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CN102735564A - High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure - Google Patents

High-sensitive biochemical sensor based on resonance oscillation type micro cantilever beam structure Download PDF

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CN102735564A
CN102735564A CN2012102435136A CN201210243513A CN102735564A CN 102735564 A CN102735564 A CN 102735564A CN 2012102435136 A CN2012102435136 A CN 2012102435136A CN 201210243513 A CN201210243513 A CN 201210243513A CN 102735564 A CN102735564 A CN 102735564A
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cantilever beam
detection circuit
whist
biochemical sensor
biochemical
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CN102735564B (en
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杨晋玲
王帅鹏
王晶晶
杨富华
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Abstract

本发明公开了一种基于谐振式微悬臂梁结构的高灵敏生化传感器,该生化传感器包括谐振腔、悬臂梁和惠斯特桥式检测电路,其中在该悬臂梁的自由端刻蚀有微柱结构(3)和储液槽(4),并刻蚀有用于流出生化溶液的漏液孔(5);该悬臂梁的支撑端连接于该惠斯特桥式检测电路,该惠斯特桥式检测电路由四个U型结构的压阻条(1)、三个输入电极(8、9、10)和两个输出电极(7、11)构成,四个压阻条(1)通过信号传输线(2)连接于输入电极(8、9、10)和输出电极(7、11)。该生化传感器通过检测吸附待测物后导致的频率变化,感知微小生化分子,具有较高的灵敏度,可探测到微小质量的生化分子,能够广泛应用于医学、化工等工程领域。

Figure 201210243513

The invention discloses a highly sensitive biochemical sensor based on a resonant micro-cantilever beam structure. The biochemical sensor includes a resonant cavity, a cantilever beam and a Whist bridge detection circuit, wherein a micro-column structure (3 ) and a liquid storage tank (4), and a leak hole (5) for flowing out biochemical solution is etched; the supporting end of the cantilever beam is connected to the Whist bridge detection circuit, and the Whist bridge detection circuit It consists of four U-shaped piezoresistive strips (1), three input electrodes (8, 9, 10) and two output electrodes (7, 11), and the four piezoresistive strips (1) pass through signal transmission lines (2 ) are connected to the input electrodes (8, 9, 10) and the output electrodes (7, 11). The biochemical sensor perceives tiny biochemical molecules by detecting the frequency change caused by the adsorption of the analyte, has high sensitivity, can detect biochemical molecules with tiny masses, and can be widely used in engineering fields such as medicine and chemical engineering.

Figure 201210243513

Description

基于谐振式微悬臂梁结构的高灵敏生化传感器Highly sensitive biochemical sensor based on resonant micro-cantilever structure

技术领域 technical field

本发明涉及MEMS领域、生物医学以及化学工程领域,尤其涉及一种基于谐振式微悬臂梁结构的高灵敏生化传感器。The invention relates to the fields of MEMS, biomedicine and chemical engineering, in particular to a highly sensitive biochemical sensor based on a resonant micro-cantilever beam structure.

背景技术 Background technique

70年代以来谐振式传感器在电子技术、测试技术、计算技术和半导体集成电路技术的基础上迅速发展起来【1】。随着MEMS科技的快速发展,谐振式传感器的尺寸减小到了微米,亚微米甚至纳米量级,可对温度、热能、磁场和质量等多种物理量进行高精度测量,因此被广泛应用于化学分析、生物检验、医药筛选和环境监测等各个领域。Since the 1970s, resonant sensors have developed rapidly on the basis of electronic technology, testing technology, computing technology and semiconductor integrated circuit technology [1] . With the rapid development of MEMS technology, the size of resonant sensors has been reduced to micron, submicron or even nanometer level, which can perform high-precision measurement of various physical quantities such as temperature, thermal energy, magnetic field and mass, so it is widely used in chemical analysis. , biological testing, pharmaceutical screening and environmental monitoring and other fields.

近几年,针对基于微悬臂梁结构的高灵敏生化检测研究已经成为研究热点【2】。2000年,Cornell大学的H.G..Craighead等人发表了关于谐振式微机械悬臂梁检测细胞的文章【3】。用PECVD制备100μm×20μm×0.32μm的Si3N4悬臂梁,在其前段涂覆O157:H7抗体后,可以选择性吸附的E.coli细胞,悬臂梁由热噪声激励,用激光PSD检测系统检测悬臂梁的振动频率,最小可检测频率变化约为10Hz,相应的在空气中可检测的最小质量约为1.5pg。2004年,美国Purdure大学的R.Bashir等人用SOI硅片制作了尺寸更小的3.6μm×1.7μm×0.03μm的单晶硅悬臂梁,谐振频率约为1.2MHz,探测灵敏度约为6.3Hz/ag,采用热噪声激励,激光PSD检测,在空气中检测到了一个天花病毒(9fg)。In recent years, research on high-sensitivity biochemical detection based on micro-cantilever structure has become a research hotspot [2] . In 2000, HG.Craighead et al. from Cornell University published an article on the detection of cells by a resonant micromechanical cantilever [3] . A 100μm×20μm×0.32μm Si 3 N 4 cantilever beam was prepared by PECVD. After coating the O157:H7 antibody on its front section, E.coli cells could be selectively adsorbed. The cantilever beam was excited by thermal noise, and a laser PSD detection system was used Detect the vibration frequency of the cantilever beam, the minimum detectable frequency change is about 10Hz, and the corresponding minimum detectable mass in air is about 1.5pg. In 2004, R. Bashir and others from Purdure University in the United States made a smaller 3.6μm×1.7μm×0.03μm single crystal silicon cantilever beam with SOI silicon wafers. The resonance frequency is about 1.2MHz and the detection sensitivity is about 6.3Hz. /ag, a smallpox virus (9fg) was detected in the air using thermal noise excitation and laser PSD detection.

