Quantum enhanced glucose detection device and detection method

Abstract

The present invention provides a quantum-enhanced glucose detection device and a detection method. The quantum-enhanced glucose detection device comprises: a sample unit, which is suitable for containing a reaction of a mixed solution of glucose and a catalyst to generate free radicals; a pump light unit, which is suitable for generating an excitation light beam and emitting the excitation light beam to the sample unit; a solid-state spin sensor, which is arranged in the sample unit and is suitable for being polarized in response to the excitation of a first excitation light beam emitted by the pump light unit, and accelerating depolarization in response to the action of free radicals, and the solid-state spin sensor also generates a fluorescence signal in response to the excitation of a second excitation light beam emitted by the pump light unit; and a detection unit, which is suitable for receiving the fluorescence signal generated by the solid-state spin sensor and determining the concentration of glucose based on the fluorescence signal.

Description

Technical Field

[0001] The present invention relates to the field of glucose detection, and more specifically to a quantum enhanced glucose detection device and detection method. Background Art

[0002] Glucose testing is of great significance for the diagnosis, control and drug development of diseases such as diabetes. At the same time, glucose testing also plays an important role in the field of food health.

[0003] The method commonly used in clinical practice to detect glucose concentration is based on the combined catalytic reaction of glucose oxidase-peroxidase (GOD-POD). Glucose generates gluconic acid and hydrogen peroxide under the action of oxidase. Peroxidase catalyzes the reaction of hydrogen peroxide with chromogens (such as tetramethylamphetamine TMB) to produce colored oxides. The resulting color change can be measured by a spectrophotometer to obtain the blood glucose concentration.

[0004] However, the sample amount required by the above detection method is large, which cannot meet the needs of detecting trace blood sugar, and will be affected to a certain extent by reducing substances such as vitamin C. Summary of the invention

[0005] In view of this, the present invention provides a quantum enhanced glucose detection device and detection method.

[0006] One aspect of the present invention provides a quantum-enhanced glucose detection device, comprising: a sample unit, adapted to accommodate a reaction of a mixed solution of glucose and a catalyst to generate free radicals; a pump light unit, adapted to generate an excitation light beam and emit the excitation light beam to the sample unit; a solid-state spin sensor, disposed in the sample unit, adapted to respond to the excitation of a first excitation light beam emitted by the pump light unit to become polarized, and to accelerate depolarization in response to the action of free radicals, the solid-state spin sensor also responding to the excitation of a second excitation light beam emitted by the pump light unit to generate a fluorescence signal; and a detection unit, adapted to receive the fluorescence signal generated by the solid-state spin sensor, and to determine the concentration of glucose based on the fluorescence signal.

[0007] According to an embodiment of the present invention, the sample unit includes a sample microchamber, and the solid-state spin sensor is arranged at the bottom of the sample microchamber and constitutes the lower bottom surface of the sample microchamber.

[0008] According to an embodiment of the present invention, the sample microchamber comprises a plurality of sample microchambers, and the plurality of sample microchambers are spaced apart and arranged on the top of the solid-state spin sensor.

[0009] According to an embodiment of the present invention, a control field unit is also included, which is suitable for emitting an electromagnetic field to the sample unit to regulate the quantum state of the solid-state spin sensor.

[0010] According to an embodiment of the present invention, the manipulation field unit includes: a microwave source, adapted to emit pulse microwaves; and a microstrip antenna, connected to the sample unit, adapted to transmit the pulse microwaves into the sample unit to apply an electromagnetic field to the solid-state spin sensor.

[0011] According to an embodiment of the present invention, the pump light unit includes: a light source, which is suitable for generating an excitation light beam with a wavelength corresponding to the solid-state spin sensor; a first wave plate, which is arranged downstream of the optical path of the light source and is used to adjust the polarization direction of the excitation light beam emitted from the first wave plate; a polarization beam splitter, which is arranged downstream of the optical path of the first wave plate and is used to split the excitation light beam to a target path according to the polarization direction; an acousto-optic modulator, which is arranged downstream of the optical path of the polarization beam splitter and is used to adjust the pulse width of the excitation light beam; a second wave plate, which is arranged downstream of the optical path of the acousto-optic modulator and is used to secondary adjust the polarization direction of the excitation light beam emitted from the second wave plate; a first reflector, which is arranged downstream of the optical path of the second wave plate and is used to reflect the excitation light beam back to the second wave plate; and a collimator, which is arranged downstream of the optical path of the polarization beam splitter and is used to spatially filter the excitation light beam and convert it into a collimated light beam output.

