KR20070050883A - Enzymeless bio and environmental sensor modules and their applications - Google Patents

Abstract

The present invention relates to a micro bio and environmental sensor module in which a bio sensor based on an electrochemical measurement of a reactive element made of a platinum electrode having a nanoporous structure is integrated with a CMOS electronic circuit. It is to implement a handy-held medical examination system and a ubiquitous health monitoring system that can measure anytime, anywhere and preserve data.

Reactive Oxygen Glucose Sensor, Sensor Module, Electrochemical Sensor, Nanoporous Platinum  

Description

Development of Reactive Bio and Environmental Sensor Modules and Their Applications {Enzymeless Bio and Environmental Sensor Modules and Their Applications}

1 is a partially combined perspective view of a bio and environmental sensor of the present invention.

FIG. 2 is a process flowchart of the bio and environmental sensor shown in FIG. 1.

3 is a perspective view of the bio and environmental sensor shown in FIG.

4 is a cross-sectional view of a perspective view of the bio and environmental sensor shown in FIG.

FIG. 5 shows a perspective view of the bio and environmental sensors of various structures in addition to the perspective view of the bio and environmental sensors shown in FIG. 3.

6 is a pen and the bio and environmental sensor module of the present invention.

7 is a thimble form of the bio and environmental sensor module.

8 is packaged into the sensor device to be equipped with the bio and environmental sensor module in a mobile phone.

The present invention relates to a micro bio and environmental sensor module in which a biosensor based on electrochemical measurement of a reactive element made of a platinum electrode having a nanoporous structure is integrated with a CMOS electronic circuit. It is about.

The definition of biosensors varies, but it can be thought of as a miniaturized sensor that closely couples a biological object to a signal transducer. Sensors that measure or use materials that are not related to living things are called chemical sensors, while bio-sensors are used when materials related to living things are targeted or used as part of a sensor. In view of the concept of biosensors, it can be said that the purpose of developing biosensors is to produce electrical signals that are proportional to the amount of any analyte or related substance. Most of this work is done in analytical labs, but the sensor has the advantage of making it simple, fast, and field-enabled by allowing the same task to be performed using very small, compact devices. The biosensors can be measured quickly, making it possible to observe a continuous change in the amount of a particular substance in near real time and inform the observer in a short enough time if any substance suddenly appears in the sample. In addition, it does not require any laboratory, expensive equipment, or skilled analytical staff to do the same thing, and enables on-the-spot measurements by non-professionals, which can be economically beneficial to meet the myriad of analytical demands.

The best commercialized biosensor is a blood glucose measurement sensor. The measurement of blood glucose is divided into non-invasive methods such as an invasive method and an optical method that directly collects and measures blood of a subject. This is shown in Figure 2, the performance has been confirmed so far, a widely used method is a strip method of measuring by dropping 10 ul or less blood to the disposable sensor strip by poking a finger. The basic structure of the strip blood glucose sensor is a concept of a so-called biosensor that combines Glucose Oxidase (GOD), originally designed by Clark et al., In 1962 with an oxygen electrode. Glucose is most commonly achieved by immobilizing glucose oxidase on a platinum electrode, which is one of the few enzymes that maintains its activity even in harsh in vitro environments. In other words, it is the most easily used enzyme for the enzyme sensor, so it is most widely used in education and industry. Also, among the target substances that can be measured by biosensors, glucose is one of the most demanding medically and industrially. For medical purposes, the demand for checking the glucose level in the blood is increasing proportionately due to the rapidly increasing diabetic patients every year, industrially it is also required in various food industries.

Current commercially available disposable and continuous measurement glucose sensors have a common point in that they use enzymes including glycosylase. In addition to commercialized sensors, the most widely studied sensors in biosensor research are blood glucose sensors using enzymes. However, enzymes are inherently difficult to maintain their intrinsic activity outside the body. Many studies have introduced a number of immobilization methods, but the activity of enzymes is still far below that of other chemical sensors using solid-state minerals in terms of reliability. This fundamental problem is most prominent in mass production systems. Even blood glucose sensors produced using the same material on the same line, the performance distribution is actually quite wide and requires a separate calibration chip. Even if the chip passes the quality inspection, there is a limit on the unused shelf life and the shelf life during use, which leads to an increase in production cost. As a result, enzymatic glucose meters are distributed at relatively high prices and cannot be recycled, which is a great burden for diabetics who frequently need to measure blood glucose.

