TWI662282B - Vibrating system for measuring blood coagulation reaction time - Google Patents

Abstract

The invention relates to a system for measuring the blood coagulation reaction time by vibration, comprising: a vibration device capable of vibrating up and down at a predetermined preset frequency and a preset amplitude; a sensor with a connecting portion and the vibration device The connection is fixed; wherein the sensor follows the vibration device to vibrate up and down in a sample to be tested to generate a raw data; the invention vibrates in a small amount of the sample to be tested through the sensor, and can combine a calculation and analysis function The external device converts the raw data into a fast response time to a coagulation reaction time to reduce the total amount of samples to be tested, and also provides accurate data.

Description

Vibrating system for measuring blood coagulation reaction time

A system for measuring the time of a blood coagulation reaction, and more particularly to a system for measuring the blood coagulation reaction time by using a microcantilever beam to vibrate in the blood to be tested.

Human coagulation mechanisms can be divided into extrinsic pathways and intrinsic pathways. When the human body suffers from external forces and causes visceral or skin injury, the exogenous and endogenous routes will interweave and work together, allowing the body to perform a restorative coagulation reaction procedure. Whether it is an exogenous pathway or an indoor source pathway, in addition to blood involvement in the coagulation reaction, various blood coagulation factors, such as fibrinogen, fibrin, and platelets, will react in the same way to make the blood as soon as possible. Coagulation, avoiding a lot of bleeding, causing shock and even life-threatening.

In general, normal human blood contains a large number of functional clotting factors, which can rapidly clotting and reduce the amount of bleeding during bleeding. However, elderly people or seriously ill patients with blood diseases may have blood clotting factors and only coagulation. The factor is also unable to coagulate normally due to insufficiency or aging, resulting in ineffective and rapid coagulation of the patient during bleeding, which may have problems with excessive or excessive blood loss.

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

Therefore, checking the blood coagulation reaction time of human blood, or testing the blood coagulation reaction time of the drug administration test, becomes an important data of the degree of human disease, and an important consideration factor for drug performance and side effect testing.

The conventional method for detecting the clotting time is to store the blood to be tested in a container and continuously stir the blood to be tested, and measure the resistance change during stirring to obtain a blood coagulation reaction time, but the machine for completing the measurement method is quite large and It is cumbersome, difficult to measure and carry, and requires more blood to be measured as a measurement sample to obtain effective blood coagulation reaction time data. It takes about 3 ml of blood to measure once, which is undoubtedly a big physical strength for seriously ill patients. burden.

In order to reduce the blood to be measured for measuring the blood coagulation reaction time, the present invention proposes a system for vibrating the blood coagulation reaction time, by measuring the blood coagulation reaction time of the blood to be tested by vibrating the microcantilever, and measuring the blood coagulation with a small amount of blood to be tested. Reaction time.

In order to achieve the above object, a vibrating system for measuring a blood coagulation reaction time comprises: a vibrating device capable of vibrating up and down at a predetermined preset frequency and a predetermined amplitude; a sensor connected to a portion The vibration device is fixedly connected. The sensor has a micro cantilever beam and a sensing unit. The micro cantilever beam is disposed on a contact surface of the sensing unit, wherein a normal of the contact surface is perpendicular to a vibration direction of the vibration device. The micro cantilever beam is electrically connected to the sensing unit; wherein the sensor is immersed in a sample to be tested while performing measurement, and the sensor can follow the vibration device to vibrate up and down in the sample to be tested Generate raw data.

Since the microcantilever is about micrometer-scale, it can vibrate in a small amount of blood to be tested, and the original data of the amplitude and time of the microcantilever is obtained, and the original data is converted into amplitude and frequency by fast Fourier through an external device. The relationship to obtain the blood coagulation reaction time of the blood to be tested, to achieve the purpose of reducing the blood to be tested. At the same time, the present invention uses a relatively small and flexible sensor. If it travels to an underdeveloped country such as Africa or a country where transportation and resources are not developed, it can provide higher convenience in carrying and using, and can even increase the number of carriers. To improve the efficiency of measurement.

10‧‧‧Vibration device

20‧‧‧ sensor

21‧‧‧Connecting Department

22‧‧‧Sensor unit

30‧‧‧Microcantilever

31‧‧‧First Nitrogen Oxide Film

32‧‧‧Polysilicon film

33‧‧‧2O2 film

34‧‧‧Second Nitrogen Oxide Film

35‧‧‧Gold chrome alloy film

50‧‧‧External devices

60‧‧‧Test container

61‧‧‧samples to be tested

LV1‧‧‧ normal blood

LV2‧‧‧ disease blood

LV3‧‧‧ seriously ill blood

A1‧‧‧ first curve

A2‧‧‧second curve

A3‧‧‧ third curve

A‧‧‧ arrows

Figure 1: Schematic representation of the invention.

