Time-domain readout devices and in vitro diagnostic devices for solid-state spin quantum mechanics
By employing pulse excitation and time-domain readout technology with a gating system, the problem of limited diagnostic sensitivity under strong background light noise was solved, thereby improving the signal-to-noise ratio and diagnostic accuracy.
Patent Information
- Application Number
- CN202411269779.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-11
- Publication Date
- 2025-10-31
- Estimated Expiration
- 2044-09-11
AI Technical Summary
Existing lock-in amplification diagnostic techniques based on nanodiamond NV centers have limited diagnostic sensitivity in environments with strong background light noise, failing to effectively reduce noise and resulting in a large number of false positive and false negative results.
Using pulse excitation and gating system time-domain readout technology, a laser module excites solid-state spin quanta to generate fluorescence signals, and a microwave module modulates the spin energy levels. Combined with a photodetector and gating system, the signal is acquired within a specific time-domain window, reducing noise and improving the signal-to-noise ratio.
It effectively reduces noise, significantly improves diagnostic sensitivity, and reduces false positive and false negative results.
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Figure CN119375190B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of in vitro diagnostic technology, and more specifically, to a time-domain readout device and an in vitro diagnostic device for solid-state spin quantum. Background Technology
[0002] In vitro diagnostics typically involves combining fluorescent markers with targets of the pathogen to be detected. These markers are then mixed with a patient's bodily fluid sample, and a test strip also labeled with the corresponding target is added. Diagnosis is made by observing the fluorescence reaction on the test strip. Currently, commonly used in vitro diagnostic techniques include those based on colloidal gold. However, the fluorescence wavelength of colloidal gold significantly overlaps with the test strip and ambient sunlight noise, leading to a high rate of false positives / false negatives when judging diagnostic results solely based on luminescence.
[0003] A diamond nitrogen vacancy (NV) center is composed of a nitrogen atom that substitutes for a carbon atom in the diamond lattice and a neighboring lattice vacancy. At room temperature, the spin coherence time of an NV center can reach the millisecond level, making it the most superior solid-state spin quantum. Based on the electron spin energy levels of a single diamond NV center and photomagnetic resonance imaging (PMMRI), precise measurements of many physical quantities can be achieved. Diamond possesses advantages such as resistance to high and low temperatures, acids and alkalis, and high pressures, exhibiting excellent environmental adaptability. Based on these properties, NV centers have significant application value in the field of precision measurement.
[0004] In recent years, based on the spin-orbit energy level characteristics of NV centers, research has shown that lock-in amplification technology can achieve sensitive detection of NV centers in environments with strong background light noise, thereby enabling medical in vitro diagnostic applications based on nanodiamonds and lock-in amplification technology. Lock-in amplification diagnostic technology based on nanodiamond NV centers effectively demodulates the emission from the nanodiamond NV centers and the noise light through modulation and demodulation, greatly improving diagnostic sensitivity and reducing the false diagnosis rate. However, before signal demodulation, it only performs partial wavelength filtering on the background noise, failing to achieve good noise reduction; therefore, its diagnostic sensitivity remains limited in practical applications. Summary of the Invention
[0005] To address at least one of the aforementioned problems, this application proposes a time-domain readout device and an in vitro diagnostic device for solid-state spin quantum mechanics.
[0006] According to a first aspect of this application, at least one embodiment of this application provides a time-domain readout device for a solid-state spin quantum, comprising: a laser module for generating a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and to polarize the spin of the solid-state spin quantum to a 0 state; a microwave module for generating a spin resonant microwave pulse to modulate the spin energy level of the solid-state spin quantum to a ±1 state; a photodetector for detecting the fluorescence signal generated by the solid-state spin quantum and generating a photon signal; a gating system connected to the laser module and the photodetector respectively, for acquiring the photon signal transmitted by the photodetector within a first time period based on the time when the laser module generates the laser signal; and a data analysis unit connected to the gating system for acquiring the photon signal forwarded by the gating system for signal analysis.
[0007] For example, in some embodiments of this application, the laser module includes a picosecond pulse laser.
[0008] For example, in some embodiments of this application, the photonic signal includes: an electrical pulse signal and / or a voltage amplitude signal.
[0009] For example, in some embodiments of this application, the gating system includes: a time-correlated counter for acquiring the photon signal transmitted by the photodetector; and a gating switch for outputting a control signal based on the time of the laser signal generated by the laser module to enable the time-correlated counter to acquire the photon signal transmitted by the photodetector within the first time period.
[0010] For example, in some embodiments of this application, the data analysis unit is also connected to the microwave module for modulating the microwave module and demodulating the photonic signal of the photodetector according to the modulation frequency.
