Integrated quantum biochip and preparation and application method thereof

Abstract

The invention discloses an integrated quantum biochip and a preparation and application method thereof, the structure of the integrated quantum biochip comprises a chip prepared by demoulding a PDMS mixed solution, an optical fiber and a diamond color center arranged in a cross-shaped groove in the chip, output laser of the optical fiber excites the diamond color center, fluorescence of excited radiation of the diamond color center is collected by the optical fiber, and the optical fiber is used for detecting the fluorescence of the diamond color center. A microwave antenna is arranged outside the diamond color center, the microwave antenna is arranged at the bottom of the chip, and a pin of the microwave antenna is connected with a radio frequency line; the preparation and application method comprises the following steps: preparing the chip; extruding and fixing a diamond color center; connecting a silica gel hose; fixing the microwave antenna; the diamond color center is excited, and microwaves are applied; fluorescence generated by stimulated radiation is output by the optical fiber circulator; the upper computer controls the microwave generator to sweep frequency; converting the received optical signal into an electric signal; the device can measure the magnetic field size and the temperature size of the trace liquid to be measured, and has the advantages of being high in spatial resolution, high in integration level, high in expansibility and high in controllability.

Description

Technical Field

[0001] The present invention belongs to the fields of quantum sensing technology, biochip and microfluidic technology, and specifically relates to an integrated quantum biochip and a preparation and application method thereof. Background Art

[0002] In recent years, diamond nitrogen vacancy (NV) color centers have attracted much attention in the fields of biomedical detection and quantum precision measurement due to their long spin coherence time (>1ms) and high sensitivity (magnetic field sensitivity reaches the order of nT / √Hz) at room temperature [Acta Physica Sinica 67(16),8-26(2018)]. However, the practical application of NV color centers in existing technologies still faces significant challenges. Traditional solutions mostly use millimeter-sized diamond crystals and rely on discrete optical systems and external microwave components, resulting in a bulky system and difficulty in integration with microfluidic chips. Experiments have shown that such designs severely limit detection stability and signal-to-noise ratio due to microwave signal attenuation and optical path alignment errors in liquid environments. In addition, the flow channel size of existing microfluidic chips does not match the spatial distribution of NV color centers, resulting in spatial resolution limited to the millimeter level [Proc. Natl. Acad. Sci. USA 113(49)14133-14138(2016)], which cannot meet the needs of precise analysis at the single cell or subcellular level. In a liquid environment, excessive material thickness in the experiment exacerbates the unevenness of microwave field coverage and dielectric loss, resulting in a significant decrease in the actual performance of optical detection magnetic resonance (ODMR) technology [Phys. Rev. Lett. 133(18), 180401(2024)]. Summary of the Invention

[0003] The present invention is proposed to solve the problems existing in the prior art, and its purpose is to provide an integrated quantum biochip and its preparation and application method.

[0004] The technical solution of the present invention is: an integrated quantum biochip, including a chip made by demolding a PDMS mixed solution, an optical fiber and a diamond color center are placed in a cross groove inside the chip, the output laser of the optical fiber excites the diamond color center, and the fluorescence emitted by the stimulated radiation of the diamond color center is collected by the optical fiber, and a microwave antenna is arranged outside the diamond color center, the microwave antenna is arranged at the bottom of the chip, and the pins of the microwave antenna are connected to the radio frequency line.

[0005] Furthermore, the optical fiber is obtained by stripping an optical fiber jumper, and the input end of the optical fiber jumper is connected to the second optical fiber ring part of the optical fiber circulator.

[0006] Furthermore, the cross groove is formed by demoulding a mold, a protective cover is provided on the chip, a silicone hose is provided in the protective cover, and the silicone hose includes a liquid inlet pipe and a liquid outlet pipe.

[0007] Furthermore, an optical fiber and a diamond color center are arranged in the long groove of the cross groove, and the end face of the optical fiber squeezes and fixes the diamond color center on the inner wall of the long groove of the cross groove in a specific direction.

