Time domain reading device and in vitro diagnosis device for solid-state spin quantum

Abstract

The invention provides a time domain reading device for solid-state spin quantum and an in-vitro diagnosis device, and relates to the technical field of in-vitro diagnosis. The time domain reading device for the solid-state spin quantum comprises a laser module which is used for exciting the solid-state spin quantum to generate a fluorescence signal and enabling the solid-state spin quantum to be subjected to spin polarization to be in a 0 state; the microwave module is used for modulating the spin energy level of the solid-state spin quantum to + / -1 state; the photoelectric detector is used for detecting a fluorescence signal generated by the solid-state spin quantum and generating a photon signal; the gating system is respectively connected with the laser module and the photoelectric detector and is used for acquiring a photon signal transmitted by the photoelectric detector in a first time period according to the time when the laser module generates the laser signal; and the data analysis unit is connected with the door control system and is used for acquiring the photon signals forwarded by the door control system so as to carry out signal analysis. Solid state spin quanta are excited to obtain photon signals, and the signal-to-noise ratio of the obtained photon signals is enhanced by a gating system to improve diagnostic sensitivity.

Description

Technical Field

[0001] The present application relates to the field of in vitro diagnostic technology, and in particular to a time domain reading device and in vitro diagnostic device for solid-state spin quanta. Background Art

[0002] In vitro diagnosis usually combines fluorescent markers with the pathogen target to be detected, mixes with the patient's body fluid sample, and then drops into a test strip with the same corresponding target marker. The disease is diagnosed by observing whether the test strip has a fluorescent reaction. At present, the commonly used technical means of in vitro diagnostic technology include colloidal gold-based in vitro diagnostic technology. However, the fluorescence wavelength of colloidal gold has a large overlap with the test strip and the ambient daylight noise. Judging the diagnostic result only from the luminescence will result in a large number of false positive / false negative results.

[0003] The diamond nitrogen vacancy (NV) color center consists of a nitrogen atom that replaces a carbon atom in the diamond lattice and an adjacent lattice vacancy. At room temperature, the spin coherence time of the NV color center can reach up to the order of ms, making it the most excellent solid-state spin quantum. Based on the electron spin energy level and optical magnetic resonance technology of a single diamond NV color center, precise measurements of many physical quantities can be achieved. Diamond has the advantages of high and low temperature resistance, acid and alkali resistance, high pressure resistance, etc., and has excellent environmental adaptability. Based on these characteristics, NV color centers have important application value in the field of precision measurement.

[0004] In recent years, based on the spin-orbit energy level characteristics of NV centers, studies have shown that phase-locked amplification technology can be used to achieve sensitive detection of NV centers in an environment with strong background light noise, thereby realizing medical in vitro diagnostic application research based on nanodiamonds and phase-locked amplification technology. The phase-locked amplification diagnostic technology based on nanodiamond NV centers can effectively demodulate the luminescence and noise light of nanodiamond NV centers through modulation and demodulation, greatly improving the diagnostic sensitivity and reducing the misdiagnosis rate. However, before signal demodulation, it only filters part of the wavelength of the background noise and fails to achieve good noise reduction. Therefore, its diagnostic sensitivity is still limited in practical use. Summary of the invention

[0005] In order to solve at least one of the above problems, the present application proposes a time-domain reading device and an in vitro diagnostic device for solid-state spin quanta.

[0006] According to the first aspect of the present application, at least one embodiment of the present application provides a time-domain reading device for solid-state spin quanta, comprising: a laser module, used to generate a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and polarize the solid-state spin quantum spin to a 0 state; a microwave module, used to generate a spin resonance microwave pulse to modulate the solid-state spin quantum spin energy level to a ±1 state; a photodetector, used to detect the fluorescence signal generated by the solid-state spin quantum and generate a photon signal; a gating system, connected to the laser module and the photodetector respectively, for obtaining the photon signal transmitted by the photodetector within a first time period according to the time when the laser module generates the laser signal; a data analysis unit, connected to the gating system, for obtaining the photon signal forwarded by the gating system for signal analysis.

