KR20170040918A

KR20170040918A - Bio sensor and sensing method thereof

Info

Publication number: KR20170040918A
Application number: KR1020150140181A
Authority: KR
Inventors: 최형선; 조철호; 조성제; 김광복; 이승민; 정선태; 조재걸
Original assignee: 삼성전자주식회사
Priority date: 2015-10-06
Filing date: 2015-10-06
Publication date: 2017-04-14
Also published as: WO2017061727A1

Abstract

Disclosed is a bio-sensor which can measure accurate concentration by reducing a time consumed for diffusing a measurement target material in blood to intercellular fluid. The bio-sensor comprises: a needle array which can be inserted into a body to measure concentration of a target material; a power applying unit for applying current to a bio-contact area of the needle array to move the target material to the needle array; and a control unit for calculating the concentration of the target material based on a signal generated in the needle array.

Description

TECHNICAL FIELD [0001] The present invention relates to a biosensor and a sensing method thereof,

The present invention relates to a sensor device, and more particularly, to a biosensor capable of accurately measuring concentration by shortening the time required for diffusion of an analyte into blood into an intracellular fluid, and a sensing method thereof.

Quantitative determination of analytes in biological fluids is useful for diagnosing and treating physiological disorders. For example, the amount of glucose (blood glucose) should be periodically checked to diagnose and prevent diabetes.

Conventionally, a biosensor using an electrochemical method has been mainly used. An electrochemical biosensor is an apparatus for measuring the amount of a substance to be measured by detecting an electrochemical signal through an enzyme reaction with an analyte using an enzyme electrode having an enzyme fixed to the electrode.

A biosensor can measure the amount of a substance to be measured in various ways. Among the methods in which blood is required to be collected, the blood glucose measurement value may be changed according to the proficiency of the blood collection method. A few times of intermittent measurement, There is a problem in that it is impossible to completely detect the change in the concentration of the liquid.

Recently, a device capable of accurately monitoring the concentration of a substance to be measured without blood collection has been developed. Typically, a complete implantable type in which the biosensor itself is completely implanted into the body and a needle-shaped sensor insertable into the subcutaneous tissue There was a minimally invasive approach.

On the other hand, since the biosensor of the minimally invasive type can be inserted into the subcutaneous tissues instead of the blood vessels to avoid direct contact with the blood, the biosensor can be manufactured for a few days by a biocompatible material, There was an advantage.

However, the minimally invasive biosensor measures the concentration of a substance to be measured, such as glucose, from the interstitial fluid (ISF) of the subcutaneous tissue. It takes time for the glucose in the blood to diffuse into the intercellular fluid to reach the biosensor do. Therefore, there is a problem that blood glucose information is transmitted about 10 minutes later than the actual blood glucose concentration change time. In the extreme case of diabetic patients, hypoglycemic shock can lead to death within minutes of the occurrence of the hypoglycemic shock, and this time delay problem needs to be addressed.

It is an object of the present invention to provide a biosensor capable of accurately measuring a concentration by shortening the time required for diffusion of a substance to be measured into an intracellular fluid and a sensing method thereof .

According to an aspect of the present invention, there is provided a biosensor comprising: a needle array insertable into a body for measuring a concentration of a target substance; And a control unit for calculating a concentration of the target substance based on a signal generated in the needle array and a power application unit for applying a current to the contact region.

In this case, the controller may control the power applying unit to adjust the amount of the applied current according to a signal generated in the needle array.

In this case, the control unit may increase the applied current amount when the concentration change rate of the target substance is not less than a predetermined value, based on a signal generated in the needle array, and when the concentration change rate of the target substance is less than a predetermined value , The power application unit may be controlled to reduce the amount of the applied current.

Meanwhile, the power applying unit may include a plurality of electrodes for applying a current to the living body region, and the plurality of electrodes may be disposed adjacent to the needle array.

In this case, the plurality of electrodes may be in a shape that can be arranged on the skin surface.

On the other hand, the plurality of electrodes may be needle-shaped.

Meanwhile, the needle array may include a counter electrode, a reference electrode, and a working electrode provided with an enzyme capable of reacting with the target substance.

Meanwhile, the controller may control the power application unit such that the current is applied at predetermined intervals.

Meanwhile, the needle array may include a support portion in which a plurality of needles are arranged.

In this case, the support portion may be in the form of a wearable band.

Meanwhile, the biosensor according to an embodiment of the present invention may further include a heating unit for applying heat to a surrounding bio-contact area adjacent to the bio-contact area of the needle array.