Figure 2 is a cross-sectional view of a microcantilever of the present invention.

Fig. 3A is a graph showing the amplitude-time curve of the sample to be tested according to the present invention.

Fig. 3B: The amplitude-frequency curve of the sample to be tested is measured by the present invention.

Figure 4A is a graph showing amplitude versus time for three blood samples of the present invention.

Figure 4B is a graph of data for three blood samples of the present invention.

Fig. 5 is a bar graph showing the maximum amplitude value and blood coagulation ratio of the three blood types of the present invention.

Referring to FIG. 1, the system for vibrating the blood coagulation reaction time of the present invention comprises: a vibrating device 10 and a sensor 20.

The vibrating device 10 can periodically vibrate at a predetermined frequency and a predetermined amplitude, wherein the vibrating device 10 can preset the preset frequency and the preset amplitude before testing, in a preferred embodiment of the present invention. The preset frequency is 10 Hz, and the predetermined amplitude is 40 micrometers (μm), so that the vibration device 10 can vibrate up and down with a sine wave, as indicated by an arrow A; 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 vibration 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 beam 30, and a wireless transmission circuit that can wirelessly transmit the measurement information of the micro cantilever beam 30 to an external device 50, wherein the micro cantilever beam 30 A contact surface of the measuring unit 22 is provided. The sensing unit 22 can be a piezoresistive microcantilever sensing chip; the external device 50 is a computer, instrument or tablet with a computational analysis function.

Referring to FIG. 2, the micro cantilever beam 30 is a composite measuring device composed of a plurality of materials. In this embodiment, the structure of the micro cantilever beam 30 is sequentially from the top layer to the bottom layer to be a plasma chemistry. a first nitrogen oxide thin film 31 (Si _x N _y ) formed by vapor deposition (PECVD) having a thickness of about 250 nm and a polysilicon film 32 (Polysilicon) formed by low pressure chemical vapor deposition (LPCVD). A ceria film 33 (SiO ₂ ) having a thickness of about 150 nm and formed by plasma chemical vapor deposition (PECVD) having a thickness of about 400 nm and a low pressure chemical vapor deposition (LPCVD) process. a second nitrogen oxide film 34 (Si _x N _y ) having a thickness of about 215 nm; a partial region between the first nitrogen oxide film 31 and the ceria film 33 is filled with an electron evaporation method ( E-beam deposition) deposited gold-chromium alloy film 35 (Au/Cr), 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 microcantilever 30 are placed in a test container 60 containing the sample 61 to be tested, and the sensor 20 and the microcantilever 30 are completely immersed in the sample to be tested. In 61, the experimental data uses a 60% aqueous glycerin solution as a sample of the sample 61 to be tested. When the blood coagulation reaction time of the patient's blood is actually measured, the amount of the patient's blood as the sample 61 to be tested is about 0.06 ml (m1). Referring to FIG. 1 , when the vibrating device 10 performs periodic vibration, the vibrating device 10 synchronously drives the sensor 20 and the micro cantilever 30 to periodically vibrate through the connecting portion 21, so that the micro cantilever beam 30 is to be tested. The sample 61 is vibrated up and down; when the microcantilever 30 vibrates in the sample to be tested 61, it is delayed by the resistance of the sample to be tested 61, and the microcantilever 30 is bent by the stress of the sample to be tested 61 to be bent up and down. Raw data is generated, which is the amplitude versus time of the micro cantilever beam 30 when the sample to be tested is vibrated. The degree of bending of the micro cantilever beam 30 is shown in FIG. 3A, and FIG. 3A is fixed. The microcantilever 30 is subjected to the amplitude change of the stress of the sample to be tested during the time, and FIG. 3A is the original data, wherein the vertical axis represents the amplitude, the horizontal axis represents the time, and the amplitude greater than zero represents that the microcantilever 30 is bent upward. An amplitude of less than zero indicates that the microcantilever 30 is bent downward.

Referring to FIG. 3B, after receiving the raw data measured by the micro cantilever 30, the sensor 20 wirelessly transmits the original data to the external device 50, and the external device 50 can receive the original data and quickly The Fourier transform (FFT) is converted into amplitude versus frequency and continuously calculates the average of the amplitude versus time. For example, if the amplitude in the first second is 100 Ω and the amplitude in the second second is 100 Ω, the average of the amplitude in the first two seconds. The value is 100 Ω; if the amplitude in the third second is 200 Ω, the average amplitude of the first three seconds is (100+200)/2=150 Ω, which is calculated sequentially. In the process of continuous calculation, 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 blood coagulation reaction time, for example, the average amplitude of the first three seconds is 150 Ω, and the amplitude of the fourth second is At 900 Ω, the clotting reaction time is four seconds. Then, a sampling amplitude corresponding to one 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 0.5 Ω.

