KR102199878B1 - apparatus for ultra-precision high-resolution bio-signal measuring and method using it - Google Patents

Abstract

The present invention relates to an ultra-precise, high-resolution bio-signal measuring apparatus and method having high measurement accuracy and improved energy efficiency,
An ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention,
A sensor unit that measures a biosignal by measuring a change in capacitance between a plurality of electrodes through which electricity is conducted and the plurality of electrodes; And, when the output voltage is greater than or equal to the reference voltage by supplying a variable current to the sensor unit and comparing the output voltage output by the supplied variable current to a reference voltage, driving to fix the variable current and supply it again to the sensor unit. It includes a control unit.

Description

Ultra-precision high-resolution bio-signal measuring and method using it}

The present invention relates to a bio-signal measuring apparatus and a measuring method, and more particularly, to an ultra-precise, high-resolution bio-signal measuring apparatus and method having high measurement accuracy and improved energy efficiency.

Biomarkers for diagnosing diseases such as malignant tumors with a simple method are very important techniques. In order to increase the detection power of these biomarkers, a method of detecting and quantifying proteins such as vascular endothelial growth factor (VEGF), which is related to cancer symptoms, has been recently developed using synthetic receptors.

What is important here is how precisely a very small amount of biomarker is detected, and the currently known method of detecting a biomarker in blood due to a change in resistance between electrodes has a problem in that the amount of resistance change is small, making it difficult to accurately detect.

Korean Patent Registration No. 10-0712027

An object of the present invention is to provide an ultra-precise, high-resolution bio-signal measuring apparatus and method with high measurement accuracy and improved energy efficiency.

An ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention,

A sensor unit measuring a biosignal by measuring a change in capacitance between a plurality of electrodes through which electricity is conducted and the plurality of electrodes; And, when the output voltage is greater than or equal to the reference voltage by supplying a variable current to the sensor unit and comparing the output voltage output by the supplied variable current to a reference voltage, driving to fix the variable current and supply it again to the sensor unit. It includes a control unit.

In the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention, the driving control unit includes: a current variable module for supplying a variable current to the sensor unit, an output voltage output by the variable current supplied to the sensor unit, and the When the output voltage is greater than or equal to the reference voltage by comparing a reference voltage, an optimum current selection module may be included to fix the current supplied from the current variable module.

In the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention, it may further include a precision reading unit for performing precise reading on the output voltage of the sensor unit by the current fixed by the optimum current selection module.

In the ultra-precise high-resolution bio-signal measuring apparatus according to an embodiment of the present invention, the precision reading unit includes an RC-low-pass filter and a delta-sigma analog-digital modulator, and includes a DC band voltage including signal information of an output voltage value. Excluded parts are canceled by the filter, and the output voltage value is converted into a digital value through the delta-sigma analog-digital modulator at the final stage.

In the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention, the sensor unit includes a receptor formed on the surface of the plurality of electrodes, and a change in capacitance between the receptor and the plurality of electrodes according to a reaction with a disease factor in blood The biosignal is measured by measuring, and the receptor is characterized in that it changes the dielectric constant between the plurality of electrodes by reacting with a very small amount of biomarker contained in the blood.

In the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention, the biomarker is VEGF (vascular endothelial growth factor), and the receptor is a peptide.

An ultra-precise, high-resolution bio-signal measurement method according to an embodiment of the present invention,

A first step of supplying a variable current to a sensor unit for measuring a biosignal by measuring a change in capacitance between a plurality of electrodes through which electricity is conducted and the plurality of electrodes; A second step of comparing an output voltage output by the variable current and a reference voltage; A third step of increasing the magnitude of the variable current and repeating the first and second steps when the output voltage is less than the reference voltage as a result of the comparison; A fourth step of setting a supply current to a fixed current value and resupplying it to the sensor unit when the output voltage is greater than or equal to the reference voltage as a result of the comparison; And a fifth step of performing precise reading on the output voltage by the resupplied current.

