TWI656345B - Prostate cancer detection module and its operation method - Google Patents

Abstract

The invention relates to a prostate cancer detecting module and a method for operating the same, which utilizes nanometer nickel oxide as a detecting film. When nickel oxide is contacted with different concentrations of hydrogen peroxide, the surface potential is changed, thereby generating a voltage. Displacement, it is possible to determine the concentration of hydrogen peroxide by detecting changes in voltage; since the sample to be tested is urine, the creatinine in the urine is oxidized to form hydrogen peroxide, which is permeable to hydrogen peroxide and oxidation. The reaction of nickel, inferring the content of creatinine in the sample, thereby assessing the possibility of having prostate cancer.

Description

Prostate cancer detection module and its operation method

The invention relates to a detection module and a method for operating the same, in particular to a detection module capable of rapidly screening prostate cancer and a method for operating the same.

Prostate cancer is a malignant tumor from the prostate. If a gene mutation in a cell causes the proliferation to be out of control, it becomes cancer. In addition to expanding the volume or invading adjacent organs, malignant cells may also migrate to other parts of the body, especially bones and lymph nodes. Prostate cancer can cause pain, dysuria, and erectile dysfunction.

Prostate cancer is mostly found in routine health checks or blood screening tests. There are still some doubts about the accuracy and efficacy of prostate specific antigen (PSA), but it is still a widely used prostate cancer screening tool. When a case of suspected prostate cancer is usually found, a biopsy is performed to establish a diagnosis. Other further examinations such as X-rays, computed tomography and bone scans help to understand whether prostate cancer has spread.

However, biopsy is an invasive method after all, and this method is not immediacy. Therefore, in order to improve the efficiency of screening prostate cancer, other methods should be sought for assistance.

In the prior art, scientists have discovered that sarcosine can be used as a biological indicator for detecting prostate cancer. However, how to quickly and conveniently find the content of sarcosine from the sample remains to be developed; the present invention That is, in this technical background, a non-intrusive fast and convenient detection method has been developed.

The main object of the present invention is to provide a prostate cancer detecting module and a method for operating the same, which utilizes a sensing film material (such as nickel oxide) to contact with different concentrations of hydrogen peroxide, thereby changing the surface potential of the sensing film. The principle, in turn, can determine the concentration of hydrogen peroxide by detecting changes in voltage, and then use the concentration of hydrogen peroxide to determine the content of creatinine in the sample.

A further object of the present invention is to provide a prostate cancer detecting module and a method for operating the same, wherein the sample detected is urine or serum, and if the urine or serum contains sarcosine, it will be oxidized. Hydrogen peroxide is formed for reaction with nickel oxide.

Another object of the present invention is to provide a prostate cancer detecting module and a method for operating the same, which can make the voltage instantaneously change due to the change of the surface potential of the sensing film as long as the urine or serum in the sample contains a trace amount of sarcosine. Producing a sufficient amount of voltage change to be detected, so it is extremely sensitive to sarcosine, and the level of creatinine in urine or serum is one of the factors for judging prostate cancer, so the present invention can be used as a prostate cancer test Use.

A further object of the present invention is to provide a prostate cancer detection module and a method for operating the same, which has a simple structure and can be used as a popular commercial detection wafer, which facilitates detection of prostate cancer and can immediately know the result.

Therefore, the present invention discloses a prostate cancer detecting module, the structure comprising: a conductive substrate; a p-type germanium semiconductor layer disposed on the conductive substrate; and a germanium oxide layer disposed on the p-type germanium semiconductor layer a sensing film disposed on the yttrium oxide layer for carrying the same; and a reference electrode disposed above the sensing film for contacting the sample; wherein the material of the sensing film is selected From nickel oxide, cerium oxide, cerium oxide, platinum, tungsten oxide, cerium, lanthanum, cerium, palladium, chromium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, zirconium oxide, tin oxide, antimony oxide , cerium oxide, cerium oxide, zinc oxide, cerium oxide, cerium oxide, molybdenum disulfide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, indium gallium zinc oxide, indium oxynitride, cerium oxide One of a group consisting of aluminum, titanium, and graphite oxide.

The method for operating the prostate cancer detecting module includes the steps of: using a reference electrode to approach a sensing film to obtain a first voltage; setting the same between the reference electrode and the sensing film to obtain a second voltage, the sample is urine or serum; and comparing the first voltage and the second voltage to obtain a difference, and using the difference to determine the content of creatinine in the sample.

