Patent Application
20220091036
The present disclosure relates to optical measurement instruments and measurement methods for measuring trace substances.
The concentration and other properties of a substance in solution can be estimated or identified by optical measurements.
So far, in order to measure the concentration of a measurement target substance in a solution, the absorbance measurement method is used as an example. As measurement apparatus, cells and cuvettes for spectrophotometers are commonly used, which require a relatively large volume of a few mL of solution using a transparent cell such as a square glass or quartz or plastic having an optical path length of about 10 mm. Recently, there has been a desire to measure trace substances from trace samples such as interstitial fluid and tear fluid with high sensitivity.
When the concentration of the target substance to be measured is low, it is impossible to increase the amount of liquid by dilution, and it is difficult to obtain a certain optical path length and measure the concentration of the substance from a sample of a trace liquid amount with high sensitivity.
According to one embodiment of the present disclosure, an apparatus for measuring a substance in a solution comprises a light source, a micro flow channel including at least a portion of an optical path of light emitted from the light source and extending along the optical path, and a photodetector for detecting light that has passed through the micro flow channel.
1. Measurement Apparatus
In some embodiments of the present disclosure, there is provided an apparatus for measuring properties such as physical properties and the concentration of a substance in a solution by an optical method. The measurement apparatus has a light source, a photodetector and a flow channel. All or a portion of the light emitted from the light source enters the flow channel. All or a portion of the light has passed through the flow channel enters the photodetector. The flow channel may be formed to be elongated in the longitudinal direction. The optical path may be defined along the longitudinal direction of the flow channel. The light may propagate within the flow channel along the longitudinal direction of the flow channel. The light that has passed through the channel is received by the photodetector. The light source may be disposed outside of the flow channel, may be disposed on a wall of the flow channel, or may be disposed within the flow channel. The photodetector may be disposed outside of the flow channel, may be disposed on a wall of the flow channel, or may be disposed within the flow channel.
The optical method used may be a spectroscopic method, an absorbance spectroscopy, or other methods. The measurement apparatus may have a configuration of a colorimeter or an absorbance spectroscope for measuring the absorbance (or transmittance) of light of a specific wavelength, and may have a configuration of a colorimeter, a color difference meter, or the like. The measurement apparatus may or may not use practically specific scientific methods. The measurement apparatus may be configured to determine a characteristic such as an unknown concentration from the output of the photodetector at the time of measurement based on the relationship between the output of the photodetector and the characteristic such as the concentration.
The light source is configured to emit electromagnetic waves. In some embodiments, the wavelength of the light source may be determined according to the absorption properties of the substance as a measurement target. In some embodiments, the wavelength of the light source may be determined based on a factor other than the absorbance characteristic of the substance as measurement target, and may be determined based on a plurality of factors.
The wavelength of the light source may be visible in some embodiments, infrared in some embodiments, or ultraviolet in some embodiments. The wavelength of the light source may be between 200 and 1500 nm (nanometers, hereinafter the same) and may be between 560 and 700 nm.
In some embodiments, the light source may be a light emitting diode (LED). In some embodiments, the light source may be a laser light source. In some embodiments, the light emission of the light source may be electroluminescence, organic EL (electroluminescence, hereinafter the same), inorganic EL, chemiluminescence, electrochemiluminescence.
In some embodiments, the flow channel may be a micro flow channel. In some embodiments, the volume of the flow channel may be smaller than or equal to a value such as 100 μL (microliter, hereinafter the same), 50 μL, 20 μL, 10 μL, 5 μL and the like.
The dimension of the cross-section of the flow channel, e.g., the cross-section perpendicular to the optical path of the portion in which the optical path is located, may be smaller than or equal to a value such as 3 mm, 2 mm, 1 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, and the like. The cross-sectional dimension may be the diameter of a circle, the dimension of the largest portion, or the dimension of the smallest portion.
In some embodiments, the light source may be fixed relative to the flow channel. In some embodiments, the photodetector may be fixed relative to the flow channel. In some embodiments, the flow channel or the member including the flow channel may be configured to be detachable from the light source and the photodetector.
The volume of the flow channel may be a volume of a portion in which the optical path is defined, or may include a volume of a portion other than a portion in which the optical path is defined, such as a liquid introduction path or a discharge portion. The volume of the flow channel may be smaller than or equal to 100 μL, 50 μL, 20 μL, 15 μL, 10 μL, 9 μL, 8 μL, 7 μL, 6 μL, 5 μL, 4 μL, 3 μL, 2 μL, 1 μL, 0.9 μL, 0.8 μL, 0.7 μL, 0.6 μL, 0.5 μL, and the like. The volume of the flow channel may be greater than or equal to 0.01 μL, 0.05 μL, 0.07 μL, 0.1 μL, 0.2 μL, 0.3 μL, 0.4 μL, 0.5 μL, 0.6 μL, 0.7 μL, 0.8 μL, 0.9 μL, 1 μL, and the like.
The cross section of the flow channel in which the optical path is defined may be circular, elliptical, a closed figure defined by a curve, or a square, a rectangular parallelepiped, or other polygons.