但是,基于悬臂梁结构的传感器仍然存在着许多技术问题,如:大面积吸附引起悬臂梁弹性常数变化,产生频率偏移而导致的测量误差;梁在液体生化环境中悬臂梁品质因子大幅降低【4】,导致检测灵敏度降低等等。另外,对于便携式器件,高灵敏的自检测结构至关重要。常用的光学探测虽然具有灵敏度高的优势,但是光学元件会增大系统的体积和成本。因此,迫切需要开发基于新型悬臂梁结构的便携式,高灵敏度的生化传感器。However, there are still many technical problems in the sensor based on the cantilever beam structure, such as: the large-area adsorption causes the change of the elastic constant of the cantilever beam, and the measurement error caused by the frequency offset; the quality factor of the cantilever beam in the liquid biochemical environment is greatly reduced .【 4] , leading to a decrease in detection sensitivity and so on. In addition, for portable devices, a highly sensitive self-detection structure is crucial. Although the commonly used optical detection has the advantage of high sensitivity, the optical components will increase the volume and cost of the system. Therefore, there is an urgent need to develop portable, highly sensitive biochemical sensors based on novel cantilever beam structures.

参考文献:references:

【1】R.T.Howe,R.S.Muller,K.J.Gabriel and W.S.N.Trimmer,Silicon micro-mechanics:sensor and actuators on a chip,IEEE Spectrum,7,29-35,1990.[1] R.T.Howe, R.S.Muller, K.J.Gabriel and W.S.N.Trimmer, Silicon micro-mechanics: sensor and actuators on a chip, IEEE Spectrum, 7, 29-35, 1990.

【2】A.Hierlemann,O.Brand,C.Hagleiter and H.Baltes,Micro-fabrication techniques for chemical/biosensor,proceedings of the IEEE,6,839-863,2003.【2】A.Hierlemann, O.Brand, C.Hagleiter and H.Baltes, Micro-fabrication techniques for chemical/biosensor, proceedings of the IEEE, 6, 839-863, 2003.

【3】B.Ilic,D.Czaplewski,H.G.Craighead,P.Neuzil,C.Campagnolo and C.Batt,Mechanical resonant immunospecific biological detector,Applied Physics Letter,77,450-452,2000.【3】B.Ilic, D.Czaplewski, H.G.Craighead, P.Neuzil, C.Campagnolo and C.Batt, Mechanical resonant immunospecific biological detector, Applied Physics Letter, 77, 450-452, 2000.

【4】Ekrem Bayraktar,Deniz Eroglu,Ata Tuna Cifilik,A MEMS based grabimetric resonator for mass sensing applications,IEEE 24th International Conference,817-820,2011.【4】Ekrem Bayraktar, Deniz Eroglu, Ata Tuna Cifilik, A MEMS based grabimetric resonator for mass sensing applications, IEEE 24th International Conference, 817-820, 2011.

发明内容 Contents of the invention

(一)要解决的技术问题(1) Technical problems to be solved

为了实现对待测分子的实时实地高灵敏检测,需要在高灵敏的频率检测技术、消除吸附导致的频率测量误差、减小检测环境对器件稳定性的影响等方面进行技术突破,本发明提出了一种基于谐振式微悬臂梁结构的高灵敏生化传感器。在悬臂梁自由端设计了局域修饰结构,可消除大面积吸附产生的频率测量误差,同时减小了溶液对悬臂梁品质因子的影响;用自集成的压阻条和惠斯特桥电路来检测悬臂梁频率变化,很好满足便携式应用需求。In order to realize the real-time on-site high-sensitivity detection of the molecules to be measured, it is necessary to make technological breakthroughs in the aspects of high-sensitivity frequency detection technology, elimination of frequency measurement errors caused by adsorption, and reduction of the impact of the detection environment on device stability. The present invention proposes a A highly sensitive biochemical sensor based on a resonant micro-cantilever structure. A local modification structure is designed at the free end of the cantilever beam, which can eliminate the frequency measurement error caused by large-area adsorption, and at the same time reduce the influence of the solution on the quality factor of the cantilever beam; Detects the frequency change of the cantilever beam, which is very suitable for portable applications.