[0011] For example, in some embodiments of this application, the solid-state spin quantum includes: diamond NV color centers and / or silicon carbide color centers.
[0012] According to a second aspect of this application, at least one embodiment of this application provides a time-domain readout device for a solid-state spin quantum, comprising: a laser module for generating a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and to polarize the spin of the solid-state spin quantum to a 0 state; a microwave module for generating a spin resonant microwave pulse to modulate the spin energy level of the solid-state spin quantum to a ±1 state; a photodetector for detecting the fluorescence signal generated by the solid-state spin quantum and generating 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 acquire the fluorescence signal generated by the solid-state spin quantum within a first time period according to the time at which the laser module generates the laser signal; and a data analysis unit connected to the photodetector for acquiring the photon signal relayed by the photodetector for signal analysis.
[0013] For example, in some embodiments of this application, the data analysis unit is also connected to the microwave module for modulating the microwave module and demodulating the photonic signal of the photodetector according to the modulation frequency.
[0014] For example, in some embodiments of this application, the solid-state spin quantum includes: diamond NV color centers and / or silicon carbide color centers.
[0015] According to a second aspect of this application, at least one embodiment of this application provides an in vitro diagnostic device, comprising: a solid-state spin quantum; and a time-domain readout device as described in any one of the first and second aspects, for exciting the solid-state spin quantum to acquire a photon signal, and enhancing the signal-to-noise ratio of the acquired photon signal through a gating system to improve diagnostic sensitivity.
[0016] Through the above example embodiments, the time-domain readout device and in vitro diagnostic device for solid-state spin quantum provided by this application, based on the technical solution of pulse excitation and gating system for time-domain readout of signal fluorescence, only collects signal light data of the time-domain gating window, which can effectively reduce noise and significantly improve the signal-to-noise ratio of the demodulated data, and further improve diagnostic sensitivity.
[0017] It should be understood that the above general description and the following detailed description are merely exemplary and do not limit this application. Attached Figure Description
[0018] The above and other objects, features, and advantages of this application will become more apparent from the detailed description of exemplary embodiments with reference to the accompanying drawings. The drawings described below are merely some embodiments of this application and are not intended to limit the scope of this application.
[0019] Figure 1A schematic diagram of a time-domain readout device for solid-state spin quantum is shown as an exemplary embodiment;
[0020] Figure 2 A schematic diagram showing a comparison of the fluorescence spectra of nitrocellulose test paper and NV color centers in an exemplary embodiment is provided.
[0021] Figure 3 A schematic diagram showing a comparison of the excited-state lifetime of nitrocellulose test paper and NV color centers in an exemplary embodiment is provided.
[0022] Figure 4 Another embodiment of an exemplary time-domain readout device for solid-state spin quantum is shown. Detailed Implementation
[0023] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments can be implemented in many forms and should not be construed as limited to the embodiments set forth herein; rather, they are provided so that this application will be thorough and complete, and will fully convey the concept of the exemplary embodiments to those skilled in the art. The same reference numerals in the drawings denote the same or similar parts, and therefore repeated descriptions of them will be omitted.
[0024] The described features, structures, or characteristics can be combined in any suitable manner in one or more embodiments. Numerous specific details are provided in the following description to give a full understanding of embodiments of this disclosure. However, those skilled in the art will recognize that the technical solutions of this disclosure can be practiced without one or more of these specific details, or other methods, components, materials, devices, etc. In these cases, well-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 merely illustrative and do not necessarily include all content and operations / steps, nor do they necessarily have to be performed in the described order. For example, some operations / steps can be broken down, while others can be combined or partially combined; therefore, the actual execution order may change depending on the specific circumstances.
[0026] The terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish different objects, not to describe a specific order. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or apparatus that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or apparatuses.
[0027] Those skilled in the art will understand that the accompanying drawings are merely schematic diagrams of exemplary embodiments, and the modules or processes in the drawings are not necessarily essential for implementing this application, and therefore cannot be used to limit the scope of protection of this application.
[0028] Figure 1 A schematic diagram of a time-domain readout device for solid-state spin quantum is shown as an exemplary embodiment.
[0029] like Figure 1 As shown, the time-domain readout 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] The system comprises the following components: a laser module 101 generates a laser signal to excite the solid-state spin quantum 20 to produce a fluorescence signal and to spin-polarize the solid-state spin quantum 20 to the 0 state; a microwave module 102 generates a spin resonant microwave pulse to modulate the spin energy level of the solid-state spin quantum 20 to the ±1 state; a photodetector 103 detects the fluorescence signal generated by the solid-state spin quantum 20 and generates a photon signal; a gating system 104 is connected to both the laser module 101 and the photodetector 103, and is used to acquire the photon signal transmitted by the photodetector 103 within a first time period based on the timing of the laser signal generated by the laser module 103; and a data analysis unit 105 is connected to the gating system 104 and is used to acquire the photon signal forwarded by the gating system 104 for signal analysis.