In the ultra-precise, high-resolution bio-signal measurement method according to an embodiment of the present invention, the fifth step includes a high-frequency noise filtering process by an RC-low-pass filter and a signal digital conversion process by a delta-sigma analog-digital modulator. Read the level.

In the ultra-precise, high-resolution biosignal measurement method according to an embodiment of the present invention, the sensor unit includes a receptor formed on the surface of the plurality of electrodes, and a change in capacitance between the receptor and the plurality of electrodes according to a reaction with a disease factor in blood The biosignal is measured by measuring, and the receptor is characterized in that it changes the dielectric constant between the plurality of electrodes by reacting with a very small amount of biomarker contained in the blood.

In the ultra-precise, high-resolution biosignal measurement method according to an embodiment of the present invention, the biomarker is VEGF (vascular endothelial growth factor), and the receptor is a peptide (Peptide).

An ultra-precise, high-resolution bio-signal measurement method according to an embodiment of the present invention,

A first step of supplying a variable current to a sensor unit that is executed by a computer and measures a change in capacitance between a plurality of electrodes conducting electricity and the plurality of electrodes to measure a living body signal; A second step of comparing an output voltage output by the variable current and a reference voltage; A third step of increasing the magnitude of the variable current and repeating the first and second steps when the output voltage is less than the reference voltage as a result of the comparison; A fourth step of setting a supply current to a fixed current value and resupplying it to the sensor unit when the output voltage is greater than or equal to the reference voltage as a result of the comparison; It can be executed by a computer-readable recording medium on which a program for executing the fifth step of performing precise reading on the output voltage by the resupplied current is recorded.

Other specific details of embodiments according to various aspects of the present invention are included in the detailed description below.

According to an embodiment of the present invention, measurement accuracy can be greatly improved by measuring a change in capacitance between electrodes rather than a method of measuring a change in resistance value of an electrode.

In addition, conventionally, in order to measure various capacitance values with a single current, the size of the current supplied by the current power supply must be very large regardless of the size of the capacitance value, so there is a problem that power consumption is very large according to the supply of a large current. According to an embodiment of the present invention, the approximate range of the output voltage is determined by comparing only the output voltage and the reference voltage in step 1, and when the approximate range is determined, precise reading is performed in step 2. Accordingly, since the size of the current power source is determined according to the size of the capacitance value, there is an advantage of preventing unnecessary power consumption.

FIG. 1 is a diagram illustrating an ultra-precise, high-resolution bio-signal measuring device (in-vivo type) according to an embodiment of the present invention and measuring a bio-signal using the measuring device.
FIG. 2 is a diagram showing various shapes and arrangements of electrodes constituting an ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention.
3 is a diagram showing shapes before and after a biomarker is attached to a receptor formed on an electrode surface.
4 is a circuit diagram illustrating a driving control unit of an ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention.
5 is a diagram illustrating an in-vitro type of an ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention.
6 is a flow chart illustrating a method of measuring a bio-signal with high precision and high resolution according to an embodiment of the present invention.
7 is a graph showing the result of measuring the amount of change in capacitance between electrodes according to the concentration of VEGF when a peptide is used as a receptor and when the peptide is not used in the ultra-precise high resolution biosignal measuring apparatus according to an embodiment of the present invention.
8 is a graph showing the amount of change in capacitance measurement between VEGF and other proteins in order to confirm the discrimination power of the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention.

The present invention is intended to illustrate specific embodiments and to be described in detail in the detailed description, since various transformations can be applied and various embodiments can be provided. However, this is not intended to limit the present invention to a specific embodiment, it is to be understood to include all conversions, equivalents, and substitutes included in the spirit and scope of the present invention.

The terms used in the present invention are only used to describe specific embodiments, and are not intended to limit the present invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In the present invention, terms such as'comprise' or'have' are intended to designate the presence of features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, but one or more other features. It is to be understood that the presence or addition of elements or numbers, steps, actions, components, parts, or combinations thereof, does not preclude in advance. Hereinafter, an ultra-precise, high-resolution bio-signal measuring apparatus and a measuring method according to an embodiment of the present invention will be described with reference to the drawings.