(二)技术方案(2) Technical solution

为了实现对待测分子进行实时高灵敏检测,本发明提供了一种基于谐振式微悬臂梁结构的高灵敏生化传感器,该生化传感器包括谐振腔、悬臂梁和惠斯特桥式检测电路,其中在该悬臂梁的自由端刻蚀有微柱结构(3)和储液槽(4),并刻蚀有用于流出生化溶液的漏液孔(5);该悬臂梁的支撑端连接于该惠斯特桥式检测电路,该惠斯特桥式检测电路由四个U型结构的压阻条(1)、三个输入电极(8、9、10)和两个输出电极(7、11)构成,四个压阻条(1)通过信号传输线(2)连接于输入电极(8、9、10)和输出电极(7、11)。In order to realize real-time high-sensitivity detection of molecules to be tested, the present invention provides a highly sensitive biochemical sensor based on a resonant micro-cantilever beam structure, which includes a resonant cavity, a cantilever beam and a Whist bridge detection circuit, wherein the cantilever beam The free end of the cantilever beam is etched with a microcolumn structure (3) and a liquid storage tank (4), and is etched with a leak hole (5) for flowing out biochemical solution; the support end of the cantilever beam is connected to the whist bridge Detection circuit, the Whistler bridge detection circuit is composed of four U-shaped piezoresistive strips (1), three input electrodes (8, 9, 10) and two output electrodes (7, 11), four The piezoresistive strip (1) is connected to input electrodes (8, 9, 10) and output electrodes (7, 11) through signal transmission lines (2).

上述方案中,该生化传感器是通过悬臂梁的频率响应来对生化分子进行高灵敏探测,悬臂梁的表面修饰有对待测分子能够特异性响应的探测单分子层结构(12),吸附待测分子(13)后改变了悬臂梁的质量,最终导致了悬臂梁的谐振频率变化;利用惠斯特桥式检测电路检测吸附生化分子前后的频率变化,来得到生化分子的质量。In the above scheme, the biochemical sensor uses the frequency response of the cantilever beam to detect biochemical molecules with high sensitivity. The surface modification of the cantilever beam has a detection monolayer structure (12) that can specifically respond to the molecule to be tested, and adsorbs the molecule to be tested. After (13), the quality of the cantilever is changed, which eventually leads to the change of the resonant frequency of the cantilever; the mass of the biochemical molecule is obtained by using the whist bridge detection circuit to detect the frequency change before and after the adsorption of biochemical molecules.

上述方案中,所述储液槽(4)用于局部修饰探测单分子层,减小大面积吸附对悬臂梁弹性常数影响而导致的频率改变。In the above solution, the liquid storage tank (4) is used for local modification and detection of the monomolecular layer to reduce the frequency change caused by the influence of large-area adsorption on the elastic constant of the cantilever beam.

上述方案中,所述微柱结构(3)用于增大吸附面积,提高检测极限。In the above solution, the microcolumn structure (3) is used to increase the adsorption area and improve the detection limit.

上述方案中,所述漏液孔(5)制作于所述储液槽(4)中,用于保证储液槽中吸附反应完成后,废液从通孔中排出,不残留在悬臂梁中。In the above scheme, the liquid leakage hole (5) is made in the liquid storage tank (4) to ensure that after the adsorption reaction in the liquid storage tank is completed, the waste liquid is discharged from the through hole and does not remain in the cantilever beam .

上述方案中,所述悬臂梁的驱动方式为压电、静电、电磁、热电或光驱动中的任一种或多种。In the above solution, the driving mode of the cantilever beam is any one or more of piezoelectric, electrostatic, electromagnetic, thermoelectric or optical driving.

上述方案中,在该惠斯特桥式检测电路中,输入电极(9)接电源信号,输出电极(7、11)作为输出电极,电输入电极(8、10)接地信号。In the above solution, in the Wheatstone bridge detection circuit, the input electrodes (9) are connected to the power signal, the output electrodes (7, 11) are used as output electrodes, and the electrical input electrodes (8, 10) are grounded to the signal.

上述方案中,所述惠斯特桥式检测电路中的电阻之一是悬臂梁支撑端的U型压阻条(1),悬臂梁的谐振频率测量是通过惠斯特桥式检测电路完成的,U型压阻条(1)用于提高对电流的束缚能力。In the above scheme, one of the resistors in the Whist bridge detection circuit is a U-shaped piezoresistive strip (1) at the support end of the cantilever beam, and the resonant frequency measurement of the cantilever beam is completed by the Whist bridge detection circuit, The U-shaped piezoresistive strip (1) is used to improve the ability to bind current.

上述方案中,所述惠斯特桥式检测电路中的四个压阻条(1)均为“U”型压阻条,四个压阻条(1)同时进行离子注入形成,最大限度地保证了电阻的一致性,有效提高了测量精度,且每个压阻条(1)的有效阻值大于等于1kΩ。In the above scheme, the four piezoresistive strips (1) in the Whist bridge detection circuit are all "U"-shaped piezoresistive strips, and the four piezoresistive strips (1) are formed by ion implantation at the same time, maximizing The consistency of resistance is guaranteed, and the measurement accuracy is effectively improved, and the effective resistance value of each piezoresistive strip (1) is greater than or equal to 1kΩ.