[0008] Furthermore, the short groove of the cross groove is connected to a silicone hose when measuring a liquid to be tested in the μL level.

[0009] Furthermore, the fluorescence outputted from the third optical fiber ring portion in the optical fiber circulator is transmitted to a photodetector after passing through an optical filter, and the photodetector is connected to a host computer.

[0010] Furthermore, the microwave antenna is arranged outside the chip in a U shape, and the U-shaped bending position corresponds to the position of the diamond color center and the optical fiber end face in the chip.

[0011] Furthermore, the microwave antenna is on the outer surface of the bottom of the chip, the microwave antenna corresponds to the position of the diamond color center inside the chip, and the microwave antenna pin is connected to the output end of the radio frequency line.

[0012] Furthermore, the input end of the radio frequency line is connected to a microwave amplifier, the output end of the radio frequency line is connected to a microwave antenna, and the input end of the microwave amplifier is connected to a microwave generator.

[0013] A method for preparing and applying an integrated quantum biochip comprises the following steps:

[0014] A. Processing the chip mold, preparing the PDMS mixed solution, and obtaining the chip;

[0015] B. Place the diamond color center and use optical fiber to squeeze and fix the diamond color center;

[0016] C. Fix the two silicone hoses to the protective cover with UV curing glue;

[0017] D. Fix the microwave antenna to the bottom outer surface of the chip, with the U-bend of the microwave antenna located directly below the diamond color center;

[0018] E. Excite the diamond color center;

[0019] F. Applying microwaves to diamond color centers;

[0020] G. The fluorescence generated by stimulated radiation from the diamond color center is output by the fiber circulator and input into the photodetector through the filter;

[0021] H. The host computer controls the microwave generator to perform frequency sweep;

[0022] I. The photodetector converts the received light signal into an electrical signal;

[0023] J. The host computer processes microwave sweep frequency signals and electrical signals.

[0024] The beneficial effects of the present invention are as follows:

[0025] The size of the diamond color center used in the present invention is 100×100×100μm. Thanks to the small size of the diamond color center, the spatial resolution of the present invention for measuring trace amounts of liquid to be tested can reach hundreds of microns. The bottom thickness of the chip made by the present invention is only 130μm. Thanks to the thin bottom of the chip, the microwave antenna can normally apply microwave signals outside the chip, thereby avoiding the interference of the liquid medium on the microwave antenna. The cross-groove volume inside the chip of the present invention is only 1.1μL, so the present invention can be used for the detection of trace amounts of liquid to be tested. The chip structure designed by the present invention is highly scalable, and multiple channels can be introduced to simultaneously realize the detection of multiple trace amounts of liquid to be tested. The closed water tank design of the chip can also be used to detect milliliter-level liquids to be tested. The concentration of the NV color center doped in the present invention is relatively high, and the diamond color center matches the size of the optical fiber end face, so the fluorescence excitation efficiency and fluorescence collection efficiency of the present invention are high.

[0026] The size of the cross groove and the number of channels in the chip of the present invention can be changed. Integrated chips of different sizes and different numbers of channels are used to meet different needs to realize the detection of trace amounts of test liquids of different types and volumes. The diamonds and optical fibers of the present invention can be replaced. Diamond centers with different NV color center concentrations are used to make integrated chips to improve chip detection sensitivity. The integrated chip can be continuously optimized by optimizing the size of the diamond center and selecting a better NV color center concentration to further improve the spatial resolution rate. Therefore, the present invention has good flexibility and high controllability.

[0027] Based on the above characteristics, the present invention can achieve stable measurement of tiny liquids to be tested with high spatial resolution and high sensitivity by virtue of the high integration of the chip and has strong practicality and scalability.

