TW202016544A - Vibratory Prothrombin Time measurement system - Google Patents

Abstract

This invention provides a vibratory Prothrombin Time (PT) measurement system, including a vibration device and a sensor; the vibration device is capable of vibrating up and down at a preset frequency and vibration amplitude; and the sensor is connected and fixed with the vibration device by a connecting part, wherein the sensor vibrates up and down with the vibration device in a to-be-measured sample to generate the original data. According to the vibratory measurement system of the present invention, the sensor vibrates in a small number of to-be-measured samples, and is combined with an external device with a computational analysis function, in this way, the original data may be subjected to Fast Fourier Transform (FFT) to obtain the Prothrombin Time (PT), so that the total number of the to-be-measured samples is reduced, and precise data can also be provided.

Description

Vibration system for measuring coagulation reaction time

A system for measuring coagulation reaction time, especially a system using micro-cantilever to vibrate in blood to be measured to measure coagulation reaction time.

The coagulation mechanism of the human body can be divided into extrinsic pathway and intrinsic pathway. When the human body is exposed to external forces and causes internal organs or skin injuries to bleed, external and internal pathways will be intertwined in complex operations to allow the body to undergo a restorative coagulation reaction procedure. Regardless of whether it is an exogenous route or an indoor source route, in addition to the blood participating in the coagulation reaction, various blood coagulation factors, such as fibrinogen, fibrin, and platelets, will also react to make the blood as soon as possible Coagulation, to avoid massive bleeding leading to shock or even life-threatening.

In general, the blood of normal people contains a large number of functional coagulation factors, which can quickly coagulate during bleeding and reduce the amount of bleeding. However, the elderly or severely ill patients with blood diseases may lack coagulation factors in their blood, and the only remaining blood coagulation factors Factors are also unable to coagulate normally due to insufficiency or aging, resulting in patients failing to coagulate effectively and quickly when hemorrhaging, and there may be a problem of excessive or excessive blood loss.

In addition, the drugs taken by patients with some diseases may inhibit the function of coagulation factors, so that these patients have no blood diseases, but due to the influence of drugs, they cannot effectively coagulate blood during bleeding, and may also cause a lot of bleeding problems. .

Therefore, checking the coagulation reaction time of the human blood, or conducting the coagulation reaction time test of the drug administration experiment, has become an important data of the human disease degree, and an important consideration factor of the drug performance and side effect test.

The conventional method for detecting the coagulation time is to hold the blood to be tested in a container and continue to stir the blood to be tested, measuring the change in resistance during stirring to obtain the coagulation reaction time, but the machine to complete this measurement method is quite large and It is bulky, difficult to measure and carry, and requires more blood to be tested as a measurement sample to obtain effective coagulation reaction time data. It takes about 3 milliliters of blood to measure one time, which is undoubtedly a major physical problem for seriously ill patients burden.

In order to reduce the blood to be tested for measuring the blood coagulation reaction time, the present invention proposes a system for measuring the blood coagulation reaction time by vibrating. By vibrating the micro-cantilever to measure the blood coagulation reaction time, the blood coagulation can be measured with a small amount of blood to be tested Reaction time.

In order to achieve the above object, a system for measuring the coagulation reaction time by vibration according to the present invention includes: a vibration device capable of vibrating up and down at a preset frequency and a preset amplitude; a sensor with a connecting part and The vibration device is connected and fixed; wherein, the sensor is immersed in a sample to be tested during the measurement, and the sensor can follow the vibration device to vibrate up and down in the sample to generate raw data.

Because the micro-cantilever is about the micrometer scale, it can vibrate in a small amount of blood to be measured, and the original data of the amplitude and time relationship of the micro-cantilever is obtained, and the raw data is converted into amplitude and frequency by fast Fourier through an external device To obtain the coagulation reaction time of the blood to be tested, so as to reduce the blood to be tested. At the same time, the present invention uses a relatively small and flexible sensor. If you travel to areas such as Africa and other backward countries or rural areas and have poor transportation and resources, it can provide greater convenience in carrying and using, and even increase the number of carrying. To improve the efficiency of measurement.

Referring to FIG. 1, the system for measuring the coagulation reaction time by vibration according to the present invention includes: a vibration device 10 and a sensor 20.

The vibration device 10 can periodically vibrate at a preset frequency and a preset amplitude, wherein the vibration device 10 can preset the preset frequency and the preset amplitude before the test, in a preferred embodiment of the present invention In this case, the preset frequency is 10 hertz (Hz), and the preset amplitude is 40 micrometers (μm), so that the vibration device 10 can vibrate up and down with a sine wave as shown by arrow A; in the following In the description, the actual measurement process of the present invention will take the above data as an example.