[0012] According to an embodiment of the present invention, the detection unit includes: a first lens, which is arranged downstream of the optical path of the fluorescent signal, and is suitable for focusing the fluorescent signal to a pinhole to perform spatial filtering on the fluorescent signal; a second lens, which is arranged downstream of the optical path of the first lens, and is suitable for collimating the fluorescent signal; a third lens, which is arranged downstream of the optical path of the second lens, and is suitable for converging the fluorescent signal; and a single-photon detector, which is used to receive the fluorescent signal converged by the third lens.

[0013] Another aspect of the present invention provides a glucose detection method, comprising: adding a mixed solution of glucose and a catalyst into a sample unit for reaction to generate free radicals; at a first moment, using a pump light unit to emit a first excitation light beam to the sample unit, so that a solid-state spin sensor in the sample unit is polarized and depolarized at an accelerated rate under the action of the free radicals; at a second moment, using the pump light unit to emit a second excitation light beam to the sample unit, so that the solid-state spin sensor generates a fluorescence signal; adjusting the time interval between the first moment and the second moment, and using a detection unit to respectively detect the fluorescence signals of the solid-state spin sensor at multiple different time intervals; and determining the concentration of glucose based on the fluorescence signals of the solid-state spin sensor at multiple different time intervals.

[0014] According to an embodiment of the present invention, before using the pump light unit to emit a second excitation light beam to the sample unit so that the solid-state spin sensor generates a fluorescence signal, it also includes using the control field unit to emit an electromagnetic field to the sample unit to regulate the quantum state of the solid-state spin sensor.

[0015] According to an embodiment of the present invention, determining the concentration of glucose based on the fluorescence signal of the solid-state spin sensor at multiple different time intervals includes: determining the population-evolution time curve based on the fluorescence signal of the solid-state spin sensor at multiple different time intervals; obtaining the depolarization rate of the solid-state spin sensor under the action of free radicals based on the population-evolution time curve; and determining the concentration of glucose based on the depolarization rate.

[0016] According to the quantum enhanced glucose detection device provided by the present invention, the free radicals after the glucose catalytic reaction are directly detected by a solid-state spin sensor, and no longer rely on a specific reducing agent chromogen; and because the solid-state spin sensor only detects free radical signals within its own surrounding range, the sample dosage can be greatly reduced to below nanoliters and the spatial resolution can be improved to the nanometer scale. While increasing the detection limit by one to two orders of magnitude, the sample dosage is also reduced to achieve excellent spatial resolution. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings, in which:

[0018] Figure 1 A schematic diagram showing the overall structure of a quantum enhanced glucose detection device according to an embodiment of the present invention;

[0019] Figure 2 A schematic diagram of a sample unit structure according to an embodiment of the present invention is shown;

[0020] Figure 3 A schematic structural diagram of a sample unit according to another embodiment of the present invention is shown;

[0021] Figure 4 A schematic diagram of a sample unit and a manipulation field unit according to an embodiment of the present invention is shown;

[0022] Figure 5 A schematic diagram showing the internal structure of an excitation light device of a pump light unit according to an embodiment of the present invention is shown;

[0023] Figure 6 A schematic diagram of the internal structure of a detection unit according to an embodiment of the present invention is shown;

[0024] Figure 7 A schematic diagram showing the internal structure of a detection unit according to another embodiment of the present invention is shown;

[0025] Figure 8 A flow chart showing a glucose detection method according to an embodiment of the present invention; and

[0026] Fig. 9FIG. 4 shows a time series of blood glucose concentration detection according to an embodiment of the present invention.

[0027] Reference numerals:

[0028] 1. Sample unit;

[0029] 11. Mix the solution;

[0030] 12. Solid-state spin sensor;

[0031] 13. Sample micro chamber;

[0032] 14. Solid-state spin probe;

[0033] 15. Piezoelectric translation stage;

[0034] 2. Pump light unit;

[0035] 21. Excitation light device;

[0036] 211. Light source;

[0037] 212. First wave film;

[0038] 213. Polarization beam splitter;

[0039] 214. Acousto-optic modulator;

[0040] 215. Second wave film;

[0041] 216. First reflector;

[0042] 217. Second reflector;

[0043] 218. Third reflector;

[0044] 219. A first collimator;

[0045] 220. A second collimator;