FIG. 1 is a diagram illustrating an ultra-precise, high-resolution bio-signal measuring device (in-vivo type) according to an embodiment of the present invention and measuring a bio-signal using the measuring device.

As shown in FIG. 1, an ultra-precise, high-resolution bio-signal measuring device (hereinafter referred to as a bio-signal measuring device) according to an embodiment of the present invention includes a sensor unit (100: 110 ~ 150) and a driving control unit (200: 210 ~ 220), and a precision reading unit 300.

The sensor unit 100 includes a substrate 110, an insulating film 120, a first electrode 130, a second electrode 140, and a receptor 150. The driving control unit 200 includes a current variable module 210 and an optimum current selection module 220. In the following description, a case in which the sensor unit 100 includes the substrate 110 and the insulating film 120 is described as an example, but according to the design, the sensor unit 100 has a plurality without the substrate 110 and the insulating film 120. It may be implemented with only the electrodes of.

The substrate 110 is a silicon substrate, and may be an n-type or p-type silicon substrate. However, the present invention is not limited or limited thereto, and may be formed of various materials such as titanium oxide, acrylic resin, epoxy resin, or polyimide.

The insulating layer 120 may be formed on the substrate 110 of a dielectric material having a low dielectric constant. For example, the insulating layer 120 may be formed of a dielectric material having a dielectric constant between 0 and 6 (0-6). Specifically, the insulating film 120 may be formed of at least one of SiO2, TiO2, Si3N4, Al2O3, CeO2, HfO2, La2O3, Ta2O5, Y2O3, ZrO2, HfAlOm ZrTiO4, SnTiO4, and SrTiO3.

The first electrode 130 is formed in one region above the insulating film 120, and the second electrode 140 is formed in the other region above the insulating film 120, and is spaced apart from the first electrode 130.

The first electrode 130 and the second electrode 140 may be formed on the substrate 110 by a bottom-up method such as a chemical vapor deposition method, a physical vapor deposition method, and an atomic layer deposition. In addition, the first electrode 130 and the second electrode 140 may be formed on the substrate 110 by a top-down method such as a mechanical peeling method or intercalation.

The surfaces of the first electrode 130 and the second electrode 140 are coated with a conductive material to allow current to flow. For example, the conductive material may be gold (Au).

As shown in FIG. 2A, the first electrode 130 and the second electrode 140 may have a size in micro units and may have a conical shape with a pointed top. Alternatively, as shown in FIG. 2B, the first electrode 130 and the second electrode 140 may be formed in a polyhedron or cylindrical shape having a predetermined height. Alternatively, as shown in FIGS. 2C and 2D, the first electrode 130 and the second electrode 140 may be disposed to be staggered at positions facing each other.

In order to have an invasive structure, a conical three-dimensional structure as shown in Fig. 2A is suitable, and can be implemented as a two-dimensional pattern as shown in Fig. 2B, which is a form when used in a non-invasive structure, and can be implemented with a relatively simple process. have. In addition, as shown in FIGS. 2C and 2D, it is possible to form a plurality of substrates instead of one substrate. In this case, when the electrodes are at opposite positions, the sensing sensitivity can be increased by increasing the capacitance between the electrodes.

When the bio-signal measuring device of the present invention is formed in an in-vivo type that directly penetrates and measures the human skin, the first electrode 130 and the second electrode 140 are formed to have a height of 600 μm or more to penetrate the human skin layer. It is preferably a conical shape.

As shown in FIG. 3, a receptor 150 is formed on the surfaces of the first electrode 130 and the second electrode 140. The receptor 150 reacts with a disease agent (biomarker) in the blood to change the dielectric constant between the two electrodes. For example, VEGF (vascular endothelial growth factor), known as a biomarker related to cancer cells, is a glycoprotein that specifically acts on vascular endothelial cells to promote cell proliferation or angiogenesis, and the first electrode 130 ) And when VEGF is formed on the surface of the second electrode 140, the VEGF and cancer cells react to change the dielectric constant between the two electrodes. The change in the dielectric constant changes the capacitance, allowing the concentration of biomarkers such as cancer cells to be known.

