Quartz crystal microbalance, and detection method and apparatus based on quartz crystal microbalance

Abstract

A quartz crystal microbalance, and a detection method and apparatus based on a quartz crystal microbalance, applied to the technical field of micro-mass measurement. The quartz crystal microbalance comprises: a resonant module, an optical imaging module, and a data processing module; the optical imaging module comprises an image collection device (5); the image collection device (5) performs optical imaging on the surface of a quartz crystal microbalance chip (3); and the data processing module determines the mass of a sample to be tested.

Description

Quartz crystal microbalance, detection methods and devices based on quartz crystal microbalance Technical Field

[0001] This invention relates to the field of micro-mass measurement technology, and in particular to a quartz crystal microbalance, a detection method and device based on the quartz crystal microbalance. Background Technology

[0002] This section is intended to provide background or context for the embodiments of the invention set forth herein. The description herein is not intended to imply that it is prior art simply because it is included in this section.

[0003] The Sauerbrey equation, applied to the mass change of hard thin films on the surface of quartz crystals, allows for the quantitative relationship between the vibrational frequency of the quartz crystal and its surface mass change. Quartz crystal microbalances have flourished as a technology for measuring mass changes at the microgram or even nanogram level. To date, quartz crystal microbalances can be used not only to measure the mass change of hard thin films, but also dissipative quartz crystal microbalances for measuring the mass change of soft thin films. Common commercially available quartz crystal microbalances have a mass sensitivity of 0.7 ng / cm². 2 .

[0004] However, the current mass sensitivity of quartz crystal microbalances cannot be further improved to pg or even fg. Since the current detection methods of quartz crystal microbalances still fall within the scope of traditional quartz crystal microbalance detection, the only way to improve mass sensitivity is to increase the resonant frequency of the quartz crystal microbalance chip. However, increasing the chip's resonant frequency requires thinning the chip, which leads to a decrease in chip strength, making it brittle and reducing its reliability and lifespan. To improve the detection mass sensitivity, innovative detection principles are needed. Furthermore, traditional electrical detection methods lack spatial resolution, meaning that traditional quartz crystal microbalances can only detect one sample at a time on the same chip surface. Traditional multi-channel quartz crystal microbalances simply perform experiments on multiple chips simultaneously; increasing the number of channels exponentially increases system complexity, making breakthroughs extremely difficult. Additionally, due to the limitations of the Sauerbrey equation, traditional quartz crystal microbalances can only test the mass changes of surface-deposited thin films. For powder samples, pretreatment is required to form a film on the surface of the quartz crystal microbalance chip before testing. Summary of the Invention

[0005] This invention provides a quartz crystal microbalance to improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequency at different positions of the quartz crystal microbalance chip, realizing multi-channel multi-sample detection on a single chip. The quartz crystal microbalance includes: a resonant module, an optical imaging module, and a data processing module.

[0006] The resonant module includes an assembly and a resonant voltage source;

[0007] The assembly includes a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested; the resonant voltage source is used to drive the quartz crystal microbalance chip.

[0008] The optical imaging module includes a microscope and image acquisition equipment;

[0009] The assembly is fixed to the stage of the microscope; the microscope is used to magnify the sample to be tested; the image acquisition device is used to perform optical imaging on the magnified sample to obtain an image and send the image to the data processing module.

[0010] The data processing module is used to analyze and process the received images to determine the optical resonant frequency of the sample under test; and to determine the mass of the sample under test based on the optical resonant frequency.

[0011] This invention also provides a detection method based on a quartz crystal microbalance to improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequency at different positions of the quartz crystal microbalance chip, realizing multi-channel, multi-sample detection on a single chip. This method is applied to the aforementioned quartz crystal microbalance and includes:

[0012] An image of the surface of a quartz crystal microbalance chip is obtained; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample under a microscope.

[0013] The image is analyzed and processed to determine the optical resonant frequency of the sample under test;

[0014] The mass of the sample is determined based on its optical resonant frequency.

[0015] This invention also provides a detection device based on a quartz crystal microbalance, used to improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequency at different positions of the quartz crystal microbalance chip, realizing multi-channel, multi-sample detection on a single chip. This device is applied to the aforementioned quartz crystal microbalance and includes:

[0016] An acquisition module is used to acquire an image of the surface of a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample to be tested magnified by a microscope;

[0017] The analysis module is used to analyze and process the image to determine the optical resonant frequency of the sample under test.

[0018] The quality determination module is used to determine the quality of the sample to be tested based on its optical resonant frequency.

[0019] This invention also provides a computer device, including a memory, a processor, and a computer program stored in the memory and executable on the processor. When the processor executes the computer program, it implements the above-described detection method based on a quartz crystal microbalance.

[0020] This invention also provides a computer-readable storage medium storing a computer program that, when executed by a processor, implements the above-described detection method based on a quartz crystal microbalance.

[0021] This invention also provides a computer program product, which includes a computer program that, when executed by a processor, implements the above-described detection method based on a quartz crystal microbalance.

[0022] Compared with traditional quartz crystal microbalances in the prior art, this invention utilizes a resonance module, an optical imaging module, and a data processing module. The resonance module includes an assembly and a resonant voltage source. The assembly includes a quartz crystal microbalance chip, on which the sample to be tested is carried. The resonant voltage source drives the quartz crystal microbalance chip. The optical imaging module includes a microscope and an image acquisition device. The assembly is fixed to the stage of the microscope. The microscope magnifies the sample to be tested. The image acquisition device performs optical imaging on the magnified sample to obtain an image and sends the image to the data processing module. The data processing module analyzes and processes the received image to determine the optical resonant frequency of the sample to be tested. Determining the mass of the sample to be tested based on the optical resonant frequency can improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequencies at different positions of the quartz crystal microbalance chip, achieving multi-channel, multi-sample detection with a single chip. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. In the drawings:

[0024] Figure 1 is a schematic diagram of a quartz crystal microbalance in an embodiment of the present invention;

[0025] Figure 2 is a schematic diagram of a specific example of a quartz crystal microbalance in an embodiment of the present invention;

[0026] Figure 3 is a schematic diagram of the connection of the resonant module in an embodiment of the present invention;

[0027] Figure 4 is a schematic diagram of an image obtained using a quartz crystal microbalance on the surface of a quartz crystal microbalance chip with only an optical tag in an embodiment of the present invention.

[0028] Figure 5 is a schematic diagram of an image obtained using a quartz crystal microbalance on the surface of a quartz crystal microbalance chip with single particles deposited around the marker particles in an embodiment of the present invention.

[0029] Figure 6 is a schematic diagram of an image obtained using a quartz crystal microbalance on the surface of a quartz crystal microbalance chip with multiple optical tags deposited to form a high-throughput array in an embodiment of the present invention.

[0030] Figure 7 is a flowchart of the detection method based on a quartz crystal microbalance in an embodiment of the present invention;

[0031] Figure 8 is a schematic diagram of the principle of determining the ellipticity when the amplitude is 0 pixels in an embodiment of the present invention;

[0032] Figure 9 is a schematic diagram illustrating the principle of determining the ellipticity when the amplitude is 10 pixels in an embodiment of the present invention;

[0033] Figure 10 is a schematic diagram of optical resonant frequency detection when the image acquisition device is a charge-coupled device in an embodiment of the present invention;

[0034] Figure 11 is a schematic diagram of the resonant frequency of the quartz crystal microbalance chip obtained by the detection method based on the quartz crystal microbalance in an embodiment of the present invention.

[0035] Figure 12 is a schematic diagram of optical resonant frequency detection when the image acquisition device is a complementary metal-oxide-semiconductor device in an embodiment of the present invention;

[0036] Figure 13 is a graph showing the relationship between pattern intensity and frequency of a quartz crystal microbalance chip obtained by using a lock-to-complement metal oxide semiconductor device in an embodiment of the present invention.

[0037] Figure 14 is a schematic diagram of the frequency change of a molecular sieve (inert to nitrogen) that has not undergone any reaction before and after being purged with nitrogen for 1 hour using a quartz crystal microbalance in an embodiment of the present invention.

