WO2019109368A1 - 新型光辅助石英晶体微天平及其检测方法 - Google Patents

新型光辅助石英晶体微天平及其检测方法 Download PDF

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WO2019109368A1
WO2019109368A1 PCT/CN2017/115776 CN2017115776W WO2019109368A1 WO 2019109368 A1 WO2019109368 A1 WO 2019109368A1 CN 2017115776 W CN2017115776 W CN 2017115776W WO 2019109368 A1 WO2019109368 A1 WO 2019109368A1
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qcm
chip
quartz crystal
light
light source
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PCT/CN2017/115776
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French (fr)
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汪杰
刘磊
董明东
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江苏大学
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Priority to US16/763,231 priority Critical patent/US11105774B2/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/036—Analysing fluids by measuring frequency or resonance of acoustic waves
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/022—Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/22—Details, e.g. general constructional or apparatus details
    • G01N29/222—Constructional or flow details for analysing fluids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/22—Details, e.g. general constructional or apparatus details
    • G01N29/32—Arrangements for suppressing undesired influences, e.g. temperature or pressure variations, compensating for signal noise
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/01—Indexing codes associated with the measuring variable
    • G01N2291/014—Resonance or resonant frequency
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/025—Change of phase or condition
    • G01N2291/0255—(Bio)chemical reactions, e.g. on biosensors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/025—Change of phase or condition
    • G01N2291/0256—Adsorption, desorption, surface mass change, e.g. on biosensors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/04—Wave modes and trajectories
    • G01N2291/042—Wave modes
    • G01N2291/0426—Bulk waves, e.g. quartz crystal microbalance, torsional waves

Definitions

  • the invention relates to the technical field of instrumentation, in particular to a novel light-assisted quartz crystal microbalance and a detection method thereof.
  • ⁇ f is the frequency change (Hz)
  • ⁇ m is the change in chip surface quality (g)
  • f 0 is the QCM chip resonance frequency (Hz)
  • A is the area of the QCM chip reaction electrode (cm 2 )
  • ⁇ q is the density ( 2.65 g/cm 3 )
  • ⁇ q is the shear modulus.
  • Quartz crystal microbalances are widely used in various fields, such as surface thickness monitoring in vacuum. This application has also greatly expanded its use as a sensor in other fields, such as airborne contamination detection, metal corrosion and protection, and high Molecular phase transition, biosensing detection, etc.
  • Quartz crystal microbalance is a powerful mark-free detection technology that has received increasing attention in various fields.
  • quartz crystal microbalances appear to lag behind the development of surface plasmon resonance (SPR), another mark-free detection technique.
  • SPR surface plasmon resonance
  • One of the important reasons for the huge commercial success of SPR technology is that, overall, the detection sensitivity of the SPR system is higher than that of the quartz crystal microbalance.
  • the sensitivity of a 5MHz quartz crystal microbalance is approximately 20 times lower than that of the corresponding SPR system.
  • the signal of the quartz crystal microbalance is not strong enough to obtain information about the object to be detected.
  • the detection sensitivity of a quartz crystal microbalance is defined as the mass change in the surface area per unit area of the QCM chip corresponding to a certain signal change value.
  • the detection sensitivity is related to the density of the surface detection object and the resonance frequency and shear modulus inherent to the chip.
  • the LOD of the quartz crystal microbalance is less than 1 ng/cm 2 , and the detection limit cannot fully meet the application requirements. For example, in the detection of clinically diagnosed subjects, the concentration of the test object is in the ng/mL level. Therefore, the sensitivity and LOD of the quartz crystal microbalance need to be improved.
  • the present invention aims to provide a quartz crystal microbalance system and a detection method with higher detection sensitivity, which does not need to reduce the thickness of the chip, resulting in chip fragmentation; and the present invention can also improve the quartz crystal micro The sensitivity of the balance system detection.
  • the present invention achieves the above technical objects by the following technical means.
  • a novel light-assisted quartz crystal microbalance characterized in that it comprises the following parts:
  • a QCM/QCM-D chip which is a sandwich structure in which a quartz crystal layer is sandwiched between two electrodes, and the chip and the electrode circuit are encapsulated by a metal, ceramic or plastic casing to form a reaction chamber, and the chip and The outer casing integrally constitutes a quartz crystal resonator;
  • a frequency counter for monitoring the resonant frequency of the QCM/QCM-D chip
  • a light source that emits light from the surface of the QCM/QCM-D chip.
  • the light source is a light source having one or more frequencies.
  • a grating unit is disposed between the light source and the QCM/QCM-D chip for controlling the illumination of the light source to the surface of the QCM/QCM-D chip.
  • the barrier unit includes a movable grating barrier and a driver capable of moving the grating barrier.