[0028] The integrated chip used in the present invention is simple to manufacture, has a precise structure and powerful functions. Its microwave antenna adopts a simple U-shaped structure, and the microwave antenna is isolated from the liquid to be measured by the chip to avoid interference caused by the liquid medium to the microwave application. The NV color center in its diamond has stable fluorescence emission and ultra-long electron spin coherence time at room temperature, so that the integrated chip based on the NV color center can achieve high-sensitivity measurement of electromagnetic fields and temperature. By reading the NV color center electron spin state through optical detection magnetic resonance (ODMR) technology, high-precision measurement of magnetic fields and temperature can be achieved.

[0029] The present invention uses chip integration technology to integrate NV color centers, optical fibers, microwave antennas and chips into one. It takes advantage of the excellent biocompatibility of diamond, the excellent quantum properties of NV color centers, the excellent light transmission capability of optical fibers, and the stability of microwave antennas in applying microwave signals outside the chip to achieve an integrated chip with high integration and high spatial resolution. The functions achieved by the present invention meet various practical applications, and the designed structure is easy to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is a schematic diagram of the integrated quantum biochip and its detection system in the present invention;

[0031] Figure 2 is a schematic diagram of the integrated quantum biochip of the present invention;

[0032] Figure 3 This is a schematic diagram of the cross groove structure in the present invention

[0033] Figure 4 It is a schematic diagram of the principle of the measurement method (optical detection magnetic resonance technology) in the present invention;

[0034] Figure 5 It is a schematic diagram of the principle of magnetic field detection in the present invention;

[0035] Figure 6 It is a schematic diagram of the temperature detection in the present invention;

[0036] in:

[0037] 1 chip 2 optical fibers

[0038] 3 diamond color center 4 microwave antenna

[0039] 5 radio frequency lines 6 cross grooves

[0040] 7 filters 8 silicone hose

[0041] 9 Laser 10 Microwave Generator

[0042] 11 Microwave amplifier 12 Photodetector

[0043] 13 Fiber Circulator 14 Host Computer

[0044] 13-1 First optical fiber ring portion 13-2 Second optical fiber ring portion

[0045] 13-3 The third optical fiber ring portion. DETAILED DESCRIPTION

[0046] Hereinafter, the present invention will be described in detail with reference to the accompanying drawings and embodiments:

[0047] like Figures 1 to 6As shown, the technical solution of the present invention is: an integrated quantum biochip, including a chip 1 made by demolding a PDMS mixed solution, an optical fiber 2 and a diamond color center 3 are placed in a cross groove 6 in the chip 1, the output laser of the optical fiber 2 excites the diamond color center 3, and the fluorescence emitted by the stimulated radiation of the diamond color center 3 is collected by the optical fiber 2, a microwave antenna 4 is provided outside the diamond color center 3, the microwave antenna 4 is provided at the bottom of the chip 1, and the pin of the microwave antenna 4 is connected to the radio frequency line 5.

[0048] The optical fiber 2 is obtained by stripping an optical fiber jumper, and the input end of the optical fiber jumper is connected to the second optical fiber ring portion 13 - 2 of the optical fiber circulator 13 .

[0049] The cross groove 6 is formed by demoulding a mold. A protective cover is provided on the chip 1. A silicone hose 8 is provided in the protective cover. The silicone hose 8 includes a liquid inlet pipe and a liquid outlet pipe.

[0050] The optical fiber 2 and the diamond color center 3 are arranged in the long groove of the cross groove 6, and the end face of the optical fiber 2 squeezes and fixes the diamond color center 3 on the inner wall of the long groove of the cross groove 6 in a specific direction.

[0051] The short groove of the cross groove 6 is connected to the silicone hose 8 when measuring the liquid to be tested in the μL level.

[0052] The fluorescence outputted by the third optical fiber ring portion 13 - 3 in the optical fiber circulator 13 passes through the optical filter 7 and is then transmitted to the photodetector 12 , which is connected to the host computer 14 .

[0053] The microwave antenna 4 is U-shaped and arranged outside the chip 1 , and the U-shaped bending position thereof corresponds to the position of the diamond color center 3 and the end face of the optical fiber 2 in the chip 1 .