[0007] For example, in some embodiments of the present application, the laser module includes a picosecond pulse laser.

[0008] For example, in some embodiments of the present application, the photon signal includes: an electrical pulse signal and / or a voltage amplitude signal.

[0009] For example, in some embodiments of the present application, the gating system includes: a time-correlated counter, used to obtain the photon signal transmitted by the photodetector; and a gating switch, used to output a control signal based on the time of the laser signal generated by the laser module so that the time-correlated counter obtains the photon signal transmitted by the photodetector within the first time period.

[0010] For example, in some embodiments of the present application, the data analysis unit is also connected to the microwave module to modulate the microwave module and demodulate the photon signal of the photodetector according to the modulation frequency.

[0011] For example, in some embodiments of the present application, the solid-state spin quantum includes: a diamond NV color center and / or a silicon carbide color center.

[0012] According to the second aspect of the present application, at least one embodiment of the present application provides a time-domain reading device for solid-state spin quanta, comprising: a laser module, used to generate a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and polarize the solid-state spin quantum spin to a 0 state; a microwave module, used to generate a spin resonance microwave pulse to modulate the solid-state spin quantum spin energy level to a ±1 state; a photodetector, used to detect the fluorescence signal generated by the solid-state spin quantum and generate a photon signal; a gating system, connected to the laser module and the photodetector respectively, for outputting a control signal to control the photodetector to obtain the fluorescence signal generated by the solid-state spin quantum within a first time period according to the time when the laser module generates the laser signal; a data analysis unit, connected to the photodetector, for obtaining the photon signal forwarded by the photodetector for signal analysis.

[0013] For example, in some embodiments of the present application, the data analysis unit is also connected to the microwave module to modulate the microwave module and demodulate the photon signal of the photodetector according to the modulation frequency.

[0014] For example, in some embodiments of the present application, the solid-state spin quantum includes: a diamond NV color center and / or a silicon carbide color center.

[0015] According to the second aspect of the present application, at least one embodiment of the present application provides an in vitro diagnostic device, comprising: a solid-state spin quantum; a time domain reading device as described in any one of the first aspect and the second aspect, used to excite the solid-state spin quantum to obtain a photon signal, and enhance the signal-to-noise ratio of the obtained photon signal through a gating system to improve diagnostic sensitivity.

[0016] Through the above-mentioned example embodiments, the present application provides a time-domain reading device and an in vitro diagnostic device for solid-state spin quanta, which is based on the technical solution of time-domain reading of signal fluorescence by pulse excitation and gating system, and only collects signal light data of the time-domain gating window, which can effectively reduce noise and greatly improve the signal-to-noise ratio of the demodulated data, thereby further improving the diagnostic sensitivity.

[0017] It should be understood that the foregoing general description and the following detailed description are exemplary only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] By describing in detail exemplary embodiments thereof with reference to the accompanying drawings, the above and other objects, features and advantages of the present application will become more apparent. The accompanying drawings described below are only some embodiments of the present application, and are not intended to limit the present application.

[0019] Figure 1A schematic diagram of a time-domain reading device for solid-state spin quanta is shown according to an exemplary embodiment;

[0020] Figure 2 A schematic diagram showing a fluorescence spectrum comparison between a nitrocellulose test paper and a NV color center according to an exemplary embodiment;

[0021] Figure 3 A schematic diagram showing a comparison of excited state lifetimes of a nitrocellulose test paper and an NV color center according to an exemplary embodiment;

[0022] Figure 4 Another embodiment of a schematic diagram of an exemplary time-domain reading device for solid-state spin quanta is shown. DETAILED DESCRIPTION

[0023] Example embodiments will now be described more fully with reference to the accompanying drawings. However, example embodiments can be implemented in many forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this application will be comprehensive and complete and will fully convey the concepts of the example embodiments to those skilled in the art. The same reference numerals in the figures represent the same or similar parts, and thus their repeated description will be omitted.

[0024] The described features, structures or characteristics may be combined in one or more embodiments in any suitable manner. In the following description, many specific details are provided to provide a full understanding of the embodiments of the present disclosure. However, those skilled in the art will appreciate that the technical solutions of the present disclosure may be practiced without one or more of these specific details, or other modes, components, materials, devices, etc. may be adopted. In these cases, known structures, methods, devices, implementations, materials or operations will not be shown or described in detail.