There are many studies to develop a biosensor of reactive nitrogen, and the present invention is based on the analysis of reactive nitrogen using a platinum electrode having a nanoporous structure (mesoporous: 2-50 nm). The condition under which the reactive metal electrochemical analysis can be performed on the platinum electrode of nanoporous structure is that the reaction rate of the sample to be measured should be different when there are several samples. If the reaction rate of the sample to be measured is slow, the reaction current is measured after the reaction of certain other samples. If the reaction rate of the sample is fast, the reaction current of the desired sample can be obtained by measuring the reaction current before the reaction of other samples. have.

Accordingly, an object of the present invention is to amplify the reaction current by using a nanoporous structure (mesoporous: 2 ~ 50nm) platinum electrode, bio and environmental sensors capable of analyzing the component of the reactive element and continuous measurement, not disposable, on the silicon substrate The aim is to implement a sensor module integrated with CMOS circuits. Furthermore, another object of the present invention is to implement a handy-held health diagnosis system and a ubiquitous health monitoring system capable of measuring anytime, anywhere and preserving data by mounting the invented bio and environmental sensor module in a portable terminal.

The present invention is a non-conductive silicon substrate portion to achieve the above object; A lead part made of platinum on an upper surface of the substrate part; An electrode part including a working electrode and a reference electrode inducing a reaction on an upper surface of the lead part; There is a sensor comprising a reaction layer and a cover to secure a space for reaction to the upper portion of the electrode portion, it can be achieved by the CMOS integrated circuit is designed to operate as a module under the non-conductive silicon substrate.

Hereinafter, a bio and environmental sensor and a sensor module according to the present invention will be described in more detail with reference to the accompanying drawings. However, the present invention is not limited thereto.

The nanoporous structure, in which the bio and environmental sensors of the present invention can act as reactive nitrogen electrochemical sensors, is described in Example 1. The following examples are only for illustrating the present invention and the present invention is not limited to the following examples.

Example 1 Method of Fabricating Platinum Electrode of Nanoporous Structure

Non-ionic surfactant C ₁₆ EO ₈ (Octaethylene glycol monohexadecyl ether) wt42%, chloroplatinic acid H ₂ PtCl ₆ (Hydrogen hexachloroplatinate hydrate) wt29%, deionized water wt29% was mixed to prepare a plating solution, the temperature of the plating solution is 85 degrees Celsius Increase to allow the plating liquid to be mixed homogeneously. The substrate on which platinum was formed was placed in a plating solution, and the temperature was lowered to 25 degrees Celsius so that the surfactant component in the plating solution could form pillars of hexagonal arrangement. In this state, a platinum electrolysis was applied to the platinum electrode by applying a negative potential of -120 mV relative to the Ag / AgCl reference electrode to form a nanoporous structure on the platinum surface. The fabricated nanoporous platinum electrode was washed several times in deionized water to allow the surfactant to be extracted cleanly. The fabricated nanoporous platinum electrode has a structure in which holes of about 2.5 nm in diameter are arranged in a hexagon at intervals of 2.5 nm.

1 is a partially combined perspective view of a bio and environmental sensor of the present invention, FIG. 2 is a process flowchart of the bio and environmental sensor shown in FIG. 1, and FIG. 3 is a perspective view of the bio and environmental sensor shown in FIG.

As shown in FIG. 1, the bio and environmental sensor according to the present invention has the structure of the bio and environmental sensor according to the present invention. The nonconductive silicon compound insulating layer 12 is formed on the silicon (Si) semiconductor CMOS circuit board 11. A substrate portion (10) formed of; A lead part 20 including a reference electrode lead 21, a working electrode lead 22, 22 ′, and an auxiliary electrode lead 23 formed of platinum on an upper surface of the substrate part; An electrode part 50 having silver / silver chloride 31 for the reference electrode formed on the upper surface of the lead part and having platinum (32, 32 ') of nanoporous structure for the working electrode; A cover layer 41 formed by coating an insulator as a whole to partially expose the electrode part 50; It consists of a reaction layer 42 formed on the upper surface of the exposed electrode portion 50. The reaction layer 42 uses a hydrophilic polymer.