The sensor 20 is connected to the vibrating device 10 through a connecting portion 21, wherein the connecting portion 21 can be a linkage rod. The sensor 20 includes a sensing unit 22, a micro-cantilever 30 and a wireless transmission circuit, which can wirelessly transmit the measurement information of the micro-cantilever 30 to an external device 50, wherein the micro-cantilever 30 It is set on a contact surface of the measuring unit 22. The sensing unit 22 can be a piezoresistive microcantilever sensing chip; the external device 50 is a computer, instrument or tablet with calculation and analysis functions.

Please further refer to FIG. 2, the micro-cantilever 30 is a composite measuring device formed by combining a plurality of materials. In this embodiment, the structure of the micro-cantilever 30 is a plasma chemistry from the top layer to the bottom layer in order. The first nitrogen oxide film 31 (Si _x N _y ) formed by vapor deposition (PECVD) has a thickness of about 250 nm, and a polysilicon film 32 (Polysilicon) formed by low pressure chemical vapor deposition (LPCVD), which A thickness of about 150 nm, a silicon dioxide thin film 33 (SiO ₂ ) formed by plasma chemical vapor deposition (PECVD), a thickness of about 400 nm, and a low pressure chemical vapor deposition (LPCVD) The second nitrogen oxide film 34 (Si _x N _y ) has a thickness of about 215 nm; a partial area between the first nitrogen oxide film 31 and the silicon dioxide film 33 is filled with an electron vapor beam deposition method ( The gold-chromium alloy film 35 (Au/Cr) deposited by E-beam deposition, wherein the thickness of the gold metal is about 150 nm, and the thickness of the chromium metal is about 15 nm.

During the experimental measurement, the sensor 20 and the micro-cantilever 30 are placed in a test container 60 containing the sample 61 to be tested, and the sensor 20 and the micro-cantilever 30 are completely immersed in the sample to be tested In 61, in this experimental data, a 60% glycerin aqueous solution is used as the sample of the test sample 61. When actually measuring the coagulation reaction time of the patient's blood, the amount of the patient's blood as the test sample 61 is about 0.06 milliliters (ml). Please refer to FIG. 1, when the vibration device 10 performs periodic vibration, the vibration device 10 synchronously drives the sensor 20 and the micro-cantilever beam 30 to vibrate periodically through the connecting portion 21, so that the micro-cantilever beam 30 is under test The sample 61 vibrates up and down; when the micro-cantilever 30 vibrates in the sample 61 to be tested due to the resistance of the sample 61 to be tested, the micro-cantilever 30 is bent up and down by the stress of the sample 61 to be tested, Raw data is generated, which is the relationship between the amplitude and time of the micro-cantilever beam 30 when the sample to be tested vibrates. The degree of bending of the micro-cantilever beam 30 up and down is shown in FIG. 3A. The amplitude of the micro-cantilever 30 after being stressed by the sample to be measured within the time, and Figure 3A is the original data, where the vertical axis represents the amplitude, the horizontal axis represents the time, and the amplitude greater than zero represents the micro-cantilever 30 bending upward, If the amplitude is less than zero, the micro-cantilever 30 is bent downward.

Please further refer to FIG. 3B. After the sensor 20 receives the raw data measured by the micro-cantilever 30, the raw data is wirelessly transmitted to the external device 50. The external device 50 can receive the raw data and quickly The Fourier transform (FFT) is converted into the relationship between amplitude and frequency, and the average value of amplitude versus time is continuously calculated. For example, if the amplitude in the first second is 100Ω and the amplitude in the second second is 100Ω, then the average amplitude of the first two seconds The value is 100Ω; and if the amplitude in the third second is 200Ω, the average value of the amplitude in the first three seconds is (100+200)/2=150Ω, calculated in order. In the continuous calculation process, if the amplitude at a certain time point is greater than or equal to six times the average value, then this time point is the coagulation reaction time, for example, the average amplitude of the first three seconds is 150Ω, and the amplitude of the fourth second is 900 Ω, the coagulation reaction time is four seconds. Next, a sampling amplitude corresponding to a sampling frequency is taken as a sample for comparison. In this embodiment, the sampling frequency is 10 Hz, and the corresponding sampling amplitude is about 0.5Ω.