4A and FIG. 4B are experimental data diagrams of vibration testing of three blood samples by the microcantilever 30. The vibration device 10 is driven by an operating condition with a preset frequency of 10 Hz and a preset amplitude of 40 micrometers. The cantilever beam 30 generates vibration. The three blood samples include normal blood LV1 in healthy adults, blood LV2 in diseases with general diseases, and LV3 in severe disease or severe disease in the elderly. The three blood samples respectively obtain a first curve A1 and a first in FIG. 4A. The second curve A2 and the third curve A3, wherein the first curve A1 corresponds to the normal blood LV1, the second curve A2 corresponds to the disease blood LV2, and the third curve A3 corresponds to the seriously ill blood LV3. After the first curve A1, the second curve A2 and the third curve A3 are fast Fourier transformed, a blood coagulation reaction time (PT) as shown in FIG. 4B can be obtained, wherein the coagulation reaction time is the first five The average of the second signal is taken as one unit, and the time required to reach six units is defined as the blood coagulation reaction time. From Fig. 4B, it can be seen that the blood coagulation reaction time of the normal blood LV1 is the shortest, only 12.1 seconds, followed by the disease blood LV2, which takes 27.1 seconds, and the blood coagulation reaction time of the severe disease blood LV3 is the longest, requiring 38.1 seconds.

Referring to FIG. 5, the maximum amplitude value measured by the normal blood LV1, the disease blood LV2, and the severe blood LV3 through the microcantilever 30 is compared and compared, as shown in FIG. 5, the normal lotion can be obtained. The maximum amplitude value of LV1 is the highest, followed by the disease blood LV2, and the lowest is the severe disease blood LV3; the other parameter is the blood coagulation ratio, and the blood coagulation ratio is the percentage of colloid weight precipitated after the blood coagulation is completed. Similarly, the normal blood LV1 has the highest blood coagulation ratio. It means that the blood coagulation factors (such as platelets, tissue thromboplastin, fibrinogen) in the normal blood LV1 function normally, and the content is also high. The blood LV3 has the lowest blood coagulation ratio, which represents the severe disease blood LV3. The clotting factor is the least and the function is not good.

The invention measures the relationship between the amplitude and the time obtained by measuring the blood to be tested by vibrating the microcantilever, and can measure the blood coagulation reaction time by using a small amount of the blood sample to be tested, thereby reducing the cost of the blood to be tested and reducing the physical burden of the patient.

Claims (5)

A vibrating system for measuring a blood coagulation reaction time, comprising: a vibrating device capable of vibrating up and down at a predetermined preset frequency and a predetermined amplitude; a sensor connected to the vibrating device by a connecting portion, The sensor has a micro cantilever beam and a sensing unit. The micro cantilever beam is disposed on a contact surface of the sensing unit, wherein a normal of the contact surface is perpendicular to a vibration direction of the vibration device, and the micro cantilever beam is The sensing unit is electrically connected; wherein the sensor is immersed in a sample to be tested while performing measurement, and the sensor can follow the vibration device to vibrate up and down in the sample to be tested to generate raw data. A system for vibrating the blood coagulation reaction time according to claim 1, the sensor comprising a wireless transmission circuit, the sensor transmitting the raw data to an external device through the wireless transmission circuit, the external device utilizing a fast Fourier The raw data is converted into an amplitude versus frequency relationship and the average of the amplitude versus time is continuously calculated. If the amplitude of the blood coagulation reaction time is as described in claim 2, if the amplitude at a certain time point is greater than or equal to six times the average value, the time point is the blood coagulation reaction time. The system for vibrating the blood coagulation reaction time according to claim 3, wherein the micro cantilever is a composite measuring device composed of a plurality of materials. The system for vibrating the blood coagulation reaction time according to claim 4, wherein the structure of the microcantilever is from a top layer to a bottom layer, a first nitrogen oxide film formed by plasma chemical vapor deposition, and a low pressure chemical a polycrystalline germanium film formed by vapor deposition, a germanium dioxide film formed by plasma chemical vapor deposition, and a second nitrogen oxide film formed by low pressure chemical vapor deposition, in the first nitrogen oxide film A partial region between the ruthenium dioxide films is filled with a gold chrome alloy film deposited by electron evaporation deposition.