  • the grating baffle is a detachable grating baffle, and the driver is an electric drive.
  • novel light-assisted quartz crystal microbalance further comprises a computer connected to the driver of the grating baffle, the oscillating circuit and the frequency counter, for controlling the operation of the driver of the grating baffle to realize the movement of the grating baffle, and controlling the oscillating circuit
  • a computer connected to the driver of the grating baffle, the oscillating circuit and the frequency counter, for controlling the operation of the driver of the grating baffle to realize the movement of the grating baffle, and controlling the oscillating circuit
  • the on-off, electric field parameters, and the data collected by the read frequency counter, and the change of the resonant frequency of the QCM/QCM-D chip during the detection process are controlled.
  • the light source generates light in a wavelength range of 100-800 nm, preferably 200-400 nm.
  • Step 1 Run the quartz crystal microbalance system to obtain the resonance frequency stable baseline of the QCM/QCM-D chip through the frequency counter;
  • Step 2 Turn on the light source switch, let the light shine on the surface of the QCM/QCM-D chip, and obtain the resonance frequency of the QCM/QCM-D chip through the frequency counter as the signal 1;
  • Step 3 The light of the light source is no longer irradiated on the surface of the QCM/QCM-D chip;
  • Step 4 Advance the object to be inspected onto the surface of the QCM/QCM-D chip, then illuminate the surface of the QCM/QCM-D chip, obtain the resonant frequency of the QCM/QCM-D chip through the frequency counter, and signal 2, compare the signal. The difference between 1 and signal 2.
  • the quartz crystal microbalance detecting method can be applied to a gas- and liquid-liquid detecting object for accommodating a gas or a liquid in an environment in which the detecting object is located and a detecting object.
  • the invention adopts a light source capable of irradiating light onto the surface of the chip, and the surface properties of the QCM/QCM-D chip are changed under the irradiation of light, and the water molecule layer adsorbed on the surface of the QCM/QCM-D chip is from QCM/QCM-D.
  • Reversible desorption on the surface of the chip electrode; source light irradiation on the surface of the QCM/QCM-D chip can cause a sharp rise in the resonant frequency.
  • the irradiation of light on the surface of the chip also causes a change in the mechanical properties and piezoelectric characteristics of the quartz crystal, thereby effectively improving the detection sensitivity of the quartz crystal microbalance device system.
  • a grating unit to control the illumination of the light source onto the surface of the chip enables the grating unit to quickly and efficiently control the illumination on the surface of the QCM/QCM-D chip as compared to a simple switch-controlled illumination that relies on the light source.
  • the test subject can include different concentrations and different kinds of compounds, covering various chemicals and biomolecules, such as tumor diagnostic markers.
  • FIG. 1 is a schematic diagram of a QCM sensor system according to the present invention.
  • Fig. 2(a) is a schematic diagram showing the general process of detecting the surface of the chip flowing through different concentrations of PBS solution by using the resonance frequency curve of QCM under the switching control of the grating unit; (b) controlling the light by using the switch of the grating unit When irradiating the surface of the QCM/QCM-D chip, the resonance frequency of the QCM changes with time to detect a data map of the surface of the chip flowing through different concentrations of the PBS solution;
  • Fig. 3 is a graph showing the relationship between the resonance frequency curve of QCM/QCM-D and the surface of the test chip flowing through different concentrations of PBS solution over time when the surface of the QCM/QCM-D chip is not irradiated with light.
  • 2-New light-assisted quartz crystal microbalance 4-computer, 6-light source, 8-grating baffle, 10-grating unit, 12-ray, 14-reaction chamber, quartz crystal in 16-QCM/QCM-D chip Slice, 18-groove, 20-QCM/QCM-D chip, 22-frequency counter.
  • the novel light-assisted quartz crystal microbalance 2 of the present invention comprises a QCM/QCM-D chip, which is a sandwich structure formed by a quartz crystal layer layer clip 16 between two electrodes.
  • the chip and the electrode circuit are encapsulated by a metal, ceramic or plastic housing formed in a reaction chamber 14, the chip and the housing integrally forming a quartz crystal resonator, and the QCM/QCM-D chip 20 is mounted in the reaction
  • the recess 18 in the bottom surface of the chamber 14 is inside.
  • the reaction chamber 14 is for accommodating gas or liquid in the environment in which the detection object is located and the detection object; an oscillating circuit provides an alternating electric field for the quartz crystal layer 16 in the QCM/QCM-D chip 20; the frequency counter 22 is used The resonant frequency of the QCM/QCM-D chip 20 is monitored; a light source 6 whose light 12 can be radiated on the surface of the QCM/QCM-D chip 20.