[0054] The microwave antenna 4 is on the outer surface of the bottom of the chip 1 . The microwave antenna 4 corresponds to the position of the diamond color center 3 inside the chip 1 , and the pin of the microwave antenna 4 is connected to the output end of the radio frequency line 5 .

[0055] The input end of the radio frequency line 5 is connected to the microwave amplifier 11 , the output end of the radio frequency line 5 is connected to the microwave antenna 4 , and the input end of the microwave amplifier 11 is connected to the microwave generator 10 .

[0056] Specifically, the chip 1 is formed by curing and demoulding the PDMS mixed solution in a mold prepared in advance, and the standing time in the mold can be but is not limited to 48 hours.

[0057] Specifically, the diamond color center 3 is prepared by chemical vapor deposition and laser cutting, and has a size of 100×100×100 μm.

[0058] Specifically, the PDMS mixed solution refers to a mixed solution of polydimethylsiloxane and a curing agent.

[0059] More specifically, the PDMS mixed solution is prepared by uniformly mixing polydimethylsiloxane and a corresponding curing agent in a mass ratio of 10:1.

[0060] Specifically, the liquid inlet and outlet pipes of the silicone hose 8 are used for inputting and outputting trace amounts of liquid to be measured. Meanwhile, the liquid inlet and outlet pipes of the silicone hose 8 can also be used for cleaning the chip 1 .

[0061] Specifically, such as Figure 1 As shown, the first fiber optic ring portion 13-1 of the fiber optic circulator 13 is connected to the output end of the laser 9, the second fiber optic ring portion 13-2 of the fiber optic circulator 13 is connected to the optical fiber 2, and the fluorescence output by the third fiber optic ring portion 13-3 of the fiber optic circulator 13 is transmitted to the photodetector 12 after passing through the filter 7, and the photodetector 12 is connected to the host computer 14.

[0062] Specifically, the host computer 14 is connected to the microwave generator 10 , the input end of the microwave amplifier 11 is connected to the microwave generator 10 , the input end of the radio frequency line 5 is connected to the microwave amplifier 11 , and the radio frequency line 5 is connected to the microwave antenna 4 .

[0063] Specifically, the outer wall of the chip 1 is 36 mm long, 10.3 mm high, and 20 mm thick, and the overall width of the chip is 16 mm.

[0064] Specifically, the long groove of the cross groove 6 is 28 mm long, the short groove is 10 mm long, and the width and height of the long and short grooves are both 0.17 mm.

[0065] Specifically, the end face of the optical fiber 2 is cut flat by a fiber cleaver. The optical fiber 2 includes an optical fiber core and a cladding. The diameter of the optical fiber core is 62.5 μm. The diameter of the optical fiber 2 can be, but is not limited to, 105 μm.

[0066] Specifically, the direction of the diamond color center 3 on the end face of the optical fiber 2 is specific.

[0067] As an implementation method, the microwave antenna 4 is bent into a U shape to facilitate application of microwaves.

[0068] Specifically, the microwave antenna 4 is placed on the outer surface of the bottom of the chip 1 and fixed by ultraviolet curing glue.

[0069] Specifically, the two pins of the microwave antenna 4 are both connected to the output side of the radio frequency line 5. The two pins of the microwave antenna 4 are welded to the output end of the radio frequency line 5.

[0070] More specifically, the microwave antenna 4 is U-shaped, and the U-shaped bend of the microwave antenna 4 is located directly below the diamond color center 3 .

[0071] More specifically, the microwave antenna 4 is a copper wire, the diameter of the microwave antenna 4 can be but is not limited to 50 μm, and the total length is about 8 cm. The two pins of the microwave antenna 4 that are not in contact with the chip 1 are both about 1 cm long.

[0072] More specifically, use wire strippers to separate the radio frequency line 5 into two parts, namely, the ground wire and the tinned copper wire. The two pins of the microwave antenna 4 are respectively wrapped around the two parts and firmly soldered with an electric soldering iron and solder.

[0073] As an embodiment, the lattice direction 100 of the diamond color center 3 is parallel to the end face of the optical fiber 2 .