In this case, the control unit increases the calorific value when the concentration change rate of the target substance is equal to or greater than a predetermined value, based on the signal generated in the needle array, and if the concentration change rate of the target substance is less than a predetermined value, It is possible to control the heating unit to reduce the temperature.

According to another aspect of the present invention, there is provided a method of sensing a biosensor including a needle array insertable into a body, the method comprising: applying a current to a body contact area of the needle array so that an object material moves to the needle array; Measuring a concentration of the target substance using the array to generate a measurement signal, and calculating a concentration of the target substance based on the generated measurement signal.

In this case, the step of applying the current may adjust the amount of current applied according to the generated measurement signal.

In this case, the step of applying the current may include: increasing the amount of applied current if the concentration change rate of the target substance is not less than a predetermined value, based on the generated measurement signal, , The amount of the applied current can be reduced.

Meanwhile, in the step of applying the current, a current may be applied through a plurality of electrodes included in the biosensor.

Meanwhile, the step of generating the measurement signal may include using a counter electrode, a reference electrode included in the needle array, and a working electrode provided with an enzyme capable of reacting with the target substance To generate the measurement signal.

Meanwhile, in the step of applying the current, the current may be applied at predetermined intervals.

Meanwhile, the sensing method according to an embodiment of the present invention may further include the step of applying heat to the surrounding bio-contact area adjacent to the bio-contact area of the needle array through the heat generating part included in the biosensor.

In this case, the step of applying the heat may increase the calorific value if the concentration change rate of the target substance is not less than a predetermined value, based on the generated measurement signal, and if the concentration change rate of the target substance is less than a predetermined value, The heat generation amount can be reduced.

1 is a block diagram for explaining a biosensor according to an embodiment of the present invention;
FIG. 2 is a view for explaining a movement of an object according to a current application of a biosensor according to an embodiment of the present invention; FIG.
3 is a view showing a needle array of a biosensor according to an embodiment of the present invention,
4 is a view for explaining an application example of a biosensor according to an embodiment of the present invention,
FIGS. 5A and 6B are diagrams for explaining a comparison between a case where a current is not applied to a biosensor and a case where a current is applied;
7 is a view for explaining a time delay reduction effect by the biosensor according to an embodiment of the present invention;
8 is a view for explaining an application example of a biosensor according to another embodiment of the present invention,
9 is a view for explaining a comparison between a case where a pressure is applied to a measurement site and a case where no pressure is applied,
10 is a flowchart illustrating a sensing method of a biosensor according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the drawings. In the following description of the present invention, detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear. The following terms are defined in consideration of the functions of the present invention, and this may vary depending on the intention or the relationship of the user, the operator, and the like. Therefore, the definition should be based on the contents throughout this specification.

1 is a view for explaining a configuration of a biosensor according to an embodiment of the present invention.

1, the biosensor 100 includes a needle array 110, a power application unit 120, and a control unit 130. [

The biosensor 100 can be classified into amperometric, potencymetric, and conductimetric according to the electrochemical method. Among them, the amperometric method measures the current generated during the enzyme reaction in the working electrode, and the potencymetric is the voltage measurement method such as the ISFET (ion-sensitive field effect transistor), and the conductimetric is the chemiresistor or black lipid membrane (BLM), and so on.

The needle array 110 is a structure for sensing the concentration of a target substance to be measured in the body.

The needle array 110 may include a plurality of needle-shaped electrodes that electrochemically sense the concentration of the target material. The needle array may include a support portion (not shown) in which a plurality of needle-like electrodes are arranged. The support will be described in more detail with reference to Figure 3.

For example, when the biosensor 100 uses an amperometric method, which is a principle of measuring the magnitude of the current flowing between the electrodes under a certain potential, the plurality of electrodes of the needle array 110 includes a working electrode, And a three electrode system of a reference electrode and a counter electrode.

The three-electrode system can measure the concentration of the target substance using enzymes and electron transfer mediators. A method of measuring the concentration of a target substance using such a three-electrode system will be apparent to those skilled in the art and will be briefly described as follows.

Specifically, when the target substance to be measured is glucose, the enzyme is immobilized on the working electrode. Examples of the enzyme include various oxidoreductases such as glucose oxidase, lactate oxidase, cholesterol oxidase, alcohol oxidase, and glucose Dehydrogenase, GOT (glutamate oxaloacetate trnasmianse), and GPT (glutamate pyruvate trnasmianse).

Examples of the electron transferring material include potassium ferricyanide, potassium ferrocyanide, hexaamineruthenium chloride, ferrocene and derivatives thereof, quinine and derivatives thereof, and the like. Substances capable of reacting with an enzyme to oxidize or reduce can be used.

