TW201604528A - Microfluidic bio-sensing device - Google Patents

Abstract

A microfluidic bio-sensing device is provided, including a microfluidic unit and a bio-sensing unit. The microfluidic unit includes a detection area. The bio-sensing unit is joined with the microfluidic unit band includes a substrate, a ruthenium oxide (RuO2) electrode layer, an insulating layer, a glucose sensing membrane, and a conductor layer. The RuO2 electrode layer is formed on the substrate. The insulating layer is formed on the RuO2 electrode layer and exposes a portion of the RuO2 electrode layer. The glucose sensing membrane is fixed on the portion of the RuO2 electrode layer, wherein the position of the glucose sensing membrane corresponds to the detection area. The conductor layer is formed on the RuO2 electrode layer and electrically connected to the glucose sensing membrane. When a liquid sample flows through the detection area, the glucose sensing membrane is configured to detect the glucose concentration of the liquid sample in dynamical condition.

Description

Microfluid biomedical sensing device

The present invention relates to a bio-sensing device, and more particularly to a glucose biomedical sensing device incorporating microfluidics technology.

The biomedical sensor was developed by Clark and Lyons in 1962 with the concept of an enzyme electrode, and the enzyme electrode was used to test the blood glucose concentration, and the first generation of biomedical sensors was created. The glucose sensor reacts with glucose and reacts with glucose by Glucose Oxidase (GOD) enzyme, which has an electrochemically active center, and the oxygen consumption during the electrochemical reaction process The concentration of hydrogen peroxide is known as the glucose concentration. In 1967, Updike and Hicks proposed the use of polyacrylamide to embed and immobilize glucose oxidase on the electrode, and oxygen as an electron acceptor to detect oxygen consumption and thus the glucose concentration. In addition, Shuang Zhao modified the glassy carbon electrode with gold nanoparticles in 2006 to increase the electron exchange rate between the electrodes and shorten the reaction time of glucose oxidase.

Compared to traditional bioanalytical techniques, microfluidics technology can help improve response speed, reduce the need to measure and improve reliability. In 1990, Manz et al. proposed a micro-full analysis system architecture that integrates analysis steps into a small space for analysis, such as sample setup, reaction, separation, and detection, with very fast reaction times. Based on the above advantages, microfluidic technology is used in many fields, such as biomedical and biomedical engineering.

At present, microfluidic devices are mostly prepared by means of excimer laser processing or microelectromechanical processing. Excimer laser processing can directly describe the processed parts, which has the advantages of rapid prototyping, but the processing surface is slightly rough; As for the microfluidic device prepared by the microelectromechanical process, although the above disadvantages can be overcome, it takes a long time and is costly. The current patent documents relating to microfluidic devices in the country can be referred to the Republic of China Patent Nos. I 393627, I 383138, M 445196, I 310786 and I 294965.

In view of this, the embodiments of the present invention provide a biomedical sensing device integrated with a microfluidic technology, which can measure a plurality of characteristic values (such as an output voltage) of a solution to be tested under dynamic conditions, thereby being able to know the solution to be tested. Glucose concentration.

In addition, the embodiment of the present invention prepares the microfluidic unit through the screen printing technology, and combines the microfluidic unit with the flexible biomedical sensing unit to complete the preparation of the microfluid biomedical sensing device, thereby effectively Reduce manufacturing costs and have the advantage of mass production.

1‧‧‧Microfluid biomedical sensing system

10‧‧‧Microfluid biomedical sensing device

22‧‧‧Injection pump

23‧‧‧Test solution

24‧‧‧Connecting tube

26‧‧‧ Waste storage

102‧‧‧First joint

104‧‧‧Second joint

106‧‧‧Fixed plate

200‧‧‧Microfluidic unit

205‧‧‧Test solution injection port

207‧‧‧Measure solution outlet

209‧‧‧Detection area

300‧‧‧ Biomedical Sensing Unit

301‧‧‧Substrate

303‧‧‧ cerium oxide electrode layer

304‧‧‧Glucosamine film

305‧‧‧reference electrode layer

306‧‧‧Wire layer

307‧‧‧Insulation

Fig. 1 is a schematic view showing a microfluid biomedical sensing system according to an embodiment of the present invention.

Figure 2 is an exploded view of the microfluidic biosensor sensing device of Figure 1.

Fig. 3A is a plan view showing the microfluidic unit in Fig. 2.

Fig. 3B is a cross-sectional view taken along the line X1-X2 in Fig. 3A.

Fig. 4 is a view showing the analysis of the flatness of the microfluidic unit of an embodiment of the present invention by a film thickness gauge.

Fig. 5 is a view showing the biomedical sensing unit in Fig. 2.

Fig. 6 is a graph showing the measurement of the glucose solution concentration of 100 mg/dL to 500 mg/dL by the microfluidic biosensor sensing system according to an embodiment of the present invention.

