JP4180472B2 - Mass sensor - Google Patents

Description

  The present invention is a QCM type mass that uses “Sauerbrey's theory” that measures mass change by the magnitude of frequency change when various minute masses (objects) interposed on a piezoelectric single crystal substrate are desorbed. It relates to sensors.

  In recent years, research on global environmental pollution problems and human genetic elucidation has been conducted. For example, identification of environmental hormone species, antigen-antibody reaction, binding of high molecular proteins (DNA-DNA, DNA-RNA) Reactions, analysis of enzyme reactions, proteome analysis, etc. are actively performed. And as these analysis methods, apparatuses, such as a gas chromatography mass spectrometer (GC-MS), a high performance liquid chromatograph (HPLC), and a surface plasmon resonance measuring device (SPR), are used. These instruments are large and expensive equipment, and at the same time have a very high analytical sensitivity. However, pretreatment of the sample requires considerable labor and time, and it is difficult to analyze multiple components simultaneously. . In addition, there is always a demand to observe the reaction process in real time, but this is not possible with the above equipment.

When a complementary binding reaction such as an antigen-antibody reaction or DNA-RNA binding occurs, a change in weight or a change in dielectric constant occurs. With the QCM mass sensor, it is possible to capture such minute changes.
Mass sensors that use piezoelectric single crystals as sensor elements can measure ng levels of weight, so it is possible to detect antigens (or antibodies) by immobilizing antibodies (or antigens) on the device surface. It becomes. Further, regarding PH and conductivity, it is possible to detect a change in conductivity by an acoustoelectric interaction. Since the reaction process can be understood as a frequency change, real-time quantitative analysis is possible by measuring and recording the state of the frequency change in real time.
(1) N. Miura, H. Higabashi, G. Sakai et al .: Piezoelectric crystal immunosensor for sensitive detection of methamphetamine (stimulant drug) in human urine Proc. Fourth Int. Meeting on Chemical Sensors, Technical Digest, Tokyo. Pp. 13- 17 (1992)

  When the mass sensor shown in FIG. 1 captures a complementary binding reaction such as an antigen-antibody reaction or a DNA-RNA binding, the mass sensor corresponds in advance on a reaction part (usually a metal electrode such as Au or Al) of the sensor element. A sensitive substance such as an antigen, antibody, or DNA is added, and in this state, it is immersed in a solution while being excited at the natural vibration frequency by an oscillation circuit or the like, and changes depending on the reaction or binding state with the target substance. The frequency change due to the mass change is measured.

  At this time, the state of the natural vibration of the sensor element is “thickness shear vibration”, and in order to induce this vibration state, metal electrodes are required on the front and back of the main surface of the sensor element. Therefore, when immersed in a solution with this structure, an unstable circuit connected with a finite impedance is added between the two electrodes due to the occurrence of electrical leakage through the solution, and the oscillation frequency is Measurement becomes difficult due to instability.

As a countermeasure against this, it is conceivable that the opposite main surface that does not contribute to the reaction is subjected to an insulation treatment and immersed in a solution, but the excitation load becomes large and it is difficult to oscillate easily. Therefore, usually, the reaction main surface must be exposed in the solution, but the opposite main surface is exposed in the gas phase.
A structural example of a conventional mass sensor is shown in FIG. This is a structure in which the sensor element can be fixed with epoxy adhesive at one end of a cylindrical holder that approximates the outer circumference of the sensor element so that the opening is closed, and the solution can be introduced into the cylinder. Is exposed in the gas phase.

  This structure can separate the gas phase and the liquid phase, but since it is already fixed with an epoxy adhesive, it is difficult to add sensitive materials before measurement, problems that are limited, In response to downsizing, the stability of vibration is remarkably deteriorated by fixing the portion where the propagation wave of the main vibration is not completely attenuated and remains, although it is in the periphery of the sensor element.

  The present invention has been made to solve the above-described problems. The sensor element can be attached to and detached from the holder portion by a polymer elastic body in which a conductor material and an insulator material are alternately arranged. Because it is fixed so that it can be clamped, it is possible to easily attach it to the holder after performing a sensor mounting operation only on the sensor element. By using a rubber material having high elasticity as the elastic body, it is possible to provide a highly stable oscillation vibration because the packing property is good and no leakage occurs, and there is no restriction of leakage vibration.

In the present invention, since a sensitive substance can be added by a sensor element alone, handling is simple, and the degree of freedom and workability of the sensitive substance material are improved. The conductive material and the insulating material is arranged in series with each other, the structure for clamping the outer peripheral portion of the sensor element from the front and back with the elastic polymer of the rubber material is easily desorbed in the holder, and surely Because of the soft support and high packing property, it is possible to secure high frequency stability as a sensor and to take measures against leakage.

  The QCM mass sensor that measures complementary binding reactions derived from biological systems, such as antigen-antibody reactions and DNA-DNA binding reactions, can also perform real-time quantitative analysis and analyze the reaction form. In doing so, it is very important and has advantages. When many different types of sensitive substances are handled and analysis is attempted in a matrix, various types of sensitive substances are fixed on the reaction part of the sensor element (usually a metal electrode such as Au or Al) accordingly. There is a need. In the present invention, the sensor element alone can be processed in such a case, and the workability is simple and reliable, so that high-precision measurement is possible, and because of the soft support and high packing structure, the sensor has a high frequency. It is a mass sensor characterized by ensuring stability and taking countermeasures against leakage.