The receptor 150 may vary depending on the type of disease to be diagnosed, and for example, a peptide may be used as the receptor 150 to diagnose the onset of cancer as described above.

The driving control unit 200 supplies a variable current to the sensor unit 100 and compares the output voltage output by the supplied variable current with a reference voltage, and when the output voltage is greater than or equal to the reference voltage, the sensor unit 100 fixes the variable current. ), and accurately reads the output voltage of the sensor unit 100 by the resupplied current.

The base capacitance is the capacitance between two electrodes in the absence of a biomarker, and the base capacitance is determined by the area of the electrode and the concentration of the receptor peptide coated on the electrode. Due to the relatively large area of the electrode, the base capacitance shows a rather large level with a relatively large value of several tens nF, and the base capacitance value shows a large difference with a maximum of several tens nF level due to the difference in concentration of the receptor peptide coated on the surface of the electrode. . For this reason, a circuit for detecting capacitance is required to have a wide dynamic range rather than a large resolution.

In order to implement a bio-signal measuring device having such a wide dynamic range, the driving control unit 200 of the present invention is configured to implement a two-step subdivision process for the output voltage Vout of the sensor unit 100. In step 1, the driving control unit 200 determines an approximate range of the output voltage by comparing only the output voltage due to the variable current and the reference voltage (can be used in the same meaning as “approximate capacitance level check”), and the approximate range is If determined, the precision reading unit 300 performs precise reading in two steps.

To this end, the driving control unit 200 includes a current variable module 210 and an optimum current selection module 220. With reference to FIG. 4, the driving control unit 200 will be described in detail.

The current variable module 210 supplies a variable current to the first and second electrodes 130 and 140 of the sensor unit 100. The current variable module 210 includes a plurality of current power sources 211 and a switch 212 that turns on/off each of the plurality of current power sources 211. The plurality of current power sources 211 may supply unit currents of the same size. Of course, it can also be designed to supply different amounts of current.

The current variable module 210 may supply 5 bits (5 bits) of variable current by connecting 2 ⁵ units (32 units) of unit current power in parallel, for example. Of course, it is not limited thereto.

The optimum current selection module 220 derives an optimum value of the current supplied from the current variable module 210. The optimum current selection module 220 compares the output voltage Vout output by the variable current supplied from the current variable module 210 to the sensor unit 100 with a preset reference voltage Vref. As a result of the comparison, when the output voltage Vout is less than the reference voltage Vref, the magnitude of the supply current of the current variable module 210 is increased. In this way, the magnitude of the supply current of the current variable module 210 is increased until the output voltage Vout reaches the reference voltage Vref. For example, increase the amount of current by increasing the number of counters in the resistor.

When the output voltage Vout is greater than or equal to the reference voltage Vref, the optimal current selection module 220 stores the amount of supply current that caused the output voltage (the number of counters) in a register, and stores this current value as a fixed current value. Set, and to re-supply the current of a fixed size to the sensor unit 100.

The fine readout unit 300 performs fine readout on the output voltage Vout by the resupplied current. The precision reading unit 300 includes an RC-low-pass filter and a delta-sigma analog-digital modulator. The part except for the DC band voltage including the signal information of the output voltage value is canceled by the filter, and the output voltage value is converted to a digital value through the delta-sigma analog-digital modulator in the final stage.

The resolution of the precision reading unit 300 exhibits a performance of 13 bits or more, and it is possible to read a capacitance level over a wide dynamic range of 18 bits or more by combining with the optimum current selection module.

5 is a diagram illustrating an in-vitro type implementation of an ultra-precise, high-resolution bio-signal measuring device according to an embodiment of the present invention. This type of bio-signal measuring apparatus may measure a bio-signal by collecting blood from a human body and inserting it into the sensor unit 100. In FIG. 5, “Power Supply” and “Clock Generator” provide power voltage and operation clock to the IC of the bio-signal measuring device. And “Logic Analyzer” analyzes the digital signal, which is the final signal from the high-resolution bio-signal measuring device IC.

