination path 112 illuminates only the surface layer 104-I within the sensing region 110.

[0099] In step 706, the optical signals emitted by the NV centers of the sensing region 110 are detected independently for each sensing region 110, for example, by imaging the fluorescence emitted from the NV centers of the sensing region 110 onto the respective channels 524 of the detector 522. This may include the step of determining the intensity of the light emitted from each sensing region, e.g., peak intensity and / or time-integrated intensity. Step 706 may further include the step of determining information about the state of the NV centers in each sensing region 110 before illumination from the determined intensity, e.g., the occupation probability of one or more spin states in the electronic ground state. For this purpose, method 700 may also include the step of applying a microwave signal and / or radio frequency (rf) signal to the substrate 104 and the sample 102 placed thereon, for example, as detailed below for method 800. Step 706 may further include the step of determining information about the intensity and / or direction of the magnetic field in each sensing region 110 from the information about the state of the NV centers. Preferably, detection is performed along an axis perpendicular to the plane on which the sensing area is located, for example, via the upper surface 104A of the substrate 104, or more preferably via the bottom surface 104B. Thus, the detection axis may also be perpendicular to the plane on which the illumination path 114 extends, minimizing interference between illumination and detection.

[0100] Figure 8 shows a flowchart of Method 800 for probing multiple samples by nuclear magnetic resonance spectroscopy using an optically addressable solid spin system, according to an exemplary embodiment of the present invention. Method 800 is similar to Method 700 and can be carried out, for example, with one of sensor chips 100, 200, 300, 400, 600, 900 and / or System 500. Method 800 will be described below using sensor chip 100 and System 500 as examples. Method 800 is not limited to the execution order shown in the flowchart of Figure 8. Method 800 may be carried out in any order, as long as it is technically feasible, and at least some of its steps, for example, steps 804 to 812 described below, may be carried out at least partially simultaneously.

[0101] Similar to Method 700, Method 800 also includes the step of preparing a sample 102 on the sensor chip 100 in step 802, for example, as described above for step 702 of Method 700. Method 800 further includes the step of applying a bias magnetic field to the substrate 104 and the sample 102 placed thereon in step 804, using, for example, coils 512A, 512B. This may also include the step of changing the strength and / or direction of the magnetic field. The bias magnetic field may be used, for example, to define the quantization axes of the NV centers and / or the spins of the object in the sample 102, and / or to adjust the energy division between the states of the object in the NV centers and / or to generate degeneracy or level crossings between states. The bias magnetic field may be applied continuously, for example, between some or all of steps 806 to 812.

[0102] Method 800 further includes, in step 806, illuminating the sensing region 110 to optically polarize the spin systems within it, for example, to prepare the spin systems to a predetermined initial state. Preferably, the sensing region 110 is illuminated by light propagating along the illumination path 112 to simultaneously excite the spin systems using, for example, one or more laser pulses. Depending on the transition rates between states of the spin systems, the optical polarization may require a large number of optical transitions, e.g., multiple excitations of the spin systems, and therefore a sufficiently large light intensity within the sensing region 110. Therefore, the amount of laser power required for optical polarization can be reduced by reusing the same laser pulse for each of the sensing regions via the illumination path. The intensity and / or duration of the laser pulses can be adjusted to achieve a predetermined excitation efficiency, for example, so that at least 90%, preferably at least 99%, of all spin systems transition to the initial state.

[0103] In step 808, the microwave signal and / or radio frequency (RF) signal are applied to the substrate 104 and the sample 102 placed thereon, for example, using a microwave antenna 514. This may also include steps to vary the amplitude, polarization, and / or frequency of the microwave signal and / or RF signal. The microwave and / or RF signal may, in particular, include one or more pulse sequences. Each of the microwave and / or RF pulse sequences may, for example, include one or more π / 2 pulses and / or π pulses to manipulate the spin states of objects such as NV centers and / or atoms, molecules, or polymers in the sample 102. The pulse sequence may, in particular, be a pulse sequence for performing nuclear magnetic resonance (NMR) spectroscopy.