The counter electrode has a polarity opposite to that of the working electrode and becomes a passage of current between the electrodes, so that the counter electrode can be formed of an electrode material having high electrical conductivity.

The reference electrode causes a constant potential to be applied to the working electrode, and no current flows to the electrode due to the high impedance. For example, a standard hydrogen electrode (SHE), a calomel (Hg / Hg ₂ Cl ₂ ) electrode, and a silver-silver chloride (Ag / AgCl) electrode are used as a reference electrode. Since they have a relatively constant potential difference, a constant electrode potential can be applied. In such a configuration, the electroactive material generated through the enzyme reactions of the target material in the three-electrode system is oxidized or reduced at the working electrode, and the generated current is measured to determine the concentration of the target material. That is, it is possible to calculate the concentration of the target substance by calculating the current-voltage relationship according to the voltage applied through the voltage source.

The needle array 110 includes a voltage source for applying a voltage to a plurality of electrodes as described above, and the voltage source may be a direct current (DC) voltage, an alternating current (AC) voltage, or a voltage in which a direct current voltage and an alternating voltage are superimposed Voltage can be applied.

When the Ag or AgCl electrode is used as the reference electrode, the voltage applied by the voltage source of the needle array 110 may be more than 0 and 1 V or less with respect to the reference electrode. When the target substance is glucose, if it exceeds 1 V, the oxidation / reduction process of other substances in blood is dominant as compared with the oxidation process, so that the amount of glucose can not be accurately measured. Since the voltage value applied through the working electrode and the reference electrode is a voltage value suitable for oxidizing only glucose in the blood, it is possible to prevent other substances in the blood from oxidizing and participating in the current component. Therefore, a more accurate blood sugar value can be obtained. In one example, when an AC voltage is applied, the frequency is more than 0 and less than or equal to 0.1 MHz.

The more the glucose in the blood is, the more the amount of oxidized glucose is increased and the current value is increased. Therefore, by measuring such a current amount, the blood sugar amount can be calculated.

A plurality of needle-shaped electrodes of the needle array 110 as described above can be fabricated using, for example, carbon, graphite, platinum-treated carbon, silver, gold, palladium or platinum.

The lengths of the needle-shaped electrodes of the needle array 110 preferably pass through the stratum corneum, but are not inserted into the subcutaneous layer where the blood vessels are distributed. Therefore, it can be appropriately selected within the range of 100 탆 to 5 mm. The density, shape and aspect ratio thereof can be appropriately selected in consideration of workability and mechanical strength.

The power application unit 120 is configured to apply a current to the body contact region of the needle array 110 so that a target substance to be measured moves to the needle array 110. [ That is, the power applying unit 120 is configured to shorten the time required for the object substance of the blood vessel to diffuse and reach the needle array 110. [

The power applying unit 120 includes a power source (ex. Battery), and includes a plurality of electrodes composed of a cathode and an anode for applying an electric current to the body.

Specifically, an iontophoresis phenomenon is induced by a current applied through the electrode in the power applying unit 120, and thus an electroosmotic flow (EOF) is applied to the needle array 110, So that the object material can be quickly reached to the needle array 110. Thereby, the concentration of the measurement target substance in the blood can be measured without time delay.

Iotophoresis refers to the process in which positive (+) ions are attracted to negative (-) electrodes and negative (-) ions are attracted to positive (+) electrodes. It is a phenomenon that a constant flow is formed so that the solution around the ion moves together with the ion.

In order for such an electroosmotic flow phenomenon to occur, the wall surface of the path through which ions are to move must be charged with negative charges, and positive and negative electrodes are applied to both sides of the path, , The positive (+) ions inside the passageway must be attracted to the negative (-) electrode by the ionosphere. This pathway can be a region between cells in the body. The electroosmotic flow phenomenon will be described in more detail with reference to FIG.

FIG. 2 is a view for explaining the electroosmotic flow in the body by the power applying unit 120, according to an embodiment of the present invention.

2, only the negative electrode 122 having a negative polarity is shown among the electrodes included in the power applying unit 120, and the electrode having a positive polarity, which is a counter electrode thereof, is not shown. 2, the negative electrode 122 of the power applying unit 120 has a needle shape and is inserted into the body from the skin according to an embodiment of the present invention.

The cell walls of the cells 21 in the body have a negative external electric charge and a positive internal electric charge. In the conditions for generating the above-described electric osmotic flow, It satisfies the condition that charge should be put out.