[0038] Figure 15 is a schematic diagram of the resonant frequency changes of 12 molecular sieves in the quartz crystal microbalance during the absorption and desorption of ammonia in the embodiment of the present invention.

[0039] Figure 16 is a structural block diagram of the data synchronization device in an embodiment of the present invention;

[0040] Figure 17 is a schematic diagram of the computer device structure according to an embodiment of the present invention. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings. Here, the illustrative embodiments of the present invention and their descriptions are used to explain the present invention, but are not intended to limit the present invention.

[0042] The acquisition, storage, use, and processing of data in this application comply with relevant laws and regulations.

[0043] To address the problems of the prior art, this invention provides a quartz crystal microbalance. Figure 1 is a schematic diagram of the quartz crystal microbalance in this invention embodiment. As shown in Figure 1, the quartz crystal microbalance in this invention embodiment may include: a resonance module, an optical imaging module, and a data processing module;

[0044] The resonant module includes an assembly and a resonant voltage source;

[0045] The assembly includes a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested; the resonant voltage source is used to drive the quartz crystal microbalance chip.

[0046] The optical imaging module includes a microscope and image acquisition equipment;

[0047] The assembly is fixed to the stage of the microscope; the microscope is used to magnify the sample to be tested; the image acquisition device is used to perform optical imaging on the magnified sample to obtain an image and send the image to the data processing module.

[0048] The data processing module is used to analyze and process the received images to determine the optical resonant frequency of the sample under test; and to determine the mass of the sample under test based on the optical resonant frequency.

[0049] The quartz crystal microbalance provided in this embodiment of the invention can improve the sensitivity of the quartz crystal microbalance, break away from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequency at different positions of the quartz crystal microbalance chip, realizing multi-channel multi-sample detection of a single chip.

[0050] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following embodiments are only used to illustrate the present invention in detail and do not limit the scope of the present invention in any way.

[0051] In one embodiment, to facilitate characterizing the frequency changes of large, irregularly shaped samples during the reaction process, when the sample to be tested meets one or any combination of the following conditions, the surface of the quartz crystal microbalance chip is also equipped with optical tags added by deposition or etching: the volume is greater than a preset volume, and the optical contrast is less than a preset optical contrast. The data processing module is specifically used to: determine the optical resonant frequencies of all optical tags and all samples to be tested within the field of view based on the received image; determine the optical resonant frequency of the optical tags based on the size of the optical tags; and comprehensively determine the mass of the sample to be tested based on the overall optical resonant frequency of the optical tags and the sample to be tested, as well as the optical resonant frequency of the optical tags.

[0052] In one embodiment, optical tags can be added to the surface of the quartz crystal microbalance chip through methods such as physical deposition, electrochemical deposition, photothermal deposition, electron beam deposition, electrochemical etching, and photochemical etching. This facilitates the characterization of frequency changes in large, irregularly shaped samples during the reaction process. For samples containing only small particles during the reaction, optical tags are not required. When measuring the reaction process of large, non-uniform samples and samples with poor optical contrast, the quartz crystal microbalance chip undergoes pretreatment. The purpose of this pretreatment is to add optical tags to the surface of the quartz crystal microbalance chip. Methods for adding optical tags include physical deposition, electrochemical deposition, photothermal deposition, electron beam deposition, electrochemical etching, and photochemical etching.

[0053] Physical deposition involves directly dispersing commercially produced, uniform-sized, non-reactive small particles in a solution according to the area density required for labeling. The solution is then directly dropped onto the surface of a quartz crystal microbalance chip, and after standing for a period of time, a uniform optical label is deposited on the surface of the quartz crystal microbalance chip.

[0054] Electrochemical deposition involves depositing inactive particles onto the electrodes of a quartz crystal microbalance chip using ultra-micro electrodes. This process allows for precise control of the position and size of optical tags.

[0055] Photothermal deposition involves using lasers and different reactive solutions to deposit inactive particles on the electrodes of a quartz crystal microbalance chip, allowing for precise control of the position and size of optical tags.

[0056] Electron beam deposition is the deposition of carbon particles at arbitrary locations on the surface of a quartz crystal microbalance chip using an electron beam from an electron microscope, allowing for precise control of the position and size of optical tags.

[0057] Electrochemical etching is a method that uses ultra-micro electrodes to etch away part of the electrodes on the surface of a quartz crystal microbalance chip. The advantage of this method is that it can precisely control the position of the optical tag, avoids additional mass load, and has no impact on reaction measurement.

[0058] Photochemical etching is a method that uses lasers and reactive solutions to etch away part of the electrodes on the surface of a quartz crystal microbalance chip. The advantage of this method is that it can precisely control the position of the optical tag, avoids additional mass load, and has no impact on reaction measurement.

[0059] In one embodiment, to determine the change in mass of the sample under test, the assembly may further include a reaction cell; the quartz crystal microbalance chip is clamped in the reaction cell; the reaction cell is a cell or flow cell in which reactants and samples are pre-encapsulated, and the flow cell provides a flow channel for the reactants to react with the sample under test on the surface of the quartz crystal microbalance chip; the image acquisition device is specifically used to: perform optical imaging on the microscopically magnified sample under test before the reaction to generate a first image; perform optical imaging on the microscopically magnified sample under test after the reaction to generate a second image; and send the first image and the second image to the data processing module; the data processing module is specifically used to: generate a first optical resonant frequency of the sample under test based on the received first image, and generate a second optical resonant frequency of the sample under test based on the received second image; and determine the change in mass of the sample under test based on the first optical resonant frequency and the second optical resonant frequency.

[0060] In one embodiment, the sample material to be tested can be a sample capable of reacting with a gas or a liquid; therefore, the reactant can be a gas or a liquid; the flow cell can be a gas flow cell or a liquid flow cell.

[0061] A reactant stream can be introduced into a flow cell to react with the sample on the surface of a quartz crystal microbalance chip, thereby detecting the change in the sample's mass. For example, the optical resonant frequency of the quartz crystal microbalance chip's surface is first calculated. Nitrogen gas is then introduced into the flow cell, followed by ammonia gas. After stabilization for a period, the optical resonant frequency is calculated again. Finally, nitrogen gas is introduced, and after stabilization for a period, the optical resonant frequency is calculated again. That is, ammonia absorption increases mass, and the resonant frequency at the particle's location decreases; nitrogen purging partially desorbs ammonia, decreasing mass, and the resonant frequency at the particle's location increases. Calculating the optical resonant frequencies of the quartz crystal microbalance chip's surface before and after the ammonia reaction yields the change in the sample's mass. Similarly, calculating the optical resonant frequencies of the quartz crystal microbalance chip's surface before and after ammonia desorption yields the change in the sample's mass before and after ammonia desorption.

[0062] The detection accuracy of the quartz crystal microbalance can also be verified by introducing gases or liquids that do not react with the surface of the quartz crystal microbalance chip. For example, it is known that molecular sieves do not absorb nitrogen. Before nitrogen was introduced, the resonant frequency of the molecular sieve was measured to be 5000050.50 Hz. After 1 hour of nitrogen introduction, the resonant frequency of the molecular sieve was measured to be 5000050.41 Hz. After repeating this process several times, it can be proven that the detection accuracy of the quartz crystal microbalance can reach 0.1 Hz. This demonstrates that by changing the detection principle, the mass sensitivity of the quartz crystal microbalance can be significantly improved, laying the foundation for future high-throughput measurements of minute masses.

[0063] In one embodiment, in order to enable the gas or liquid to react with the sample to be tested carried on the surface of the quartz crystal microbalance chip through the flow cell, the assembly also includes a peristaltic pump connected to the flow cell; the peristaltic pump is used to drive the gas or liquid through the flow cell.

[0064] In one embodiment, a light window may be provided on the flow cell to allow light to enter or exit the flow cell and acquire an image; the light window is used to allow light to enter or exit the flow cell; the microscope is specifically used to magnify the surface of the quartz crystal microbalance chip through the light window.