For a better understanding and understanding of the features and advantages of the present invention, the preferred embodiments and the detailed description are described as follows:

First, referring to FIG. 1 , in a preferred embodiment of the present invention, the prostate cancer detecting module disclosed on the hardware structure comprises: a conductive substrate 1, a p-type germanium semiconductor layer 2, and an oxidation. The germanium layer 3, a sensing film 4, and a reference electrode 5. Wherein, the p-type germanium semiconductor layer 2 is disposed on the conductive substrate 1; the tantalum oxide layer 3 is disposed on the p-type germanium semiconductor layer 2; the sensing film 4 is disposed on the tantalum oxide layer 3; and the reference electrode 5 is Located above the sensing film 4. Wherein, the material of the sensing film is selected from the group consisting of nickel oxide, cerium oxide, cerium oxide, platinum, tungsten oxide, cerium, lanthanum, cerium, palladium, chromium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, and oxidation. Bismuth, zirconia, tin oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, molybdenum disulfide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, oxidation One of a group consisting of indium gallium zinc, indium oxynitride, cerium oxide, aluminum, titanium, and graphite oxide. The material selection of the above sensing film is based on its contact with hydrogen peroxide, which causes a change in surface potential, and based on cost considerations, nickel oxide is a preferred choice; further, bismuth, antimony, aluminum and titanium are in a general preservation environment. It is easy to oxidize by itself and cannot be used. Therefore, although it has the potential as a sensing film, it is necessary to additionally include a procedure for cleaning the surface before use.

In the structure of the above preferred embodiment, the conductive substrate 1 is a copper-plated printed circuit board, which can be used as one electrode end of the reference electrode 5 among the prostate cancer detecting modules. The p-type germanium semiconductor layer 2 and the germanium oxide layer 3 located above the conductive substrate 1 can make the present invention have the characteristics of an electrolyte-insulator-semiconductor sensor, and the preparation method thereof can be referred to a general one. The semiconductor process uses a combination of chemical vapor deposition (CVD), plasma assisted chemical vapor deposition (PECVD), evaporation, electron gun evaporation, and magnetron sputtering to form a stack of different materials. In order to improve electrical conductivity, in a preferred embodiment, the p-type germanium semiconductor layer 2 and the conductive substrate 1 may further comprise an aluminum electrode layer 6. The reference electrode 5 can be selected from silver-silver chloride or other reference electrodes having a fixed potential difference.

In a preferred embodiment of the present invention, nickel oxide is used as the material of the sensing film 4, which does not completely cover the yttrium oxide layer 3 in a thick film manner, but spreads nickel oxide in the form of nano particles. Above the yttrium oxide layer 4, the thickness of the film layer is 1 to 2 nm, preferably 2 nm. In another preferred embodiment, the titanium oxide film may be further formed using the titanium oxide nanoparticles, and is not limited to the formation of the film layer using only the nickel oxide nanoparticles. The titanium oxide film may be disposed under the sensing film 4, or may be mixed with nickel oxide nanoparticles and titanium oxide nanoparticles to form a film layer by sputtering, that is, the titanium oxide film system and the sensing film 4 The mixture is disposed on the ruthenium oxide layer 3. In still another preferred embodiment, the titanium oxide film can be annealed in an oxygen atmosphere at a temperature of 650 ° C after the preparation, and the annealing time is about 30 minutes.

Referring to FIG. 1 , in the operation of the present invention, a liquid sample is dropped on the surface of the sensing film 4, and at least one resin may be further disposed on the yttrium oxide layer 3 in order to avoid excessive flow of excess sample. Block 7, the resin block 7 can be separated from the yttrium oxide layer 3 by a detection space, and the sensing film 4 is located on the surface of the detection space above the yttrium oxide layer 3. The material of the resin block 7 may be SU-8, which is usually a material of a negative photoresist, and after being formed by spin coating in the present invention, it is baked to serve as a resin block 7 for the space for detecting the space.

In addition, the prostate cancer detecting module of the present invention may further comprise an outer casing 8 composed of an epoxy resin, which can protect the structural film layer located inside the outer casing 8 from contamination or oxidation, and prolong the prostate. The life of the cancer detection module.

