Biological substance cumulative amount measurement device and biological substance cumulative amount measurement method

Abstract

A biological substance cumulative amount measurement device 1 for measuring a cumulative amount of a biological substance generated in a living body, said device including: a biofuel cell 20 for generating power using a specific biological substance 13 as a substrate; a power storage unit 40 for storing electric energy generated through power generation by the biofuel cell 20; and a communication unit 50 for outputting information on the electric energy stored in the power storage unit 40 in response to a trigger from the outside.

Description

Biomass Accumulation Measurement Device and Biomass Accumulation Measurement Method

[0001] The present invention relates to a biomass accumulation measurement device and a biomass accumulation measurement method.

[0002] Some sensors for measuring the amount of ketone bodies generated in the living body by fat metabolism are known. Patent Document 1 discloses a sensor for measuring the concentration of ketone bodies in blood. Patent Document 2 discloses a sensor for measuring the concentration of ketone bodies in urine. Patent Document 3 discloses a sensor for measuring the concentration of ketone bodies in exhaled breath.

[0003] Further, Patent Document 4 discloses a lactate sensor applying a biofuel cell. Patent Document 5 also discloses a device combining a sensor (biofuel cell, power generation unit) and a capacitor (power storage unit).

[0004] Japanese Patent Application Laid-Open No. 2022-185218, Japanese Patent Application Laid-Open No. 2019-144248, Japanese Patent Application Laid-Open No. 2017-207424, Japanese Patent Application Laid-Open No. 2020-134344, International Publication No. 09 / 037840

[0005] The ketone body amount sensors disclosed in Patent Documents 1, 2, and 3 are intended to measure the instantaneous ketone body concentration at the time of measurement and to determine the pathological condition at the measurement time point. On the other hand, in order to determine the success or failure of a diet under carbohydrate restriction (ketogenic diet), it is necessary to measure the amount of fat burned (accumulated amount of fat burning) over a certain period under carbohydrate restriction.

[0006] Patent Document 4 uses a biofuel cell as a sensor, but is characterized in using the generated electrical energy as energy for self-driving. Since the sensor uses the electromotive force (current value) of the biofuel cell as an index, it is not a device for measuring the integrated amount of an object.

[0007] Patent Document 5 features a biofuel cell used as a sensor, which stores energy needed for self-propulsion and intermittently activates external communication (radio wave transmission) once a certain amount of energy has been accumulated. As a sensor, it uses the frequency of external communication as an indicator, and therefore does not provide instantaneous measurements. Rather, it is a device that indicates whether the concentration of the target substance is increasing or decreasing at the time of measurement. This is also not a device that measures the cumulative amount of the target substance.

[0008] This invention has been made in view of the above-mentioned circumstances, and aims to provide a biomaterial cumulative amount measuring device that can measure the cumulative amount of biomaterials generated in a living body.

[0009] The biomaterial cumulative amount measuring device of the present invention is a measuring device for measuring the cumulative amount of biomaterials generated in a living body, and comprises a biofuel cell that generates electricity using a specific biomaterial as a substrate, a power storage unit that stores the electrical energy generated by the biofuel cell, and a communication unit that outputs information of the electrical energy stored in the power storage unit in response to an external trigger.

[0010] The present invention relates to a method for measuring the cumulative amount of biomaterials, which uses the biomaterial cumulative amount measuring device of the present invention, wherein a specific biomaterial is used as a substrate to generate electricity using the biofuel cell, the electrical energy generated by the biofuel cell is stored in the energy storage unit, and information on the electrical energy stored in the energy storage unit is output from the communication unit by an external trigger.

[0011] According to the present invention, it is possible to provide a biomolecular cumulative amount measuring device that can measure the cumulative amount of biomolecules generated in a living organism.

[0012] Figure 1 shows an example of the use of the biomaterial accumulation measurement device. Figure 2 is a schematic cross-sectional view of a biofuel cell and skin tissue when a biofuel cell is in use. Figure 3 is a schematic diagram showing an example of the configuration of the biomaterial accumulation measurement device. Figure 4 is a schematic diagram showing an example of the configuration of a biomaterial accumulation measurement device equipped with a receiving unit. Figure 5 is a schematic diagram showing a detailed example of the configuration of a biomaterial accumulation measurement device. Figure 6 is a schematic diagram showing another example of the configuration of a biomaterial accumulation measurement device.