Next, an ultra-precision, high-resolution biosignal measurement method according to an embodiment of the present invention will be described with reference to FIG. 6. 6 is a flow chart illustrating a method of measuring an ultra-precise, high-resolution bio-signal according to an embodiment of the present invention.

As shown in Figure 6, the ultra-precise, high-resolution biosignal measurement method according to an embodiment of the present invention, the step of supplying a variable current to the sensor unit 100 (S110, S120), comparing the output voltage and the reference voltage In step S130, when the comparison result, when the output voltage is less than the reference voltage, increases the magnitude of the variable current (S140), and when the comparison result, when the output voltage is higher than the reference voltage, the magnitude of the supply current is fixed current value And resupplying to the sensor unit (S150), and performing precise reading (S160).

The current variable module 210 supplies a variable current to the first and second electrodes 130 and 140 of the sensor unit 100. In this case, the first variable current supplied is the minimum unit current nio (n=1), and may be, for example, 1 μA. (S110, S120)

Next, the output voltage Vout output by the variable current is compared with the preset reference voltage Vref. (S130) For example, the preset reference voltage may be 100mV.

As a result of the comparison, when the output voltage is less than the reference voltage, it is difficult to read the correct capacitance level with the corresponding output voltage, and thus the magnitude of the variable current is increased to derive an appropriate output voltage, and steps S120 and S130 are repeated. (S140) By turning on at least one switch among a plurality of unit current power supplies connected in parallel, the magnitude of the variable current is increased by one unit. (io --> 2io)

As a result of repeating the steps S120 and S130, when the output voltage becomes more than the reference voltage, the corresponding current value is set as a fixed current value, and a current of a fixed set size is resupplied to the sensor unit 100. (S150)

Then, a precise reading is performed on the output voltage by the resupplied current. (S200)

Among the above steps, steps S110 to S150 are performed by the current variable module 210 and the optimal current selection module 220, and determine an approximate range of the output voltage by comparing only the output voltage by the variable current and the reference voltage. The step S200 is performed by the precision reading unit 300, and is a step of reading and confirming an accurate capacitance level through a high-frequency noise filtering process by a filter and a signal digital conversion process by a delta-sigma analog-digital modulator. .

Next, the effects of the ultra-precise, high-resolution bio-signal measuring apparatus and measuring method according to an embodiment of the present invention will be described with reference to FIGS. 7 and 8.

7 is a graph showing the result of measuring the amount of change in capacitance between electrodes according to the concentration of VEGF when a peptide is used as a receptor and when the peptide is not used in the ultra-precise high-resolution biosignal measuring apparatus according to an embodiment of the present invention.

Referring to FIG. 7, the amount of change in capacitance is increasing according to the concentration of VEGF, which is a biomarker, and in particular, it can be seen that the amount of change in capacitance when the peptide is used is about 3 to 22 times larger than the amount of change in capacitance when not used. have. Accordingly, it can be seen that when the receptor is formed on the electrode surface of the sensor unit as in the embodiment of the present invention, the capacitance exhibits a very large amount of change, so that the detection power is greatly improved.

8 is a graph showing the amount of change in capacitance measurement between VEGF and other proteins in order to confirm the discrimination power of the ultra-precise, high-resolution bio-signal measuring apparatus according to an embodiment of the present invention.

Referring to FIG. 8, when a peptide is formed as a receptor on the electrode surface of the sensor unit and VEGF is detected as in the present invention, it can be seen that the amount of change in capacitance appears larger than that of other types of proteins, and thus discriminating power is present.

On the other hand, in the related art, in order to measure various capacitance values with a single current, the magnitude of the current supplied by the current power source must be very large regardless of the magnitude of the capacitance value, and thus power consumption is very large according to the supply of a large current.