[0074] Specifically, the optical fiber 2 is obtained by removing the protective cover and the coating layer of the optical fiber 2 from the optical fiber jumper, and a fiber cleaver is used to cut the optical fiber 2 into a flat end face. The length of the optical fiber 2 is 3 cm.

[0075] More specifically, the squeezing effect between the end face of the optical fiber 2 and the inner wall of the long groove of the cross groove 6 ensures that the lattice crystal direction 100 in the diamond color center 3 is parallel to the end face of the optical fiber 2.

[0076] A method for preparing and applying an integrated quantum biochip comprises the following steps:

[0077] A. Processing a mold for chip 1 and preparing a PDMS mixed solution to obtain chip 1;

[0078] B. Place the diamond color center 3 and squeeze and fix the diamond color center 3 with the optical fiber 2;

[0079] C. Fix the two silicone hoses 8 to the protective cover using UV curing glue;

[0080] D. Fix the microwave antenna 4 to the bottom outer surface of the chip 1, with the U-shaped bend of the microwave antenna 4 located directly below the diamond color center 3;

[0081] E. Exciting diamond color center 3;

[0082] F. applying microwaves to the diamond color center 3;

[0083] G. The fluorescence generated by the stimulated radiation of the diamond color center 3 is output by the optical fiber circulator 13 and input into the photodetector 12 through the filter 7;

[0084] H. The host computer 14 controls the microwave generator 10 to perform frequency sweep;

[0085] I. The photodetector 12 converts the received optical signal into an electrical signal;

[0086] J. The host computer 14 processes the microwave frequency sweep signal and the electrical signal.

[0087] Specifically, step A processes the mold of chip 1 and prepares the PDMS mixed solution to obtain chip 1, as follows:

[0088] a1. The mold is made by CNC cutting technology. The mold material is acrylic and the chemical composition is polymethyl methacrylate.

[0089] a2. Mix polydimethylsiloxane and curing agent in a mass ratio of 10:1 and stir evenly to obtain a PDMS mixed solution filled with bubbles. Leave it in a dust cover for 1 hour or use a vacuum machine to remove bubbles to obtain a clean and bubble-free PDMS mixed solution.

[0090] a3. Cast the mold with the PDMS mixed solution, heat it at 60°C for 1 hour under vacuum conditions or let it stand at room temperature of 25°C for 48 hours, and then solidify the PDMS mixed solution to form chip 1.

[0091] a4. Separating the cured chip 1 from the mold, ie, demoulding, to obtain the chip 1.

[0092] Specifically, step E excites the diamond color center 3 as follows:

[0093] The laser 9 emits laser light which is input into the optical fiber jumper through the optical fiber circulator 13 and output through the optical fiber 2 to excite the diamond color center 3.

[0094] Specifically, step F applies microwaves to the diamond color center 3 as follows:

[0095] The microwave generator 10 generates microwaves which are amplified by the microwave amplifier 11 and input into the radio frequency line 5 . The radio frequency line 5 outputs the microwaves to the microwave antenna 4 , which applies the microwaves to the diamond color center 3 .

[0096] Specifically, the laser excitation, fluorescence collection, microwave frequency sweeping and photoelectric conversion processes involved in the above steps are all performed simultaneously.

[0097] Specifically, the working process of the integrated chip is as follows:

[0098] First, after initialization is completed in step E for a long time, step E is performed to excite the NV color center, causing the NV color center to undergo energy level transition and emit red light through stimulated radiation;

[0099] Then, a microwave field is applied to the diamond color center 3 while the laser is exciting the diamond color center 3. At a specific microwave frequency, the fluorescence emitted by the diamond color center 3 is the weakest.

[0100] Then, the photodetector 12 collects the fluorescence emitted by the stimulated radiation of the NV color center doped in the diamond color center 3 and converts the optical signal into an electrical signal;

[0101] Finally, the host computer 14 processes the received signal to form an ODMR spectrum, and the magnetic field change and temperature change can be obtained from the resonance frequency difference or center frequency shift in the spectrum.