[0065] In one embodiment, in order to make the acquired image of the surface of the quartz crystal microbalance chip clearer and more stable, the optical imaging module may further include: a light source; the light source is used to illuminate the surface of the quartz crystal microbalance chip.

[0066] In one embodiment, the imaging method of the optical imaging module may include one of the following: transmission bright-field imaging, reflection bright-field imaging, reflection dark-field imaging, and differential interferometry imaging.

[0067] Figure 2 is a schematic diagram of a specific example of a quartz crystal microbalance in an embodiment of the present invention, wherein 1—light source, 2—electrochemical reaction flow cell with light window or gas or liquid flow cell with light window, 3—quartz crystal microbalance chip with optical tag, 4—microscope objective lens, 5—camera (image acquisition device), 6—semi-transparent and semi-reflective mirror, 7—lens combining objective lens and dark field condenser, 8—polarizer, 9—Wollaston prism, 10—condenser lens. As shown in Figure 2, Figure 2 illustrates the structure of the quartz crystal microbalance when the optical imaging module adopts different imaging methods. Figure 2(a) is a schematic diagram of imaging and detecting the resonant frequency of the quartz crystal microbalance chip using transmission bright field imaging, Figure 2(b) is a schematic diagram of imaging and detecting the resonant frequency of the quartz crystal microbalance chip using reflection dark field imaging, and Figure 2(c) is a schematic diagram of imaging and detecting the resonant frequency of the quartz crystal microbalance chip using differential interference imaging. The image captured by camera 5 in Figure 2(c) is a differential interference image. The optical path components in Figures 2(a), 2(b), and 2(c) are mature commercial optical microscopy imaging systems that only require assembly. For different microscopic imaging optical paths, the flow cell with the optical window needs to be designed differently depending on the optical window configuration.

[0068] In one embodiment, to test the accuracy of the mass of the sample under test determined based on the optical resonant frequency, the resonance module may further include a frequency counter; the frequency counter is used to acquire the electrical resonant frequency of the sample under test and send the electrical resonant frequency to the data processing module; the data processing module is also used to: determine the mass of the sample under test based on the electrical resonant frequency; the mass of the sample under test determined based on the electrical resonant frequency can be used as a reference for the mass of the sample under test determined based on the optical resonant frequency. The electrical resonant frequency acquired by the frequency counter can be obtained by integrating and averaging the optical resonant frequencies at all positions on the surface of the quartz crystal microbalance chip. Figure 3 is a schematic diagram of the connection of the resonance module in an embodiment of the present invention, wherein, 2—an electrochemical reaction flow cell with an optical window or a gas or liquid flow cell with an optical window, 3—a quartz crystal microbalance chip with an optical tag, 11—a frequency counter, and 12—a resonant voltage source. The resonant voltage source provides an AC voltage signal to the quartz crystal microbalance chip, and the frequency counter is used to measure the electrical frequency as a reference for the frequency measured by the resonant imaging.

[0069] In one embodiment, to improve the efficiency and accuracy of obtaining the optical resonant frequency, the image acquisition device can specifically be used to: perform optical imaging on the surface of the quartz crystal microbalance chip in a frequency scanning manner, and send the images scanned at different frequencies to the data processing module. By taking an image at each frequency and measuring its ellipticity through frequency scanning, a typical resonant curve can be obtained by plotting the ellipticity against the frequency.

[0070] In one embodiment, the image acquisition device can be a charge-coupled device (CCD) or a complementary metal-oxide-semiconductor (CMOS) device. Figure 4 is a schematic diagram of an image obtained using a quartz crystal microbalance chip with only optical tags on its surface in an embodiment of the present invention. In Figure 4(a), a schematic diagram of surface deposited particles on the surface of the quartz crystal microbalance chip with only optical tags is shown. In Figure 4(b), an optical image obtained using a quartz crystal microbalance chip in a static state on its surface with only optical tags is shown. In Figure 4(c), an optical image obtained using a quartz crystal microbalance chip in a resonant state on its surface with only optical tags is shown. Figure 5 is a schematic diagram of an image obtained using a quartz crystal microbalance on the surface of a quartz crystal microbalance chip with single particles deposited around the marker particles in an embodiment of the present invention. In Figure 5(a), it is a schematic diagram of the surface deposited particles on the surface of the quartz crystal microbalance chip with single particles deposited around the marker particles. In Figure 5(b), it is an optical image obtained using a quartz crystal microbalance in the static state of the quartz crystal microbalance chip with single particles deposited around the marker particles. In Figure 5(c), it is an optical image obtained using a quartz crystal microbalance in the resonant state of the quartz crystal microbalance chip with single particles deposited around the marker particles.

[0071] As shown in Figure 4, in this embodiment, when using a charge-coupled device (CCD) for imaging, the exposure time of the CCCD is much longer than the single motion cycle time of the quartz crystal microbalance chip. Therefore, the motion process on the surface of the quartz crystal microbalance chip cannot be observed. However, comparing the optical label on the surface of the quartz crystal microbalance chip in the resonant state and the unpowered (static) state, it can be found that the optical label in the unpowered (static) state is a circular spot with a bright center and dark edges. In the resonant state, the quartz crystal microbalance chip reciprocates at high speed. Since the exposure time is much longer than the reciprocating motion cycle, the circular spot will widen into an ellipse along the vibration direction. The amplitude of the quartz crystal at that spot can be quantitatively obtained by using the ellipticity of the central spot. By scanning the frequency, an image can be taken at each frequency and its ellipticity can be measured. Plotting the ellipticity against the frequency will yield a typical resonance curve. The ellipticity is 1 at frequencies far from the optical resonant frequency, and the ellipticity is the largest (>1) at the optical resonant frequency.

[0072] As shown in Figure 4(c), in the resonant state, the high-speed reciprocating motion of the quartz crystal microbalance chip causes the optical tag image to broaden.

[0073] As shown in Figures 4 and 5, compared to the case without deposited particles, the ellipticity of the optical tag decreases significantly due to the increase in local mass. The change in mass can be judged by the change in the optical resonant frequency of the optical tag.

[0074] Figure 6 illustrates the principle of high-throughput array analysis using multiple deposited optical tags. Microfabrication techniques allow for the formation of 100 optical tag particles on a gold film, arranged in a 10x10 array. Utilizing protein array chip technology, 100 different protein molecules can be modified around each dot, with each micro-region measuring approximately 100 micrometers. When molecules in solution selectively bind to specific protein regions, the resonant frequency of the optical tag at the center of that region decreases. This increases the efficiency of traditional quartz crystal microbalances by 100 times. As shown in Figure 6(c), the different ellipticities of the particle images reflect the local mass distribution.

[0075] In one embodiment, to improve the efficiency and accuracy of obtaining the optical resonant frequency, the data processing module is specifically used to: when the image acquisition device is a charge-coupled device (CCD), perform the following processing on the images of multiple frequency scans sent by the CCCD: determine the FWHM (Full width at half maximum) of the light spot in the image in the first and second directions; compare the FWHM of the light spot in the first and second directions, and take the ratio of the larger value to the smaller value in the comparison results as the ellipticity; determine the relationship curve between ellipticity and frequency based on multiple frequencies and their corresponding ellipticities, and take the frequency corresponding to the maximum value of ellipticity in the relationship curve as the optical resonant frequency of the sample under test; the first direction is perpendicular to the second direction.

[0076] In one embodiment, to improve the efficiency and accuracy of obtaining the optical resonant frequency, the data processing module is specifically used to: when the image acquisition device is a charge-coupled device (CCD), fit the images scanned at different frequencies sent by the CCCD to obtain the fitted image for each frequency; use a deconvolution algorithm to determine the motion path range of the light spot in the fitted image; determine the relationship curve between the motion path range of the light spot and the frequency based on multiple frequencies and the corresponding motion path range of the light spot; and take the frequency corresponding to the maximum value of the motion path range in the relationship curve as the optical resonant frequency of the sample under test.