[0046] 22. Dichroic mirror;

[0047] 23. Objective lens;

[0048] 3. Detection unit;

[0049] 31. Filter;

[0050] 32. First lens;

[0051] 33. Pinhole;

[0052] 34. Second lens;

[0053] 35. The third lens;

[0054] 36. Single photon detector;

[0055] 37. Thin film spectrometer;

[0056] 38. The fourth lens;

[0057] 39. CCD camera;

[0058] 4. Control field unit;

[0059] 41. Microwave source;

[0060] 42. Microstrip antenna. DETAILED DESCRIPTION

[0061] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

[0062] The terms used herein are only for describing specific embodiments and are not intended to limit the present invention. The terms "comprise", "include", etc. used herein indicate the existence of features, steps, operations and / or components, but do not exclude the existence or addition of one or more other features, steps, operations or components.

[0063] All terms used herein, including technical and scientific terms, have the meanings commonly understood by those skilled in the art, unless otherwise defined. It should be noted that the terms used herein should be interpreted as having a meaning consistent with the context of this specification, and should not be interpreted in an idealized or overly rigid manner.

[0064] When using expressions such as "at least one of A, B, and C, etc.", it should generally be interpreted as the meaning of the expression generally understood by those skilled in the art. For example, "a system having at least one of A, B, and C" should include but not be limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc. When using expressions such as "at least one of A, B, or C, etc.", it should generally be interpreted as the meaning of the expression generally understood by those skilled in the art. For example, "a system having at least one of A, B, or C" should include but not be limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.

[0065] It should also be noted that the directional terms mentioned in the embodiments, such as "upper", "lower", "front", "back", "left", "right", etc., are only reference directions of the drawings and are not intended to limit the scope of protection of the present invention. Throughout the drawings, the same elements are represented by the same or similar reference numerals. Conventional structures or configurations will be omitted when they may cause confusion in the understanding of the present invention.

[0066] Figure 1 A schematic diagram showing the overall structure of a quantum enhanced glucose detection device according to an embodiment of the present invention is shown.

[0067] like Figure 1 As shown, the quantum enhanced glucose detection device provided by the present invention includes a sample unit 1, a pump light unit 2, a solid-state spin sensor 12 and a detection unit 3. The sample unit 1 can be used to accommodate the reaction of a mixed solution 11 of glucose and a catalyst to generate free radicals. The pump light unit 2 is used to generate an excitation light beam and emit the excitation light beam to the sample unit 1. The solid-state spin sensor 12 is arranged in the sample unit 1, and can be polarized in response to the excitation of the first excitation light beam emitted by the pump light unit 2, and accelerate depolarization in response to the action of free radicals; the solid-state spin sensor 12 also generates a fluorescence signal in response to the excitation of the second excitation light beam emitted by the pump light unit 2. The detection unit 3 is suitable for receiving the fluorescence signal generated by the solid-state spin sensor 12, and determining the concentration of glucose based on the fluorescence signal.

[0068] In such an embodiment, the free radicals after the glucose catalytic reaction are directly detected by the solid-state spin sensor 12, which no longer relies on a specific reducing agent chromogen. And because the solid-state spin sensor 12 only detects free radical signals within a small range around itself, the sample amount can be greatly reduced to less than nanoliters and the spatial resolution can be improved to the nanometer scale. While increasing the detection limit by one to two orders of magnitude, the sample amount can also be reduced to achieve excellent spatial resolution.

[0069] According to an embodiment of the present invention, the catalyst includes a glucose oxidation catalyst and a hydrogen peroxide catalyst. The glucose catalyst can be any catalyst that can catalyze the oxidation and decomposition of glucose to produce hydrogen peroxide, such as gold nanoparticles and glucose oxidase (GOD); the hydrogen peroxide catalyst can be any catalyst and catalytic method that can accelerate the decomposition of hydrogen peroxide to produce free radicals, such as nanoparticles containing iron atoms, nanodiamonds or laser irradiation catalysis. Glucose generates hydrogen peroxide under the action of the glucose oxidation catalyst, and then further generates hydroxyl radicals under the action of the hydrogen peroxide catalyst.