Please refer to FIG. 1 . The microfluid biomedical sensing system 1 of the embodiment of the present invention mainly includes a microfluid biomedical sensing device 10 , an injection pump 22 , two connecting tubes 24 , and a waste liquid storage device 26 . The injection pump 22 and the waste liquid reservoir 26 are respectively connected to the microfluid biomedical sensing device 10 through a connecting tube 24. The injection pump 22 can inject a solution to be tested 23 into the microfluid biomedical sensing device 10, and the biomedical sensing unit 300 in the microfluid biomedical sensing device 10 (see Figures 2 and 5). The test solution 23 is measured and at least one sensing signal is obtained. The biomedical sensing unit 300 can be electrically connected to an external signal analysis system (not shown), and the signal analysis system executes the sensing signal. Store, analyze, display and other functions. In addition, the waste reservoir 26 is used to provide sufficient storage space for the measured waste liquid.

Next, referring to FIG. 2, a microfluidic body according to an embodiment of the present invention The medical sensing device 10 mainly includes a plurality of first bonding members 102, a plurality of second bonding members 104, two fixing plates 106, a microfluidic unit 200, and a biomedical sensing unit 300, wherein the microfluidic unit 200 is assembled into a medical doctor. Above the sensing unit 300, the two fixing plates 106 are respectively used as an upper cover and a lower cover, and the microfluidic unit 200 and the biomedical sensing unit 300 are clamped in the center through the sandwich structure, and the first bonding members 102 and The second bonding member 104 can lock components such as the microfluidic unit 200, the biomedical sensing unit 300, and the two fixing plates 106 stacked on each other to complete assembly of the microfluid biomedical sensing device 10. In this embodiment, the fixing plate 106 is, for example, an acrylic plate, and the first coupling member 102 and the second coupling member 104 are, for example, stainless steel screws and stainless steel nuts.

Figure 3A shows the top view of the microfluidic unit 200 in Figure 2 Fig. 3B is a cross-sectional view taken along the line X1-X2 in Fig. 3A. As can be seen from the figures 3A and 3B, the microfluidic unit 200 of the present embodiment includes a solution injection port 205 to be tested, a solution solution outlet port 207, and a detection region 209, wherein the detection region 209 is connected to the solution injection port to be tested. 205 and the solution outlet outlet 207.

In addition, please refer to the figures 1 to 3B together, the micro of this embodiment The fixed plate 106 as the upper cover of the fluid biomedical sensing device 10 is further formed with a plurality of openings corresponding to the solution injection port 205 of the microfluidic unit 200 and the solution flow outlet 207 to be tested. In this way, the solution 23 to be tested can pass through the opening on the fixing plate 106 and the solution injection port 205 of the microfluidic unit 200. After entering the detection area 209, the microfluidic biosensor sensing device 10 is discharged through the opening of the solution outlet 207 and the fixing plate 106 of the microfluidic unit 200, and enters the waste reservoir 26 for collection.

It should be specially noted that this embodiment is by screen printing machine. (screen printer), the designed screen is coated with epoxy resin, and screen-printed on a stainless steel substrate, and then placed in an oven and baked at 130 ° C for 30 minutes to complete the first layer of mother Model preparation. According to the different height requirements of the microfluidic unit 200, the screen printing can be repeated on the stainless steel substrate to increase the height of the master mold, thereby satisfying the actual height requirement of the microfluidic unit 200.

The material of the microfluidic unit 200 is preferably dimethyloxane Poly-dimethylsiloxane (PDMS). The microfluidic unit 200 is obtained by mixing PDMS and a curing agent in a volume ratio of 10:1 and resting on the above-mentioned master mold, and curing at a temperature of 70 ° C and 90 minutes, and finally releasing the film.

Figure 4 shows the film thickness gauge (Thin film) The measurement results of the flatness of the microfluidic unit according to an embodiment of the present invention are measured. The measurement results show that the method of using multiple screen printing can effectively improve the flatness of the microfluidic unit and reduce the burr phenomenon. In addition, the master mold of the microfluidic unit is prepared by the screen printing process, which is convenient, fast and does not require the use of a mask, thereby greatly reducing the manufacturing cost and improving the conventional excimer laser processing or MEMS. The process method prepares the shortcomings of the microfluidic device.

Referring to FIG. 5, the biomedical sensing unit 300 of the embodiment of the present invention mainly includes a substrate 301, a ruthenium dioxide (RuO ₂ ) electrode layer 303, a plurality of glucose enzyme films 304, and a patterned reference electrode. Layer 305, a patterned wire layer 306, and a patterned insulating layer 307.

It should be noted that the substrate 301 of the present embodiment is a flexible substrate (for example, a plastic (PET) substrate), and the ruthenium dioxide (RuO ₂ ) electrode layer 303 can be deposited by a radio frequency sputtering (RF sputtering) process. Above the substrate 301. In addition, the wire layer 306 is formed over the ceria electrode layer 303 and includes a plurality of wires, and the reference electrode layer 305 is also formed over the ceria electrode layer 303 and includes a plurality of rectangular electrodes, wherein the rectangular electrodes and the wires are mutually Electrical connection. In this embodiment, the material of the wire layer 306 and the reference electrode layer 305 includes silver paste or other conductive colloid, and the wire layer 306 and the reference electrode layer 305 can be simultaneously formed on the ceria electrode by screen printing technology. Above layer 303. The insulating layer 307 covers the position other than the wiring layer 306 on the ceria electrode layer 303 and the reference electrode layer 305, and exposes a plurality of regions of the ceria electrode layer 303 (as shown in FIG. 5 to the wire layer 306). a plurality of square patterns). In the present embodiment, the material of the insulating layer 307 includes an epoxy resin or other insulating colloid, and can be formed over the cerium oxide electrode layer 303 by a screen printing technique.