上述方案中,在所述惠斯特桥式检测电路的传输线之间刻蚀出隔离槽结构,用于减少传输线之间信号的串扰,保证惠斯特桥式检测电路的测量精度。In the above solution, an isolation groove structure is etched between the transmission lines of the Whistler bridge detection circuit to reduce signal crosstalk between the transmission lines and ensure the measurement accuracy of the Whistler bridge detection circuit.

(三)有益效果(3) Beneficial effects

从上述技术方案可以看出,本发明的有益效果是:As can be seen from the foregoing technical scheme, the beneficial effects of the present invention are:

1、本发明提供的基于谐振式悬臂梁结构的高灵敏生化传感器,当悬臂梁在谐振频率处谐振时,位移变化将导致悬臂梁末端压阻条的电阻变化,从而引起悬臂梁基片上惠斯特桥电路的输出电压变化。在悬臂梁自由端设计了带微柱的储液槽结构,用于局部吸附待测分子,消除了大面积吸附引起的悬臂梁弹性常数改变,从而产生的频率变化导致的测量误差,同时减小了溶液对悬臂梁品质因子的影响;而且通过微柱设计增大吸附面积,提高检测极限。在储液槽结构中制作了微通孔,保证储液槽中吸附反应完成后,废液从通孔中排出,不残留在悬臂梁上。谐振式微悬臂梁结构的传感器具有较高的灵敏度,可探测到微小质量的生化分子,能够广泛应用于医学、化工等工程领域。1. The high-sensitivity biochemical sensor based on the resonant cantilever beam structure provided by the present invention, when the cantilever beam resonates at the resonance frequency, the displacement change will cause the resistance change of the piezoresistive strip at the end of the cantilever beam, thereby causing the Whisper resistance on the cantilever beam substrate. The output voltage of the special bridge circuit changes. A liquid storage tank structure with micropillars is designed at the free end of the cantilever beam for local adsorption of molecules to be measured, eliminating the change in the elastic constant of the cantilever beam caused by large-area adsorption, resulting in measurement errors caused by frequency changes, while reducing The influence of the solution on the quality factor of the cantilever beam is eliminated; and the adsorption area is increased through the micro-column design, and the detection limit is improved. Micro through holes are made in the liquid storage tank structure to ensure that after the adsorption reaction in the liquid storage tank is completed, the waste liquid is discharged from the through holes and does not remain on the cantilever beam. The sensor with resonant micro-cantilever beam structure has high sensitivity, can detect biochemical molecules with tiny mass, and can be widely used in engineering fields such as medicine and chemical industry.

2、本发明提供的基于谐振式悬臂梁结构的高灵敏生化传感器,通过在基片上制作检测电路,使得该传感器可以实现自检测功能,进而可以舍弃庞大的光学检测设备,减小了探测器的体积,实现了探测设备的便携化,这也是本发明的优势所在。2. The high-sensitivity biochemical sensor based on the resonant cantilever beam structure provided by the present invention can realize the self-detection function by making the detection circuit on the substrate, and then can abandon the huge optical detection equipment, reducing the detector’s The volume realizes the portability of the detection equipment, which is also the advantage of the present invention.

3、本发明提供的基于谐振式微悬臂梁结构的高灵敏生化传感器,通过在悬臂梁前端刻蚀出微柱结构和储液槽结构,提高了修饰区的有效面积和对待测分子的吸附能力。3. The high-sensitivity biochemical sensor based on the resonant micro-cantilever beam structure provided by the present invention improves the effective area of the modification area and the adsorption capacity of the molecules to be measured by etching the micro-column structure and the liquid storage tank structure at the front end of the cantilever beam.

4、本发明提供的基于谐振式微悬臂梁结构的高灵敏生化传感器,惠斯特桥式检测电路中,采用“U”型压阻条能较好的束缚电流,且惠斯特桥式检测电路中四个压阻条同时采用离子注入工艺形成,保证了其初始阻值的一致性。4. In the high-sensitivity biochemical sensor based on the resonant micro-cantilever beam structure provided by the present invention, in the whist bridge detection circuit, the use of "U" type piezoresistive strips can better restrain the current, and the whist bridge detection circuit The four piezoresistive strips are formed by ion implantation at the same time, which ensures the consistency of their initial resistance values.

5、本发明提供的基于谐振式微悬臂梁结构的高灵敏生化传感器,高掺杂离子注入形成连接四个压阻条的导线,并在导线之间刻出隔离槽,降低导线间的信号串扰。每个压阻的有效阻值最小不能小于1kΩ,保证惠斯特电桥的输出信号大于外接处理电路的噪声。5. The high-sensitivity biochemical sensor based on the resonant micro-cantilever beam structure provided by the present invention uses highly doped ion implantation to form wires connecting four piezoresistive strips, and isolation grooves are carved between the wires to reduce signal crosstalk between wires. The minimum effective resistance of each piezoresistor cannot be less than 1kΩ, so as to ensure that the output signal of the Whistler bridge is greater than the noise of the external processing circuit.