[0031] According to some embodiments, the laser module 101 includes a picosecond pulsed laser that excites a solid-state spin quantum 20 using a picosecond pulsed laser.
[0032] According to some embodiments, the photonic signal includes an electrical pulse signal and / or a voltage amplitude signal.
[0033] According to the example embodiment, the photodetector 103 in this application is in continuous operation mode for acquiring wavelength-filtered fluorescence signals. The wavelength filtering range can be set by the user to achieve the desired effect. Figure 2 For example, the filtering range is set to 607-796nm to perform preliminary filtering on the test strip fluorescence. The obtained fluorescence includes NV fluorescence and the remaining test strip 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 can be 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 switch 1042.
[0036] The time-correlation counter 1041 is used to acquire 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-correlation counter 1041 acquires the photon signal generated by the photodetector in the first time period.
[0037] According to the 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 modulation frequency.
[0038] According to some embodiments, the solid-state spin quantum 20 includes diamond NV color centers and silicon carbide color centers, etc. This application is only using this as an example, but is not limited thereto.
[0039] This application uses diamond NV color centers as an example. Clinically commonly used nitrocellulose test strips exhibit significant fluorescence emission in the visible light band, which largely overlaps with the fluorescence of diamond NV color centers. Figure 2 As shown. 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, such as... Figure 3 As shown.
[0040] According to the example embodiment, the first time period can be set by the user. Figure 3 For example, since the excited state lifetime of diamond NV centers is relatively long, while that of nitrocellulose test paper is relatively short, the nitrocellulose test paper basically completes the fluorescence photon emission and returns to the ground state within 5 ns. Therefore, the period of 6-29 ns is selected as the first time period, i.e. Figure 3 The time-domain gating window in this example is the first time period. This application uses this as an example only, but it is not limited to this.
[0041] This application provides a time-domain readout device for solid-state spin quantum mechanics. Based on the technical solution of pulse excitation and gating system for time-domain readout of signal fluorescence, it only collects signal light data from the time-domain gating window, which can effectively reduce noise and significantly improve the signal-to-noise ratio of the demodulated data, thereby further improving diagnostic sensitivity.
[0042] Figure 4 Another embodiment of an exemplary time-domain readout device for solid-state spin quantum is shown.
[0043] This application also provides a time-domain readout device for solid-state spin quantum mechanics, such as... Figure 4 As shown, the time-domain readout 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] The system comprises the following components: a laser module 101 generates a laser signal to excite the solid-state spin quantum 20 to produce a fluorescence signal and to spin-polarize the solid-state spin quantum 20 to the 0 state; a microwave module 102 generates a spin resonant microwave pulse to modulate the spin energy level of the solid-state spin quantum 20 to the ±1 state; a photodetector 103 detects the fluorescence signal generated by the solid-state spin quantum 20 and generates a photon signal; a gating system 104 is connected to both the laser module 101 and the photodetector 103, and controls the photodetector 103 to acquire the fluorescence signal generated by the solid-state spin quantum 20 within a first time period based on the timing of the laser signal generation by the laser module 101; and a data analysis unit 105 is connected to the photodetector 103 and acquires the photon signal relayed by the photodetector for signal analysis.
[0045] According to some embodiments, the laser module 101 includes a picosecond pulsed laser that excites a solid-state spin quantum 20 using a picosecond pulsed laser.
[0046] According to some embodiments, the photonic signal includes an electrical pulse signal and / or a voltage amplitude signal.
[0047] According to the example embodiment, the photodetector 103 in this application is in a gated operation mode. The photodetector 103 is used to receive control signals 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 immediately turns on to perform photoelectric detection in the first time period, collects the fluorescence signal that has been filtered by the set wavelength in the optical path and generates a photon signal, which is then sent to the data analysis unit 105.
[0048] The wavelength filtering setting can be customized. Figure 2 For example, the filtering range is set to 607-796nm to perform preliminary filtering of the test strip fluorescence.
[0049] Furthermore, the first time period can be set by the user. Figure 3 For example, since the excited state lifetime of diamond NV centers is relatively long, while that of nitrocellulose test paper is relatively short, the nitrocellulose test paper basically completes the fluorescence photon emission and returns to the ground state within 5 ns. Therefore, the period of 6-29 ns is selected as the first time period, i.e. Figure 3 The time-domain gating window in this example is the first time period. This application uses this as an example only, but it is not limited to this.