Embodiments of the present invention will be described below with reference to the accompanying drawings. 2 is a perspective view (FIG. 2 (a)) of a mass sensor element 3 used in the mass sensor of the present invention in which electrodes 2 are formed on both main surfaces of the piezoelectric single crystal substrate 1, and a cross-sectional view (FIG. FIG. 2 (b)) is shown. The vibration mode of this element is “thickness shear vibration”, and the frequency is selected according to the viscosity and density of the solution. At this time, a method of changing the frequency of the fundamental wave or a method of changing the frequency by overtone vibration is used, and usually vibrations of several MHz to several tens of MHz are often used. FIG. 2A shows an example in which the metal electrode 2 is formed on the sensor element, and FIG. 2B shows an example in which a sensitive substance is added to the metal electrode 2 immersed in the solution.
Usually, the sensitive substance is formed by spin coating, vapor deposition, deposition, LB film formation, or the like.

FIG. 3 shows a rubber-like polymer elastic body 4 in which a conductor material and an insulator material are alternately and continuously arranged. A conductor material and an insulator material having a thickness of several tens to a hundred microns are alternately arranged. It is arranged and formed in the longitudinal direction (string shape), and both ends are joined to form a ring shape. The cross section and ring shape are usually circular, but the shape is particularly difficult. Absent. However, since the sensor element has a structure in which the two outer peripheral portions of the main surface of the sensor element are sandwiched, it is desirable that the sensor element be disposed on the surface that passes through the center of the plate thickness and is parallel to the plate thickness.
The electrode 2 on the sensor element and the external electrode are connected via a conductive portion of a ring-shaped rubber material polymer elastic body 4 in which conductor materials and insulator materials are alternately arranged in the longitudinal direction, and oscillates. Is possible. With the alternately arranged conductor material and insulator material, the electrode on the mass sensor element and the other electrode of the external connection terminal can be separated and connected.

  FIG. 4 is a cross-sectional view showing the structure of the mass sensor element 3 incorporated in a holder. The inner peripheral diameter portion near one end of the holder is enlarged to increase the height of the ring-shaped rubber material. The structure is such that the molecular elastic body 4 can be inserted and can be fixed at a stepped portion. Since the polymer elastic body 4 comes into contact with the solution, the whole is made of an insulator. Next, after putting the sensor element so that the reaction surface is on the solution side, a polymer elastic body 4 of a ring-shaped rubber material in which a conductor material and an insulator material are alternately arranged is put and standardized by a stopper. Fix at a constant pressure. At this time, the polymer elastic body 4 is appropriately crushed and is electrically connected to an electrode prepared in advance on the inner peripheral portion of the holder, thereby establishing electrical connection between the sensor element and the outside (oscillator).

  FIG. 6 is an example of a configuration diagram of an apparatus for measuring mass using the mass sensor of the present invention. However, the mass sensor section shows a cross section. The mass sensor fabricated with the above structure is placed in a thermostat that is precisely temperature controlled for the purpose of eliminating the influence of temperature fluctuations, together with the oscillation circuit, and the solution used for the measurement is also stored in the thermostat. Managed by temperature conditions. For frequency measurement, a frequency counter is used. As a reference of the counter, it is desirable to use a signal generated by an Rb oscillation and a highly stable crystal oscillator. Data obtained by the frequency counter has a structure that can be processed by a computer with a desired algorithm.

  As another embodiment of the present invention, as shown in FIG. 5, both electrodes 2 on the piezoelectric single crystal substrate 1 may have a holder structure that realizes a gas phase environment.

  This sensor has been described with respect to examples of measuring mass changes due to reactions and bonds in solution, but it is also effective for measurements in the gas phase, such as measuring the content of environmental pollutants such as dioxins. Easy processing of a wide variety of sensitive materials and the support of the sensor element can be fixed softly, so a very stable frequency can be obtained, enabling accurate measurement regardless of the gas phase or liquid phase. It becomes.

It is a conceptual diagram which shows an example of the conventional liquid phase measurement mass sensor. It is the elements on larger scale which show the sensor element used for this invention. It is a conceptual diagram of the polymeric elastic body of a ring-shaped rubber material. It is sectional drawing which shows the structure of this mass sensor. It is a conceptual diagram which shows an example of the mass sensor used in the gaseous-phase environment which is another Example of this invention. It is a conceptual diagram which shows the structural example of a minute mass measuring device.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Piezoelectric single crystal substrate 2 Electrode 3 Mass sensor element 4 Polymer elastic body (ring shape)

Claims (1)

Are formed electrodes on both surfaces of a piezoelectric single crystal substrate, in the mass sensor in which the electrodes are drawn out around the piezoelectric single crystal substrate, the holder is formed a stepped portion for holding the mass sensor element, the stepped difference portion The mass sensor element and the outer peripheral portion of the main surface of the substrate of the mass sensor element are arranged in a ring shape, and at least one of the mass sensor elements is arranged in a structure sandwiched by a polymer elastic body in which conductive material and insulating material are alternately arranged. The mass sensor, wherein the electrode on the outer peripheral portion of the substrate main surface on the mass sensor element and the external connection terminal of the holder are connected and connected .

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