When the power application unit 120 applies an electric current to the body, positive ions such as Na ⁺ , K ^+, and the like existing in the body pass through the cell walls of the cells 21, And the interstitial fluid (ISF) near the positive (+) ions is moved toward the negative (-) electrode 122 together with the positive (+) ions by the electroosmotic flow, As a result, the interstitial fluid (ISF) including the target substance 30 to be measured present near the blood vessel can be rapidly moved toward the needle array 110 by the electroosmotic flow. That is, it is possible to shorten the time required for the object substance 30 contained in the intercellular fluid (ISF) to reach the needle array 110.

The amount of current applied to the body through the electrode of the power applying unit 120 can be selected to be sufficient to form the above-described electroosmotic flow while minimizing the influence to the user. The amount of current may vary depending on the shape of the electrode of the power applying unit 120.

For example, when the electrode of the power applying unit 120 has a needle shape like the needle-like electrodes of the needle array 110, the electrodes can contact the body fluid through the stratum corneum, so that the resistance can be reduced. In this case, the amount of current can be selected from 0.001 to 2 mA. If the electrode of the power application unit 120 is not insertable into the body but can be placed on the surface of the skin, the amount of current may be selected within a range larger than when the electrode is inserted into the body. In a form that can be placed on the surface of the skin, it can be made in the form of an adhesive material that can be adhered to the skin.

Meanwhile, the power application unit 120 may apply the current continuously or in a pulse form, that is, at predetermined intervals.

When a current is applied at a predetermined interval, the power consumed can be saved more than when it is applied continuously.

3 is a diagram illustrating an example of a biosensor 100 in a case where electrodes of a power applying unit 120 have a needle shape like an electrode of a needle array 110 according to an embodiment of the present invention.

3, the biosensor 100 includes electrodes 111, 112, and 113 of the needle array 110 arranged on the support 140 and the electrodes 140 of the power application unit 120, (121, 122).

The support 140 may be formed of a non-conductive material. For example, the support portion 140 may be formed of a flexible material, and in particular, may be formed of an elastic body (e.g., rubber). When the support portion 140 is formed of an elastic body, the electrodes 111, 112, 113, 121, and 122 can be closely inserted into the body. In addition, when the support portion 140 is formed of an elastic body, it can be easily worn on a body part such as an arm, and the speed at which a target material to be measured moves to the needle array 110 can be increased by pressing the worn part. In this case, the support portion 140 may have a band shape.

As described above, the needle array 110 may include a three electrode system composed of a counter electrode 111, a working electrode 112 provided with an enzyme capable of reacting with a target substance to be measured, and a reference electrode 113.

The power application unit 120 includes both electrodes 121 and 122 and applies current to the body through the electrodes 121 and 122. Both electrodes 121 and negative electrodes 122 may be disposed adjacent to the electrodes 111, 112, and 113 of the needle array 110 on the support 140. The arrangement state shown in Fig. 3 is merely an example, but is not limited thereto.

When both the electrode 121 and the negative electrode 122 of the power application unit 120 are needle-shaped, the amount of current applied to the body through the electrode 121 may be selected from 0.001 to 2 mA. It is preferable that the lengths of the both electrodes 121 and the negative electrode 122 are not inserted into the subcutaneous layer through which the blood vessel is distributed. Therefore, it can be appropriately selected within the range of 100 탆 to 5 mm. The density, shape and aspect ratio thereof can be appropriately selected in consideration of workability and mechanical strength.

Both the electrode 121 and the negative electrode 122 may be formed of a metal, for example, a noble metal such as platinum, gold, and silver, or may be formed of an alloy containing them. In particular, platinum and silver are sanitarily advantageous because they have a sterilizing effect by catalysis.

FIG. 4 shows an application example of the biosensor 100 according to an embodiment of the present invention.

Referring to FIG. 4, the counter electrode 111, the working electrode 112, the reference electrode 113, the positive electrode 121, and the negative electrode 122 described in FIG. 3 can be inserted into the body. An electric current for forming the electroosmotic flow is applied through the positive electrode 121 and the negative electrode 122. In this case, a constant amount of current is applied. When an electric current is applied, an electroosmotic flow is formed in which an intercellular fluid (ISF) containing a substance to be measured in the blood of the subcutaneous layer is moved in accordance with the movement flow of the anion and / or the cation as shown in FIG. 4, Can be rapidly moved toward the counter electrode 111, the working electrode 112, and the reference electrode 113 without time delay.

Therefore, the concentration value of the target substance in the actual blood can be accurately calculated without delay.