[0104] In steps 810 and 812, the sensing regions 110 are illuminated to optically excite the NV centers within them, as described above, for example, for method 700, and the fluorescence intensity emitted from each sensing region 110 is measured. Some or all of steps 804 to 812 may be repeated multiple times and / or performed at least partially simultaneously. In a preferred embodiment, the NV centers within the sensing regions 110 are read out using a coherently averaged synchronous readout (CASR) scheme including a synchronous microwave pulse sequence for readout and alternating blocks of illumination pulses, as described, for example, by DRGlenn et al. in Nature 555, 351-354 (2018) and international publication brochure 2018 / 052497.

[0105] Figures 9a and 9b schematically show a sensor chip 900 according to an exemplary embodiment of the present invention, where Figure 9a shows a top view (not to scale) of the sensor chip 900 and Figure 9b shows a cross-sectional side view (not to scale) of the sensor chip 900. The sensor chip 900 is similar to the sensor chip 600 described above and also comprises a substrate 104 having a plurality of sensing regions 110 arranged within a frame 602.

[0106] In this example, the sensing region 110 forms a plurality of sets 110-A, 110-B, 110-C, and 110-D, each of which may comprise a plurality of sensing regions 110 arranged along a straight line, for example, as shown in Figure 9a. The sensor chip 900 includes a light guide system configured to provide respective optical paths 112-A, 112-B, 112-C, and 112-D for each of the sets of sensing regions 110-A to 110-D, with each of the optical paths 112-A to 112-D connecting each of the sensing regions 110 within their respective sets. For this purpose, the light guide system includes a plurality of beam splitters 902 that divide the incident optical path into optical paths 112-A to 112-D. The beam splitters 902 may be located, for example, on a frame 602 adjacent to the side surface 104-C of the substrate 104. The light guide system further comprises micromirrors 904 on which light propagating along optical path 112-D is reflected. In some embodiments, the beam splitter 902 and micromirrors 904 may be adjustable, for example, tiltable around one or two axes. The beam splitter 902 may be a polarizing beam splitter or preferably an unpolarizing beam splitter, and the transmission-to-reflection ratio may be selected, for example, so that the incident light is split into equal parts, i.e., so that the optical output is the same in each of the optical paths 112-A to 112-D. In other words, the reflectivity of the beam splitter 902 may increase along the incident light path from the first beam splitter to the last beam splitter.

[0107] In some embodiments, the frame 602, beam splitter 902, and / or micromirror 904 may not be part of the sensor chip 900, but rather part of a system such as 500. parallelIt may also be part of a system for magnetic sensing. In other words, the illumination system 506 may include, for example, a beam splitter 902 and / or micromirrors 904 for coupling laser beams into optical paths / illumination paths 112-A to 112-D that sequentially intersect with the sensing regions 110 of each set 110-A to 110-D. Similarly, the frame 602 may consist of a substrate 104, or form a mount configured to receive a sensor chip 502 comprising it, or be part of such a mount.

[0108] In yet another example, the light guide system of the sensor chip 900 or the illumination system 506 of the system 500 may be configured to combine laser beams generated by multiple laser sources into paths 112-A to 112-D, for example, by using a separate laser source for each of the illumination paths 112-A to 112-D. The light guide or illumination system may include, for example, micromirrors instead of a beam splitter 902 to combine the laser beams generated by the laser sources into their respective paths 112-A to 112-D.

[0109] In the example shown in Figure 9b, the sensor chip 900 includes a plurality of sample areas 106, each containing a hydrophilic coating 906 on the upper surface 104A of a substrate 104 configured to attract or bind to microdroplets 102 of the sample fluid. In other examples, the sensor chip 900 may additionally or alternatively include microfluidic sample wells similar to those of the sensor chips 100 and 200 described above, for example.