[0025] The flowcharts shown in the accompanying drawings are only exemplary and do not necessarily include all the contents and operations / steps, nor must they be executed in the order described. For example, some operations / steps can be decomposed, and some operations / steps can be combined or partially combined, so the actual execution order may change according to actual conditions.

[0026] The terms "first", "second", etc. in the specification and claims of this application and the above-mentioned drawings are used to distinguish different objects, rather than to describe a specific order. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not limited to the listed steps or units, but optionally includes steps or units that are not listed, or optionally includes other steps or units inherent to these processes, methods, products or devices.

[0027] Those skilled in the art will appreciate that the drawings are merely schematic diagrams of example embodiments, and the modules or processes in the drawings are not necessarily necessary for implementing the present application, and therefore cannot be used to limit the scope of protection of the present application.

[0028] Figure 1 A schematic diagram of a time-domain reading device for solid-state spin quanta is shown according to an exemplary embodiment.

[0029] like Figure 1 As shown, the time-domain reading device 10 for solid-state spin quantum includes: a laser module 101 , a microwave module 102 , a photodetector 103 , a gating system 104 and a data analysis unit 105 .

[0030] Among them, the laser module 101 is used to generate a laser signal to excite the solid-state spin quantum 20 to generate a fluorescence signal and polarize the solid-state spin quantum 20 to a 0 state. The microwave module 102 is used to generate a spin resonance microwave pulse to modulate the spin energy level of the solid-state spin quantum 20 to a ±1 state. The photodetector 103 is used to detect the fluorescence signal generated by the solid-state spin quantum 20 and generate a photon signal. The gating system 104 is connected to the laser module 101 and the photodetector 103 respectively, and is used to obtain the photon signal transmitted by the photodetector 103 within the first time period according to the time of the laser signal generated by the laser module 103. The data analysis unit 105 is connected to the gating system 104, and is used to obtain the photon signal forwarded by the gating system 104 for signal analysis.

[0031] According to some embodiments, the laser module 101 includes a picosecond pulse laser, and uses the picosecond pulse laser to excite the solid-state spin quantum 20 .

[0032] According to some embodiments, the photon signal includes an electrical pulse signal and / or a voltage amplitude signal.

[0033] According to an exemplary embodiment, the photodetector 103 in the present application is in a continuous working mode for acquiring a wavelength-filtered fluorescence signal. The wavelength filtering range can be set by oneself, so that Figure 2 For example, the filter range is set to 607-796 nm, so as to perform preliminary filtering processing on the test paper fluorescence. The acquired fluorescence includes NV fluorescence and remaining test paper fluorescence and generates a photon signal, which is sent to the gating system 104 .

[0034] According to some embodiments, wavelength filtering can be accomplished by a filter, for example, a filter is installed between the solid-state spin quantum 20 and the photodetector 103 to achieve wavelength filtering.

[0035] The gate control system 104 includes a time-related counter 1041 and a gate control switch 1042 .

[0036] The time-correlated counter 1041 is used to obtain the photon signal transmitted by the photodetector 103. The gate switch 1042 is used to output a control signal according to the time when the laser module 101 generates the laser signal so that the time-correlated counter 1041 obtains the photon signal generated by the photodetector in the first time period.

[0037] According to an example embodiment, the data analysis unit 105 is also connected to the microwave module 102 for modulating the microwave module 102 and demodulating the photon signal of the photodetector 103 according to the modulated frequency.

[0038] According to some embodiments, the solid-state spin quantum 20 includes: diamond NV color center and silicon carbide color center, etc. This application only takes this as an example, but is not limited to this.

[0039] This application takes diamond NV color center as an example. The nitrocellulose test paper commonly used in clinical practice has a large fluorescence emission in the visible light band, which has a large overlap with the fluorescence of diamond NV color center, such as Figure 2 However, by measuring the excited state lifetimes of both nitrocellulose test paper and diamond NV color centers, it can be found that the excited state lifetime of nitrocellulose test paper is relatively short, as shown in Figure 3 shown.