  • the light source 6 is a light source having one or more frequencies capable of generating light having a wavelength in the range of 100-800 nm, preferably 200-400 nm, such as 365 nm. If the frequency of the light emitted by the light source 6 is smaller or the energy and power of the irradiated light are increased, it will have a better effect.
  • the light 12 emitted from the light source 6 is irradiated onto the surface of the QCM/QCM-D chip 20 to change its surface properties, and the water molecules adsorbed on the surface of the QCM/QCM-D chip are reversibly solved from the surface of the QCM/QCM-D chip 20.
  • Adsorption can increase the resonant frequency of the QCM/QCM-D chip.
  • the irradiation of light on the surface of the chip also causes a change in the mechanical properties and piezoelectric characteristics of the quartz crystal in the chip, thereby effectively improving the detection sensitivity of the quartz crystal microbalance 2 device system.
  • the sensitivity of the quartz crystal microbalance 2 system can be increased by more than ten times.
  • the novel light-assisted quartz crystal microbalance 2 includes a grating unit 10 disposed between the light source 6 and the QCM/QCM-D chip 20 for controlling the light 12 of the light source 6 to illuminate the QCM/QCM-D chip. 20 light on the surface.
  • the barrier unit 10 includes a movable light baffle 8, and a driver for changing the position of the baffle 8.
  • the grating shutter 8 is detachable.
  • the grating baffle 8 can provide more protection from the illumination from the source 6 to the surface of the QCM/QCM-D chip 20.
  • the drive is preferably controlled by a control unit mounted on the computer 4.
  • the opening or closing of the barrier unit 10 can be controlled by the computer 4 connected to the barrier unit 10, and control is performed by using software installed on the computer 4, thereby controlling the illumination onto the surface 20 of the QCM/QCM-D chip 20.
  • the computer 4 is connected to the reaction chamber 14 of the quartz crystal resonator and the frequency counter 22 to control the oscillation circuit, the electric field parameters, and the data acquired by the frequency counter 22, and to obtain the resonance frequency of the QCM/QCM-D chip 20 during the detection process. Variety.
  • the method for detecting a novel light-assisted quartz crystal microbalance 2 according to the present invention comprises the following steps:
  • Step 1 Run the quartz crystal microbalance 2 system, and obtain a stable baseline of the quartz crystal resonance frequency in the QCM/QCM-D chip 20 through the frequency counter 22;
  • Step 2 Turn on the light source 6 switch, let the light illuminate the surface of the QCM/QCM-D chip 20, and obtain the resonant frequency of the quartz crystal in the QCM/QCM-D chip 20 through the frequency counter 22 as the signal 1;
  • Step 3 The light of the light source 6 is no longer irradiated on the surface of the QCM/QCM-D chip 20;
  • Step 4 Advancing the object to be detected onto the surface of the QCM/QCM-D chip 20, and then illuminating the surface of the QCM/QCM-D chip 20 with the light 12, and obtaining the resonance frequency of the QCM/QCM-D chip 20 by the frequency counter 22, Signal 2 compares the difference between signal 1 and signal 2.
  • the light source 12 of the light source 6 is controlled to be irradiated onto the surface of the QCM/QCM-D chip 20 by the grating unit 10 between the light source 6 and the QCM/QCM-D chip 20.
  • the application of the grating unit 10 enables fast, efficient and accurate control of light illumination onto the surface of the QCM/QCM-D chip 20, which is much faster and more efficient than a simple switch that relies on the light source 6 to control illumination.
  • the detection method can be carried out in a gaseous state or in a liquid state, and the chamber 12 is for accommodating a gas or a liquid in an environment in which the object to be detected is detected, and detecting the object.
  • the test subject can include different concentrations and different kinds of compounds, covering various chemicals and biomolecules, such as tumor diagnostic markers.
  • Figure 2 (a) shows the general process of detecting a liquid sample by changing the resonant frequency of a quartz crystal with time when the grating unit 10 is turned on and off using the novel photo-assisted quartz crystal microbalance 2 of the present invention.
  • Schematic diagram. The moment a represents the operation of "injecting water” onto the surface of the QCM/QCM-D chip 20, and the quartz crystal resonance frequency is the highest before the injection of water, during which only air is present on the surface of the QCM/QCM-D chip 20. Injecting water onto the surface of the QCM/QCM-D chip 20 causes the frequency to drop to a lower value.
  • the time b indicates the operation of "turning on the grating".
  • the grating After the grating is turned on, the light of the light source 6 is irradiated onto the surface of the QCM/QCM-D chip 20, and the resonance frequency of the quartz crystal is increased.
  • the c moment represents the operation of "turning off the grating", and when the grating is turned off, the resonance frequency of the quartz crystal drops to a lower level.