[0013] The present invention will now describe the apparatus and method for measuring the cumulative amount of biomolecules. However, the present invention is not limited to the following configurations and can be modified and applied as appropriate without altering the essence of the invention. Furthermore, a combination of two or more of the preferred configurations of the present invention described below also constitutes the present invention.

[0014] The biomaterial cumulative amount measuring device of the present invention is a measuring device for measuring the cumulative amount of biomaterials generated in a living body, and comprises a biofuel cell that generates electricity using a specific biomaterial as a substrate, a power storage unit that stores the electrical energy generated by the biofuel cell, and a communication unit that outputs information of the electrical energy stored in the power storage unit in response to an external trigger.

[0015] Figure 1 shows an example of the use of the biomaterial accumulation measurement device. The biomaterial accumulation measurement device 1 shown in Figure 1 is attached to a living body (a person's right arm in Figure 1) when in use. The biomaterial accumulation measurement device 1 comprises a biofuel cell 20 and an external circuit 30. The biofuel cell 20 has a biomaterial acquisition unit 21 in the part that comes into contact with the living body. The biomaterial acquisition unit 21 has a microneedle 25 as a projection. When the microneedle 25 is pressed against the skin of the living body, the microneedle 25 penetrates the skin. From the microneedle 25, the biomaterial that will serve as the substrate is drawn into the biomaterial accumulation measurement device 1.

[0016] On the side of the biomaterial accumulation measuring device 1 opposite to the microneedle 25, a biofuel cell 20 is provided that generates electricity using the aspirated biomaterial as a substrate.

[0017] Figure 2 is a schematic cross-sectional view of a biofuel cell and skin tissue during use. The biofuel cell 20 is equipped with a biomaterial acquisition section 21 in the part that comes into contact with the living body. The biomaterial acquisition section 21 comprises a base material 24 and a biomaterial introduction section provided on the adhesive surface 23 of the base material 24. The biomaterial introduction section has microneedles 25 as protrusions.

[0018] A battery section 22, which functions as a battery in the biofuel cell 20, is provided on the surface of the substrate 24 opposite to the microneedle 25. In the battery section, the anode (fuel electrode) 26 is positioned in contact with the substrate 24, and a separator 28 and a cathode (reducing electrode) 27 are stacked on top of it in that order, with the anode 26 and cathode 27 connected by an external circuit 30.

[0019] Figure 2 shows skin tissue 14, which is part of a living organism. Adipocytes 15 and interstitial fluid 10 are present within the skin tissue 14.

[0020] Microneedles 25 penetrate the skin and reach the interstitial fluid 10. Biomolecules 13, which are generated in the body and present in the interstitial fluid 10, reach the anode 26 through the microneedles 25. The anode 26 holds a biomolecule-dependent enzyme 11 corresponding to a specific biomolecule, and the biomolecule 13 reacts with the biomolecule-dependent enzyme 11. An example of the structure of the anode 26 is a structure in which the biomolecule-dependent enzyme 11 is held on a carrier such as porous carbon. Alternatively, a mesh-structured sheet may be provided between the microneedles 25 and the carrier, allowing the biomolecule 13 to permeate the mesh structure. The reaction between the biomolecule 13 and the biomolecule-dependent enzyme 11 is usually an oxidation reaction of the biomolecule 13, and this reaction generates electrons and protons. The generated electrons and protons move to the cathode 27 via the external circuit 30 and separator 28, respectively. At the cathode 27, oxygen is reduced by oxygen reductase 12, generating electrical energy, and the battery section 22 functions as a battery. An example of the structure of the cathode 27 is a structure similar to that of the anode 26, in which oxygen reductase 12 is held on a carrier such as porous carbon. Alternatively, a mesh-structured sheet may be provided on the outside of the cathode 27, so that oxygen is supplied to the cathode by permeating through the mesh structure.