[0070] According to an embodiment of the present invention, Figure 1As shown, the pump light unit 2 includes an excitation light device 21, a dichroic mirror 22 and an objective lens 23. The excitation light beam emitted by the excitation light device 21 is directed toward the objective lens 23 through the dichroic mirror 22, and then focused onto the solid-state spin sensor 12 through the objective lens 23. The fluorescence signal generated by the solid-state spin sensor 12 is also collected by the objective lens 23 and reflected toward the dichroic mirror 22. Because the wavelength of the fluorescence signal is relatively large, it is reflected into the detection unit 3 by the dichroic mirror 22, so that the detection unit 3 detects the fluorescence signal.

[0071] In an illustrative embodiment, Figure 1 As shown, the sample unit 1 further includes a piezoelectric displacement stage 15. The sample is placed on the piezoelectric displacement stage 15 and can be moved with nanometer-level precision.

[0072] According to an embodiment of the present invention, the light source 211 may be a laser, a light emitting diode or a laser diode.

[0073] According to an embodiment of the present invention, the solid-state spin sensor 12 may be a diamond / nano-diamond particle containing a nitrogen vacancy (NV) color center, or a silicon carbide containing a divacancy color center (VV), or a silicon carbide containing a boron vacancy color center (VB - ) and gallium arsenide containing nickel-nitrogen vacancies and other color centers, all of which can be used for room-temperature light-detected magnetic resonance measurements.

[0074] According to an embodiment of the present invention, the solid-state spin sensor 12 can transition from a ground state to an excited state under the excitation of an excitation light beam of a specific wavelength, thereby polarizing the color center of the solid-state spin sensor 12. For example, corresponding to the spin sensor of the NV color center, an excitation light beam with a wavelength of 532nm or 593nm can be selected for excitation to polarize the NV color center.

[0075] According to an embodiment of the present invention, after the solid-state spin sensor 12 is polarized, it will spontaneously relax to a thermal equilibrium state, i.e., depolarize. The electron spin of the free radicals in the mixed solution will accelerate the speed of the NV color center depolarization. The more free radicals there are, the faster the NV color center depolarizes. The state of the solid-state spin (i.e., the population) will affect the intensity of the fluorescence signal generated by the solid-state spin sensor 12. By detecting the fluorescence signal of the solid-state spin sensor 12 after the free radicals have affected it for a period of time, the concentration of free radicals in the mixed solution can be reflected, thereby determining the concentration of glucose.

[0076] Figure 2 A schematic diagram of the structure of a sample unit according to an embodiment of the present invention is shown.

[0077] According to an embodiment of the present invention, Figure 2 As shown, the sample unit 1 includes a sample microchamber 13 , and the solid-state spin sensor 12 is disposed at the bottom of the sample microchamber 13 and constitutes the lower bottom surface of the sample microchamber 13 .

[0078] Specifically, Figure 2 As shown, the sample microchamber 13 includes an outer wall, and a channel for inputting the mixed solution 11 is arranged above the outer wall. The solid-state spin sensor 12 can be a diamond rich in solid-state spin probes 14, which are arranged at the bottom of the outer wall, and a holding space for holding the mixed solution 11 is formed between the outer wall and the diamond. The outer shell can also be provided with a light-transmitting area to allow the transmission of an excitation beam or fluorescence.

[0079] In such an embodiment, a mixed solution 11 of glucose and a catalyst is dripped onto the upper surface of the diamond. Since the solid-state spin probe 14 only detects free radical signals near itself, it can emit an excitation light beam with a larger spot, so that the solid-state spin sensor 12 excites multiple electron spins at the same time, and the multiple electron spins can respectively detect free radicals at different spatial locations of the mixed solution 11. Different electron spin signals can be collected by the detection unit 3, and the detection of glucose concentrations at different spatial locations of the mixed solution 11 in the sample microchamber 13 can be realized.

[0080] In another illustrative embodiment, the solid-state spin sensor 12 may also use solid-state spin nanoparticles. In this case, the solid-state spin sensor 12 does not constitute the lower bottom surface of the sample microchamber 13, but the solid-state spin nanoparticles are placed in different spatial positions of the sample microchamber 13 to respectively detect the glucose concentrations at different spatial positions of the mixed solution 11.

[0081] Figure 3 FIG. 4 is a schematic structural diagram of a sample unit according to another embodiment of the present invention.

[0082] According to an embodiment of the present invention, Figure 3 As shown, the sample microchamber 13 includes a plurality of sample microchambers 13 , and the plurality of sample microchambers 13 are arranged on the top of the solid-state spin sensor 12 at intervals.