[0110] The light guide system of the sensor chip 900 includes waveguides formed within the substrate 104 to provide optical paths 112-A to 112-D through the substrate 104. In this example, the thickness of the substrate 104 perpendicular to the top surface 104A is selected to be small enough that the top surface 104A and bottom surface 104B of the substrate 104 form a one-dimensional plane or slab waveguide. Light propagating along optical paths 112-A to 112-D may be confined along the Z-axis in Figure 9b by total internal reflection from the top surface 104A and bottom surface 104B, for example. The thickness of the substrate 104 may be, for example, 10 μm to 30 μm. Each of the optical paths 112-A to 112-D may extend along a straight line through the substrate 104, as shown in Figure 9a. Additionally or alternatively, one or more of the optical paths 112-A to 112-D may comprise at least two non-parallel segments, for example, non-parallel segments intersecting at one of the beam splitters 902 as shown in Figure 9a. In some embodiments, the light guide system may further comprise a reflective coating or cladding layer (not shown) on the top surface 104A and / or bottom surface 104B to form a waveguide. To couple the laser beam 908 into the waveguide, the light guide system of the sensor chip 900 or the illumination system 506 of system 500 may comprise one or more focusing elements, such as a lens (not shown), for focusing the laser beam 908 onto the incident facet of the waveguide, for example, the side surface 104C of the substrate, as shown in Figure 9b. In some examples, the light guide system may comprise one or more two-dimensional waveguides (not shown) defining one or more of the optical paths 112-A to 112-D, for example, a plurality of two-dimensional waveguides extending parallel to each other. In some embodiments, the sensing region 110 may extend through the entire substrate 104 perpendicular to the top surface 104A, as shown in Figure 9b. In other words, the depth of the surface layer 104-I may correspond to the thickness of the substrate 104. In some embodiments, the sensor chip 900 may not have a planar waveguide between the top surface 104A and the bottom surface 104B, but the substrate 104 of the sensor chip 900 may be similar to, for example, the substrate of the sensor chip 100 in Figure 1 or the sensor chip 200 in Figure 2a described above.For this reason, the thickness of the substrate 104 may be increased to, for example, a value of 100 μm to 1 mm.

[0111] In some embodiments, the light guide system of the sensor chip 900 or the illumination system 506 of system 500 may include one or more diffractive optical elements (not shown) instead of, or in addition to, the beam splitter 902 and the micromirror 904. Each of the diffractive optical elements may be configured to split an incident light beam, such as a laser beam 908, into two or more beams by diffraction. Each of the diffractive optical elements may be configured, for example, to imprint a phase pattern and / or intensity pattern onto the incident beam, so that the incident beam is split into two or more beams due to interference between different parts of the incident beam. Each of the diffractive optical elements may include, for example, a phase mask and / or a diffraction grating. The light guide system of the sensor chip 900 or the illumination system 506 of system 500 may further include one or more focusing elements, such as one or more lenses, which may be configured, for example, to refract and / or deflect the two or more beams generated by the diffractive optical elements, some or all of which may propagate at an angle to the incident beam to form a parallel beam pattern similar to, for example, that shown in Figure 9a. For this purpose, the diffractive optical elements may be positioned, for example, at the focal plane of each focusing element.

[0112] The embodiments of the present invention disclosed herein constitute only specific examples for illustrative purposes. The present invention can be carried out in many ways with numerous modifications without altering the underlying basic characteristics. Accordingly, the present invention is defined only by the following claims. [Explanation of Symbols]