[0021] The structure of the microneedle is not particularly limited as long as it can introduce biomolecules contained in the interstitial fluid into the battery section, but it is preferably a porous and / or hollow body. More preferably a porous body. When the microneedle is a porous body, in addition to diffusion based on the concentration gradient of biomolecules contained in the interstitial fluid, the biomolecules can be introduced into the battery section by the capillary force of the porous body, thus improving the efficiency of biomolecules introduction.

[0022] The shape of the microneedle is not particularly limited as long as it can be inserted into the skin, but it is preferable that it be conical or pyramidal in shape. More preferably, it is conical.

[0023] The material of the microneedles is preferably a biocompatible polymer, metal, resin, etc., that is not harmful to living organisms. Specifically, examples of materials for the protrusions include alginate, hyaluronic acid, curdlan, chitin, chitosan, glucomannan, polymalic acid, collagen, collagen peptide, hydroxypropyl cellulose, gelatin, silicon, titanium, silicone, polylactic acid (PLA), polyglycolic acid (PLA), PLA-PGA copolymers, etc., or plasma-treated versions thereof. Among these, biodegradable materials (biosoluble materials) are more preferable, and even more preferably hyaluronic acid, collagen, and polylactic acid, with polylactic acid being particularly preferred.

[0024] The length of the microneedle is not particularly limited as long as it can be inserted into the skin, but it is preferably 100 μm or more and 3000 μm or less. This allows for less invasive introduction of biological material into the battery. The length of the projection is more preferably 150 μm or more and 1500 μm or less, even more preferably 150 μm or more and 1000 μm or less, and particularly preferably 200 μm or more and 800 μm or less.

[0025] The diameter of the base of the microneedle (maximum diameter of the projection) is preferably 50 μm or more and 1000 μm or less. This allows for less invasive skin insertion. More preferably, the diameter of the base of the microneedle is 100 μm or more and 800 μm or less.

[0026] The number of microneedles in the biomaterial introduction section is not particularly limited, but it is preferably 25 or more and 250,000 or less. More preferably 2,500 or more and 50,000 or less.

[0027] There are no particular restrictions on the density of microneedles in the biomaterial introduction section, but it is 1 needle / cm². ２ That's 10,000 pieces / cm ２ The following is preferable. More preferably 100 strands / cm ２ That's 2000 pieces / cm. ２ The following applies:

[0028] The method for manufacturing the microneedles in the biomaterial introduction section is not particularly limited, but examples include injection molding of the material that forms the microneedles.

[0029] Examples of biomolecules include substances produced during the metabolism of fats and sugars. Examples of biomolecules produced during fat metabolism include ketone bodies and glycerol. When the biomolecule is a ketone body, it is preferable that the fuel electrode is equipped with ketone body dehydrokenase. When the biomolecule is glycerol, it is preferable that the fuel electrode is equipped with glycerol dehydrokenase.

[0030] Lactic acid is an example of a biomolecule produced during sugar metabolism. When the biomolecule is lactic acid, it is preferable that the fuel electrode be equipped with lactate dehydrogenase. The degree of lactic acid accumulation can serve as an indicator of fatigue. By measuring the cumulative amount of lactic acid, it is possible to estimate the rate of sugar metabolism, the degree of fatigue, and the cause of fatigue.

[0031] By pre-determining the biomolecular-response enzymes present in the fuel electrode, an electromotive force is generated in the biofuel cell when biomolecular-response enzymes react with biomolecular-response enzymes in the interstitial fluid. The electrical energy generated by the biofuel cell is stored in the energy storage unit, and the cumulative amount of biomolecular-response enzymes reacting with the interstitial fluid can be measured from the information on the amount of electrical energy stored in the energy storage unit.

[0032] In other words, if the fuel electrode is equipped with ketone body dehydrokenase, the cumulative amount of ketone bodies will be measured, and if the fuel electrode is equipped with glycerol dehydrokenase, the cumulative amount of glycerol will be measured. By setting the biomolecule-compatible enzyme equipped in the fuel electrode, the cumulative amount of the target biomolecule can be measured.