[0083] Specifically, Figure 3 As shown, the sample unit 1 includes an outer wall and a plurality of inner walls arranged inside the outer wall, and the inner walls can be arranged at intervals on the upper surface of the diamond, so that a plurality of sample micro chambers 13 are formed between different inner walls and between the inner wall and the outer wall to respectively accommodate a plurality of groups of mixed solutions 11. The diamond part at the bottom of each sample micro chamber 13 contains a solid spin probe 14.

[0084] In such an embodiment, a plurality of high-throughput sample microchambers 13 are arranged above the diamond, and since the solid-state spin probe 14 only detects free radical signals nearby, the solid-state spin sensor 12 simultaneously excites a plurality of electron spins through the excitation light beam, and respectively detects free radicals in the mixed solution 11 in different sample microchambers 13. Different electron spin signals can be collected by the detection unit, and simultaneous detection of multiple groups of samples can be achieved.

[0085] Figure 4 A schematic diagram of a sample unit and a manipulation field unit according to an embodiment of the present invention is shown.

[0086] According to an embodiment of the present invention, Figure 1 and 4 As shown, the glucose detection device further includes a control field unit 4 adapted to emit an electromagnetic field to the sample unit 1 to regulate the quantum state of the solid-state spin sensor 12 .

[0087] In such an embodiment, the solid-state spin sensor 12 can be precisely quantum controlled by the control field. When the solid-state spin sensor 12 is in a specific quantum state, the rate at which it spontaneously decays back to the thermal equilibrium state can be slowed down, so when measuring the effect of free radicals on its depolarization rate, it will be more sensitive and accurate.

[0088] According to an embodiment of the present invention, Figure 4 As shown, the control field unit 4 includes a microwave source 41 and a microstrip antenna 42. The microwave source 41 is suitable for emitting pulse microwaves; the microstrip antenna 42 is connected to the sample unit 1 and is suitable for transmitting the pulse microwaves into the sample unit 1 to apply an electromagnetic field to the solid-state spin sensor 12.

[0089] According to an embodiment of the present invention, the microwave source 41 may further include a microwave amplifying device and a switching device. The microwave amplifying device is used to enhance the power of the microwave field.

[0090] According to an embodiment of the present invention, the manipulation field unit 4 can form a manipulation field around the solid-state spin sensor 12 by applying pulses of a specific length and frequency, and the manipulation field can resonate with the electron spin of the solid-state spin sensor 12, thereby changing its spin state. By designing a manipulation field sequence, the electron spin of the solid-state spin sensor 12 (such as the NV color center) can be regulated to a specific quantum state.

[0091] According to an embodiment of the present invention, the control field can be a single-frequency control field, or a dual-frequency control field synthesized by a first frequency control field and a second frequency control field, or an amplitude-modulated control field, a frequency-modulated control field, a phase-modulated control field, or a control field modulated by amplitude shift keying, a control field modulated by frequency shift keying, a control field modulated by phase shift keying, or a modulated control field or a single-frequency combined pulse control field.

[0092] Figure 5 A schematic diagram of the internal structure of an excitation light device 21 of a pump light unit according to an embodiment of the present invention is shown.

[0093] According to an embodiment of the present invention, Figure 5As shown, the pump light unit 2 includes an excitation light device 21, which includes a light source 211, a first wave plate 212, a polarization beam splitter 213, an acousto-optic modulator 214, a second wave plate 215, a first reflector 216 and a collimator.

[0094] According to an embodiment of the present invention, the light source 211 is used to generate an excitation light beam of a wavelength corresponding to the solid-state spin sensor 12. The first wave plate 212 is arranged downstream of the optical path of the light source 211, and is used to adjust the polarization direction of the excitation light beam emitted from the first wave plate 212. The polarization beam splitter 213 is arranged downstream of the optical path of the first wave plate 212, and is used to split the excitation light beam to the target path according to the polarization direction. The acousto-optic modulator 214 is arranged downstream of the optical path of the polarization beam splitter 213, and is suitable for adjusting the pulse width of the excitation light beam. The second wave plate 215 is arranged downstream of the optical path of the acousto-optic modulator 214; it is used to secondary adjust the polarization direction of the excitation light beam emitted from the second wave plate 215. The first reflector 216 is arranged downstream of the optical path of the second wave plate 215, and is suitable for reflecting the excitation light beam back to the second wave plate 215. The collimator is arranged downstream of the optical path of the polarization beam splitter 213, and is used to spatially filter the excitation light beam and convert it into a collimated light beam output.