[0077] There are three methods for acquiring optical resonant frequencies using charge-coupled devices (CCDs): The first method is one-dimensional fitting, which involves fitting the field-wheat-hump (FWHM) of the acquired image along both the x and y directions. The FWHM in the x and y directions is compared, and the ratio of the larger to the smaller value is taken as the ellipticity. A frequency-driven method is used to obtain the ellipticity versus frequency curve; the optical resonant frequency is the one with the largest ellipticity. The second method is two-dimensional fitting, which involves fitting the acquired image in two dimensions. This simultaneously yields the FWHM along the major and minor axes of the ellipse, as well as the angle between the ellipse axis and the horizontal direction of the image. The ratio of the FWHM along the major and minor axes is the ellipticity. Again, a frequency-driven method is used to obtain the ellipticity versus frequency curve; the optical resonant frequency is the one with the largest ellipticity. The third method is the deconvolution method. The deconvolution method regards the image of the high-speed motion of the quartz crystal microbalance chip surface captured by the low-frequency camera as the convolution of the static image and the motion path of the quartz crystal microbalance chip surface. By simultaneously capturing the static image and the blurred image during the high-speed motion, the deconvolution algorithm can be used to obtain the motion path. Through frequency scanning, a curve is plotted with the range of the motion path versus the frequency. The maximum range of the motion path is the optical resonant frequency.

[0078] In one embodiment, to improve the efficiency and accuracy of obtaining the optical resonant frequency, the data processing module is specifically used to: when the image acquisition device is a lock-in complementary metal-oxide-semiconductor device (LOCSD), determine the optical intensity of images scanned at different frequencies sent by the LOCSD; based on multiple frequencies and the corresponding optical intensities of the images, determine the relationship curve between the optical intensity of the image and the frequency, and take the frequency corresponding to the maximum value of the optical intensity in the relationship curve as the optical resonant frequency of the sample under test.

[0079] The method of fitting the vibration amplitude of a quartz crystal microbalance surface to acquire optical resonant frequencies using a lock-complementary metal-oxide-semiconductor (LOM) device is a hardware solution. This invention represents a secondary development of the LOM device application. When the quartz crystal microbalance chip vibrates at high frequencies, images with the same intensity but opposite phase appear on both sides of the sample in the image captured by the LOM device. The greater the vibration amplitude of the quartz crystal microbalance surface, the greater the optical intensity of the images with the same intensity but opposite phase on both sides of the sample. By plotting a curve of optical intensity against frequency, this method can reduce the difficulty of image post-processing.

[0080] Compared with traditional quartz crystal microbalances in the prior art, this invention utilizes a resonance module, an optical imaging module, and a data processing module. The resonance module includes an assembly and a resonant voltage source. The assembly includes a quartz crystal microbalance chip, on which the sample to be tested is carried. The resonant voltage source drives the quartz crystal microbalance chip. The optical imaging module includes a microscope and an image acquisition device. The assembly is fixed to the stage of the microscope. The microscope magnifies the sample to be tested. The image acquisition device performs optical imaging on the magnified sample to obtain an image and sends the image to the data processing module. The data processing module analyzes and processes the received image to determine the optical resonant frequency of the sample to be tested. Determining the mass of the sample to be tested based on the optical resonant frequency can improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequencies at different positions of the quartz crystal microbalance chip, achieving multi-channel, multi-sample detection with a single chip.

[0081] To improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequencies at different positions of the quartz crystal microbalance chip to achieve multi-channel, multi-sample detection on a single chip, this invention also provides a detection method based on a quartz crystal microbalance. This method is applied to the aforementioned quartz crystal microbalance. Figure 7 is a flowchart of the detection method based on a quartz crystal microbalance in this invention. As shown in Figure 7, the detection method based on a quartz crystal microbalance may include:

[0082] Step 701: Obtain an image of the surface of the quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample to be tested magnified by a microscope;

[0083] Step 702: Analyze and process the image to determine the optical resonant frequency of the sample under test;

[0084] Step 703: Determine the mass of the sample to be tested based on its optical resonant frequency.

[0085] In one embodiment, to determine the accuracy of the optical resonant frequency of the sample under test, the detection method based on a quartz crystal microbalance may further include: obtaining the electrical resonant frequency of the sample under test, wherein the electrical resonant frequency is acquired by collecting data from the quartz crystal microbalance chip using a frequency counter. The electrical resonant frequency can be measured using a quartz crystal microbalance including a frequency counter, and the electrical resonant frequency measured by the frequency counter serves as a reference for the optical resonant frequency measured by resonant imaging. The electrical resonant frequency acquired by the frequency counter can be obtained by integrating and averaging the optical resonant frequencies at all locations on the surface of the quartz crystal microbalance chip.

[0086] In one embodiment, analyzing and processing an image to determine the optical resonant frequency of the sample under test may include: performing the following processing on images scanned at different frequencies, wherein the images scanned at different frequencies are transmitted when the image acquisition device is a charge-coupled device (CCD): determining the full width at half maximum (FWHM) of the light spot in the image in a first direction and a second direction; comparing the FWHM of the light spot in the first direction and the second direction, and taking the ratio of the larger value to the smaller value in the comparison result as the ellipticity; determining the relationship curve between ellipticity and frequency based on multiple frequencies and their corresponding ellipticities, and taking the frequency corresponding to the maximum value of ellipticity in the relationship curve as the optical resonant frequency of the sample under test; the first direction is perpendicular to the second direction.

[0087] Figure 8 is a schematic diagram of the principle for determining the ellipticity when the amplitude is 0 pixels in an embodiment of the present invention. In Figure 8(a), the optical image of the quartz crystal microbalance chip surface when the amplitude is 0 pixels in an embodiment of the present invention is shown. In Figure 8(b), the drawing result after two-dimensional fitting using the optical image of the quartz crystal microbalance chip surface when the amplitude is 0 pixels in an embodiment of the present invention is shown, and its height represents the optical intensity value. Figure 9 is a schematic diagram of the principle for determining the ellipticity when the amplitude is 10 pixels in an embodiment of the present invention. In Figure 9(a), the optical image of the quartz crystal microbalance chip surface when the amplitude is 10 pixels in an embodiment of the present invention is shown. In Figure 9(b), the drawing result after two-dimensional fitting using the optical image of the quartz crystal microbalance chip surface when the amplitude is 10 pixels in an embodiment of the present invention is shown, and its height represents the optical intensity value. As shown in Figures 8 and 9, the ellipticity can be determined by a two-dimensional fitting method. The FWHM is obtained by performing two-dimensional fitting on the image of the light spot. The ratio of the major axis to the minor axis of the ellipse is used as the ellipticity. The ellipticity versus frequency curve shown in Figure 10 is obtained by using a frequency scanning method. The frequency corresponding to the maximum value of the ellipticity can be accurately determined by fitting. The corresponding frequency is the optical resonant frequency corresponding to the position of the optical label on the surface of the quartz crystal microbalance chip.

[0088] In one embodiment, analyzing and processing the image to determine the optical resonant frequency of the sample under test may include: performing the following processing on images scanned at different frequencies, wherein the images scanned at different frequencies are sent when the image acquisition device is a charge-coupled device (CCD); fitting the images scanned at different frequencies to obtain a fitted image for each frequency; using a deconvolution algorithm to determine the motion path range of the light spot in the fitted image; determining the relationship curve between the motion path range of the light spot and the frequency based on multiple frequencies and the corresponding motion path ranges of the light spot; and taking the frequency corresponding to the maximum value of the motion path range in the relationship curve as the optical resonant frequency of the sample under test. Figure 10 is a schematic diagram of optical resonant frequency detection when the image acquisition device is a CCD in an embodiment of the present invention. Figure 10 shows the images of the light spot captured by the CCD at different frequencies and the corresponding ellipticity, and also shows the relationship curve between the ellipticity and the frequency.