[0113] 100 sensor chips 102 samples 104 circuit board 104A Top surface of circuit board 104 104B Bottom surface of circuit board 104 104C, 104D Side view of substrate 104 104-I Surface layer 106 Sample Site 108 well layer 110 Sensing Area 112 Light path α Normal incidence angle of the optical path 114 Broadband Reflective Coating 116 Dichroic Reflective Coating 200 sensor chips 202,204 Reflective coating 206 Immersion Lens β Horizontal incidence angle of the optical path 300 sensor chips 302 Retroreflective structure 302A,302B Slope 400 sensor chips 402 Waveguide 500 parallel System for magnetic sensing 502 Sensor Chip 504 Mount 506 Lighting System 506A Adjustable Mirror 506B Beam Shaper 508 Laser Source 510 Incoming optical path 512A, 512B Magnet Coil 514 Microwave Antenna 516 Imaging System 518 Objective lens 520 Imaging Path 522 detectors 524 Detector 522 Channel 600 sensor chips 602 frames 604 Lateral opening 606 Retroreflective structure 700 Method for probing multiple samples using a solid-state spin system 702 Steps to prepare the sample 704 Step to illuminate the sensing area 706 Steps for detecting an optical signal 800 A method for probing multiple samples using nuclear magnetic resonance spectroscopy. 802 Steps to prepare the sample 804 Step of applying a bias magnetic field 806 Steps to illuminate the sensing area for optical polarization 808 Step of applying microwave pulses 810 Step of illuminating the sensing area for optical readout 812 Steps to measure fluorescence intensity 900 sensor chips 902 Beam Splitter 904 Micromirror 906 Hydrophilic coating 908 Laser beam

Claims

1. Sensor chips (100, 200, 300, 400, 600, 900) for parallel magnetic sensing of multiple samples (102), An optically transparent substrate (104) having multiple optically addressable solid spin systems arranged in multiple sensing regions (110) within a surface layer (104-I) below the upper surface (104A) of the substrate (104), Multiple sample areas (106), each sample area (106) is positioned on its respective sensing area (110), and A light guide system configured to provide an optical path (112) that connects each of the sensing regions (110) and sequentially intersects each of the sensing regions (110), and that passes through the substrate (104), A sensor chip (100) equipped with the following.

2. The sensor chip (100, 200, 300, 400, 600, 900) according to claim 1, wherein the optical path (112) comprises at least two segments that are not parallel to each other.

3. The light guide system includes one or more reflective coatings (114, 116, 202, 204) on the top surface (104A), bottom surface (104B), and / or side surfaces (104C, 104D) of the substrate (104), wherein the sensor chip (100, 200) is according to claim 1 or 2.

4. The light guide system is, A dichroic reflective coating (116) on the bottom surface (104B) of the substrate (104), configured to reflect light of the absorption wavelength of the solid spin system and transmit light of the emission wavelength of the solid spin system, and / or A broadband reflective coating (114) on the upper surface (104A) of the substrate (104) is provided, wherein the broadband reflective coating (114) is configured to reflect light at the absorption wavelength and emission wavelength of the solid spin system, The sensor chip (100) according to claim 3.

5. The light guide system comprises one or more retroreflective structures (302, 606) on or adjacent to the side surfaces (104C, 104D) of the substrate (104), and each of the retroreflective structures (302, 606) comprises a pair of inclined surfaces (302A, 302B) configured to retroreflect a light beam propagating through the substrate (104) along the optical path (112), the sensor chip (300, 600) according to any one of claims 1 to 4.

6. The light guide system comprises a focusing element positioned between sensing regions (110) along the optical path (112), wherein the focusing element is configured to refocus the light beam propagating along the optical path (112), according to any one of claims 1 to 5, the sensor chip (300, 600).

7. The sensor chip (300) according to claim 6, wherein the focusing element comprises curved surfaces (302A, 302B) on the surface (104C, 104D) of the substrate (104) to which the light beam is reflected.

8. The light guiding system comprises a planar waveguide configured to confine light propagating along the waveguide (402) in the substrate (104), particularly the optical path (112), in a direction perpendicular to the upper surface (104A) of the substrate (104), according to any one of claims 1 to 7, the sensor chip (400, 900).

9. The sensor chip (200) according to any one of claims 1 to 8, further comprising a plurality of immersion lenses (206) on the bottom surface (104B) of the substrate (104), each of the immersion lenses (206) being positioned below each of the sensing regions (110).