[0050] According to the 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 modulation frequency.
[0051] According to some embodiments, the solid-state spin quantum 20 includes diamond NV color centers and silicon carbide color centers, etc. This application is only using this as an example, but is not limited thereto.
[0052] This 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 of the time-domain readout devices 10 described above, used to excite the solid-state spin quantum to obtain photon signals, and to enhance the signal-to-noise ratio of the obtained photon signals through a gating system to improve diagnostic sensitivity. The specific working principle of the time-domain readout device 10 is as described above, and therefore will not be repeated here.
[0053] It should be clearly understood that this application describes how specific examples are formed and used, but this application is not limited to any details of these examples. Rather, based on the teachings of the disclosure of this application, these principles can be applied to many other embodiments.
[0054] Furthermore, it should be noted that the above figures are merely illustrative representations of the processes included in the method according to exemplary embodiments of this application, and are not intended to be limiting. It is readily understood that the processes shown in the above figures do not indicate or limit the temporal order of these processes. Additionally, it is readily understood that these processes may be executed synchronously or asynchronously, for example, in multiple modules.
[0055] Exemplary embodiments of this application have been specifically shown and described above. It should be understood that this application is not limited to the detailed structures, arrangements, or implementation methods described herein; rather, this application is intended to cover various modifications and equivalent arrangements contained within the spirit and scope of the appended claims.
Claims
1. A time-domain readout device for solid-state spin quantum mechanics, characterized in that, include: A laser module is used to generate a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and to polarize the solid-state spin quantum to the 0 state. A microwave module is used to generate spin resonant microwave pulses to modulate the solid-state spin quantum spin energy level to ±1 states. A photodetector, in continuous operation mode, is used to detect the fluorescence signal generated by the wavelength-filtered solid-state spin quantum and generate a photon signal, the fluorescence signal including solid-state spin quantum fluorescence and residual test paper fluorescence; A gating system, connected to both the laser module and the photodetector, is used to acquire the photon signal transmitted by the photodetector within a first time period based on the time at which the laser module generates the laser signal. The gating system includes: A time-correlated counter is used to acquire the photon signal transmitted by the photodetector; A gate switch is used to output a control signal based on the time of the laser signal generated by the laser module, so that the time-related counter acquires the photon signal transmitted by the photodetector within the first time period; The data analysis unit, connected to the gating system, is used to acquire the photon signals forwarded by the gating system for signal analysis.
2. The time-domain readout device as described in claim 1, characterized in that, The laser module includes a picosecond pulse laser.
3. The time-domain readout device as described in claim 1, characterized in that, The photon signal includes: Electrical pulse signals and / or voltage amplitude signals.
4. The time-domain readout device as described in 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 modulation frequency.
5. The time-domain readout device as described in claim 1, characterized in that, The solid-state spin quantum includes: diamond NV color centers and / or silicon carbide color centers.
6. A time-domain readout device for solid-state spin quantum mechanics, characterized in that, include: A laser module is used to generate a laser signal to excite the solid-state spin quantum to generate a fluorescence signal and to polarize the solid-state spin quantum to the 0 state. A microwave module is used to generate spin resonant microwave pulses to modulate the solid-state spin quantum spin energy level to ±1 states. The photodetector is in gated operation mode; A gating system, connected to the laser module and the photodetector respectively, is used to output a control signal to control the photodetector to acquire the fluorescence signal generated by the solid-state spin quantum during a first time period, based on the time when the laser module generates the laser signal. The photodetector is used to receive the control signal from the gating system. The photodetector is in a closed state unless triggered by the gating system. When triggered by the gating system, the photodetector is used to detect the fluorescence signal generated by the wavelength-filtered solid-state spin quantum during the first time period and generate a photon signal, the fluorescence signal including solid-state spin quantum fluorescence and residual test paper fluorescence; The data analysis unit, connected to the photodetector, is used to acquire the photon signal relayed by the photodetector for signal analysis.
7. The time-domain readout device as described in claim 6, 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 modulation frequency.
8. The time-domain readout device as described in claim 6, characterized in that, The solid-state spin quantum includes: diamond NV color centers and / or silicon carbide color centers.
9. An in vitro diagnostic device, characterized in that, include: Solid-state spin quantum; The time-domain readout device according to any one of claims 1-8 is used to excite the solid-state spin quantum to obtain a photon signal, and to enhance the signal-to-noise ratio of the obtained photon signal through a gating system to improve diagnostic sensitivity.
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