In addition, the plurality of exposed regions of the foregoing cerium oxide electrode layer 303 Above the domain, a plurality of circular glucose enzyme films 304 (such as the plurality of circular patterns shown in FIG. 5) are disposed, and a plurality of wires of the wire layer 306 are electrically connected. In the present embodiment, the glucose enzyme film 304 is fixed on the cerium oxide electrode layer 303 by using a perfluorosulfonic acid polymer (Nafion) particle embedding method, whereby the glucose enzyme film 304 can be used as a sensing electrode and used for detecting The glucose concentration in the solution to be tested, and the wire layer 306 can transmit a plurality of sensing signals generated by the glucose enzyme film 304 to an external signal analysis system (not shown) for storage, analysis or display. In addition, the reference electrode layer 305 can be used to provide a ground voltage level, and the insulating layer 307 can avoid interference of ions in the solution other than the sensing functional region (corresponding to the positions of the sensing electrodes and the reference electrode layer). It should be understood that the sensing functional area of the biomedical sensing unit 300 corresponds to the detection area 209 of the microfluidic unit 200 (Figs. 3A and 3B).

In summary, the present invention provides a microfluidic medical sensory device The plurality of characteristic values (for example, output voltage) of the solution to be tested can be measured under dynamic conditions, thereby further knowing the glucose concentration of the solution to be tested. Fig. 6 is a graph showing the measurement of the glucose solution concentration of 100 mg/dL to 500 mg/dL by the microfluidic biosensor sensing system according to an embodiment of the present invention, wherein the flow rate of the injection pump is 15 μl per minute. It can be seen from the results that the sensitivity (Sensitivity) and linearity of the microfluidic biosensor sensing system of the present embodiment are 0.256 mV/(mg/dL) and 0.998, respectively.

In addition, the embodiment of the present invention prepares a microflow through screen printing technology. And the microfluidic unit is combined with the flexible biomedical sensing unit to complete the preparation of the microfluid biomedical sensing device in the microfluid biomedical sensing system, thereby effectively reducing the manufacturing cost and having The advantage of large quantitative production.

Although the present invention has been disclosed above in the foregoing embodiments, it is not intended to limit the invention. Those skilled in the art having the ordinary skill in the art can make some modifications and refinements without departing from the spirit and scope of the invention. Therefore, the scope of the invention is defined by the scope of the appended claims.

10‧‧‧Microfluid biomedical sensing device

102‧‧‧First joint

104‧‧‧Second joint

106‧‧‧Fixed plate

200‧‧‧Microfluidic unit

300‧‧‧ Biomedical Sensing Unit

Claims (10)

A microfluid biomedical sensing device comprising: a microfluidic unit having a detection area; and a biomedical sensing unit coupled with the microfluidic unit, wherein the biomedical sensing unit comprises: a substrate; a dioxide a germanium electrode layer is formed on the substrate; an insulating layer is formed on the germanium dioxide electrode layer and exposes a region of the germanium dioxide electrode layer; a glucose enzyme film is fixed on the germanium dioxide electrode layer In the region, the position of the glucose enzyme film corresponds to the detection region; and a wire layer is formed on the cerium oxide electrode layer and electrically connected to the glucose saccharide film; wherein, when the solution to be tested flows through the When the region is detected, the glucose enzyme film is used to measure the glucose concentration of the solution to be tested under dynamic conditions. The microfluidic biomedical sensing device of claim 1, wherein the substrate is a flexible substrate. The microfluidic biomedical sensing device of claim 1 or 2, wherein the ceria electrode layer is deposited on the substrate by a radio frequency sputtering process. The microfluidic biomedical sensing device of claim 1, wherein the material of the insulating layer comprises an epoxy resin, and the insulating layer is formed on the ceria electrode layer by a screen printing technique. The microfluidic biomedical sensing device according to claim 1, wherein the glucose enzyme film is fixed on the ceria electrode layer by perfluorosulfonic acid polymer microparticle embedding. The microfluidic biomedical sensing device of claim 1, wherein the material of the wire layer comprises silver paste, and the wire layer is formed on the ceria electrode layer by a screen printing technique. The microfluidic biomedical sensing device of claim 1, wherein the master mold of the microfluidic unit is prepared by screen printing technology. The microfluidic biomedical sensing device of claim 1, wherein the material of the microfluidic unit comprises dimethyloxane. The microfluidic biomedical sensing device of claim 1, wherein the biomedical sensing unit further comprises a reference electrode layer formed on the ceria electrode layer and electrically connected to the wire layer, The reference electrode layer is used to provide a ground voltage level. The microfluidic biomedical sensing device of claim 9, wherein the material of the reference electrode layer comprises silver paste, and the reference electrode layer is formed on the ceria electrode layer by a screen printing technique.