10. The sensor chip (100, 200) according to any one of claims 1 to 9, wherein the sample portion (106) is a microfluidic sample well formed on the upper surface (104A) of the substrate (104) or in a well layer (108) disposed on the upper surface (104A) of the substrate (104).

11. The sensing region (110) is arranged in a two-dimensional array within the surface layer (104-I) of the substrate (104) in the sensor chip (200, 300, 400, 600, 900) according to any one of claims 1 to 10.

12. The distance (d) between adjacent sensing regions (110) ２ ) is the width (d) of the sensing area (110) in a plane parallel to the upper surface (104A). １ A sensor chip (200) according to any one of claims 1 to 11, which is at least twice the size of the sensor chip (200).

13. The solid spin system is arranged across the entire surface layer (104-I) of the substrate (104), and the optical path (112) connecting the sensing region (110) does not intersect with the surface layer (104-I) outside the sensing region (110), or The density of the solid spin system in the substrate (104) outside the sensing region (110) is at least 100 times, preferably at least 1000 times, smaller than the density of the solid spin system within the sensing region (110), and at least a portion of the optical path (112) extends into the surface layer (104-I) between the sensing regions (110). A sensor chip (100, 200, 900) according to any one of claims 1 to 12.

14. The sensor chip (100, 200, 300, 400, 600, 900) according to any one of claims 1 to 13, wherein the substrate (104) contains diamond, and the solid spin system is a diamond-colored center, particularly a nitrogen vacancy center.

15. A system (500) for parallel magnetic sensing of multiple samples (102) using a sensor chip (502), wherein the sensor chip (502) is An optically transparent substrate (104), comprising a plurality of optically addressable solid spin systems arranged in a plurality of sensing regions (110) within a surface layer (104-I) below the upper surface (104A) of the substrate (104), The aforementioned system (500) A mount (504) configured to receive the sensor chip (502), A lighting system (506) configured to excite a solid spin system in the sensing region (110) by coupling a laser beam generated by a laser source (508) to an optical illumination path (112) passing through the substrate (104), wherein the optical illumination path (112) sequentially intersects with each of the sensing regions (110), and the lighting system (506) A system (500) equipped with [this feature].

16. The system (500) according to claim 15, wherein the light illumination path (112) comprises at least two segments that are not parallel to each other.

17. The laser beam propagating along the aforementioned light illumination path (112) The upper surface (104A) of the substrate (104) in the vicinity of each of the sensing regions (110), and / or Reflected sequentially from the surface of the substrate (104) perpendicular to the upper surface (104A), particularly from the side surfaces (104C, 104D) of the substrate (104) perpendicular to the upper surface (104A), The system (500) according to claim 16.

18. The system (500) according to claim 17, wherein at least one of the reflections is caused by total internal reflection at the surface (104A, 104B, 104C, 104D) of the substrate (104).

19. The lighting system (506) is configured to couple the laser beam to a waveguide (402) in the substrate (104) that forms at least a portion of the optical illumination path (112), the system (500) according to any one of claims 15 to 18.

20. The system (500) according to any one of claims 15 to 19, wherein the light illumination path (112) forms a periodic non-intersecting pattern in a plane parallel to the upper surface (104A) of the substrate (104).

21. The illumination system (506) comprises one or more focusing elements positioned between sensing regions (110) along the light illumination path (112), wherein the focusing elements are configured to refocus the laser beam propagating along the light illumination path (112), and / or The illumination system (506) includes a beam shaper (506B) configured to convert the laser beam into a Bessel beam. The system (500) according to any one of claims 15 to 20.

22. The sensing region (110) forms a first set of sensing regions (110-A), and the sensor chip (502) further comprises a second set of sensing regions (110-B, 110-C, 110-D), and The illumination system (506) includes a beam splitter (902) configured to couple the laser beam to a first illumination path (112-A) that sequentially intersects each of the sensing regions in the first set (110-A) and a second illumination path (112-B, 112-C, 112-D) that sequentially intersects each of the sensing regions in the second set (110-B, 110-C, 112-D). The system (500) according to any one of claims 15 to 21.