[0095] In an illustrative embodiment, Figure 5 As shown, the excitation light beam is first emitted from the light source 211 to the first wave plate 212. The first wave plate 212 is a half-wave plate, which can allow the excitation light beam to pass through the polarization beam splitter 213, and then be emitted to the second wave plate 215 through the acousto-optic modulator 214. The second wave plate 215 can be a quarter wave plate. After passing through the second wave plate 215, it is emitted back through the first transmitting mirror, and after passing through the second wave plate 215 and the acousto-optic modulator 214, it is emitted to the polarization beam splitter 213. At this time, after the polarization direction is changed again by the quarter wave plate, the excitation light beam can be refracted by the polarization beam splitter 213 to the second reflector 217 and the third reflector 218, and finally a collimated light beam is output through the first collimator 219 and the second collimator 220.

[0096] Figure 6 A schematic diagram of the internal structure of a detection unit according to an embodiment of the present invention is shown.

[0097] According to an embodiment of the present invention, Figure 6As shown, the detection unit 3 includes a filter 31, a first lens 32, a second lens 34, a third lens 35 and a single-photon detector 36. The first lens 32 is arranged downstream of the optical path of the fluorescent signal, and is suitable for focusing the fluorescent signal to the pinhole 33 to filter the fluorescent signal. The second lens 34 is arranged downstream of the optical path of the first lens 32, and is suitable for collimating the fluorescent signal. The third lens 35 is arranged downstream of the optical path of the second lens 34, and is suitable for converging the fluorescent signal. The single-photon detector 36 is used to receive the fluorescent signal converged by the third lens 35.

[0098] In an illustrative embodiment, Figure 6 As shown, after the fluorescence signal is emitted from the sample unit 1, it is focused by the first lens 32 and converged on the pinhole 33, and then collimated by the second lens 34 after being spatially filtered by the pinhole 33, and then converged by the third mirror into the single photon detector 36 to detect the fluorescence signal.

[0099] In an illustrative embodiment, the detection unit 3 may further be provided with a filter 31 before the first lens 32 for filtering the fluorescence signal to filter out the fluorescence in a non-collection band so that only the fluorescence emitted by the sensor can pass through.

[0100] Figure 7 A schematic diagram of the internal structure of a detection unit according to another embodiment of the present invention is shown.

[0101] According to an embodiment of the present invention, Figure 7 As shown, the detection unit 3 is Figure 6 Based on the illustrated embodiment, a thin film spectrometer 37 , a fourth lens 38 and a CCD camera 39 may be further included.

[0102] Specifically, the thin film spectrometer 37 is disposed between the filter 31 and the first lens 32 , and the fluorescence signal can be detected by the CCD camera 39 after passing through the thin film spectrometer 37 and the fourth lens 38 .

[0103] In an illustrative embodiment, different pixel units of a CCD camera may be used to detect the imaging of glucose concentrations of a sample at different spatial locations.

[0104] Figure 8 A flow chart of a glucose detection method according to an embodiment of the present invention is shown.

[0105] like Figure 8 As shown, the glucose detection method includes operations S810 to S850.

[0106] In operation S810, a mixed solution of glucose and a catalyst is added into the sample unit to react and generate free radicals.

[0107] In operation S820, at a first moment, a pump light unit is used to emit a first excitation light beam to a sample unit, so that a solid-state spin sensor in the sample unit is polarized and depolarized at an accelerated rate under the action of free radicals.

[0108] In operation S830, at a second time, a second excitation light beam is emitted to the sample unit by using the pump light unit, so that the solid-state spin sensor generates a fluorescent signal.

[0109] In operation S840, the time interval between the first moment and the second moment is adjusted, and the fluorescence signals of the solid-state spin sensor at a plurality of different time intervals are respectively detected by a detection unit.

[0110] In operation S850, the concentration of glucose is determined according to the fluorescence signal of the solid-state spin sensor at a plurality of different time intervals.

[0111] According to an embodiment of the present invention, after glucose generates free radicals under the catalysis of the glucose oxidation catalyst and the hydrogen peroxide catalyst, the pump light unit first emits a first excitation light beam of a specific wavelength to the solid-state spin sensor, so that the solid-state spin state of the solid-state spin sensor transitions from the ground state to the excited state, and polarization occurs. At this time, the free radicals generated in the sample unit will accelerate the decay of the solid-state spin state from the excited state to the thermal equilibrium state. After waiting for a period of time, the pump light unit is used to emit a second excitation light beam to excite the fluorescence signal of the solid-state spin sensor, and the fluorescence signal can be detected by the detection unit.