[0089] According to the detection method of the quartz crystal microbalance based on the principle of resonance imaging provided in this embodiment, this embodiment further provides a frequency detection method, which may include the following steps:

[0090] Step 1) Pre-treat the quartz crystal microbalance chip by adding an optical tag to the surface using an electrochemical deposition method;

[0091] Step 2) Install the quartz crystal microbalance chip into the gas flow cell with an optical window;

[0092] Step 3) Taking the reflected dark-field imaging method as an example, fix the assembly consisting of a quartz crystal microbalance and a gas flow cell on the microscope stage. Turn on the light source and charge-coupled device.

[0093] Step 4) Turn on the power to the resonant voltage source and frequency counter and preheat them. Connect the assembly of the quartz crystal microbalance and the gas flow cell to the resonant voltage source and frequency counter. Adjust the focal length of the microscope and image acquisition equipment.

[0094] Step 5) Use a resonant voltage source to output an AC signal, and simultaneously use a charge-coupled device to record the vibration image of the optical tag of the quartz crystal microbalance chip and the electrical resonant frequency of the frequency counter.

[0095] Step 6) Fit the recorded image, and further fit the ellipticity obtained by fitting to obtain the resonance frequency, i.e., the optical resonance frequency.

[0096] Taking molecular sieve as an example, the precise optical resonant frequency can be obtained by calculating according to the above steps. Figure 11 is a schematic diagram of the resonant frequency of the quartz crystal microbalance chip obtained by the detection method based on quartz crystal microbalance in this embodiment of the invention. In Figure 11(a), the original image of the particles on the surface of the quartz crystal microbalance chip is shown. In Figure 11(b), the maximum amplitude image on the surface of the quartz crystal microbalance chip is shown. In Figure 11(c), the relationship curve between the ellipticity and frequency of the quartz crystal microbalance chip obtained by the detection method based on quartz crystal microbalance in this embodiment of the invention is shown. As shown in Figure 11(c), the optical resonant frequency calculated and measured according to the above steps is 5001649.1Hz.

[0097] In one embodiment, analyzing and processing an image to determine the optical resonant frequency of the sample under test may include: performing the following processing on images scanned at different frequencies, wherein the images scanned at different frequencies are sent by the image acquisition device when it is a complementary metal-oxide-semiconductor device: determining the optical intensity of the images scanned at different frequencies; determining the relationship curve between the optical intensity of the image and the frequency based on multiple frequencies and the corresponding optical intensities of the images, and taking the frequency corresponding to the maximum value of the optical intensity in the relationship curve as the optical resonant frequency of the sample under test.

[0098] Figure 12 is a schematic diagram of optical resonant frequency detection when the image acquisition device is a lock-complementary metal-oxide-semiconductor device (LOM). Information on the DC component, vibration amplitude, and phase can be obtained from the image acquired by the LOM. Figure 12(a) shows the DC component of a quartz crystal microbalance surface image with an amplitude of 0 pixels when the image acquisition device is a LOM in this embodiment of the invention. Figure 12(b) shows the DC component of a quartz crystal microbalance surface image with an amplitude of 0.5 pixels when the image acquisition device is a LOM in this embodiment of the invention. Figure 12(c) shows the vibration amplitude of a quartz crystal microbalance surface image with an amplitude of 0 pixels when the image acquisition device is a LOM in this embodiment of the invention. Figure 12(c) also shows the vibration amplitude of a quartz crystal microbalance surface image with an amplitude of 0.5 pixels when the image acquisition device is a LOM in this embodiment of the invention. As shown in Figure 12(c), when the amplitude is 0 pixels, there is no phase information or vibration amplitude information. As shown in Figure 12(d), when the quartz crystal microbalance chip vibrates, i.e., the amplitude is 0.5 pixels, images with the same intensity but opposite phase appear on both sides of the sample in the captured image, as shown in Figure 12(d) as a crescent-shaped pattern with a phase difference of 180° between the two sides. The greater the vibration amplitude on the surface of the quartz crystal microbalance, the greater the optical intensity of the images with the same intensity but opposite phase on both sides of the sample. Plotting the vibration amplitude optical intensity against frequency can reduce the difficulty of image post-processing. The optical resonant frequency can be determined by fitting the plotted image.

[0099] In one embodiment, to achieve the detection of minute mass changes, the detection method based on a quartz crystal microbalance may further include: acquiring a first image and a second image; the first image being an optical image of the sample to be tested before reacting with the reactants; the second image being an optical image of the sample to be tested after reacting with the reactants; generating a first optical resonant frequency of the sample to be tested based on the first image; generating a second optical resonant frequency of the sample to be tested based on the second image; determining a first mass of the sample to be tested based on the first optical resonant frequency; determining a second mass of the sample to be tested based on the second optical resonant frequency; and determining the change in mass of the sample to be tested based on the first mass and the second mass of the sample to be tested.

[0100] According to the detection method of the quartz crystal microbalance based on the principle of resonance imaging provided in this embodiment, this embodiment further provides a method for detecting micro-mass changes, which includes the following steps:

[0101] Step 1) First, unlock the intercomplementary metal-oxide-semiconductor devices to preheat them;

[0102] Step 2) Turn on the power to the resonant voltage source and frequency counter and preheat them. Connect the resonant voltage source as a synchronous clock to the lock-complementary metal-oxide-semiconductor device. Connect the other path of the resonant voltage source to the signal synchronization module of the lock-complementary metal-oxide-semiconductor device and test the accuracy of the synchronization signal.

[0103] Step 3) Taking the reflected dark field imaging method as an example, fix the assembly composed of the quartz crystal microbalance chip and the gas flow cell on the microscope stage and turn on the light source;

[0104] Step 4) Adjust the focal length of the optical imaging system;

[0105] Step 5) Use a resonant voltage source to output an AC signal, and synchronously use a lock-and-match metal-oxide-semiconductor device to record the vibration amplitude intensity image of the optical tag of the quartz crystal microbalance chip and the electrical resonant frequency of the frequency counter.

[0106] Step 6) Extract the vibration amplitude intensity of the recorded image, and further fit the vibration amplitude intensity to obtain the optical resonant frequency;

[0107] Step 7) Perform a single-particle reaction and test the reaction frequency during the reaction process;

[0108] Step 8) After the reaction is complete, extract the vibration amplitude intensity of the recorded image, and further fit the vibration amplitude intensity to obtain the optical resonant frequency;

[0109] Step 9) The change in reaction frequency during the reaction process can be converted into a change in mass, thereby obtaining a kinetic curve of the mass change. The frequency measurements before and after the reaction will be used as the benchmark for the frequency change.

[0110] Figure 13 is a curve showing the relationship between pattern intensity and frequency of the quartz crystal microbalance chip obtained by using a complementary metal-oxide-semiconductor device (CMOS) in an embodiment of the present invention. Taking a molecular sieve as an example, the precise optical resonant frequency can be obtained by following the above steps. As shown in Figure 13, the amplitude of the particles on the surface of the quartz crystal microbalance chip is different at different frequencies. By fitting the curve showing the relationship between pattern intensity and frequency of the quartz crystal microbalance chip obtained by using a complementary metal-oxide-semiconductor device, the frequency value corresponding to the maximum vibration amplitude of the image before the reaction is measured, that is, the optical resonant frequency before the reaction is 5000050.50 Hz.

[0111] Furthermore, Figure 14 is a schematic diagram of the frequency change of an unreacted molecular sieve (inert to nitrogen) before and after purging with nitrogen (N2) for 1 hour using a quartz crystal microbalance in an embodiment of the present invention. Figure 14(a) shows the frequency change of the unreacted molecular sieve (inert to nitrogen) before purging with nitrogen for 1 hour using a quartz crystal microbalance in an embodiment of the present invention. As shown in Figure 14(a), it is known that the molecular sieve does not absorb nitrogen. The resonant frequency of the molecular sieve was measured to be 5000050.50 Hz before nitrogen was introduced. Figure 14(b) shows the frequency change of the unreacted molecular sieve (inert to nitrogen) after purging with nitrogen for 1 hour using a quartz crystal microbalance in an embodiment of the present invention. As shown in Figure 14(b), the resonant frequency of the molecular sieve was measured to be 5000050.41 Hz after purging with nitrogen for 1 hour. After repeating this process several times, it can be proven that the frequency accuracy of the quartz crystal microbalance measured using the resonance principle can reach 0.1 Hz.