6、本发明提供的基于谐振式微悬臂梁结构的高灵敏生化传感器,形成悬臂梁阵列式排布,可实现多个待测物的同时测量6. The high-sensitivity biochemical sensor based on the resonant micro-cantilever structure provided by the present invention forms a cantilever array arrangement, which can realize simultaneous measurement of multiple objects to be measured

7、本发明提供的基于谐振式微悬臂梁结构的高灵敏生化传感器,可采用不同驱动方式,如压电、电磁或光驱动等,实现便携式应用。7. The high-sensitivity biochemical sensor based on the resonant micro-cantilever structure provided by the present invention can adopt different driving methods, such as piezoelectric, electromagnetic or optical drive, etc., to realize portable applications.

附图说明 Description of drawings

图1是依照本发明实施例的基于谐振式微悬臂梁结构的高灵敏生化传感器的结构示意图;1 is a schematic structural view of a highly sensitive biochemical sensor based on a resonant micro-cantilever structure according to an embodiment of the present invention;

图2是图1所示基于谐振式微悬臂梁结构的高灵敏生化传感器的剖面示意图Figure 2 is a schematic cross-sectional view of the highly sensitive biochemical sensor based on the resonant micro-cantilever structure shown in Figure 1

图3是惠斯特桥式检测电路测量原理图;Fig. 3 is a measurement schematic diagram of the Whist bridge detection circuit;

图4是依照本发明实施例的由两个图1所示的生化传感器构成的生化传感器阵列在吸附生化分子后的示意图;4 is a schematic diagram of a biochemical sensor array composed of two biochemical sensors shown in FIG. 1 after adsorbing biochemical molecules according to an embodiment of the present invention;

图5是依照本发明实施例的由多个图1所示的生化传感器构成的生化传感器阵列的结构示意图;Fig. 5 is a schematic structural diagram of a biochemical sensor array composed of a plurality of biochemical sensors shown in Fig. 1 according to an embodiment of the present invention;

附图标记说明:Explanation of reference signs:

1.压阻条;2.信号传输线;3.微柱结构;4.储液槽;5.漏液孔;6.谐振腔;7.11.输出电极;8.9.10.输入电极;12.探测单分子层;13.待测生化分子;14.参考梁。1. Piezoresistive strip; 2. Signal transmission line; 3. Microcolumn structure; 4. Liquid storage tank; 5. Leakage hole; 6. Resonant cavity; 7.11. Output electrode; Molecular layers; 13. Biochemical molecules to be measured; 14. Reference beams.

具体实施方式 Detailed ways

为使本发明的目的、技术方案和优点更加清楚明白,以下结合具体实施例,并参照附图,对本发明进一步详细说明。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

本发明提供了一种基于谐振式微悬臂梁结构的高灵敏生化传感器,通过采用前端具有微柱结构3、储液槽4和漏液孔5的微悬臂梁结构实现高灵敏度高精度测量生化分子。The invention provides a high-sensitivity biochemical sensor based on a resonant micro-cantilever structure, which can measure biochemical molecules with high sensitivity and high precision by adopting a micro-cantilever structure with a micro-column structure 3, a liquid storage tank 4 and a liquid leakage hole 5 at the front end.

如图1所示,图1是依照本发明实施例的基于谐振式微悬臂梁结构的高灵敏生化传感器的结构示意图,图2为图1的剖面图。该单悬臂梁传感器件包括谐振腔、悬臂梁和惠斯特桥式检测电路。其中在该悬臂梁的前端刻蚀出微柱结构3和储液槽4,并刻蚀流出生化溶液的漏液孔5;该悬臂梁的后端连接于该惠斯特桥式检测电路,该惠斯特桥式检测电路由四个U型结构的压阻条1、输入电极8、9、10和输出电极7、11构成,四个压阻条1通过信号传输线2连接于输入电极8、9、10和输出电极7、11,在本发明的一个实施例中,电极9接电源信号,电极7与电极11作为输出电极,电极8及电极10接地信号,从而得到惠斯特桥式检测电路。As shown in FIG. 1 , FIG. 1 is a schematic structural view of a highly sensitive biochemical sensor based on a resonant micro-cantilever structure according to an embodiment of the present invention, and FIG. 2 is a cross-sectional view of FIG. 1 . The single cantilever beam sensing device includes a resonant cavity, a cantilever beam and a Whist bridge detection circuit. Wherein the microcolumn structure 3 and the liquid storage tank 4 are etched at the front end of the cantilever beam, and the liquid leakage hole 5 flowing out of the biochemical solution is etched; the rear end of the cantilever beam is connected to the Whist bridge detection circuit, the The Whistler bridge detection circuit consists of four U-shaped piezoresistive strips 1, input electrodes 8, 9, 10 and output electrodes 7, 11, and the four piezoresistive strips 1 are connected to the input electrodes 8, 1 through signal transmission lines 2. 9, 10 and output electrodes 7, 11. In one embodiment of the present invention, electrode 9 is connected to the power signal, electrode 7 and electrode 11 are used as output electrodes, and electrode 8 and electrode 10 are grounded signals, thereby obtaining Whist bridge detection circuit.