  • a sample to be inspected is injected on the surface of the QCM/QCM-D chip 20, and thereafter, when the grating is turned on again at time b1, the resonance frequency is increased to a medium level due to light irradiation on the surface of the QCM/QCM-D chip 20.
  • Fig. 2(b) is a data diagram showing changes in concentration of different concentrations of phosphate buffer solution (PBS) by using the novel photo-assisted quartz crystal microbalance 2 of the present invention, wherein the resonance frequency is in accordance with time (unit: minute) )Variety.
  • PBS phosphate buffer solution
  • Illumination 28 on the surface of the QCM/QCM-D chip 20 results in an increase in the resonant frequency of the chip, and then the resonant frequency decreases after the illumination is turned off. Thereafter, at time e, a 0.016 mmol/L PBS buffer solution was injected on the surface of the QCM/QCM-D chip 20. Once the grating unit 10 is turned on again for illumination, it can be seen that the illumination 28 on the surface of the QCM/QCM-D chip 20 causes the resonant frequency of the quartz crystal to increase. Subsequently, the illumination is turned off causing the resonance frequency to decrease again.
  • FIG. 2 shows that the surface of the QCM/QCM-D chip 20 can be irradiated with light to enhance the resonance frequency signal (frequency 28) of the quartz crystal to detect a change in the concentration of the low concentration PBS buffer.
  • the 0.08mmol/L PBS buffer solution was switched to 0mmol/L PBS buffer solution (ie pure water), and the resonance frequency curve increased by about 2.4Hz, especially when the concentration of the PBS buffer was 0.016mmol. After /L switches to pure water, the resonance frequency curve rises by about 1 Hz.
  • FIG. 3 shows the resonance frequency signal of the QCM/QCM-D chip 20 when the same concentration of the PBS buffer solution in FIG. 2(b) is injected as the detection target after the surface illumination assist to the QCM/QCM-D chip 20 is not used.
  • 28 data graph that changes over time. It can be seen that, as at time d, a 0.08 mmol/L PBS buffer solution was injected, and the resonance frequency slightly increased. Thereafter, as shown in time e, a 0.016 mmol/L PBS buffer solution was injected, and the resonance frequency of the quartz crystal was further increased slightly. Thereafter, as indicated at time f, pure water was injected for detection, and the resonance frequency showed a weak and indistinguishable change. .