[0112] According to an embodiment of the present invention, in a solid-state spin system, such as a nitrogen-vacancy (NV) color center in diamond, the spin state can directly affect the fluorescence intensity. For example, in an NV color center, different states of the electron spin (e.g. |m S =0> and |m S =±1>) will show different fluorescence emission characteristics when excited by laser of specific frequency. Through excitation, microwave pulse manipulation and measurement of fluorescence intensity, the solid-state spin state can be indirectly detected and manipulated.

[0113] According to an embodiment of the present invention, by adjusting the time interval between the first moment and the second time, repeating operations S820~S830, and using the detection unit to obtain fluorescence signals at different time intervals, the depolarization rate of the solid-state spin state (occupancy) under the influence of free radicals can be determined. Since the more free radicals there are, the faster the depolarization rate, the concentration of the free radicals can be determined by the depolarization rate, thereby determining the concentration of glucose.

[0114] Fig. 9 FIG. 4 shows a time series of blood glucose concentration detection according to an embodiment of the present invention.

[0115] like Fig. 9As shown, at a first moment, a first excitation light beam 910 is emitted through the pump spectrum unit, and after a time interval T, a second excitation light beam 920 is emitted through the pump spectrum unit at a second moment, and at the same time, at the second moment, a fluorescence signal 930 of the solid-state spin sensor is detected by the detection unit. By changing the time interval T, the fluorescence signals 930 of the solid-state spin sensor at multiple different time intervals can be obtained.

[0116] According to an embodiment of the present invention, before using the pump light unit to emit a second excitation light beam to the sample unit so that the solid-state spin sensor generates a fluorescence signal, it also includes using the control field unit to emit an electromagnetic field to the sample unit to regulate the quantum state of the solid-state spin sensor.

[0117] According to an embodiment of the present invention, after the sample to be tested and the catalyst are placed in the sample unit to react and generate free radicals, the pump light unit can be used to emit excitation light of a specific wavelength to initialize the solid-state spin sensor, and the control field device can control the quantum state of the solid-state spin by applying a pulse of a specific length, so that the solid-state spin is in a specific quantum state. The solid-state spin can relax from a specific quantum state to a thermal equilibrium state, slowing down the relaxation rate, and being more sensitive when measuring the influence of free radicals on its depolarization rate.

[0118] According to an embodiment of the present invention, determining the concentration of glucose based on the fluorescence signal of the solid-state spin sensor at multiple different time intervals includes: determining the population-evolution time curve based on the fluorescence signal of the solid-state spin sensor at multiple different time intervals; obtaining the depolarization rate of the solid-state spin sensor under the action of free radicals based on the population-evolution time curve; and determining the concentration of glucose based on the depolarization rate.

[0119] In such an embodiment, the fluorescence signal is measured by the solid-state spin sensor, and no destructive treatment or sampling of the sample is required, thereby realizing a non-invasive detection method. The population-evolution time curve reflects the depolarization process of the solid-state spin sensor under the action of free radicals. By analyzing this curve, the depolarization rate can be accurately calculated, and by measuring the depolarization rate, the concentration of glucose can be indirectly inferred.

[0120] The embodiments of the present invention are described above. However, these embodiments are only for the purpose of illustration, and are not intended to limit the scope of the present invention. Although each embodiment is described above, it does not mean that the measures in each embodiment cannot be used in combination. The scope of the present invention is defined by the attached claims and their equivalents. Without departing from the scope of the present invention, those skilled in the art may make various substitutions and modifications, which should all fall within the scope of the present invention.

Claims

1. A quantum enhanced glucose detection device, characterized in that: include: A sample unit (1) is adapted to receive a reaction of a mixed solution (11) of glucose and a catalyst to generate free radicals; A pump light unit (2), adapted to generate an excitation light beam and emit the excitation light beam to the sample unit (1); A solid-state spin sensor (12) is configured as a sensor for optical detection of magnetic resonance measurements and containing a solid-state spin carrier of a color center, and is disposed in the sample unit (1), and is adapted to generate polarization in response to excitation by a first excitation light beam emitted by the pump light unit (2), and to accelerate depolarization in response to the action of the free radicals, and the solid-state spin sensor (12) also generates a fluorescence signal in response to excitation by a second excitation light beam emitted by the pump light unit (2); The detection unit (3) is adapted to receive the fluorescence signal generated by the solid-state spin sensor (12), and determine the depolarization rate of the solid-state spin sensor (12) under the action of free radicals based on the fluorescence signal, so as to determine the concentration of glucose according to the depolarization rate.