悬臂梁后端的压阻条1随着悬臂梁谐振幅值而发生变化,通过惠斯特桥式检测电路将电阻变化转换成相同频率的电压信号,R1为压变电阻,R2,R3,R4为固定电阻,初始时它们的阻值相同均为R,受力后压变电阻的变化为ΔR,则输出信号为:The piezoresistive strip 1 at the rear end of the cantilever beam changes with the resonance amplitude of the cantilever beam, and the resistance change is converted into a voltage signal of the same frequency through a Whist bridge detection circuit. R 1 is a piezoresistor, R 2 , R 3 , R 4 is a fixed resistor, their initial resistance is the same as R, the change of piezoresistor after stress is ΔR, then the output signal is:

ΔVΔV == RR 11 RR 33 ·&Center Dot; RR 22 RR 44 (( RR 11 ++ RR 22 )) (( RR 33 ++ RR 44 )) EE. == ΔRΔR 44 RR EE.

通过压阻条后端的信号传输线2、输出电极7、11最终将测量信号输出。利用悬臂梁的频率变化检测悬臂梁前端吸附的生化分子13。悬臂梁的表面被修饰了对待测分子能够特异性响应的探测单分子层结构12,吸附待测分子后,使得其谐振频率发生改变,通过对谐振频率的检测进而将待测生化分子表征出来,梁基模共振频率为:Through the signal transmission line 2 at the rear end of the piezoresistive strip, the output electrodes 7, 11 finally output the measurement signal. The frequency change of the cantilever beam is used to detect the biochemical molecule 13 adsorbed at the front end of the cantilever beam. The surface of the cantilever beam is modified with a detection monolayer structure 12 that can specifically respond to the molecules to be tested. After the molecules to be tested are adsorbed, their resonant frequency changes, and the biochemical molecules to be tested are characterized by detecting the resonant frequency. The resonant frequency of the beam fundamental mode is:

ff 00 == 11 22 ππ kk mm **

其中,k为梁的劲度系数,m*为梁的有效质量。Among them, k is the stiffness coefficient of the beam, and m * is the effective mass of the beam.

如果认为其劲度系数不随所加负载而变化,则频率的偏移可以表示为If it is considered that its stiffness coefficient does not change with the applied load, the frequency shift can be expressed as

ΔfΔf == -- ff 00 22 mm ** ΔmΔm **

则悬臂梁可探测的质量随频率的变化为Then the detectable mass of the cantilever beam varies with frequency as

ΔmΔm ** == -- 22 mm ** ff 00 ΔfΔ f

依据此原理可获得待测生化分子的吸附质量。According to this principle, the adsorption mass of the biochemical molecule to be tested can be obtained.

为了提高吸收特征分子能力,在悬臂梁的前端刻蚀出微柱结构3,增加了梁前端修饰区的有效面积,并且制作出储液槽4,使待测生化分子充分反应。同时,在悬臂前端制作出生化溶液的流液孔5,以避免生化溶液残留对悬臂梁造成损害。In order to improve the ability to absorb characteristic molecules, the microcolumn structure 3 is etched at the front end of the cantilever beam to increase the effective area of the modification area at the front end of the beam, and a liquid storage tank 4 is made to fully react the biochemical molecules to be tested. At the same time, a flow hole 5 for the biochemical solution is made at the front end of the cantilever to avoid damage to the cantilever caused by the residue of the biochemical solution.

为了保证一致性,该惠斯特桥式检测电路中的四个压阻条1同时离子注入形成且采用“U”型结构能较好的束缚电流。In order to ensure consistency, the four piezoresistive strips 1 in the Whistler bridge detection circuit are formed by ion implantation at the same time and adopt a "U"-shaped structure to better confine current.

为了保证该惠斯特桥式检测电路输出的信号能够满足外接处理电路的噪声分辨问题,每个压阻条1的有效阻值最小不能小于1kΩ。In order to ensure that the signal output by the Whistler bridge detection circuit can meet the noise resolution problem of the external processing circuit, the minimum effective resistance of each piezoresistive strip 1 cannot be less than 1 kΩ.

连接四个压阻条1的信号传输线2是由高掺杂B离子形成,并在信号传输线之间刻出隔离槽,减低信号传输线之间的信号串扰。The signal transmission lines 2 connecting the four piezoresistive strips 1 are formed by highly doped B ions, and isolation grooves are carved between the signal transmission lines to reduce the signal crosstalk between the signal transmission lines.