[0112] Figure 15 is a schematic diagram showing the resonant frequency changes of the 12 molecular sieves during the absorption and desorption of ammonia in a quartz crystal microbalance in this embodiment of the invention. Figures (a)-(l) in Figure 15 respectively show the resonant frequency changes of the 1st to 12th molecular sieves during the absorption and desorption of ammonia in a quartz crystal microbalance in this embodiment of the invention. As shown in Figure 15, the reaction process is as follows: nitrogen gas is introduced first, followed by ammonia gas. In this experiment, a frequency scan is performed before the gas is introduced and another frequency scan is performed after the gas is completely introduced. The number of frequency scans on the horizontal axis in Figure 15 represents the stages of this experiment. That is, the first frequency scan is performed before the ammonia gas is introduced; the second frequency scan is performed after the ammonia gas has stabilized for a period of time; the third frequency scan is performed after the ammonia gas is introduced and before the nitrogen gas is introduced; and the fourth frequency scan is performed after the nitrogen gas is introduced. In other words, with ammonia absorption, the mass increases, and the resonant frequency at the particle's location decreases; with nitrogen purging, ammonia is partially desorbed, the mass decreases, and the resonant frequency at the particle's location increases. This process simultaneously detected 12 molecular sieve particles, validating its potential for multi-channel detection. Furthermore, since a single molecular sieve particle has a volume of only 1 cubic micrometer and a mass of 1.96 pg, while its ammonia adsorption mass is only 2%, the mass change is only 40 fg. This demonstrates that by changing the detection principle, the mass sensitivity of the quartz crystal microbalance can be significantly improved, laying the foundation for future high-throughput measurements of minute masses.

[0113] Compared with traditional micro-mass detection methods in the prior art, this invention utilizes a resonance module, an optical imaging module, and a data processing module. The resonance module includes an assembly and a resonant voltage source. The assembly includes a quartz crystal microbalance chip. The sample to be tested is carried on the surface of the quartz crystal microbalance chip. The resonant voltage source drives the quartz crystal microbalance chip. The optical imaging module includes a microscope and an image acquisition device. The assembly is fixed to the stage of the microscope. The microscope magnifies the sample to be tested. The image acquisition device performs optical imaging on the magnified sample to obtain an image and sends the image to the data processing module. The data processing module analyzes and processes the received image to determine the optical resonant frequency of the sample to be tested. Determining the mass of the sample to be tested based on the optical resonant frequency can improve the sensitivity of the quartz crystal microbalance, break free from the limitations of the Sauerbrey equation, and simultaneously measure the resonant frequencies at different positions of the quartz crystal microbalance chip, achieving multi-channel, multi-sample detection with a single chip.

[0114] This invention also provides a data synchronization device, as described in the following embodiments. Since the principle by which this device solves the problem is similar to the detection method based on a quartz crystal microbalance, the implementation of this device can refer to the implementation of the detection method based on a quartz crystal microbalance; repeated details will not be elaborated further.

[0115] Figure 16 is a structural block diagram of the detection device based on a quartz crystal microbalance in an embodiment of the present invention. As shown in Figure 16, the detection device based on a quartz crystal microbalance, applied to the aforementioned quartz crystal microbalance, may include:

[0116] The acquisition module 1601 is used to acquire an image of the surface of the quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample to be tested magnified by a microscope;

[0117] Analysis module 1602 is used to analyze and process the image to determine the optical resonant frequency of the sample under test;

[0118] The quality determination module 1603 is used to determine the quality of the sample to be tested based on the optical resonant frequency of the sample.

[0119] In one embodiment, the detection device based on a quartz crystal microbalance may further include: an electrical resonant frequency determination module, used for:

[0120] The electrical resonant frequency of the sample to be tested is obtained by using a frequency counter to collect the sample to be tested carried on the surface of the quartz crystal microbalance chip.

[0121] The mass of the sample is determined based on its electrical resonant frequency.

[0122] In one embodiment, the detection device based on a quartz crystal microbalance may further include: a mass change determination module, used for:

[0123] Acquire a first image and a second image; the first image is an optical image of the sample to be tested before reacting with the reactants; the second image is an optical image of the sample to be tested after reacting with the reactants.

[0124] A first optical resonant frequency of the sample under test is generated based on the first image; a second optical resonant frequency of the sample under test is generated based on the second image.

[0125] The first mass of the sample to be tested is determined based on the first optical resonant frequency; the second mass of the sample to be tested is determined based on the second optical resonant frequency.

[0126] The change in mass of the sample is determined based on its first mass and second mass.

[0127] In one embodiment, the analysis module 1602 is specifically used for:

[0128] The following processing is performed on images scanned at different frequencies, where the images are transmitted when the image acquisition device is a charge-coupled device (CCD):

[0129] Determine the full width at half maximum (FWHM) of the light spot in the image in the first and second directions;

[0130] The FWHM of the light spot in the first and second directions are compared, and the ratio of the larger value to the smaller value in the comparison results is taken as the ellipticity.

[0131] Based on multiple frequencies and their corresponding ellipticities, a curve relating ellipticity to frequency is determined, and the frequency corresponding to the maximum ellipticity in the curve is taken as the optical resonant frequency of the sample under test; the first direction is perpendicular to the second direction.

[0132] In one embodiment, the analysis module 1602 is specifically used for:

[0133] The following processing is performed on images scanned at different frequencies, where the images are transmitted when the image acquisition device is a charge-coupled device (CCD):

[0134] Images scanned at different frequencies are fitted to obtain fitted images for each frequency. The deconvolution algorithm is then used to determine the range of the motion path of the light spot in the fitted image.

[0135] Based on multiple frequencies and the corresponding movement path range of the light spot, the relationship curve between the movement path range of the light spot and the frequency is determined, and the frequency corresponding to the maximum value of the movement path range in the relationship curve is taken as the optical resonant frequency of the sample under test.

[0136] In one embodiment, the analysis module 1602 is specifically used for:

[0137] The following processing is performed on images scanned at different frequencies, where the images are transmitted by the image acquisition device when it is a complementary metal-oxide-semiconductor device:

[0138] Determine the optical intensity of images scanned at different frequencies;

[0139] Based on multiple frequencies and the corresponding optical intensities of the images, the relationship curve between the optical intensity of the image and the frequency is determined, and the frequency corresponding to the maximum value of the optical intensity in the relationship curve is taken as the optical resonant frequency of the sample under test.

[0140] Based on the aforementioned inventive concept, as shown in Figure 17, the present invention also proposes a computer device 1700, including a memory 1710, a processor 1720, and a computer program 1730 stored in the memory 1710 and executable on the processor 1720. When the processor 1720 executes the computer program 1730, it implements the aforementioned detection method based on a quartz crystal microbalance.

[0141] Based on the aforementioned inventive concept, this invention proposes a computer-readable storage medium storing a computer program, which, when executed by a processor, implements the aforementioned detection method based on a quartz crystal microbalance.

[0142] Based on the aforementioned inventive concept, the present invention proposes a computer program product, which includes a computer program that, when executed by a processor, implements a detection method based on a quartz crystal microbalance.