However, in the present invention, in order to measure various capacitance values, that is, to secure a wide dynamic range, it is configured to implement a two-step subdivision process for the output voltage of the sensor unit, and in the first step, the output voltage and the variable current The approximate output voltage range was determined by comparing only the reference voltage, and when the approximate range was determined, precise reading was performed in step 2. Accordingly, since the size of the current power source is determined according to the size of the capacitance value, there is an advantage of preventing unnecessary power consumption.

As described above, one embodiment of the present invention has been described, but those of ordinary skill in the relevant technical field add, change, delete or add components within the scope not departing from the spirit of the present invention described in the claims. Various modifications and changes can be made to the present invention by means of the like, and it will be said that this is also included within the scope of the present invention.

100: sensor unit 110: substrate
120: insulating film 130: first electrode
140: second electrode 150: receptor
200: drive control unit 210: current variable module
220: optimal current selection module 300: precision reading unit

Claims (11)

A sensor unit that measures a biosignal by measuring a change in capacitance between a plurality of electrodes through which electricity is conducted and the plurality of electrodes; And a driving control unit for supplying a variable current to the sensor unit and comparing the output voltage output by the supplied variable current to a reference voltage, and fixing the variable current and resupplying it to the sensor unit when the output voltage is higher than the reference voltage. Including,
The sensor unit includes a receptor formed on the surface of the plurality of electrodes, and measures a biosignal by measuring a change in capacitance between the receptor and the plurality of electrodes according to a reaction with a disease factor in the blood, and the receptor is included in the blood. Ultra-precise, high-resolution bio-signal measuring device, characterized in that the dielectric constant between the plurality of electrodes is changed by reacting with a very small amount of biomarker. The method according to claim 1, wherein the driving control unit,
A current variable module for supplying a variable current to the sensor unit,
Ultra-precise, high-resolution, including an optimal current selection module for fixing the current supplied from the current variable module when the output voltage is greater than or equal to the reference voltage by comparing the output voltage output by the variable current supplied to the sensor unit with the reference voltage Bio-signal measuring device. The method according to claim 2,
Ultra-precise, high-resolution bio-signal measurement device further comprising a precision reading unit for performing a precise reading on the output voltage of the sensor unit by the current fixed by the optimal current selection module. The method of claim 3, wherein the precision reading unit,
RC-low-pass filter and delta-sigma analog-digital modulator are included, and the part except for the DC band voltage that contains signal information of the output voltage value is canceled by the filter, and the delta-sigma analog-digital modulator in the final stage Ultra-precise, high-resolution bio-signal measuring device that converts the output voltage value into a digital value. delete The method according to claim 1,
The biomarker is VEGF (vascular endothelial growth factor), and the receptor is a peptide (Peptide). A first step of supplying a variable current to a sensor unit for measuring a biosignal by measuring a change in capacitance between a plurality of electrodes through which electricity is conducted and the plurality of electrodes;
A second step of comparing an output voltage output by the variable current and a reference voltage;
A third step of increasing the magnitude of the variable current and repeating the first and second steps when the output voltage is less than the reference voltage as a result of the comparison;
A fourth step of setting a supply current to a fixed current value and resupplying it to the sensor unit when the output voltage is greater than or equal to the reference voltage as a result of the comparison;
A fifth step of performing a precise reading on the output voltage by the resupplied current,
The sensor unit includes a receptor formed on the surface of the plurality of electrodes, and measures a biosignal by measuring a change in capacitance between the receptor and the plurality of electrodes according to a reaction with a disease factor in the blood, and the receptor is included in the blood. Ultra-precise, high-resolution biosignal measurement method, characterized in that the dielectric constant between the plurality of electrodes is changed by reacting with a very small amount of biomarker. The method of claim 7,
The fifth step is a high-precision, high-resolution biosignal measurement method of reading a precise capacitance level through a high-frequency noise filtering process by an RC-low-pass filter and a signal digital conversion process by a delta-sigma analog-digital modulator. delete The method of claim 7,
The biomarker is VEGF (vascular endothelial growth factor), and the receptor is a peptide (Peptide). A computer-readable recording medium that is executed by a computer and records a program for executing each step of the ultra-precise, high-resolution bio-signal measuring method according to claim 7.

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