  • the 0.08 mmol/L PBS buffer solution was switched to 0 mmol/L PBS buffer solution (ie pure water), and the resonance frequency curve increased by about 1 Hz, especially when the concentration of the PBS buffer was 0.016 mmol/ After switching to pure water, the change in resonance frequency is difficult to distinguish.
  • Figure 3 illustrates that after illuminating the surface of the chip on the QCM/QCM-D chip 20, the concentration of 0.08 mmol/L, 0.016 mmol/L and 0 mmol/L (pure water) in PBS buffer will cause resonance of the quartz crystal.
  • the frequency change is too small to be detected. Therefore, the change in the resonance frequency of the conventional quartz crystal is not sufficient to distinguish the changes in the concentrations of 0.08 mmol/L, 0.016 mmol/L, and 0 mmol/L. Therefore, the application of illumination increases the sensitivity of the system.

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Abstract

一种新型光辅助石英晶体微天平（2）及其检测方法，所述微天平包括QCM/QCM-D芯片（20）、振荡电路、频率计数器（22）、计算机（4）、反应小室（14）和一个光源（6），该光源（6）发出的光线能够辐射在QCM/QCM-D芯片（20）表面上。通过增设能够将光线照射到芯片表面的光源，在光辐照下，QCM/QCM-D芯片（20）表面性质发生改变，光源光辐照在QCM/QCM-D芯片（20）表面能引发共振频率的急剧上升。相应地，光辐照在所述芯片（20）表面上也引起了石英晶体力学性质和压电特性的改变，从而能够有效提高石英晶体微天平设备系统的检测灵敏度。

Description

新型光辅助石英晶体微天平及其检测方法 技术领域
本发明涉及仪器仪表技术领域，尤其是一种新型光辅助石英晶体微天平及其检测方法。
背景技术
Pierre和Jacques Curie在1880年发现当石英晶体在外力作用下产生沿一定方向的形变后，在石英晶体内部将产生极化效应，即石英晶体的相反的表面上将各自堆积正电荷和负电荷。随后Gabriel Lippman提出可以利用电磁场在晶体中产生应力。这个论点为随后的实验结果所证实。
由Sauerbrey教授的研究归纳如下一个方程来描述石英晶体共振频率和芯片表面质量之间的关系，即Sauerbrey方程，被应用于指导石英晶体微天平的各种应用。
Figure PCTCN2017115776-appb-000001
式中Δf为频率变化(Hz)，Δm为芯片表面质量的变化(g)，f 0为QCM芯片共振频率(Hz)，A为QCM芯片反应电极的面积(cm 2)，ρ q为密度(2.65g/cm 3)，μ q为剪切模量。
石英晶体微天平被广泛用于各种领域，如在真空中表面厚度的监测，这一应用也大大扩展了其作为传感器在其他领域的应用，如大气污染物的检测、金属腐蚀及保护、高分子相转变、生物传感检测等。
石英晶体微天平是一种强大的无需标记的检测技术，在各种领域得到越来越多的关注。然而，石英晶体微天平与另一无标记检测技术表面等离子体共振(surface plasmon resonance，SPR)比较起来发展显得滞后。SPR技术得到巨大的商业成功，重要原因之一是总体而论，SPR系统的检测灵敏度比石英晶体微天平高。5MHz的石英晶体微天平的灵敏度大约比相应SPR系统低20倍。在某些应用中，如小分子相互作用检测和痕量检测中，石英晶体微天平的信号不够强而得不到检测对象的相关信息。
石英晶体微天平的检测灵敏度定义为对应于一定信号变化值的QCM芯片单位表面面积上的质量变化。检测灵敏度与表面检测对象的密度及芯片所固有的共振频率，剪切模量有关。Sauerbrey方程确定对于5MHz AT-cut石英晶体微天平芯片，检测的灵敏度约为1Hz＝17.7ng/cm 2。