[0102] Specifically, the quantum state information of the NV color center can be obtained through the above steps. The specific process is as follows:

[0103] k1. Perform step E separately to complete the preparation work for NV color center spin initialization, i.e., spin quantum state manipulation. The specific process is as follows:

[0104] Laser 9 emits green light, and after continuously exciting the NV color center for a period of time, initialization is completed.

[0105] k2. The preparations are complete. Steps E and F are now performed simultaneously to manipulate the quantum state of the NV color center doped within the diamond color center. The specific process is as follows:

[0106] k21. Laser 9 emits 532nm green light, which is input into the fiber jumper input through fiber circulator 13. The NV color center in diamond color center 3 fixed at the end face of optical fiber 2 is excited. Diamond color center 3 then emits red light, which is collected by optical fiber 2 and input into the fiber jumper. The collected fluorescence is output from fiber circulator 13, filtered out the green light by filter 7, and then input into the input of photodetector 12.

[0107] k22. While the laser excites the diamond color center, the microwave generator 10 inputs the microwave into the microwave amplifier 11. The microwave is amplified by the microwave amplifier 11 and then output. The amplified microwave is input into the ground wire of the radio frequency line 5 and the tinned microwave antenna, and finally input into the microwave antenna 4.

[0108] k3. By changing the microwave frequency, the fluorescence intensity emitted by the diamond color center will change accordingly. The photodetector 12 converts the changing fluorescence signal into a changing electrical signal. Sweep the microwave frequency.

[0109] k4. The host computer 14 processes the frequency sweep signal and the electrical signal to form an ODMR spectrum.

[0110] Specifically, step B includes a method for preparing the diamond color center 3, which is as follows:

[0111] b11. Synthesize diamond color center 3 crystals with a crystal orientation of 100 by CVD (chemical vapor deposition).

[0112] b12. Use a laser to cut the diamond color center 3 into a 100-micron cube along the 100 lattice direction.

[0113] b13. Characterize the NV color center by fluorescence spectroscopy and optically detected magnetic resonance (ODMR) technology to ensure that its optical and spin properties meet the requirements.

[0114] b14. X-ray diffraction confirmed that the internal lattice direction of the cut diamond color center is indeed the 100 direction.

[0115] Specifically, step B includes a method of fixing the diamond color center 3 on the end face of the optical fiber 2 in a specific direction, and the specific process is as follows:

[0116] b21. Use wire strippers to remove the protective cover and coating at the output end of the fiber jumper to obtain optical fiber 2.

[0117] b22. Use a cleaver to cut the end face of the optical fiber 2 flat, and wipe the optical fiber 2 clean with a dust-free cloth soaked in alcohol, and place the optical fiber 2 and the diamond color center 3 into the long groove of the cross groove 6 in the chip 1.

[0118] b23. While ensuring that the diamond lattice crystal direction 100 is parallel to the end face of the optical fiber 2, the diamond color center 3 is squeezed to the inner wall of the long groove through the optical fiber 2.

[0119] Specifically, step D fixes the microwave antenna 4 to the bottom outer surface of the chip 1 as follows:

[0120] d11. Make the microwave antenna 4 into a U shape and place the U-shaped microwave antenna 4 close to the outer surface of the bottom of the chip.

[0121] d12. Place the U-shaped bend just below the diamond color center 3.

[0122] d13. Apply an appropriate amount of UV glue solution between the bend of microwave antenna 4 and its pins, and cure with UV light. Similarly, apply an appropriate amount of UV glue to the position where the pins of microwave antenna 4 do not touch the chip, and cure with UV light.

[0123] Specifically, step D includes a method for fixing the two pins of the microwave antenna 4 and the output end of the radio frequency line 5, which is as follows:

[0124] d21. Use wire strippers to remove the protective cover of RF cable 5 and separate the ground wire and tinned copper wire in RF cable 5 into two strands.