Looking at the formation process of the bio and environmental sensor having the above structure in detail as follows.

As shown in FIG. 2 (a), the semiconductor CMOS circuit board 11 in the substrate part 10 may include gallium arsenide (GaAs), gallium nitride (GaN), and silicon germanium (including silicon (Si) semiconductor). CMOS circuits are integrated on compound semiconductor substrates such as SiGe) and silicon carbide (SiC) to control and measure sensors. As shown in FIG. 2B, a substrate on which an insulating layer 12 of non-conductive silicon oxide (SiO ₂ ) or silicon nitride (SiN _X ) is formed is used as an upper surface of the semiconductor CMOS circuit board 11. It was.

As shown in FIG. 2C, a lead portion 20 is formed on an upper surface of the substrate portion 10. The lead portion 20 includes a reference electrode lead 21, a working electrode lead 22, 22 ′, The auxiliary electrode lead 23 is formed.

As shown in FIG. 2 (d), the working electrodes 52 are formed on the upper surfaces of the working electrode leads 22 and 22 ′ by electrodeposition of platinum having a nanoporous structure. As shown, an ink of silver or silver / silver chloride (Ag / AgCl) mixture is screen printed on the upper surface of the reference electrode lead 21 to form the reference electrode 51, and nothing is formed on the upper surface of the auxiliary electrode lead 23. It is used as the auxiliary electrode 53 without making it.

The cover layer 41 formed by coating an insulator on all parts of the electrode part 50 except for the upper part of the electrode part to partially expose the electrode part 50 and the hydrophilic formed on the exposed electrode part upper surface of the electrode part 50. It consists of the reaction layer 42 using a polymer. Finally, a cover to protect the sensor from the outside is mounted on the module in a slide form so that the sensor is exposed only when necessary.

In addition, a method of manufacturing a module including the bio and environmental sensors is to first integrate a CMOS circuit for controlling the sensor on the semiconductor substrate to form a sensor on the upper surface and then integrated packaging. The CMOS circuit includes a control unit for controlling the applied voltage of the sensor, an amplifier for amplifying the reaction current, and an analog / digital converter for converting the digital value. When packaging, the sensor-exposed part is made of a slide type opening / closing part so that the sensor can be exposed only when necessary.

4 is a cross-sectional view of a perspective view of the bio and environmental sensor shown in FIG. In FIG. 4, the outermost size 61 of the electrode allows the size of the reaction current to be adjusted by adjusting the size of the sensor, and the diameter 62 of the reference electrode is selected to have a minimum size, but the actual size can be selected. Do it. The spacing 63 between the reference electrode and the working electrode should be as small as possible but not shorted during the process. The width 64 of the working electrode is a variable for controlling the magnitude of the reaction current, thereby obtaining an optimized reaction current. The spacing 65 between the working electrode and the auxiliary electrode is also related to the magnitude of the reaction current. If the spacing is narrow, a large amount of current may flow, but if it is too close, a malfunction may result. The thickness 66 of the auxiliary electrode is selected to an appropriate thickness to fabricate a sufficient current to flow.

FIG. 5 shows a perspective view of the bio and environmental sensors of various structures in addition to the perspective view of the bio and environmental sensors shown in FIG. 3.

6 to 8 are exemplary diagrams to which the bio and environmental sensor modules of the present invention are applied.

Figure 6 (a) is to implement the bio and environmental sensor module of the present invention in the form of a pen. Figure 6 (b) is applied to a twin pen mounted with two shims is an example of applying the bio and environmental sensor module of the present invention as a biosensor. A needle 73 is mounted on one core 71 and a sensor module 72 is mounted on the other core 71. First, the needle 73 is protruded to detect blood, and then the sensor module 72 is protruded from the core to which the blood is collected and measured. 6 (c) is a method in which a sensor 73 is mounted on one core 71 and a needle 73 is formed thereon to simultaneously measure blood collection. The measured values are displayed on a small display window 74 made in the body of the pen, and the respective displayed values are stored. Stored values are monitored in real time on media such as mobile phones and computers through wireless communication modules as needed. To use the pen-type sensor again, dip the tip of the sensor into the cleaning solution and wash it again.