The control unit 130 controls the overall operation of the biosensor 100.

In particular, the control unit 130 may calculate the concentration of the target substance to be measured based on the signal generated in the needle array 110. [

Specifically, the needle array 110 includes a voltage source for applying a voltage to a plurality of electrodes as described above, and the control unit 130 controls the voltage applied to the electrode array 110 such that the voltage source is a direct current (DC) voltage, It is possible to control to apply a voltage of any one of the voltages superimposed on the voltage.

When the target substance to be measured is glucose, the controller 130 can set the voltage applied by the voltage source of the needle array 110 to be within the range of more than 0 to 1 V with respect to the reference electrode (using Ag or AgCl as the reference electrode). When it exceeds 1V, the oxidation / reduction process of other substances in the blood is dominant over the oxidation process, so that the amount of glucose can not be accurately measured. Since the voltage value applied to the working electrode 112 and the reference electrode 113 is a voltage value suitable for oxidizing only glucose in the blood, it is possible to prevent other substances in the blood from oxidizing and participating in the current component. Therefore, a more accurate blood sugar value can be obtained. The more the glucose in the blood is, the more the amount of oxidized glucose is increased and the current value is increased. Therefore, by measuring such a current amount, the blood sugar amount can be calculated.

The controller 130 senses a current corresponding to a voltage applied by the voltage source of the needle array 110 as a generation signal and can calculate the concentration of a target substance to be measured using the amount of current. That is, the current value corresponding to the applied voltage can be sensed and the calculation using the current value can be performed to calculate the concentration of the target substance. In one embodiment, the controller 130 may include an analog-to-digital converter (ADC), a computing unit, and a memory. The current value can be input through the ADC and converted to a digital value. The operation unit outputs the concentration value of the target substance using the digital current value output from the ADC. The calculated concentration values are stored in the memory.

The control unit 130 may control the power application unit 120 to adjust the amount of current applied to the living body region in which the needle array 110 is disposed according to a signal generated in the needle array 110. That is, the controller 130 can determine the amount of current to be applied according to the measured concentration of the target substance.

For example, when the change rate of the concentration of the target substance is greater than a predetermined value, the control unit 130 increases the amount of applied current, and if the rate of change of the concentration of the target substance is less than a predetermined value, The power supply unit 120 can be controlled.

For example, when the target substance is glucose and the rate of change of the concentration thereof is high, it is necessary to measure the concentration quickly, so that the amount of applied current is increased. For example, it is important to measure the blood sugar level on time because a blood sugar shock may occur when the blood sugar level of a diabetic patient suddenly changes. Therefore, it is necessary to increase the amount of applied current.

Conversely, when the rate of change of the concentration of glucose is low, it is less necessary to measure quickly, and therefore, the amount of current to be applied may be reduced in order to reduce power consumption.

In order to reduce the power consumption, the controller 130 may control the power applying unit 120 to be applied at predetermined intervals instead of continuously applying the current.

The calculated concentration value may be displayed on a display device (not shown) provided in the biosensor 100 or may be transmitted to an external device through a communication unit (not shown) of the biosensor 100. In this case, the amount of blood glucose can be confirmed in a device such as a smart phone.

According to the above-described various embodiments, information on the concentration of the substance to be actually analyzed can be delivered without delay. These are shown in Figures 5A and 5B for comparison.

FIG. 5A is a graph showing the relationship between the actual intravascular glucose concentration over time and the intracellular fluid (ISF) in the case where no iontophoresis is induced due to no current applied to the biosensor (No Iontophoresis) FIG. 5B is a graph for explaining the glucose concentration in the case where an electroosmotic flow is induced by applying a current to a biosensor according to an embodiment of the present invention to induce iontophoresis, The intravascular glucose concentration and the intracellular fluid (ISF) glucose concentration will be described.

Referring to FIG. 5A, when the amount of glucose is measured without applying a current to induce iontophoresis, as shown in the right graph, when compared with the concentration of glucose in the actual blood (real blood glucose) It can be seen that there is a somewhat large time delay between glucose ISF Glucose concentration in the measured intracellular fluid.

On the other hand, referring to FIG. 5B, when an electric current is applied to induce iontophoresis and the amount of glucose (indicated by "G") is measured, real blood glucose (glucose) When compared to the concentration, it can be seen that the time delay between the concentration of glucose (Sensor ISF Glucose) in the intracellular fluid measured by the sensor is greatly shortened. That is, when the electroosmotic flow is formed, the glucose concentration in the intracellular fluid can reflect the actual glucose concentration in the blood vessel without significant error.