[0125] d22. The two pins of microwave antenna 4 are respectively wound around two strands of wire.

[0126] d23. Use a soldering iron and solder to fix the two pins and two wires of microwave antenna 4.

[0127] As a more specific implementation:

[0128] Based on the above integrated quantum biochip, ODMR spectrum can be observed under zero field, as shown in the attached Figure 4 shown.

[0129] Based on the above integrated quantum biochip, due to the Zeeman effect, two resonance peaks can be observed at the center frequency of the ODMR spectrum under an external magnetic field, corresponding to the two resonance frequencies as shown in the attached figure. Figure 5 shown.

[0130] The resonance frequency of the resonance peak in the spectrum and the actual magnetic field satisfy the formula:

[0131] V=2αγB (1)

[0132] Among them, V is the difference between the two resonant frequencies, α is the cosine value of the angle between the actual magnetic field and the NV color center axis, γ is the electron spin magnetic ratio, and B is the magnetic field size.

[0133] It can be seen from the above formula that the degree of splitting of the two resonance peaks, that is, the difference in the center frequency of the resonance peaks, is proportional to the magnitude of the axial NV color center magnetic field. When the high spatial resolution fiber integrated sensor of the diamond color center NV color center is used to detect the magnetic field to be measured, the axial magnetic field will cause m s =±1 dedegeneracy, which appears as two split resonance peaks in the ODMR spectrum. As the magnetic field increases, the degree of splitting of the resonance peaks changes linearly.

[0134] Therefore, the present invention can obtain the magnitude of the magnetic field by quantitatively detecting the splitting degree of the resonance peak through the ODMR technology.

[0135] As another more specific implementation:

[0136] Based on the above integrated quantum biochip, since the zero-field splitting is related to temperature, temperature changes will cause the center frequency of the ODMR spectral line to shift, as shown in the attached Figure 6 shown.

[0137] The following formula (2) is the principle formula for the frequency shift of the ODMR spectrum center frequency caused by temperature change:

[0138]

[0139] Where T is the temperature of the object under test, and D is the zero-field splitting value. As can be seen from the above formula, the temperature T and the zero-field splitting value D are approximately linearly related. When the temperature increases, the zero-field splitting value D decreases, which is manifested in the ODMR spectrum as a shift of the center frequency toward low frequencies.

[0140] Therefore, the present invention can obtain the magnitude of the magnetic field by quantitatively detecting the movement of the resonance peak through the ODMR technology.

[0141] The present invention uses chip integration technology to integrate NV color centers, optical fibers, microwave antennas and chips into one, utilizing the excellent biocompatibility of diamond, the outstanding quantum properties of NV color centers, the excellent light transmission capability of optical fibers, and the stability of microwave antennas in applying microwave signals outside the chip to achieve an integrated chip with high integration and high spatial resolution.

[0142] The advantages of the present invention are as follows: The diamond color center used in the present invention measures 100×100×100 μm. Due to the small size of the diamond color center, the spatial resolution of the present invention for measuring trace amounts of liquid to be tested can reach hundreds of microns. The bottom thickness of the chip produced by the present invention is only 130 μm. Due to the thin chip bottom, the microwave antenna can normally apply microwave signals outside the chip, thus avoiding interference from the liquid medium on the microwave antenna. The cross-groove volume within the chip of the present invention is only 1.1 μL, so the present invention can be used for detecting trace amounts of liquid to be tested. The concentration of NV color centers doped in the present invention is high, and the diamond color center matches the size of the optical fiber end face, resulting in high fluorescence excitation and fluorescence collection efficiencies. The chip structure designed in the present invention is highly scalable, and multiple channels can be introduced to simultaneously detect multiple trace amounts of liquid to be tested. The closed water tank design of the chip can also detect milliliter-level liquids to be tested. The present invention has significant room for improvement. The spatial resolution can be further improved by replacing small-sized diamonds with tapered optical fibers of corresponding sizes. The detection sensitivity can also be further improved by increasing the concentration of NV color centers within the diamond. Based on the above advantages, the present invention can detect slight changes in temperature and magnetic field of trace liquids to be tested in fields such as electrochemistry and biomedicine by virtue of high integration and high spatial resolution.