Figure 7 (a) is to implement a bio and environmental sensor module in the form of thimble. First, the microneedle 84 is formed to dull the pain in the exposed part of the bio and environmental sensor module 83 of the present invention and then mounted on the thimble 80. The needle 84 of the mounted sensor comes out at the time stored by the autoprogramming and draws blood and shows the measured value in real time through the display device 81 of the body. The produced thimble 80 is equipped with a device for displaying and storing data can be monitored from time to time measured values. If necessary, the communication module 82 may be mounted to enable real-time monitoring by interworking with media such as mobile phones and computers. Figure 7 (c) is a shape wearing a sensor thimble on the finger.

8 is packaged with a sensor device 92 to mount the bio and environmental sensor module to a mobile phone. The manufactured bio and environmental sensor device 92 is manufactured with a connection connector 93 that can be connected to a data communication connector of a mobile phone. The measurement result connected to the data communication connector 91 of the portable communication terminal 90 may be monitored in real time.

The three-electrode sensor system according to the present invention implements an electrochemical sensor that analyzes biomaterials and environmental substances without using enzymes by using mesoporous platinum electrodes as working electrodes, thereby enabling continuous biomonitoring or environmental monitoring. In addition, the three-electrode sensor system is implemented on a semiconductor substrate and manufactured with a micro bio and environmental sensor module integrated with a CMOS circuit to implement a handy-held health (or environmental) diagnosis system and a ubiquitous health (environment) monitoring system.

Claims (11)

An integrated packaging module with an electronic circuit in which a three- or two-electrode sensor having a nanoporous platinum (or gold) electrode as a working electrode, a reference electrode, or an auxiliary electrode is formed on a substrate. The method of claim 1, Substrates used include compound semiconductor substrates or silicon compounds such as gallium arsenide (GaAs), gallium nitride (GaN), silicon germanium (SiGe) and silicon carbide (SiC), including silicon (Si) semiconductors that can be integrated with CMOS circuits. , PDMS, Glass, SU-8, etc. The method of claim 1, Nanoporous structure refers to a structure in which holes of 2 to 100 nanometers are arranged on the surface. The method of claim 1, The nanoporous structure platinum electrode may be replaced with a platinum black electrode or a carbon nanotube electrode. The method of claim 1, The structure of the three-electrode sensor system takes the structure of FIGS. The method of claim 1, As the reference electrode of the three-electrode sensor system, silver / silver chloride, a standard hydrogen electrode or a caramel electrode may be applied. The material for packaging the top of the three-electrode sensor system is a hydrophilic polymer membrane, which is polyurethane (PU), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyfluorosulfonate, hydroxyethyl cellulose (HEC) Materials such as hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), cellulose acetate or polyamidi. The method of claim 5, Portions outside the top of the sensor electrode are coated with a Teflon- or ceramic-based material. The method of claim 1, As for the application of the three-electrode sensor system having a mesoporous platinum electrode as the working electrode, The packaged sensor has been applied to a pen-type blood analyzer The structure of the pen-type blood analyzer is a twin-pen type blood glucose meter with two pens, one pen is collected with blood and the other is equipped with a sensor to measure blood glucose, It is a structure that has a single pen. The tip of the sensor rod is equipped with a blood sampling needle, and a sensor is mounted at the bottom of the blood sampling needle to directly measure the blood glucose of the collected blood. The method of claim 1, As for the application of the three-electrode sensor system having a mesoporous platinum electrode as the working electrode, Packaged sensors have been applied to thimble-type blood analyzers A blood glucose meter having a shape similar to a thimble. A sensor unit in which a blood collection needle is packaged on a sensor is opened and opened as needed to analyze blood, and has a structure that has a display window for checking the measured value immediately or a wireless communication module. It is possible to monitor in real time by interworking with media such as mobile terminal and computer. The method of claim 1, As for the application of the three-electrode sensor system having a mesoporous platinum electrode as the working electrode, The packaged sensor is made of a module that can be connected to a mobile terminal. It is a type designed to connect the manufactured blood analysis module to the data communication connector of the mobile terminal.

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