6A is a graph showing the relationship between the actual blood glucose concentration and the height from the blood vessel in the case where the iontophoresis phenomenon is not induced because no current is applied to the biosensor (No Iontophoresis) FIG. 6B is a graph illustrating the relationship between glucose concentration in an ISF according to an embodiment of the present invention, and FIG. 6B is a graph illustrating the relationship between glucose concentration and glucose concentration in the case where an electroosmosis flow is formed by inducing iontophoresis by applying a current to the biosensor (ISF) according to the actual blood and intracellular glucose concentration and the height from the blood vessel.

6A, when the amount of glucose is measured without applying current to induce iontophoresis, as shown in the right graph, the concentration of glucose (ISF Glucose) in the intercellular fluid increases as the distance from the blood vessel increases (Real Blood Glucose) concentration in blood vessels.

On the other hand, referring to FIG. 6B, when the current for inducing the iontophoresis phenomenon is applied and the amount of glucose (indicated by "G") is measured, glucose in the intracellular fluid Sensor ISF Glucose concentration is not significantly different from actual blood glucose concentration. That is, when the electroosmotic flow is formed, the glucose in the blood rapidly spreads toward the biosensor, so that even if the biosensor is separated from the blood vessel, the value measured by the biosensor reflects the glucose concentration in the actual blood vessel without any significant error .

FIG. 7 is a graph showing the results of measurement of the concentration (measured value in accordance with the embodiment) by applying an electric current according to an embodiment of the present invention to form an electric osmotic flow And the concentration (actual value) of the analyte in the actual blood.

Specifically, FIG. 7 shows the case where the time delay is shortened when the concentration of the target substance is measured by forming an electroosmotic flow by applying a current, as compared with the case where the concentration of the target substance is measured without applying a current, Which is close to the concentration value of the substance.

In the above description, a method of applying a current to shorten the time delay has been described, but it is also possible to employ a method of applying a pressure. For example, when the biosensor 100 is manufactured in the form of a band and then worn, the pressure increases even toward the blood vessel wall, and the rate at which the substance in the blood diffuses out of the blood vessel can be further accelerated. This embodiment will be described in detail with reference to FIG.

FIG. 8 is a view illustrating an application example of the biosensor 100 according to another embodiment of the present invention.

Referring to FIG. 8, the biosensor 100 may be fabricated in combination with the band 200. The user may wear this on his / her arm as shown in the body part, for example, as shown in Fig. By the pressure applied by the band 200, the rate at which the substance to be measured in the blood diffuses out of the blood vessel can be accelerated. In addition, since the biosensor 100 is manufactured in the band shape, the biosensor 100 can be more conveniently carried.

FIG. 9 is a graph for comparing the measurement results of concentration of glucose, which is a target substance, with and without a band pressure applied to the biosensor arrangement region.

9 (a), according to an embodiment of the present invention, when the biosensor 100 is attached to a measurement site without a band, that is, without external pressure, as shown in the right graph, (Sensor ISF Glucose) concentration in the intracellular fluid measured by the sensor is slightly delayed when compared to the concentration of Real Blood Glucose.

9 (b), when a certain pressure is applied to the measurement target site using the biosensor 100 and the band 200 together according to another embodiment of the present invention, As shown in FIG. 9A, the time delay between glucose ISF glucose concentration in the intracellular fluid measured by the sensor is shorter than that in the case of FIG. 9A, as compared with the actual blood glucose concentration. This is because the glucose in the blood vessel can be diffused more rapidly into the intercellular fluid by applying a certain pressure to the site where the biosensor 100 is disposed.

According to another embodiment of the present invention, in order to speed up diffusion of a target substance to be measured out of a blood vessel, air is diluted inside a bowl-shaped instrument, and the apparatus is attached to the skin to urge the blood toward the blood vessel wall. The biosensor 100 can be applied. That is, it uses the principle of mechanism such as the bush. In this case, the biosensor 100 can be combined with a mechanism such as a bush.

According to yet another embodiment, the biosensor 100 may further include a heating unit (not shown) for applying heat to the living body contact area of the needle array 110 and the neighboring living body contact area. For example, the heating portion may be realized by an electric hot wire.

The present embodiment utilizes the principle that, by applying heat, the analyte in blood can diffuse more rapidly.

In this case, the control unit 130 may control the heat generating unit to adjust the amount of heat applied to the living body area in which the needle array 110 is disposed according to the signal generated by the needle array 110. [ That is, the control unit 130 can determine the calorific value according to the concentration value of the measured substance.