[0143] This invention revolutionizes the traditional frequency detection approach of quartz crystal microbalances by transforming the detection of quartz crystal resonant frequencies from electrical to optical detection. This significantly increases the throughput of traditional quartz crystal microbalances while maintaining the accuracy of frequency measurements. This invention utilizes the principle of resonant imaging to simultaneously measure the resonant frequencies at different locations on the quartz crystal microbalance chip, thereby studying the resonant frequency variations of non-uniformly distributed single-particle samples and further investigating the mass changes of single-particle samples during the reaction process. Since the mass changes across the entire chip surface do not need to be considered, the mass sensitivity of the quartz crystal microbalance can be accurate to the fg level. Furthermore, various techniques can be used to deposit different samples on the chip surface, enabling multi-channel, multi-sample detection on a single chip. This invention proposes a novel detection principle in the field of micro-mass detection, broadening the application range of quartz crystal microbalances and improving their sensitivity. Moreover, because this device overcomes the theoretical limitations of the Sauerbrey equation, it can significantly improve the detection limit of the quartz crystal microbalance without increasing its resonant frequency. The beneficial effect of this invention is that it significantly improves the detection throughput of quartz crystal microbalances and greatly increases the detection limit of quartz crystal microbalances.

[0144] Those skilled in the art will understand that embodiments of the present invention can be provided as methods, systems, or computer program products. Therefore, the present invention can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, the present invention can take the form of a computer program product embodied on one or more computer-usable storage media (including, but not limited to, disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0145] This invention is described with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions specified in one or more blocks of the flowchart illustrations and / or one or more blocks of the block diagrams.

[0146] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing device to function in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means that implement the functions specified in one or more flowcharts and / or one or more block diagrams.

[0147] These computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer-implemented process, such that the instructions, which execute on the computer or other programmable apparatus, provide steps for implementing the functions specified in one or more flowcharts and / or one or more block diagrams.

[0148] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A quartz crystal microbalance, characterized in that, include: The module consists of a resonant module, an optical imaging module, and a data processing module. The resonant module includes an assembly and a resonant voltage source; The assembly includes a quartz crystal microbalance chip; The surface of the quartz crystal microbalance chip carries the sample to be tested; the resonant voltage source is used to drive the quartz crystal microbalance chip. The optical imaging module includes a microscope and image acquisition equipment; The assembly is fixed to the stage of the microscope; the microscope is used to magnify the sample to be tested; the image acquisition device is used to perform optical imaging on the magnified sample to obtain an image and send the image to the data processing module. The data processing module is used to analyze and process the received images to determine the optical resonant frequency of the sample under test; and to determine the mass of the sample under test based on the optical resonant frequency. The data processing module is specifically used for: The image acquisition device is a charge-coupled device (CCD), and the following processing is performed on the images scanned at multiple frequencies sent by the CCCD: The full width at half maximum (FWHM) of the light spot in the image is determined in the first and second directions; the FWHM of the light spot in the first and second directions are compared, and the ratio of the larger to the smaller value in the comparison result is taken as the ellipticity; Based on multiple frequencies and their corresponding ellipticities, a relationship curve between ellipticity and frequency is determined, and the frequency corresponding to the maximum ellipticity in the relationship curve is taken as the optical resonant frequency of the sample under test; The first direction is perpendicular to the second direction; Alternatively, the data processing module is specifically used for: the image acquisition device is a charge-coupled element (CCElement), fitting images scanned at different frequencies sent by the CCElement to obtain a fitted image for each frequency, using a deconvolution algorithm to determine the motion path range of the light spot in the fitted image; based on multiple frequencies and the corresponding motion path range of the light spot, determining the relationship curve between the motion path range of the light spot and the frequency, and using the frequency corresponding to the maximum value of the motion path range in the relationship curve as the optical resonant frequency of the sample under test; Alternatively, the data processing module is specifically used for: the image acquisition device being a lock-in complementary metal-oxide-semiconductor device (MODS), determining the optical intensity of images scanned at different frequencies by the MODS; based on multiple frequencies and the corresponding optical intensities of the images, determining the relationship curve between the optical intensity of the image and the frequency, and taking the frequency corresponding to the maximum optical intensity in the relationship curve as the optical resonant frequency of the sample under test.

2. The quartz crystal microbalance as described in claim 1, characterized in that, The assembly also includes a reaction cell; the quartz crystal microbalance chip is clamped in the reaction cell; the reaction cell is a flow cell or a cell in which the reactants and the sample are pre-encapsulated, and the flow cell is used to provide a flow channel for the reactants so that the reactants react with the sample to be tested on the surface of the quartz crystal microbalance chip. The image acquisition device is specifically used for: performing optical imaging on the microscopically magnified sample before the reaction to generate a first image; performing optical imaging on the microscopically magnified sample after the reaction to generate a second image; and sending the first image and the second image to the data processing module. The data processing module is specifically used to: generate a first optical resonant frequency of the sample under test based on the received first image, generate a second optical resonant frequency of the sample under test based on the received second image, and determine the change in mass of the sample under test based on the first and second optical resonant frequencies.

3. The quartz crystal microbalance as described in claim 2, characterized in that, The reactants are gases or liquids; the flow cell is a gas flow cell or a liquid flow cell.

4. The quartz crystal microbalance as described in claim 2, characterized in that, The assembly also includes a peristaltic pump connected to a flow cell; the peristaltic pump is used to drive the reactants through the flow cell.

5. The quartz crystal microbalance as described in claim 2, characterized in that, The reaction tank is equipped with a light window; the light window is used to allow light to enter or exit the reaction tank. The microscope is specifically used to magnify the sample to be tested on the surface of a quartz crystal microbalance chip through a light window.

6. The quartz crystal microbalance as described in claim 1, characterized in that, The optical imaging module also includes a light source; the light source is used to illuminate the surface of the quartz crystal microbalance chip.

7. The quartz crystal microbalance as described in claim 1, characterized in that, The resonant module also includes a frequency counter; the frequency counter is used to acquire the electrical resonant frequency of the sample under test and send the electrical resonant frequency to the data processing module. The data processing module is also used to determine the mass of the sample to be tested based on the electrical resonant frequency.

8. The quartz crystal microbalance as described in claim 1, characterized in that, When the sample to be tested meets one or any combination of the following conditions, the surface of the quartz crystal microbalance chip also carries an optical tag added by deposition or etching: the volume is greater than a preset volume and the optical contrast is less than a preset optical contrast. The data processing module is specifically used to: determine the optical resonant frequency of the optical tag and the sample under test as a whole based on the received image; determine the optical resonant frequency of the optical tag based on the size of the optical tag; and determine the mass of the sample under test based on the optical resonant frequency of the optical tag and the sample under test as a whole, and the optical resonant frequency of the optical tag.

9. The quartz crystal microbalance as described in claim 1, characterized in that, The imaging methods of the optical imaging module include one of the following: transmission bright-field imaging, reflection bright-field imaging, reflection dark-field imaging, and differential interferometry imaging.

10. The quartz crystal microbalance as described in claim 1, characterized in that, The image acquisition device is specifically used to: perform optical imaging on the sample to be tested on the surface of the quartz crystal microbalance chip in a frequency scanning manner, and send the images scanned at different frequencies to the data processing module.

11. A detection method based on a quartz crystal microbalance, characterized in that, An application is made in a quartz crystal microbalance, the quartz crystal microbalance comprising: a resonant module, an optical imaging module, and a data processing module; The resonant module includes an assembly and a resonant voltage source; The assembly includes a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested; the resonant voltage source is used to drive the quartz crystal microbalance chip. The optical imaging module includes a microscope and image acquisition equipment; The assembly is fixed to the stage of the microscope; the microscope is used to magnify the sample to be tested; the image acquisition device is used to perform optical imaging on the magnified sample to obtain an image and send the image to the data processing module. The data processing module is used to analyze and process the received images to determine the optical resonant frequency of the sample under test; and to determine the mass of the sample under test based on the optical resonant frequency. The data processing module is specifically used for: The image acquisition device is a charge-coupled device (CCD), and the following processing is performed on the images scanned at multiple frequencies sent by the CCCD: The full width at half maximum (FWHM) of the light spot in the image is determined in the first and second directions; the FWHM of the light spot in the first and second directions are compared, and the ratio of the larger to the smaller value in the comparison result is taken as the ellipticity; Based on multiple frequencies and their corresponding ellipticities, a relationship curve between ellipticity and frequency is determined, and the frequency corresponding to the maximum ellipticity in the relationship curve is taken as the optical resonant frequency of the sample under test; The first direction is perpendicular to the second direction; Alternatively, the data processing module is specifically used for: the image acquisition device is a charge-coupled element (CCElement), fitting images scanned at different frequencies sent by the CCElement to obtain a fitted image for each frequency, using a deconvolution algorithm to determine the motion path range of the light spot in the fitted image; based on multiple frequencies and the corresponding motion path range of the light spot, determining the relationship curve between the motion path range of the light spot and the frequency, and using the frequency corresponding to the maximum value of the motion path range in the relationship curve as the optical resonant frequency of the sample under test; Alternatively, the data processing module is specifically used for: the image acquisition device is a lock-in complementary metal-oxide-semiconductor device (MODS), determining the optical intensity of images scanned at different frequencies sent by the MODS; based on multiple frequencies and the corresponding optical intensities of the images, determining the relationship curve between the optical intensity of the image and the frequency, and taking the frequency corresponding to the maximum value of the optical intensity in the relationship curve as the optical resonant frequency of the sample under test. The detection method based on a quartz crystal microbalance includes: An image of the surface of a quartz crystal microbalance chip is obtained; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample under a microscope. The image is analyzed and processed to determine the optical resonant frequency of the sample under test; The mass of the sample is determined based on its optical resonant frequency.