石英晶体微天平芯片共振频率的提高将能促进石英晶体微天平检测灵敏度的提高，但是因为超薄的石英晶体片非常脆弱，提高共振频率对制作超薄的石英晶体芯片提出了更高的要求。因此，通过减小石英晶体芯片厚度的方式来提高检测灵敏度有着一定的限制。正是因为这个限制，目前大多数石英晶体微天平的生产商都通过优化电路提高检测信号的分辨力，最终降低检测限(limit of detection，LOD)，LOD检测值为最小的可以检测到的检测对象的浓度、质量的变化值，LOD与检测灵敏度及信号的准确度有关。
石英晶体微天平的LOD低于1ng/cm 2，这个检测极限不能完全达到应用的要求，如在临床诊断对象的检测中，检测对象的浓度在ng/mL级别。因此，石英晶体微天平的灵敏度及LOD亟需改进提高。
发明内容
针对现有技术中的不足，本发明旨在提供一种具有更高检测灵敏度的石英晶体微天平系统及检测方法，不需减少芯片的厚度，造成芯片破碎；同时本发明也能够提高石英晶体微天平系统检测的灵敏度。
本发明是通过以下技术手段实现上述技术目的的。
新型光辅助石英晶体微天平，其特征在于，包括以下部分：
一个QCM/QCM-D芯片，该芯片为石英晶体片层夹在两片电极之间构成的三明治结构，该芯片及电极电路被金属、陶瓷或塑料外壳封装，形成一个反应小室，所述芯片及所述外壳整体构成了石英晶体谐振器；
一个振荡电路，为QCM/QCM-D芯片中的石英晶体提供交变电场；
频率计数器，用于监测QCM/QCM-D芯片的共振频率；
一个光源，该光源发出的光线能够辐射在QCM/QCM-D芯片表面上。
进一步地，所述光源为具有一个或多个频率的光源。
进一步地，所述光源与QCM/QCM-D芯片之间设有光栅单元，用于控制光源的光线照射到QCM/QCM-D芯片表面上的光照。
进一步地，光栅单元包含一个可移动的光栅挡板和一个能够移动光栅挡板的驱动器。
进一步地，所述光栅挡板为可拆卸的光栅挡板，驱动器为电驱动器。
进一步地，新型光辅助石英晶体微天平还包括一台计算机，与光栅挡板的驱动器、振荡电路、频率计数器相连，用于控制光栅挡板的驱动器的工作实现光栅挡板的移动，控制振荡电路的通断、电场参数，以及读取频率计数器采集的数据、并得出检测过程中QCM/QCM-D芯片共振频率的变化。
进一步地，光源产生光的波长范围为100-800nm，较佳的为200-400nm。
新型光辅助石英晶体微天平的检测方法，其特征在于，包含以下几个步骤：
步骤1.运行石英晶体微天平系统，通过频率计数器获取QCM/QCM-D芯片共振频率稳定基线；
步骤2.打开光源开关，让光照射到QCM/QCM-D芯片表面上，通过频率计数器获取QCM/QCM-D芯片的共振频率，作为信号1；
步骤3.使光源的光不再照射QCM/QCM-D芯片表面；
步骤4.将待检测对象推进到QCM/QCM-D芯片表面，然后使光线照到QCM/QCM-D芯片表面，通过频率计数器获取QCM/QCM-D芯片的共振频率，为信号2，比较信号1和信号2的差别。
进一步地，通过设置光源与QCM/QCM-D芯片之间的光栅单元，控制光源的光线是否照射到QCM/QCM-D芯片表面上。
进一步地，所述石英晶体微天平检测方法能够适用在气态和液态的检测对象，所述石英晶体谐振器用于容纳检测对象所处环境中的气体或液体以及检测对象。
本发明通过增设能够将光线照射到芯片表面的光源，在光辐照下，QCM/QCM-D芯片表面性质发生改变，QCM/QCM-D芯片表面上吸附的水分子层从QCM/QCM-D芯片电极表面上可逆地解吸附；光源光辐照在QCM/QCM-D芯片表面能引发共振频率的急剧上升。相应地，光辐照在所述芯片表面上也引起了石英晶体力学性质和压电特性的改变，从而能够有效提高石英晶体微天平设备系统的检测灵敏度。
另外，使用光栅单元来控制光源照射到芯片表面上的光，与简单的依靠光源的开关控制光照相比，光栅单元能够快速有效准确地控制QCM/QCM-D芯片表面上的光照。检测对象可包括不同浓度、不同种类的化合物，涵盖各种化学品和生物分子，如肿瘤诊断标志物。
附图说明
图1为本发明所述QCM传感器系统的示意图；
图2中(a)为在光栅单元的开关控制之下，利用QCM的共振频率曲线随着时间变化检测芯片表面流经不同浓度PBS溶液的一般过程示意图；(b)利用光栅单元的开关控制光照射QCM/QCM-D芯片表面上时，QCM的共振频率随着时间变化检测芯片表面流经不同浓度的PBS溶液的数据图；
图3为不使用光照射QCM/QCM-D芯片表面上时，QCM/QCM-D的共振频率曲线 随着时间变化，检测芯片表面流经不同浓度的PBS溶液的数据图。
图中：
2-新型光辅助石英晶体微天平，4-计算机，6-光源，8-光栅挡板，10-光栅单元，12-光线，14-反应小室，16-QCM/QCM-D芯片中的石英晶体片层，18-凹槽，20-QCM/QCM-D芯片，22-频率计数器。
具体实施方式
下面结合附图以及具体实施例对本发明作进一步的说明，但本发明的保护范围并不限于此。