For example, the control unit 130 may increase the calorific value when the rate of change of the concentration of the target substance is greater than a predetermined value, and may control the heating unit to decrease the calorific value when the rate of change of the concentration of the target substance is less than a predetermined value.

For example, when the target substance is glucose and the rate of change of the concentration thereof is high, it is necessary to measure the concentration thereof rapidly, so that the calorific value is increased so that the glucose diffusion is accelerated. For example, it is important to measure the blood sugar level on time because a blood sugar shock may occur when the blood sugar level of a diabetic patient suddenly changes. It is therefore necessary to increase the applied heat.

Conversely, if the concentration of glucose is low the rate of change is less needed to quickly measure, so as to reduce power consumption, the amount of calorie is reduced.

Embodiments described in the present invention may be applied to various types of application specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), programmable logic devices (PLDs), field programmable gate arrays (FPGAs) Controllers, controllers, micro-controllers, microprocessors, and other units for performing other functions. In some cases, the embodiments described herein may be implemented by the controller 130 itself. According to a software implementation, embodiments such as the procedures and functions described herein may be implemented with separate software modules. Each of the software modules may perform one or more of the functions and operations described herein.

10 is a flowchart illustrating a sensing method of a biosensor including a needle array insertable into a body according to an embodiment of the present invention.

First, a current is applied to a living body contact area of a needle array so that a target substance to be measured moves to a needle array (S1010).

In this case, the controller 130 controls the power applying unit 120 to apply a constant current per time. The amount of current is set to such an extent that the target substance to be measured can be moved to the needle array by the electroosmotic flow, and at the same time, the user is set to such an extent that he does not feel any inconvenience. Preferably between 0.001 and 2 mA.

According to another embodiment, the controller 130 may apply a current at predetermined intervals, and the amount of current applied may be set to be the same. Also in this case, the amount of current is set to such a degree that the target substance to be measured can be moved to the needle array by the electroosmotic flow, and at the same time, the user is set to such an extent that no inconvenience is felt. Preferably between 0.001 and 2 mA.

Then, a measurement signal is generated by measuring the concentration of the target substance using the needle array (S1020). Specifically, the needle array includes a working electrode provided with an enzyme capable of reacting with a target substance, and the control unit 130 controls the current value of the working electrode and the counter electrode generated for the voltage applied between the working electrode and the reference electrode Can be generated as a measurement signal.

Then, the concentration of the target substance is calculated based on the generated measurement signal (S1030). Specifically, the controller 130 may calculate the concentration of the target substance by performing calculations using the relationship between the measured current and the applied voltage. The method of calculating the concentration of the target substance using the enzyme is obvious to those skilled in the biosensor field, and a detailed description thereof will be omitted.

Meanwhile, in the above-described embodiments, the concentration of the target substance to be measured is measured using the electrochemical detection method, but the present invention is not limited thereto. That is, any of the concentration measurement methods can be used as long as various embodiments of the present invention for rapidly diffusing a target substance into an intercellular fluid are applicable. For example, SERS (Surface-enhanced Raman spectroscopy), NIR (Near-infrared), Mid-IR (Mid-Infrared) or the like may be used as an optical detection method or ultrasonic waves or high frequency waves may be used.

In addition, in the above-described embodiments, the iontophoresis phenomenon by current application is used to rapidly diffuse the target substance into the intercellular fluid, but the present invention is not limited thereto. For example, various methods can be used, such as applying a pressure to the concentration measurement site (for example, using a band) and attaching a mechanism in a vaccuum state to the skin to draw blood toward the skin.

In this case, the amount of current applied can be adjusted according to the generated measurement signal. For example, when the concentration change rate of the target substance is greater than or equal to a specific value, the amount of applied current may be increased, and if the concentration change rate is less than a specific value, the amount of applied current may be decreased based on the generated measurement signal. For example, the concentration change rate is determined by the slope value of the measured concentration, and when the absolute value of the concentration gradient is 0.5 or more, a current larger than the basic current value can be applied.

The current may be applied through a plurality of electrodes included in the biosensor 100. [ For example, the plurality of electrodes may have a shape that can be attached to the surface of the skin, or a needle shape that can be inserted into the body.

On the other hand, the current may be applied continuously, or may be applied at predetermined intervals in the form of pulses. This can be set by the user.