[0143] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. An integrated quantum biochip, characterized by: The invention comprises a chip (1) made by demoulding a PDMS mixed solution, an optical fiber (2) and a diamond color center (3) are placed in a cross groove (6) in the chip (1), the output laser of the optical fiber (2) excites the diamond color center (3), and the fluorescence emitted by the stimulated radiation of the diamond color center (3) is collected by the optical fiber (2), a microwave antenna (4) is arranged outside the diamond color center (3), the microwave antenna (4) is arranged at the bottom of the chip (1), and the pin of the microwave antenna (4) is connected to the radio frequency line (5).

2. The integrated quantum biochip according to claim 1, characterized in that: The optical fiber (2) is obtained by stripping an optical fiber jumper, and the input end of the optical fiber jumper is connected to the second optical fiber ring part (13-2) of the optical fiber circulator (13).

3. The integrated quantum biochip according to claim 1, characterized in that: The cross groove (6) is formed by demoulding a mold. A protective cover is provided on the chip (1). A silicone hose (8) is provided in the protective cover. The silicone hose (8) includes a liquid inlet pipe and a liquid outlet pipe.

4. The integrated quantum biochip according to claim 1, characterized in that: An optical fiber (2) and a diamond color core (3) are arranged in the long groove of the cross groove (6), and the end face of the optical fiber (2) squeezes and fixes the diamond color core (3) on the inner wall of the long groove of the cross groove (6) in a specific direction.

5. The integrated quantum biochip according to claim 1, characterized in that: The short groove of the cross groove (6) is connected to the silicone hose (8) when measuring the liquid to be tested in the μL level.

6. The integrated quantum biochip according to claim 2, characterized in that: The fluorescence outputted from the third optical fiber ring portion (13-3) in the optical fiber circulator (13) is transmitted to the photodetector (12) after passing through the filter (7), and the photodetector (12) is connected to the host computer (14).

7. The integrated quantum biochip according to claim 1, characterized in that: The microwave antenna (4) is arranged in a U-shape outside the chip (1), and the U-shaped bending position thereof corresponds to the positions of the diamond color center (3) and the end face of the optical fiber (2) in the chip (1).

8. The integrated quantum biochip according to claim 1, characterized in that: The microwave antenna (4) is located on the outer surface of the bottom of the chip (1), the microwave antenna (4) corresponds to the position of the diamond color center (3) inside the chip (1), and the pin of the microwave antenna (4) is connected to the output end of the radio frequency line (5).

9. The integrated quantum biochip according to claim 8, characterized in that: The input end of the radio frequency line (5) is connected to the microwave amplifier (11), the output end of the radio frequency line (5) is connected to the microwave antenna (4), and the input end of the microwave amplifier (11) is connected to the microwave generator (10).

10. The method for preparing and applying an integrated quantum biochip according to claim 1, characterized in that: The following steps are involved: A. Processing a mold of the chip (1), preparing a PDMS mixed solution, and obtaining the chip (1); B. Place the diamond color center (3) and squeeze and fix the diamond color center (3) with the optical fiber (2); C. Fix the two silicone hoses (8) on the protective cover using UV curing glue; D. Fixing the microwave antenna (4) on the bottom outer surface of the chip (1), with the U-shaped bend of the microwave antenna (4) located directly below the diamond color center (3); E. Excite the diamond color center (3); F. applying microwaves to the diamond color center (3); G. The fluorescence generated by the stimulated radiation of the diamond color center (3) is output by the optical fiber circulator (13) and input into the photodetector (12) through the filter (7); H. The host computer (14) controls the microwave generator (10) to perform frequency sweep; I. The photodetector (12) converts the received optical signal into an electrical signal; J. The host computer (14) processes the microwave sweep frequency signal and the electrical signal.

Images