Please refer to FIGS. 4A and 4B, which are experimental data graphs of the vibration test of three blood samples using the micro-cantilever 30. The vibration device 10 drives the micro-device with the operating condition of a preset frequency of 10 Hz and a preset amplitude of 40 μm. The cantilever 30 generates vibration. The three blood samples include normal blood LV1 for measuring healthy adults, disease blood LV2 for general diseases, and serious blood LV3 for serious or elderly patients. The three blood samples respectively obtain a first curve A1 and a first curve in FIG. 4A. A second curve A2 and a third curve A3, wherein the first curve A1 corresponds to normal blood LV1, the second curve A2 corresponds to disease blood LV2, and the third curve A3 corresponds to severe disease blood LV3. After fast Fourier transforming the first curve A1, the second curve A2 and the third curve A3, the coagulation reaction time (Prothrombin Time, PT) shown in FIG. 4B can be obtained, wherein the coagulation reaction time is the top five The average of the second signal is a unit, and the time required to reach six units is defined as the coagulation reaction time. It can be seen from FIG. 4B that the normal blood LV1 has the shortest coagulation reaction time, only 12.1 seconds, followed by the disease blood LV2, which requires 27.1 seconds, and the severely ill blood LV3 has the longest coagulation reaction time, which requires 38.1 seconds.

Please refer to FIG. 5 and compare the maximum amplitude values of the normal blood LV1, disease blood LV2, and severe disease blood LV3 measured by the micro-cantilever 30, as shown in FIG. 5, the maximum amplitude value of the normal lotion LV1 can be obtained The highest, followed by the disease blood LV2, the lowest is the seriously ill blood LV3; another parameter is the coagulation ratio, the coagulation ratio is the weight percentage of colloids precipitated after the coagulation is completed. Similarly, the normal blood LV1 has the highest coagulation ratio, which represents the normal blood The functions of various coagulation factors (such as platelets, tissue thromboplastin, fibrinogen) in LV1 are normal, and the content is also large. The coagulation rate of LV3 in the seriously ill blood is the lowest, which means that the content of coagulation factors in the LV3 in the seriously ill blood is the least. , The function is not good.

The invention uses the vibration micro-cantilever to measure the relationship between the amplitude of the blood to be tested and the time, and can use a small amount of blood samples to measure the coagulation reaction time, thereby reducing the cost of obtaining the blood to be tested and reducing the patient's physical burden.

10: Vibration device 20: Sensor 21: Connection 22: Sensing unit 30: micro cantilever 31: First nitrogen oxide film 32: Polycrystalline silicon film 33: Silicon dioxide film 34: Second nitrogen oxide film 35: Gold-chromium alloy film 50: external device 60: Test container 61: sample to be tested LV1: normal blood LV2: disease blood LV3: Severely ill blood A1: First curve A2: Second curve A3: Third curve A: Arrow

Figure 1: Schematic diagram of the present invention. Figure 2: Cross-sectional view of the micro-cantilever beam of the present invention. Figure 3A: The present invention measures the amplitude-time curve of the sample to be measured. Figure 3B: The present invention measures the amplitude-frequency curve of the sample to be measured. Figure 4A: Amplitude-time curves of three types of blood of the present invention. Figure 4B: Data charts of three types of blood of the present invention. Figure 5: A bar graph of the maximum amplitude value and coagulation ratio of the three types of blood of the present invention.

10: Vibration device

20: Sensor

21: Connection

22: Sensing unit

30: micro cantilever

50: external device

60: Test container

61: sample to be tested

A: Arrow

Claims (6)

A vibratory system for measuring coagulation reaction time includes: a vibrating device capable of vibrating up and down at a preset frequency and a preset amplitude; a sensor connected and fixed to the vibrating device by a connecting part; Wherein, the sensor is immersed in a sample to be tested during measurement, and the sensor can follow the vibration device to vibrate up and down in the sample to generate raw data. The vibration-type system for measuring coagulation reaction time according to claim 1, the sensor has a micro-cantilever and a sensing unit, the micro-cantilever is disposed on a contact surface of the sensing unit, wherein The normal is perpendicular to the vibration direction of the vibration device, and the micro-cantilever beam is electrically connected to the sensing unit. The system for measuring the coagulation reaction time by vibration according to claim 2, the sensor includes a wireless transmission circuit, the sensor transmits the raw data to an external device through the wireless transmission circuit, and the external device uses fast Fourier Convert the raw data into the relationship between amplitude and frequency, and continue to calculate the average amplitude over time. According to the system for measuring the coagulation reaction time by vibration according to claim 3, if the amplitude of a certain time point is greater than or equal to six times the average value, then this time point is the coagulation reaction time. According to the system for measuring the coagulation reaction time by vibration according to claim 4, the micro-cantilever beam is a composite measuring device formed by combining multiple materials. As described in claim 5, a system for measuring the coagulation reaction time by vibration, the structure of the micro-cantilever from the top layer to the bottom layer is a first nitrogen oxide film formed by plasma chemical vapor deposition method, a low-pressure chemical A polysilicon film formed by vapor deposition, a silicon dioxide film formed by plasma chemical vapor deposition, and a second nitrogen oxide film formed by low-pressure chemical vapor deposition. Part of the area between the silicon dioxide films is filled with a gold-chromium alloy film deposited by electron vapor beam deposition.

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