In addition, the amount of heat applied by the heat generating part such as a heat wire included in the biosensor 100 can be adjusted according to the generated measurement signal. For example, based on the generated measurement signal, if the concentration change rate of the target substance is not less than a specific value, the calorific value is increased, and if the concentration change rate is less than the specific value, the calorific value can be reduced. For example, the concentration change rate is determined by the slope value of the measured concentration, and when the absolute value of the gradient of concentration is 0.5 or more in a state in which the predetermined basic calorific value is applied, a larger calorific value than the calorific value can be applied.

According to various embodiments described above, the sensing method may be implemented as a program including an executable algorithm that may be executed in a computer, the program being stored in a non-transitory computer readable medium . Such non-transiently readable media can be used in various devices.

A non-transitory readable medium is a medium that stores data for a short period of time, such as a register, cache, memory, etc., but semi-permanently stores data and is readable by the apparatus. In particular, the programs for carrying out the various methods described above may be stored in non-volatile readable media such as CD, DVD, hard disk, Blu-ray disk, USB, memory card, ROM and the like.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is clearly understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the invention as defined by the appended claims. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention.

100: Biosensor 110: Needle array
120: power applying unit 130:

Claims

In the biosensor,
A needle array insertable into the body for measuring the concentration of a substance of interest;
A power applying unit configured to apply a current to the biometric contact area of the needle array such that the target material moves to the needle array; And
And a controller for calculating a concentration of the target substance based on a signal generated in the needle array.

The method according to claim 1,
Wherein,
And controls the power applying unit to adjust the amount of the applied current according to a signal generated in the needle array.

3. The method of claim 2,
Wherein,
If the concentration change rate of the target substance is greater than or equal to a predetermined value based on a signal generated in the needle array, the amount of applied current is increased, and if the concentration change rate of the target substance is less than a predetermined value, The control unit controls the power application unit to control the power supply unit.

The method according to claim 1,
The power-
And a plurality of electrodes for applying a current to the living body region,
Wherein the plurality of electrodes are disposed adjacent to the needle array.

5. The method of claim 4,
Wherein the plurality of electrodes comprise:
Wherein the biosensor is a shape that can be placed on the surface of the skin.

5. The method of claim 4,
Wherein the plurality of electrodes comprise:
Wherein the biosensor has a needle shape.

The method according to claim 1,
The needle array includes:
Wherein the biosensor comprises a counter electrode, a reference electrode, and a working electrode provided with an enzyme capable of reacting with the target substance.

The method according to claim 1,
Wherein,
And controls the power application unit so that current is applied at predetermined intervals.

The method according to claim 1,
Wherein the needle array includes a support having a plurality of needles arranged therein.

10. The method of claim 9,
The support portion
Wherein the biosensor has a wearable band shape.

The method according to claim 1,
Further comprising: a heating unit for applying heat to a surrounding biocontact area adjacent to the biocontact area of the needle array.

12. The method of claim 11,
Wherein,
Wherein the control unit controls the heating unit to decrease the heating value when the concentration change rate of the target substance is greater than or equal to a predetermined value based on a signal generated in the needle array and if the concentration change rate of the target substance is less than a predetermined value, Wherein the biosensor is a biosensor.

A sensing method of a biosensor including a needle array insertable into a body,
Applying an electrical current to the biocontact region of the needle array such that the target material moves into the needle array;
Measuring a concentration of the target substance using the needle array to generate a measurement signal; And
And calculating the concentration of the target substance based on the generated measurement signal.

14. The method of claim 13,
The step of applying the current comprises:
And adjusting an amount of current applied according to the measurement signal.

15. The method of claim 14,
The step of applying the current comprises:
Increasing the amount of applied current when the concentration change rate of the target substance is greater than or equal to a predetermined value based on the generated measurement signal and decreasing the amount of applied current when the concentration change rate of the target substance is less than a predetermined value A sensing method characterized by:

14. The method of claim 13,
The step of applying the current comprises:
Wherein a current is applied through a plurality of electrodes included in the biosensor.

14. The method of claim 13,
Wherein the step of generating the measurement signal comprises:
Wherein the measurement signal is generated using a working electrode provided with a counter electrode, a reference electrode, and an enzyme capable of reacting with the target substance contained in the needle array Sensing method.

14. The method of claim 13,
The step of applying the current comprises:
And a current is applied at predetermined intervals.

14. The method of claim 13,
And applying heat to a surrounding biocompatible area adjacent to the biocontact area of the needle array through a heating part included in the biosensor.

20. The method of claim 19,
Wherein applying the heat comprises:
Wherein the calorific value is increased if the concentration change rate of the target substance is greater than or equal to a predetermined value based on the generated measurement signal and the calorific value is decreased if the concentration change rate of the target substance is less than a predetermined value.