如图1所示，本发明所述的新型光辅助石英晶体微天平2，包括一个QCM/QCM-D芯片，该芯片为石英晶体片层夹16在两片电极之间构成的三明治结构，该芯片及电极电路被金属、陶瓷或塑料外壳封装，形成在一个反应小室14中，所述芯片及所述外壳整体构成了石英晶体谐振器，所述QCM/QCM-D芯片20安装在所述反应小室14底面上的凹槽18内。所述反应小室14用于容纳检测对象所处环境中的气体或液体以及检测对象；一个振荡电路为QCM/QCM-D芯片20中的石英晶体片层16提供交变电场；频率计数器22，用于监测QCM/QCM-D芯片20的共振频率；一个光源6，该光源6的光线12能够辐射在QCM/QCM-D芯片20表面上。所述光源6为具有一个或多个频率的光源，能够产生光的波长范围为100-800nm，较佳的为200-400nm，如365nm。如果光源6发出的光频率更小或者辐照光的能量、功率提高，那么将具有更好的效果。
光源6发射出的光12，照射QCM/QCM-D芯片20表面后使其表面性质发生改变，QCM/QCM-D芯片表面上吸附的水分子从QCM/QCM-D芯片20表面上可逆地解吸附，能提高QCM/QCM-D芯片的共振频率。相应地，光辐照在芯片表面上也引起了芯片中石英晶体力学性质和压电特性的改变，从而能够有效提高石英晶体微天平2设备系统的检测灵敏度。通过应用光源6，可以将石英晶体微天平2系统的灵敏度提高十倍以上。
进一步地，所述新型光辅助石英晶体微天平2包括一个设置在光源6和QCM/QCM-D芯片20之间的光栅单元10，用于控制光源6的光线12照射到QCM/QCM-D芯片20表面上的光照。该光栅单元10包括可移动的光挡板8，以及用于改变挡板8位置的驱动器。驱动器的种类很多，可以选用电驱动器。所述光栅挡板8为可拆卸的。光栅挡板8可以提供更多保护，屏蔽光源6发出的到QCM/QCM-D芯片20表面上的光照。驱动器最好由安装在计算机4的控制单元控制。
光栅单元10的打开或关闭，可以通过与光栅单元10连接的计算机4来控制，通过 使用安装在计算机4上的软件来执行控制，以此控制照射到QCM/QCM-D芯片20表面20上的光12。
计算机4连接石英晶体谐振器的反应小室14和频率计数器22，以控制振荡电路、电场参数，以及读取频率计数器22采集的数据、并得出检测过程中QCM/QCM-D芯片20共振频率的变化。
本发明所述的新型光辅助石英晶体微天平2的检测方法，包含以下几个步骤：
步骤1.运行石英晶体微天平2系统，通过频率计数器22获取QCM/QCM-D芯片20中石英晶体共振频率稳定基线；
步骤2.打开光源6开关，让光照射到QCM/QCM-D芯片20表面上，通过频率计数器22获取QCM/QCM-D芯片20中的石英晶体的共振频率，作为信号1；
步骤3.使光源6的光不再照射QCM/QCM-D芯片20表面；
步骤4.将待检测对象推进到QCM/QCM-D芯片20表面，然后使光线12照到QCM/QCM-D芯片20表面，通过频率计数器22获取QCM/QCM-D芯片20的共振频率，为信号2，比较信号1和信号2的差别。
较佳的，在检测过程中，通过设置光源6与QCM/QCM-D芯片20之间的光栅单元10控制光源6的光线12是否照射到QCM/QCM-D芯片20表面上。应用光栅单元10可快速有效准确地控制光照射到QCM/QCM-D芯片20表面上，光栅单元10远比简单的依赖光源6的开关控制光照迅速而高效。所述检测方法能够在气态下或液态下进行，所述小室12用于容纳检测对象所处环境中的气体或液体，以及检测对象。检测对象可包括不同浓度、不同种类的化合物，涵盖各种化学品和生物分子，如肿瘤诊断标志物。
图2中(a)所示为利用本发明所述的新型光辅助石英晶体微天平2，在光栅单元10被打开和关闭时，石英晶体的共振频率随时间的变化来检测液体样本的一般过程的示意图。a时刻表示“注入水”到QCM/QCM-D芯片20表面上的操作，在注入水之前石英晶体共振频率是最高的，在此期间QCM/QCM-D芯片20表面上只存在空气。在QCM/QCM-D芯片20表面上注入水后会导致频率下降到一个较低的值。b时刻表示“打开光栅”的操作，打开光栅后，光源6的光照射到QCM/QCM-D芯片20表面，石英晶体的共振频率增加。c时刻表示“关闭光栅”的操作，当光栅关闭时，石英晶体的共振频率下降到一个较低的水平。随后在QCM/QCM-D芯片20表面上注入检测对象样本，此后b1时刻当光栅再次打开时，由于光照射在QCM/QCM-D芯片20表面，共振频率增加到中等水平。c1时刻当光栅最后关闭时，石英晶体的共振频率再次下降到较低值。通过比较两次打开光栅单元 之后共振频率的差值即可分析检测对象的有关信息。图2中(b)所示为利用本发明所述的新型光辅助石英晶体微天平2检测不同浓度的磷酸盐缓冲溶液(PBS)的浓度变化的数据图，其中共振频率随时间(单位：分钟)变化。最初，d时刻，向QCM/QCM-D芯片20表面上注入0.08mmol/L PBS缓冲溶液。QCM/QCM-D芯片20表面的光照28导致芯片共振频率增加，随后，关闭光照后共振频率降低。之后e时刻，在QCM/QCM-D芯片20表面注入0.016mmol/L PBS缓冲溶液。再一次打开光栅单元10进行光照，可以看到QCM/QCM-D芯片20表面上的光照28导致石英晶体的共振频率增加。随后，光照被关闭导致共振频率再次降低。此后，如f时刻所示，在QCM/QCM-D芯片20表面注入纯水，打开光栅单元10进行光照可以看到，QCM/QCM-D芯片20表面的光照28导致芯片共振频率增加。最后，当QCM/QCM-D芯片20表面的光照被关闭时，QCM/QCM-D芯片20共振频率再次降低。