[0033] Furthermore, if the biomaterial accumulation measuring device is a device that measures the accumulated amount of glycerol, a lipolytic enzyme such as lipase may be loaded onto the biomaterial acquisition part, and by inserting this into the skin, the lipolytic enzyme may be released into the body to break down fat. By measuring the accumulated amount of glycerol obtained by fat breakdown, the amount of fat breakdown can be measured.

[0034] Figure 3 is a schematic diagram showing an example of the configuration of a biomaterial accumulation measurement device. The biomaterial accumulation measurement device 1 shown in Figure 3 comprises a biofuel cell 20, a power storage unit 40, and a communication unit 50. Electrical energy generated by the biofuel cell 20 can be stored in the power storage unit 40, and information about the electrical energy stored in the power storage unit 40 can be output from the communication unit 50. The microneedle 25 of the biomaterial acquisition unit 21 is inserted into the skin tissue 14, which is a living organism.

[0035] The energy storage unit is the part that stores the electrical energy generated by the biofuel cell. The energy storage unit is preferably capable of both storing and discharging energy, and is preferably a capacitor or a secondary battery. If the energy storage unit is capable of both storing and discharging energy, the biomaterial accumulation measurement device can be used repeatedly. If the energy storage unit is a capacitor, the type of capacitor is not limited, and multilayer ceramic capacitors, electrolytic capacitors, film capacitors, electric double-layer capacitors, etc., can be used. If the energy storage unit is a capacitor, the capacitor may be an electronic component (chip component), or it may be a capacitor unit provided as part of the wiring of a circuit board.

[0036] If the energy storage unit is a secondary battery, the type of secondary battery is not limited, and lithium-ion secondary batteries, nickel-metal hydride secondary batteries, etc., can be used.

[0037] The communication unit outputs information about the electrical energy stored in the power storage unit in response to an external trigger. The communication unit is preferably a wireless communication circuit. Furthermore, it is preferable that the communication unit uses a communication device (RFID device) employing RFID (Radio Frequency Identification) technology, and specifically, a short-range wireless communication circuit (NFC circuit) is provided. An external trigger could be the proximity of a device such as a smartphone to the communication unit. When a smartphone approaches the communication unit, power is generated by electromagnetic induction, and this power is used for communication. In other words, the biomaterial accumulation measuring device of the present invention does not use the electrical energy stored in the power storage unit as energy for communication in the communication unit. Although communication is performed using power generated by an external trigger, the power required for communication is small, and can be sufficiently supplied by the power generated by the external trigger, thus eliminating the need for other power sources for communication.

[0038] In this specification, "bringing the trigger device and the communication unit close together" includes changing the distance between the trigger device and the communication unit in a direction that reduces their proximity, and bringing the trigger device and the communication unit close together and making contact (touching).

[0039] Trigger devices include smartphones, smartwatches, IC cards, and exercise equipment such as treadmills. When the trigger device is a mobile device such as a smartphone or smartwatch, power is generated by bringing the mobile device close to the communication unit of the biomaterial accumulation measuring device. On the other hand, when the trigger device is a stationary device such as a treadmill, power is generated by bringing the communication unit of the biomaterial accumulation measuring device close to a designated part of the stationary device.

[0040] The biomaterial accumulation measuring device may further include a receiving unit. The receiving unit is the part that receives information on the electrical energy stored in the energy storage unit, which is output from the communication unit, and is a device that is physically separated from the biofuel cell, energy storage unit, and communication unit.

[0041] Figure 4 is a schematic diagram showing an example of the configuration of a biological substance integrated amount measuring device including a receiving unit. Figure 4 shows a receiving unit 60 that receives information output from the communication unit 50 of the biological substance integrated amount measuring device 1 shown in Figure 3. The receiving unit 60 is a device physically separated from the biofuel cell 20, the power storage unit 40, and the communication unit 50.

[0042] If the receiving unit is a device that serves as an external trigger for the communication unit, it is possible to receive information from the communication unit almost simultaneously with the generation of power by the communication unit, and since the distance between the communication unit and the receiving unit during information reception is short, communication can be performed with extremely low power, which is preferable. Examples of the receiving unit include mobile devices such as smartphones and smartwatches, and exercise devices such as running machines.