[0040] According to an exemplary embodiment, the first time period can be set voluntarily. Figure 3 For example, since the excited state lifetime of diamond NV color center is long, while the excited state lifetime of nitrocellulose test paper is short, the nitrocellulose test paper basically completes the fluorescence photon emission and returns to the ground state within 5ns, so the 6-29ns period is selected as the first period, that is, Figure 3 The time domain gating window in is the first time period. This application only takes this as an example, but the application is not limited to this.

[0041] The present application provides a time-domain reading device for solid-state spin quanta, which is a technical solution for time-domain reading of signal fluorescence based on pulse excitation and gating system. It only collects signal light data of the time-domain gating window, which can effectively reduce noise and greatly improve the signal-to-noise ratio of the demodulated data, further improving the diagnostic sensitivity.

[0042] Figure 4 Another embodiment of a schematic diagram of an exemplary time-domain reading device for solid-state spin quanta is shown.

[0043] The present application also provides a time domain reading device for solid-state spin quantum, such as Figure 4 As shown, the time-domain reading device 10 for solid-state spin quantum includes: a laser module 101 , a microwave module 102 , a photodetector 103 , a gating system 104 and a data analysis unit 105 .

[0044] Among them, the laser module 101 is used to generate a laser signal to excite the solid-state spin quantum 20 to generate a fluorescence signal and polarize the solid-state spin quantum 20 to a 0 state. The microwave module 102 is used to generate a spin resonance microwave pulse to modulate the spin energy level of the solid-state spin quantum 20 to a ±1 state. The photodetector 103 is used to detect the fluorescence signal generated by the solid-state spin quantum 20 and generate a photon signal. The gate control system 104 is connected to the laser module 101 and the photodetector 103 respectively, and is used to control the photodetector 103 to obtain the fluorescence signal generated by the solid-state spin quantum 20 within a first time period according to the time when the laser module 101 generates the laser signal. The data analysis unit 105 is connected to the photodetector 103, and is used to obtain the photon signal forwarded by the photodetector for signal analysis.

[0045] According to some embodiments, the laser module 101 includes a picosecond pulse laser, and uses the picosecond pulse laser to excite the solid-state spin quantum 20 .

[0046] According to some embodiments, the photon signal includes an electrical pulse signal and / or a voltage amplitude signal.

[0047] According to the exemplary embodiment, the photodetector 103 in the present application is in a gated working mode. The photodetector 103 is used to receive a control signal from the gated system 104: when not triggered by the gated system 104, that is, before the first time period, the photodetector 103 is in a closed state; after being triggered by the gated system 104, the photodetector 103 is immediately turned on to perform photoelectric detection in the first time period, collects the fluorescence signal after the set wavelength filtering in the optical path, generates a photon signal, and sends it to the data analysis unit 105.

[0048] The wavelength filter can be set by yourself. Figure 2 For example, the filter range is set to 607-796nm to perform preliminary filtering on the test paper fluorescence.

[0049] In addition, the first period can be set by yourself. Figure 3 For example, since the excited state lifetime of diamond NV color center is long, while the excited state lifetime of nitrocellulose test paper is short, the nitrocellulose test paper basically completes the fluorescence photon emission and returns to the ground state within 5ns, so the 6-29ns period is selected as the first period, that is, Figure 3 The time domain gating window in is the first time period. This application only takes this as an example, but the application is not limited to this.

[0050] According to an example embodiment, the data analysis unit 105 is also connected to the microwave module 102 for modulating the microwave module 102 and demodulating the photon signal of the photodetector 103 according to the modulated frequency.

[0051] According to some embodiments, the solid-state spin quantum 20 includes: diamond NV color center and silicon carbide color center, etc. This application only takes this as an example, but is not limited to this.

[0052] The present application also provides an in vitro diagnostic device, such as Figure 1 or Figure 4 As shown, the in vitro diagnostic device includes: a solid-state spin quantum 20 and any time domain reading device 10 as described above, which is used to excite the solid-state spin quantum to obtain a photon signal, and enhance the signal-to-noise ratio of the obtained photon signal through a gating system to improve the diagnostic sensitivity. The specific working principle of the time domain reading device 10 is as described above, so it will not be repeated here.