图2中(b)显示可利用光照射QCM/QCM-D芯片20表面来增强石英晶体的共振频率信号(频率28)来检测低浓度的PBS缓冲液浓度的变化。可以从数据图中看到，0.08mmol/L PBS缓冲溶液切换到0mmol/L PBS缓冲溶液(即纯水)，共振频率曲线上升了约2.4Hz，尤其是当检测对象PBS缓冲液浓度从0.016mmol/L切换到纯水后，共振频率曲线上升了约1Hz。
图3示显示当不使用向QCM/QCM-D芯片20表面光照辅助后，注入图2中(b)中相同浓度的PBS缓冲溶液作为检测对象时，QCM/QCM-D芯片20的共振频率信号28随着时间而变化的数据图。可以看出，如d时刻，注入0.08mmol/L的PBS缓冲溶液，共振频率有微小的上升。之后，如e时刻所示，注入0.016mmol/L PBS缓冲溶液进行，石英晶体的共振频率进一步略微增加，此后，如f时刻所示，注入纯水进行检测，共振频率出现微弱的难以分辨的变化。可以从数据图中看到，0.08mmol/L PBS缓冲溶液切换到0mmol/L PBS缓冲溶液(即纯水)，共振频率曲线上升了约1Hz，尤其是当检测对象PBS缓冲液浓度从0.016mmol/L切换到纯水后，共振频率的变化难以分辨。
图3说明关闭照射到QCM/QCM-D芯片20上芯片表面上的光照后，浓度为0.08mmol/L，0.016mmol/L和0mmol/L(纯水)的PBS缓冲液将导致石英晶体的共振频率变化太小而不能被检测到。因此，传统石英晶体的共振频率的变化不足以区分0.08mmol/L，0.016mmol/L和0mmol/L浓度的变化。因此，光照的应用提高了系统的灵敏度。
所述实施例为本发明的优选的实施方式，但本发明并不限于上述实施方式，在不背 离本发明的实质内容的情况下，本领域技术人员能够做出的任何显而易见的改进、替换或变型均属于本发明的保护范围。

Claims (10)

  1. 新型光辅助石英晶体微天平(2)，其特征在于，包括以下部分：
    一个QCM/QCM-D芯片(20)，该芯片为石英晶体片层夹(16)在两片电极之间构成的三明治结构，该芯片及电极电路被金属、陶瓷或塑料外壳封装，形成在一个反应小室(12)中，所述芯片及所述外壳整体构成了石英晶体谐振器；
    一个振荡电路，为QCM/QCM-D芯片(20)中的石英晶体提供交变电场；
    频率计数器(22)，用于监测QCM/QCM-D芯片(20)的共振频率；
    一个光源(6)，该光源(6)发出的光线(12)能够辐射在QCM/QCM-D芯片(20)表面上。
  2. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，所述光源(6)为具有一个或多个频率的光源(6)。
  3. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，所述光源(6)与QCM/QCM-D芯片(20)之间设有光栅单元(10)，用于控制光源(6)的光线(12)照射到QCM/QCM-D芯片(20)表面上的光照。
  4. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，光栅单元(10)包含一个可移动的光栅挡板(8)和一个能够移动光栅挡板(8)的驱动器。
  5. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，所述光栅挡板(8)为可拆卸的光栅挡板(8)，驱动器为电驱动器。
  6. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，新型光辅助石英晶体微天平还包括一台计算机(4)，与光栅挡板(8)的驱动器、振荡电路、频率计数器(22)相连，用于控制光栅挡板(8)的驱动器的工作实现光栅挡板(8)的移动，控制振荡电路的通断、电场参数，以及读取频率计数器(22)采集的数据、并对比得出检测过程中QCM/QCM-D芯片(20)共振频率的变化。
  7. 根据权利要求1所述的新型光辅助石英晶体微天平(2)，其特征在于，光源(6)产生光的波长范围为100-800nm，较佳的为200-400nm。
  8. 根据权利要求1所述的新型光辅助石英晶体微天平(2)的检测方法，其特征在于，包含以下几个步骤：
    步骤1.运行QCM/QCM-D系统，通过频率计数器(22)获取QCM/QCM-D芯片(20)中石英晶体共振频率稳定基线；
    步骤2.打开光源(6)开关，让光照射到QCM/QCM-D芯片(20)表面上，通过频 率计数器(22)获取QCM/QCM-D芯片(20)的石英晶体的共振频率，作为信号1；
    步骤3.使光源(6)的光不再照射QCM/QCM-D芯片(20)表面；
    步骤4.将待检测对象推进到QCM/QCM-D芯片(20)表面，然后使光线(12)照到QCM/QCM-D芯片(20)表面，通过频率计数器(22)获取QCM/QCM-D芯片(20)的石英晶体的共振频率，为信号2，比较信号1和信号2差值。
  9. 根据权利要求8所述的检测方法，其特征在于，通过设置光源(6)与QCM/QCM-D芯片(20)之间的光栅单元(10)控制光源(6)的光线(12)是否照射到QCM/QCM-D芯片(20)表面上。
  10. 根据权利要求8所述的检测方法，其特征在于，所述检测方法能够在气态下或液态下进行检测；所述反应小室(14)用于容纳检测对象所处环境中的气体或液体，以及检测对象。
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