[0043] Further, it is preferable that the biological substance integrated amount measuring device further includes an output unit that outputs the information received by the receiving unit. Examples of the output unit include the displays of various devices such as smartphones, smartwatches, and running machines. The receiving unit and the output unit may be physically integrated devices. Since devices such as smartphones have their own power sources, the output unit can be operated by power supplied from the power source.

[0044] Furthermore, the same device as the receiving unit and the output unit may include a storage unit (memory, SSD, etc.) where the information received by the receiving unit is recorded, and a control unit (CPU, etc.) that performs calculations on the information received by the receiving unit. If the device as the receiving unit and the output unit is a smartphone, a smartwatch, a running machine, etc., it can include both the storage unit and the control unit. The receiving unit, the storage unit, and the control unit may be physically integrated devices. Since devices such as smartphones have their own power sources, the storage unit, the control unit, etc. can be operated by power supplied from the power source.

[0045] Taking the case where the triggering device is a smartphone and the integrated amount of ketone bodies is measured as an example, the operation of the entire biological substance integrated amount measuring device is shown. When the smartphone approaches the communication unit, electric power is generated by electromagnetic induction. With the generated electric power, information on the electrical energy stored in the power storage unit is output from the communication unit, and the smartphone receives the information. The information is converted into the integrated amount of fat burning by the control unit. Since the information is the information on the electrical energy stored in the power storage unit, the amount of ketone bodies consumed by the biofuel cell is calculated from the magnitude of the electrical energy, and the fat burning amount is calculated from the amount of ketone bodies. By combining the information on the driving time of the biological substance integrated amount measuring device, the integrated amount of fat burning amount within the driving time (for example, within the time of exercise) can be obtained. By displaying the integrated amount of fat burning amount on the display (output unit) of the smartphone, the user can confirm the integrated amount of fat burning amount.

[0046] FIG. 5 is a schematic diagram showing an example of the configuration of the biological substance integrated amount measuring device in detail. In FIG. 5, the power storage unit 40 is shown by the circuit symbol of a capacitor. The communication unit 50 is a unit in which an ADC (Analog / Digital converter) 80 and an NFC circuit 90 are integrated into one chip. An AMP (amplifier) 70 is connected to the chip of the communication unit 50, and the power generated by the NFC circuit 90 is supplied to the AMP 70 with the proximity of the receiving unit 60 as a trigger. The information (voltage) on the electrical energy stored in the power storage unit 40 is amplified by the AMP 70, and the voltage information is read by the ADC 80. The information read by the ADC 80 is output from the NFC circuit 90.

[0047] The biomaterial accumulation measuring device of the present invention may be configured for use without direct contact with the living body. Figure 6 is a schematic diagram showing another example of the configuration of the biomaterial accumulation measuring device. The biomaterial accumulation measuring device 2 shown in Figure 6 does not have a biomaterial acquisition unit that comes into contact with the living body. Biomaterials contained in sweat vaporized on the surface of skin tissue 14 can be used as a substrate to generate electricity using a biofuel cell 20. Sweat may contain ketones, and the amount of ketones in sweat increases in particular when dieting under carbohydrate restriction. Therefore, by measuring the accumulated amount of ketones in sweat, the amount of fat burned over a certain period under carbohydrate restriction can be measured.

[0048] In order to introduce biomolecules contained in sweat into a biofuel cell, it is preferable that the surface of the fuel electrode of the biofuel cell be equipped with a porous structure that absorbs sweat, or a highly permeable structure (such as a mesh structure). In addition to sweat, ketone bodies may also be contained in gases emitted from the skin (body odor) and exhaled breath, so biomolecules such as ketone bodies contained in exhaled breath can be used as a substrate to generate electricity using a biofuel cell.

[0049] The present invention relates to a method for measuring the cumulative amount of biomaterials, which uses the biomaterial cumulative amount measuring device of the present invention, wherein a specific biomaterial is used as a substrate to generate electricity using the biofuel cell, the electrical energy generated by the biofuel cell is stored in the energy storage unit, and information on the electrical energy stored in the energy storage unit is output from the communication unit by an external trigger.