2. The device according to claim 1, characterized in that The sample unit (1) comprises a sample microchamber (13), and the solid-state spin sensor (12) is arranged at the bottom of the sample microchamber (13) and constitutes the lower bottom surface of the sample microchamber (13).

3. The device according to claim 2, characterized in that The sample microchamber (13) comprises a plurality of sample microchambers (13), and the plurality of sample microchambers (13) are arranged at intervals on the top of the solid-state spin sensor (12).

4. The device according to claim 1, characterized in that It also includes a control field unit (4) adapted to emit an electromagnetic field to the sample unit (1) so as to regulate the quantum state of the solid-state spin sensor (12).

5. The device according to claim 4, characterized in that The control field unit (4) comprises: a microwave source (41) adapted to emit pulsed microwaves; and A microstrip antenna (42) is connected to the sample unit (1) and is suitable for transmitting the pulse microwave into the sample unit (1) to apply an electromagnetic field to the solid-state spin sensor (12).

6. The device according to any one of claims 1 to 5, characterized in that: The pump light unit (2) comprises: A light source (211) adapted to generate an excitation light beam having a wavelength corresponding to the solid-state spin sensor (12); A first wave plate (212), arranged downstream of the optical path of the light source (211), and used for adjusting the polarization direction of the excitation light beam emitted from the first wave plate (212); A polarization beam splitter (213), arranged downstream of the optical path of the first wave plate (212), and used for splitting the excitation light beam into a target path according to the polarization direction; an acousto-optic modulator (214), arranged downstream of the optical path of the polarization beam splitter (213), and adapted to adjust the pulse width of the excitation light beam; A second wave plate (215) is arranged downstream of the optical path of the acousto-optic modulator (214); and is used for secondary adjustment of the polarization direction of the excitation light beam emitted from the second wave plate (215); A first reflector (216), disposed downstream of the optical path of the second wave plate (215), and adapted to reflect the excitation light beam back to the second wave plate (215); A collimator is arranged downstream of the optical path of the polarization beam splitter (213) and is used to spatially filter the excitation light beam and convert it into a collimated light beam output.

7. The device according to any one of claims 1 to 5, characterized in that: The detection unit (3) comprises: A first lens (32) is arranged downstream of the optical path of the fluorescent signal, and is suitable for focusing the fluorescent signal onto the pinhole (33) to filter the fluorescent signal; A second lens (34), disposed downstream of the optical path of the first lens (32), and adapted to collimate the fluorescent signal; A third lens (35), disposed downstream of the optical path of the second lens (34), adapted to converge the fluorescent signal; and The single-photon detector (36) is used to receive the fluorescent signal converged by the third lens (35).

8. A method for detecting glucose based on the device according to any one of claims 1 to 7, characterized in that: include: Adding a mixed solution of glucose and a catalyst into the sample unit to react and generate free radicals; At a first moment, a pump light unit is used to emit a first excitation light beam to the sample unit, so that the solid-state spin sensor in the sample unit is polarized and depolarized at an accelerated rate under the action of the free radicals; At a second moment, a pump light unit is used to emit a second excitation light beam to the sample unit, so that the solid-state spin sensor generates a fluorescence signal; adjusting the time interval between the first moment and the second moment, and using a detection unit to respectively detect the fluorescence signals of the solid-state spin sensor at a plurality of different time intervals; The concentration of glucose is determined according to the fluorescence signal of the solid-state spin sensor at a plurality of different time intervals.

9. The method according to claim 8, characterized in that Before the pump light unit is used to emit a second excitation light beam to the sample unit so that the solid-state spin sensor generates a fluorescent signal, the method further includes: The control field unit is used to emit an electromagnetic field to the sample unit to regulate the quantum state of the solid-state spin sensor.

10. The method according to claim 8 or 9, characterized in that: Determining the concentration of glucose according to the fluorescence signal of the solid-state spin sensor at a plurality of different time intervals comprises: Determining a population-evolution time curve according to the fluorescence signal of the solid-state spin sensor at a plurality of different time intervals; According to the population-evolution time curve, the depolarization rate of the solid-state spin sensor under the action of the free radical is obtained; Based on the depolarization rate, the glucose concentration is determined.

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