As previously stated, the structure disclosed herein operates in the form of a liquid sample on the surface of the sensing membrane 4, and the composition of the sample is urine in a preferred embodiment of the invention. It is known that the content of creatinine in urine or serum is closely related to the detection of prostate cancer. Therefore, the present invention uses a chemical reaction to detect changes in CV (Capacitance to Voltage) to determine whether urine or serum contains muscle. Amino acid.

The sample used in the present invention is urine, and if it contains sarcosine, the creatinine reacts with the following reaction formula 1: (Reaction formula 1) The oxidation of sarcosine in the urine produces hydrogen peroxide, which means that if hydrogen peroxide is present in the sample, it means that the urine contains sarcosine, and the higher the concentration of hydrogen peroxide, the muscle The higher the content of amino acids, the more obvious the characterization of prostate cancer. The above oxidation reaction can be carried out by mixing sarcosine oxidase (SOD) as a catalyst in the sample. In order to confirm the presence of hydrogen peroxide and its concentration, the present invention contacts the sample with the sensing film, and when the nickel oxide is contacted with hydrogen peroxide, the following reaction of the reaction formula 2 and the reaction formula 3 is carried out: (Reaction formula 2) NiO + OH ^- → NiOOH (Reaction formula 3) 2NiOOH + H ₂ O ₂ → 2NiO + 2H ₂ O + O ₂ wherein the reaction formula 2 is nickel oxide forming nickel hydroxide (Nickel oxyhydroxide) in an alkaline environment, Then, in the reaction formula 3, it is further reacted with hydrogen peroxide to be reduced to nickel oxide, and the oxidation number of the nickel is changed from +2 to +3, and the potential is changed to transmit the change in the detection voltage of the detection module structure. The level of creatinine in the urine can be judged sensitively and instantaneously to assess whether there is prostate cancer.

Based on the above principles and the disclosure of the hardware architecture, please refer to FIG. 2, in a preferred embodiment of the prostate cancer detecting module of the present invention, the operating method includes the following steps: Step S1: using a reference electrode and a sensing The film is approached to obtain a first voltage; Step S2: setting the same between the reference electrode and the sensing film to obtain a second voltage, the sample is urine or serum; and step S3: comparing the first voltage And the second voltage is used to obtain a difference, and the difference is used to determine the content of creatinine in the sample.

Please refer to FIGS. 3A and 3B, which are in different acid-base environments, respectively, when the nickel oxide film and the titanium oxide film are disposed on the yttrium oxide layer of the structure of the detection module disclosed in the present invention. The performance of its sensitivity. During the test, the thickness of the nickel oxide film and the titanium oxide film were both 2 nm and immersed in a buffer solution having a pH of pH 2 to pH 10. As shown in the figure, different acid-base environments will change the measured reference voltage, which is because the surface potential of the sensing film (ie, the nickel oxide film and the titanium oxide film) changes and can pass through the CV. This change was detected by the measurement method. Referring further to the comparison of Fig. 4, it is understood that the titanium oxide film can have a good acid-base sensitivity of about 50 mV/pH, a linearity of 0.99, a nickel oxide film of 37 mV/pH, and a linear value of 0.98; Cerium oxide is only 34mV/pH with a linear value of 0.79. In the foregoing preferred embodiment, the invention uses a mixture of titanium oxide as a part of the sensing film for the purpose of improving the sensitivity of detection; and using a ruthenium oxide or nickel oxide film as a part of the sensing film, but also having an effect, Titanium is preferred.

Please refer to Figure 5, which shows the results of detection of hydrogen peroxide by different concentrations of hydrogen peroxide in different materials as sensing films. The test is carried out in 10 mM PBS buffer solution, ambient pH. Is 7. As shown by the results, in fact, a nickel oxide film is apparently reacted to hydrogen peroxide, and materials such as titanium oxide and cerium oxide have no activity with hydrogen peroxide. Therefore, the present invention requires the use of nickel oxide as the main material of the sensing film.

In addition, when the invention is applied, a buffer solution may be further added between the sensing film and the reference electrode, and the use of the buffer solution may affect the pH value of the sample to adjust the substrate bias.