[0050] An embodiment of the measurement method is as described above as a method for using the biomaterial cumulative amount measuring device of the present invention. In the biomaterial cumulative amount measuring method of the present invention, the biofuel cell is provided with a biomaterial acquisition unit in the part that comes into contact with the living body, the biomaterial acquisition unit comprises a substrate and a biomaterial introduction unit, the biomaterial introduction unit has a projection, and it is preferable to insert the projection into the living body and introduce the biomaterial that will serve as the substrate into the biofuel cell from the projection.

[0051] When the biomaterial accumulation measuring device of the present invention is used repeatedly, it is preferable to replace the biomaterial acquisition unit. If the biomaterial acquisition unit comprises a substrate and microneedles, it is preferable to replace the substrate and microneedles together. That is, it is preferable that the biomaterial acquisition unit is detachable and disposable. Alternatively, the entire biofuel cell, including the biomaterial acquisition unit, may be replaced. The biofuel cell can be used as a disposable item. The energy storage unit and communication unit can be used repeatedly.

[0052] 1, 2 Biomaterial Accumulation Measurement Device 10 Interstitial fluid 11 Biomaterial-compatible enzyme 12 Oxygen reductase 13 Biomaterial 14 Skin tissue 15 Adipose cells 20 Biofuel cell 21 Biomaterial acquisition unit 22 Battery unit 23 Application surface 24 Substrate 25 Microneedle (protrusion, biomaterial introduction unit) 26 Anode 27 Cathode 28 Separator 30 External circuit 40 Energy storage unit 50 Communication unit 60 Receiving unit 70 AMP (Amplifier) ​​80 ADC (Analog / Digital Converter) 90 NFC circuit

Claims

1. A measuring device for measuring the cumulative amount of biomolecules produced in a living organism, comprising: a biofuel cell that generates electricity using a specific biomolecule as a substrate; a power storage unit that stores the electrical energy generated by the biofuel cell; and a communication unit that outputs information about the electrical energy stored in the power storage unit in response to an external trigger.

2. The biofuel cell is provided with a biomaterial acquisition unit in the part that comes into contact with a living body, the biomaterial acquisition unit comprises a base material and a biomaterial introduction unit, and the biomaterial introduction unit has a protrusion, the biomaterial cumulative amount measuring device according to claim 1.

3. The biomaterial cumulative amount measuring device according to claim 1 or 2, wherein the specific biomaterial is a ketone body, and the fuel electrode of the biofuel cell is equipped with ketone body dehydrokenase.

4. The biomaterial cumulative amount measuring device according to claim 1 or 2, wherein the specific biomaterial is glycerol, and the fuel electrode of the biofuel cell is equipped with glycerol dehydrokenase.

5. The biomaterial accumulation measurement device according to any one of claims 1 to 4, wherein the energy storage unit is a capacitor or a secondary battery.

6. The biomaterial cumulative amount measuring device according to any one of claims 1 to 5, wherein the communication unit is a wireless communication circuit.

7. The biomaterial cumulative amount measuring device according to any one of claims 1 to 6, wherein the communication unit is an RFID device.

8. A biological substance cumulative amount measuring device according to any one of claims 1 to 7, further comprising: a receiving unit that receives information from the communication unit; and an output unit that outputs the information received by the receiving unit.

9. A method for measuring the cumulative amount of biomaterials using the biomaterial cumulative amount measuring device described in any one of claims 1 to 8, wherein electricity is generated by the biofuel cell using a specific biomaterial as a substrate, the electrical energy generated by the biofuel cell is stored in the energy storage unit, and information on the electrical energy stored in the energy storage unit is output from the communication unit by an external trigger.

10. The biofuel cell is provided with a biomaterial acquisition unit in the part that comes into contact with a living body, the biomaterial acquisition unit comprises a substrate and a biomaterial introduction unit, the biomaterial introduction unit has a projection, the projection is inserted into a living body, and a biomaterial that will serve as a substrate is introduced into the biofuel cell from the projection, the method for measuring the cumulative amount of biomaterial according to claim 9.

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