实际应用时,谐振工作模式下采用压电驱动的方式进行驱动,分别测量出吸附生化分子前后的谐振频率,通过两个频率之差从而得到吸附生化分子的质量,其频率从惠斯特桥式检测电路末端的输出电极7及电极11间的交流电压信号频率测量得出。In practical applications, piezoelectric drive is used in the resonant working mode, and the resonant frequencies before and after the adsorption of biochemical molecules are measured respectively, and the mass of the adsorbed biochemical molecules is obtained through the difference between the two frequencies. It is obtained by measuring the frequency of the AC voltage signal between the output electrode 7 and the electrode 11 at the end of the detection circuit.

如图3所示,图3为惠斯特桥式检测电路测量原理图,其中悬臂梁根部的压阻条1等效于电路中的R4电阻,对应的其余三个压阻条1分别为R1、R2、R3,并且四个压阻条1具有相同尺寸且B离子掺杂浓度相同,保证了其初始阻值均为R。As shown in Figure 3, Figure 3 is a measurement schematic diagram of a Whist bridge detection circuit, in which the piezoresistive strip 1 at the root of the cantilever beam is equivalent to the R4 resistance in the circuit, and the corresponding remaining three piezoresistive strips 1 are respectively R 1 , R 2 , R 3 , and the four piezoresistive strips 1 have the same size and the same doping concentration of B ions, which ensures that their initial resistance values are all R.

为了实现同时测量多种生化分子,将多个如图1所示的生化传感器集成在一起制作了生化传感器阵列,并且选取其中一个生化传感器为参考梁14。In order to measure multiple biochemical molecules simultaneously, multiple biochemical sensors as shown in FIG. 1 are integrated to form a biochemical sensor array, and one of the biochemical sensors is selected as the reference beam 14 .

如图4所示,图4是依照本发明实施例的由两个图1所示的生化传感器构成的生化传感器阵列在吸附生化分子后的示意图。生化传感器的悬臂梁表面被修饰了对待测分子13能够特异性响应的探测单分子层结构12,吸附待测分子13改变了悬臂梁的质量,最终导致了悬臂梁的频率变化。利用惠斯特桥式检测电路检测在吸附生化分子前后的频率变化,可得到待测生化分子的质量。As shown in FIG. 4 , FIG. 4 is a schematic diagram of a biochemical sensor array composed of two biochemical sensors shown in FIG. 1 after adsorbing biochemical molecules according to an embodiment of the present invention. The surface of the cantilever beam of the biochemical sensor is modified with a detection monolayer structure 12 capable of specifically responding to the molecule 13 to be tested, and the adsorption of the molecule 13 to be tested changes the mass of the cantilever beam, which eventually leads to a change in the frequency of the cantilever beam. The mass of the biochemical molecule to be detected can be obtained by using the whist bridge detection circuit to detect the frequency change before and after the adsorption of the biochemical molecule.

如图5所示,图5是依照本发明实施例的由多个图1所示的生化传感器构成的生化传感器阵列的结构示意图,生化传感器阵列中的一个生化传感器作为参考梁14,其余每个生化传感器的悬臂梁表面可修饰对不同待测分子13特异性响应的探测单分子层12,阵列结构可同时测量多种生化分子。As shown in Figure 5, Figure 5 is a schematic structural view of a biochemical sensor array composed of a plurality of biochemical sensors shown in Figure 1 according to an embodiment of the present invention, one biochemical sensor in the biochemical sensor array serves as a reference beam 14, and each of the other The surface of the cantilever beam of the biochemical sensor can be modified with a detection monolayer 12 that responds specifically to different molecules to be measured 13, and the array structure can simultaneously measure multiple biochemical molecules.

以上所述的具体实施例,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施例而已,并不用于限制本发明,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。The specific embodiments described above have further described the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims (10)