12. The detection method based on a quartz crystal microbalance as described in claim 11, characterized in that, Also includes: The electrical resonant frequency of the sample to be tested is obtained by using a frequency counter to collect data from a quartz crystal microbalance chip. The mass of the sample is determined based on its electrical resonant frequency.

13. The detection method based on a quartz crystal microbalance as described in claim 11, characterized in that, Also includes: Acquire a first image and a second image; the first image is an optical image of the sample to be tested before reacting with the reactants. The second image is an optical image of the test sample after it has reacted with the reactants; The first optical resonant frequency of the sample under test is generated based on the first image; The second optical resonant frequency of the sample under test is generated based on the second image; The first mass of the sample to be tested is determined based on the first optical resonant frequency. The second mass of the sample to be tested is determined based on the second optical resonant frequency. The change in mass of the sample is determined based on its first mass and second mass.

14. The detection method based on a quartz crystal microbalance as described in claim 11, characterized in that, The image is analyzed and processed to determine the optical resonant frequency of the sample under test, including: The following processing is performed on images scanned at different frequencies, where the images are transmitted when the image acquisition device is a charge-coupled device (CCD): Determine the full width at half maximum (FWHM) of the light spot in the image in the first and second directions; The FWHM of the light spot in the first and second directions are compared, and the ratio of the larger value to the smaller value in the comparison results is taken as the ellipticity. Based on multiple frequencies and their corresponding ellipticities, a curve relating ellipticity to frequency is determined, and the frequency corresponding to the maximum ellipticity in the curve is taken as the optical resonant frequency of the sample under test; the first direction is perpendicular to the second direction.

15. The detection method based on a quartz crystal microbalance as described in claim 11, characterized in that, The image is analyzed and processed to determine the optical resonant frequency of the sample under test, including: The following processing is performed on images scanned at different frequencies, where the images are transmitted when the image acquisition device is a charge-coupled device (CCD): Images scanned at different frequencies are fitted to obtain fitted images for each frequency. The deconvolution algorithm is then used to determine the range of the motion path of the light spot in the fitted image. Based on multiple frequencies and the corresponding movement path range of the light spot, the relationship curve between the movement path range of the light spot and the frequency is determined, and the frequency corresponding to the maximum value of the movement path range in the relationship curve is taken as the optical resonant frequency of the sample under test.

16. The detection method based on a quartz crystal microbalance as described in claim 11, characterized in that, The image is analyzed and processed to determine the optical resonant frequency of the sample under test, including: The following processing is performed on images scanned at different frequencies, where the images are transmitted by the image acquisition device when it is a complementary metal-oxide-semiconductor device: Determine the optical intensity of images scanned at different frequencies; Based on multiple frequencies and the corresponding optical intensities of the images, the relationship curve between the optical intensity of the image and the frequency is determined, and the frequency corresponding to the maximum value of the optical intensity in the relationship curve is taken as the optical resonant frequency of the sample under test.

17. A detection device based on a quartz crystal microbalance, characterized in that, The system includes a quartz crystal microbalance, which comprises: a resonant module, an optical imaging module, and a data processing module. The resonant module includes an assembly and a resonant voltage source; The assembly includes a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested; the resonant voltage source is used to drive the quartz crystal microbalance chip. The optical imaging module includes a microscope and image acquisition equipment; The assembly is fixed to the stage of the microscope; the microscope is used to magnify the sample to be tested; the image acquisition device is used to perform optical imaging on the magnified sample to obtain an image and send the image to the data processing module. The data processing module is used to analyze and process the received images to determine the optical resonant frequency of the sample under test; and to determine the mass of the sample under test based on the optical resonant frequency. The data processing module is specifically used for: The image acquisition device is a charge-coupled device (CCD), and the following processing is performed on the images scanned at multiple frequencies sent by the CCCD: The full width at half maximum (FWHM) of the light spot in the image is determined in the first and second directions; the FWHM of the light spot in the first and second directions are compared, and the ratio of the larger to the smaller value in the comparison result is taken as the ellipticity; Based on multiple frequencies and their corresponding ellipticities, a relationship curve between ellipticity and frequency is determined, and the frequency corresponding to the maximum ellipticity in the relationship curve is taken as the optical resonant frequency of the sample under test; The first direction is perpendicular to the second direction; Alternatively, the data processing module is specifically used for: the image acquisition device is a charge-coupled element (CCElement), fitting images scanned at different frequencies sent by the CCElement to obtain a fitted image for each frequency, using a deconvolution algorithm to determine the motion path range of the light spot in the fitted image; based on multiple frequencies and the corresponding motion path range of the light spot, determining the relationship curve between the motion path range of the light spot and the frequency, and using the frequency corresponding to the maximum value of the motion path range in the relationship curve as the optical resonant frequency of the sample under test; Alternatively, the data processing module is specifically used for: the image acquisition device is a lock-in complementary metal-oxide-semiconductor device (MODS), determining the optical intensity of images scanned at different frequencies sent by the MODS; based on multiple frequencies and the corresponding optical intensities of the images, determining the relationship curve between the optical intensity of the image and the frequency, and taking the frequency corresponding to the maximum value of the optical intensity in the relationship curve as the optical resonant frequency of the sample under test. The detection device based on the quartz crystal microbalance also includes: An acquisition module is used to acquire an image of the surface of a quartz crystal microbalance chip; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample to be tested magnified by a microscope; The analysis module is used to analyze and process the image to determine the optical resonant frequency of the sample under test. The quality determination module is used to determine the quality of the sample to be tested based on its optical resonant frequency.

18. A computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, When the processor executes the computer program, it implements a detection method based on a quartz crystal microbalance, the method comprising: An image of the surface of a quartz crystal microbalance chip is obtained; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample under a microscope. The image is analyzed and processed to determine the optical resonant frequency of the sample under test; The mass of the sample is determined based on its optical resonant frequency.

19. A computer-readable storage medium, characterized in that, The computer-readable storage medium stores a computer program that, when executed by a processor, implements a detection method based on a quartz crystal microbalance, the method comprising: An image of the surface of a quartz crystal microbalance chip is obtained; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample under a microscope. The image is analyzed and processed to determine the optical resonant frequency of the sample under test; The mass of the sample is determined based on its optical resonant frequency.

20. A computer program product, characterized in that, The computer program product includes a computer program that, when executed by a processor, implements a detection method based on a quartz crystal microbalance, the method comprising: An image of the surface of a quartz crystal microbalance chip is obtained; the surface of the quartz crystal microbalance chip carries the sample to be tested, and the image is obtained by optical imaging of the sample under a microscope. The image is analyzed and processed to determine the optical resonant frequency of the sample under test; The mass of the sample is determined based on its optical resonant frequency.

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