In summary, the present invention discloses in detail a prostate cancer detecting module and a method for operating the same, wherein the detected sample is urine or serum, and if the urine or serum contains creatinine associated with prostate cancer, Hydrogen peroxide can be generated by oxidation of sarcosine, and then the surface of the sensing film is changed by the reaction of the sensing film of nickel oxide with hydrogen peroxide, thereby detecting the voltage. The change of the hydrogen peroxide concentration, and then the estimation of the content of sarcosine in the sample, which has the characteristics of fast detection and high sensitivity, is undoubtedly a developmental prostate cancer detection module and its operation method.

The above is only the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention, and the variations, modifications, and modifications of the shapes, structures, features, and spirits described in the claims of the present invention. All should be included in the scope of the patent application of the present invention.

1‧‧‧Electrical substrate

2‧‧‧p-type germanium semiconductor layer

3‧‧‧Oxide layer

4‧‧‧Sensing film

5‧‧‧ reference electrode

6‧‧‧Aluminum electrode layer

7‧‧‧ resin block

8‧‧‧ Shell

S1~S3‧‧‧ steps

1 is a cross-sectional structural view of a prostate cancer detecting module according to a preferred embodiment of the present invention; FIG. 2 is a flow chart showing the steps of a preferred embodiment of the present invention; FIGS. 3A and 3B: It is a voltage test chart of a preferred embodiment of the present invention, which respectively represents a standardized capacitance of a titanium oxide film and a nickel oxide film in different acid-base environments; FIG. 4 is a preferred embodiment of the present invention. Examples of voltage test diagrams for indicating the sensitivity of layers of different materials; and Figure 5 is a voltage test diagram of a preferred embodiment of the invention for indicating the degree of reaction of different materials with hydrogen peroxide.

Claims (9)

A prostate cancer detecting module, the structure comprising: a conductive substrate; a p-type germanium semiconductor layer disposed on the conductive substrate; a germanium oxide layer disposed on the p-type germanium semiconductor layer and a sensing film disposed And a reference electrode disposed above the sensing film for contacting the sample; wherein the material of the sensing film is selected from nickel oxide, oxidized Antimony, antimony oxide, platinum, tungsten oxide, antimony, bismuth, antimony, palladium, chromium oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, zirconium oxide, tin oxide, antimony oxide, antimony oxide, antimony oxide , zinc oxide, antimony oxide, antimony oxide, molybdenum disulfide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, antimony oxide, indium gallium zinc oxide, indium oxynitride, antimony oxide, aluminum, titanium, and oxidation One of the group consisting of graphite; and wherein the urine containing sarcosine is added to the creatinine oxidase to generate hydrogen peroxide to contact the sensing film to cause the metal oxidation number in the sensing film to generate a potential Change, use the reference electrode Touch sensing membrane potential changes in the sense of this as a test. The prostate cancer detecting module according to claim 1, wherein the conductive substrate is a copper-plated printed circuit board. The prostate cancer detecting module according to claim 1, wherein the p-type germanium semiconductor layer and the conductive substrate comprise an aluminum electrode layer. The prostate cancer detecting module according to claim 1, wherein the sensing film has a thickness of 1 to 2 nm. The prostate cancer detecting module according to claim 1, wherein the cerium oxide layer further comprises at least one resin block, wherein the resin block is separated by a detection space, and the sensing film is located in the detection space. On the yttrium oxide layer. The prostate cancer detecting module according to claim 1, further comprising a titanium oxide film disposed under the sensing film. The prostate cancer detecting module according to claim 1, further comprising a titanium oxide film which is mixed with the sensing film and disposed on the cerium oxide layer. A method for operating a prostate cancer detecting module according to claim 1, wherein the method comprises: using a reference electrode to approach a sensing film to obtain a first voltage; setting the same as the reference electrode and Between the sensing films, a second voltage is obtained, the sample is urine; and the first voltage and the second voltage are compared to obtain a difference, and the difference is used to determine the sarcosine in the sample. The material of the sensing film is selected from the group consisting of nickel oxide, cerium oxide, cerium oxide, platinum, tungsten oxide, cerium, lanthanum, cerium, palladium, chromium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide. , yttria, zirconia, tin oxide, cerium oxide, cerium oxide, cerium oxide, zinc oxide, cerium oxide, cerium oxide, molybdenum disulfide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide, cerium oxide One of a group consisting of indium gallium zinc oxide, indium oxynitride, antimony oxide, aluminum, titanium, and graphite oxide. The method for operating a prostate cancer detecting module according to claim 8 wherein the sample comprises a creatine oxidase.