1.一种基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,该生化传感器包括谐振腔、悬臂梁和惠斯特桥式检测电路,其中在该悬臂梁的自由端刻蚀有微柱结构(3)和储液槽(4),并刻蚀有用于流出生化溶液的漏液孔(5);该悬臂梁的支撑端连接于该惠斯特桥式检测电路,该惠斯特桥式检测电路由四个U型结构的压阻条(1)、三个输入电极(8、9、10)和两个输出电极(7、11)构成,四个压阻条(1)通过信号传输线(2)连接于输入电极(8、9、10)和输出电极(7、11)。1. A highly sensitive biochemical sensor based on a resonant micro-cantilever beam structure, characterized in that the biochemical sensor comprises a resonant cavity, a cantilever beam and a Whist bridge detection circuit, wherein the free end of the cantilever beam is etched with a microcolumn structure (3) and a liquid storage tank (4), and are etched with leakage holes (5) for flowing out biochemical solutions; the supporting end of the cantilever beam is connected to the Whist bridge detection circuit, and the Whist bridge detection circuit The detection circuit is composed of four U-shaped piezoresistive strips (1), three input electrodes (8, 9, 10) and two output electrodes (7, 11), and the four piezoresistive strips (1) pass through the signal transmission line (2) Connected to input electrodes (8, 9, 10) and output electrodes (7, 11). 2.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,该生化传感器是通过悬臂梁的频率响应来对生化分子进行高灵敏探测,悬臂梁的表面修饰有对待测分子能够特异性响应的探测单分子层结构(12),吸附待测分子(13)后改变了悬臂梁的质量,最终导致了悬臂梁的谐振频率变化;利用惠斯特桥式检测电路检测吸附生化分子前后的频率变化,来得到生化分子的质量。2. the highly sensitive biochemical sensor based on resonant micro-cantilever beam structure according to claim 1, is characterized in that, this biochemical sensor is to carry out highly sensitive detection to biochemical molecule by the frequency response of cantilever beam, and the surface modification of cantilever beam has The probe monolayer structure (12) that can specifically respond to the molecule to be tested changes the mass of the cantilever beam after adsorbing the molecule to be tested (13), which eventually leads to a change in the resonant frequency of the cantilever beam; using a Whist bridge detection circuit Detect the frequency change before and after adsorption of biochemical molecules to obtain the mass of biochemical molecules. 3.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述储液槽(4)用于局部修饰探测单分子层,减小大面积吸附对悬臂梁弹性常数影响而导致的频率改变。3. the highly sensitive biochemical sensor based on the resonant micro-cantilever beam structure according to claim 1, characterized in that, the liquid storage tank (4) is used for local modification and detection of monomolecular layers, reducing the absorption of large areas on the cantilever beam The frequency change due to the influence of the elastic constant. 4.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述微柱结构(3)用于增大吸附面积,提高检测极限。4. The highly sensitive biochemical sensor based on the resonant micro-cantilever structure according to claim 1, characterized in that, the micro-column structure (3) is used to increase the adsorption area and improve the detection limit. 5.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述漏液孔(5)制作于所述储液槽(4)中,用于保证储液槽中吸附反应完成后,废液从通孔中排出,不残留在悬臂梁中。5. the highly sensitive biochemical sensor based on the resonant micro-cantilever beam structure according to claim 1, characterized in that, the leakage hole (5) is made in the liquid storage tank (4) to ensure that the liquid storage After the adsorption reaction in the tank is completed, the waste liquid is discharged from the through hole and does not remain in the cantilever beam. 6.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述悬臂梁的驱动方式为压电、静电、电磁、热电或光驱动中的任一种或多种。6. The highly sensitive biochemical sensor based on the resonant micro-cantilever structure according to claim 1, wherein the driving mode of the cantilever is any one of piezoelectric, electrostatic, electromagnetic, thermoelectric or optical drive or Various. 7.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,在该惠斯特桥式检测电路中,输入电极(9)接电源信号,输出电极(7、11)作为输出电极,电输入电极(8、10)接地信号。7. the highly sensitive biochemical sensor based on the resonant micro-cantilever beam structure according to claim 1, is characterized in that, in this Whist bridge detection circuit, input electrode (9) connects power supply signal, output electrode (7, 11) As output electrodes, the electrical input electrodes (8, 10) are grounded signals. 8.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述惠斯特桥式检测电路中的电阻之一是悬臂梁支撑端的U型压阻条(1),悬臂梁的谐振频率测量是通过惠斯特桥式检测电路完成的,U型压阻条(1)用于提高对电流的束缚能力。8. the highly sensitive biochemical sensor based on resonant micro-cantilever beam structure according to claim 1, is characterized in that, one of the resistance in the described Whist bridge detection circuit is the U-shaped piezoresistive bar ( 1), the resonant frequency measurement of the cantilever beam is accomplished through the Whist bridge detection circuit, and the U-shaped piezoresistive strip (1) is used to improve the binding capacity of the current. 9.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,所述惠斯特桥式检测电路中的四个压阻条(1)均为“U”型压阻条,四个压阻条(1)同时进行离子注入形成,最大限度地保证了电阻的一致性,有效提高了测量精度,且每个压阻条(1)的有效阻值大于等于1kΩ。9. The highly sensitive biochemical sensor based on the resonant micro-cantilever beam structure according to claim 1, wherein the four piezoresistive strips (1) in the Whist bridge detection circuit are all "U" type Piezoresistive strips, four piezoresistive strips (1) are formed by ion implantation at the same time, which ensures the consistency of resistance to the greatest extent and effectively improves the measurement accuracy, and the effective resistance value of each piezoresistive strip (1) is greater than or equal to 1kΩ . 10.根据权利要求1所述的基于谐振式微悬臂梁结构的高灵敏生化传感器,其特征在于,在所述惠斯特桥式检测电路的传输线之间刻蚀出隔离槽结构,用于减少传输线之间信号的串扰,保证惠斯特桥式检测电路的测量精度。10. The highly sensitive biochemical sensor based on the resonant micro-cantilever beam structure according to claim 1, wherein an isolation groove structure is etched between the transmission lines of the Whist bridge detection circuit for reducing the transmission line The crosstalk between the signals ensures the measurement accuracy of the Whist bridge detection circuit.
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