23. The system (500) according to any one of claims 15 to 22, further comprising an imaging system (516) configured to collect light emitted by a solid spin system within the sensing region (110), wherein the imaging system (516) is configured to simultaneously determine the intensity of the emitted light for each of the sensing regions (110).

24. A microwave antenna (514) or microwave resonator for applying a microwave signal to the substrate (104) and / or the plurality of samples (102), Magnets (512A, 512B) for applying a bias magnetic field to the substrate (104) and / or the plurality of samples (102), The system further comprises one or more of the following: a laser source (508) for generating a laser beam for the illumination system (506), The system (500) according to any one of claims 15 to 23.

25. A system (500) according to any one of claims 15 to 24, further comprising a sensor chip (100, 200, 300, 400) according to any one of claims 1 to 14.

26. A method (700, 800) for probing multiple samples (102) using an optically addressable solid spin system, A step of preparing the sample (102) on a sensor chip (100, 200, 300, 400, 502, 600, 900) having an optically transparent substrate (104), wherein the solid spin system is arranged within a plurality of sensing regions (110), and each of the samples (102) is arranged adjacent to each of the sensing regions (110), The steps include: connecting each of the sensing regions (110) and illuminating the sensing regions (110) with light propagating along the optical path (112) that sequentially intersects each of the sensing regions (110) through the substrate (104), thereby simultaneously exciting the solid spin systems within each of the sensing regions (110); For each of the sensing regions (110), the step of detecting the optical signal emitted by the solid spin system within each of the sensing regions (110), A method including (700, 800).

27. The step of illuminating the sensing area (110) is: The steps of sequentially reflecting the light propagating along the light illumination path (112) from the surface (104A) of the substrate (104) near each of the sensing regions (110), and / or The step includes sequentially reflecting the light propagating along the light illumination path (112) from surfaces perpendicular to the plane on which the sensing area (110) is located, particularly the sides (104C, 104D) of the substrate (104), The method according to claim 26 (700, 800).

28. The method according to claim 26 or 27 (700, 800), wherein the step of illuminating the sensing region (110) includes coupling the light to the light illumination path (112) through the side surface (104C) of the substrate (104).

29. The method according to any one of claims 26 to 28 (700, 800), wherein the step of illuminating the sensing region (110) includes the step of coupling the light to a waveguide (402) extending between the sensing regions (110).

30. The method according to any one of claims 26 to 29 (700, 800), wherein the step of illuminating the sensing regions (110) includes the step of refocusing the light propagating along the light illumination path (112) between the sensing regions (110).

31. The method according to any one of claims 26 to 30 (700, 800), wherein the distribution of solid spin systems in the light illumination path (112) and the substrate (104) is selected such that the density of excited solid spin systems in the sensing region (110) is at least 100 times, preferably at least 1000 times, that in the adjacent region of the substrate (104).

32. The method according to any one of claims 26 to 31 (700, 800), wherein the sensing region (110) is located in a surface layer (104-I) below the upper surface (104A) of the substrate (104), and the optical signal is detected along an axis perpendicular to the upper surface (104A), preferably passing through the bottom surface (104B) of the substrate (104).

33. The method according to any one of claims 26 to 32 (700, 800), wherein the step of detecting the optical signal includes the step of imaging the light emitted from the sensing region (110) onto a multi-channel detector (522), and each channel (524) of the multi-channel detector (522) is associated with each of the sensing regions (110).

34. The steps include applying a bias magnetic field to the sensing region (110) and / or the plurality of samples (102), The steps include: optically polarizing the solid spin system within the sensing region (110) by illuminating the sensing region (110) along the light illumination path (112); The steps include applying microwave and / or radio frequency signals to the sensing region (110) and / or the plurality of samples (102), The method further includes one or more of the steps of: exciting the solid spin system within the sensing region (110) by illuminating the sensing region (110) along the light illumination path (112) in order to induce the optical signal to be detected, The method according to any one of claims 26 to 33 (800).

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