[0053] It should be clearly understood that the present application describes how to form and use specific examples, but the present application is not limited to any details of these examples. On the contrary, based on the teaching of the content disclosed in the present application, these principles can be applied to many other embodiments.

[0054] In addition, it should be noted that the above figures are only schematic illustrations of the processes included in the method according to the exemplary embodiments of the present application, and are not intended to be limiting. It is easy to understand that the processes shown in the above figures do not indicate or limit the time sequence of these processes. In addition, it is also easy to understand that these processes can be performed synchronously or asynchronously, for example, in multiple modules.

[0055] The exemplary embodiments of the present application are specifically shown and described above. It should be understood that the present application is not limited to the detailed structures, configurations or implementations described herein; on the contrary, the present application is intended to cover various modifications and equivalent configurations included in the spirit and scope of the appended claims.

Claims

1. A time domain reading device for solid-state spin quantum, characterized in that: include: A laser module, used for generating a laser signal to excite the solid-state spin quantum to generate a fluorescent signal, and to polarize the solid-state spin quantum to a 0 state; A microwave module, used for generating spin resonance microwave pulses to modulate the solid-state spin quantum spin energy level to a ±1 state; A photodetector, used to detect the fluorescence signal generated by the solid-state spin quantum and generate a photon signal; a gating system, connected to the laser module and the photodetector respectively, and configured to obtain a photon signal transmitted by the photodetector within a first time period according to a time when the laser module generates the laser signal; A data analysis unit is connected to the gating system and is used to obtain the photon signal forwarded by the gating system to perform signal analysis.

2. The time domain reading device according to claim 1, characterized in that: The laser module includes a picosecond pulse laser.

3. The time domain reading device according to claim 1, characterized in that: The photon signal comprises: Electrical pulse signal and / or voltage amplitude signal.

4. The time domain reading device according to claim 1, characterized in that: The door control system comprises: A time-correlated counter, used for acquiring a photon signal transmitted by the photodetector; The gate switch is used to output a control signal according to the time of the laser signal generated by the laser module so that the time-related counter obtains the photon signal transmitted by the photodetector within the first time period.

5. The time domain reading device according to claim 1, characterized in that: The data analysis unit is also connected to the microwave module, and is used to modulate the microwave module and demodulate the photon signal of the photodetector according to the modulated frequency.

6. The time domain reading device according to claim 1, characterized in that: The solid-state spin quantum includes: diamond NV color center and / or silicon carbide color center.

7. A time domain reading device for solid-state spin quantum, characterized in that: include: A laser module, used for generating a laser signal to excite the solid-state spin quantum to generate a fluorescent signal, and to polarize the solid-state spin quantum to a 0 state; A microwave module, used for generating spin resonance microwave pulses to modulate the solid-state spin quantum spin energy level to a ±1 state; A photodetector, used to detect the fluorescence signal generated by the solid-state spin quantum and generate a photon signal; A gate control system, connected to the laser module and the photodetector respectively, for outputting a control signal to control the photodetector to obtain the fluorescence signal generated by the solid-state spin quantum within a first time period according to the time when the laser module generates the laser signal; The data analysis unit is connected to the photoelectric detector and is used to obtain the photon signal forwarded by the photoelectric detector to perform signal analysis.

8. The time domain reading device according to claim 7, characterized in that: The data analysis unit is also connected to the microwave module, and is used to modulate the microwave module and demodulate the photon signal of the photodetector according to the modulated frequency.

9. The time domain reading device according to claim 7, characterized in that: The solid-state spin quantum includes: diamond NV color center and / or silicon carbide color center.

10. An in vitro diagnostic device, characterized in that: include: Solid-state spin quantum; The time-domain reading device according to any one of claims 1 to 9 is used to excite the solid-state spin quantum to obtain a photon signal, and enhance the signal-to-noise ratio of the obtained photon signal through a gating system to improve diagnostic sensitivity.

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