The length of the optical path in the flow channel may be greater than or equal to a value such as 2 mm, 3 mm, 4 mm, 5 mm, 7 mm, 10 mm, 12 mm, 15 mm, 20 mm, 25 mm, 30 mm, and the like. The length of the optical path in the micro flow channel may be less than or equal to a value such as 100 mm, 90 mm, 80 mm, 70 mm, 60 mm, 50 mm, 40 mm, 30 mm, or the like.
In some embodiments, the flow channel may have an inlet for introducing a solution and an outlet for discharging the solution. By having an inlet and an outlet, it is possible to substantially avoid, for example, air or air bubbles from remaining in the flow channel at the time of introducing the solution, and to facilitate replacement of the solution. In some embodiments, the inlet and the outlet may be the same and may have an air hole. In some embodiments, the flow channel of the portion where the optical path is defined may have an inlet and an outlet of the solution in the flow channel at both ends.
In some embodiments, some or all of the inner walls of the flow channel may be hydrophilic. It is expected that the hydrophilic micro flow channel reduces a non-uniform distribution when the solution is introduced into the micro flow channel and avoids the generation of bubbles.
In some embodiments, the photodetector may include a photodiode. In some embodiments, the photodetector may include a device for measuring brightness. The photodetector may be a CCD, a photomultiplier, a scintillator, or the like. In some embodiments, the photodetector may be a spectrometer.
A solution 132 including a measurement target substance 131 is introduced from the inlet 112. From the outlet 113, the solution 132 can be discharged from the flow channel 111 by suction or pressurization from the inlet 112. Outside both ends of the optical path 123 in the flow channel 111, a light source 121 and a photodetector 122 are disposed. In
In some embodiments, the solution inlet and outlet may be fluidly coupled to the flow channel at an entrance end (one end) and an exit end (the other end). In some embodiments, the inlet and the outlet may be fluidly coupled at both ends of the optical path in the flow channel. In some embodiments, the inlet and the outlet may be arranged such that no dead space is substantially formed in the flow channel or such that a dead space is avoided. Thus, the arrangement of the inlet and the outlet substantially avoids air bubbles from forming in the flow channel and affecting the optical measurement, such as during the introduction of the solution.
In some embodiments, the apparatus may further include a shield configured to prevent light from other than the light source from being substantially detected by the photodetector.
In some embodiments, the apparatus or the flow channel may be disposed in a shielded box. In some embodiments, it may be a flow channel member having a shielding function.
In some embodiments, the member forming the flow channel may include a shielding material.
In some embodiments, the light source may have a plurality of peak wavelengths. In some embodiments, the light source may include two or more light sources. The plurality of light sources may generate electromagnetic waves or light of a plurality of wavelengths or a plurality of wavelength regions different from each other. In some embodiments, the peak wavelength (the wavelength at which the output value is the highest among the ranges or spectral distributions of light emission) of a light source may be different from at least one of the plurality of light sources. In some embodiments, one peak wavelength (or frequency) may be a wavelength (or frequency) characteristic of the absorption characteristic of the measurement target substance or a wavelength in its vicinity, and the other peak wavelength may be a wavelength (or frequency) having no influence or less influence of the absorption characteristic. In some embodiments, the light source may include a plurality of light sources each having a different peak wavelength.
In
In some embodiments, the apparatus may be configured to introduce light from only one of the plurality of light sources into the optical path. In some embodiments, the apparatus may further comprise a light source control mechanism for selecting a light source in such a manner. In some embodiments, the apparatus may have a mechanism or a light source control mechanism that passes only the light used for the measurement and blocks the light not used for the measurement. In some embodiments, it may have a drive controller of the light source for driving only the light source for emitting the peak wavelength used for measurement and not driving the other light sources. In some embodiments, the apparatus may include a drive controller for controlling the light emission of the plurality of light sources. In some embodiments, the light source control mechanism may include a drive controller for controlling the emission of the plurality of light sources.
In some embodiments, the apparatus may have an additional photodetector (which may alternatively be referred to as second photodetector, adjustment photodetector, or the like). The adjustment photodetector can be used to observe or measure the emission of the light source to control the emission of the light source. Such a photodetector may be disposed outside the light path of the light emitted by the light source, and may be configured to receive and measure a portion of the light emitted by the light source.
In some embodiments, the apparatus may include a controller that receives information (for example, intensity or brightness of received light) regarding the light characteristics from the adjustment photodetector and controls the light emission of the light source. The controller may control the amount of light emitted by the light source to be substantially constant over time.
In some embodiments, the apparatus may be configured to regulate the temperature of the solution in the flow channel. In some embodiments, the apparatus may further comprise a temperature controller or adjuster that regulates the temperature of the solution in the flow channel.
In some embodiments, the temperature within the flow channel may be controlled by regulating or keeping constant the temperature outside of the apparatus or outside of the members forming the micro flow channels. The temperature of the atmosphere of the components forming the apparatus or the micro flow channel may be regulated, and the temperature of the portions or blocks in contact therewith may be regulated.
The temperature in the micro flow channel or near the micro flow channel may be measured by a temperature sensor. Temperature control may be performed using measured temperature information (temperature, changes in temperature, calculations based on multiple temperature measurements, and the like).
In some embodiments, the apparatus may include a heater. The heater may be disposed in the vicinity of the micro flow channel. The heater may be configured to control the temperature of the solution.
In some embodiments, the member forming the flow channel may have a higher heat capacity than the solution in the flow channel. If the heat capacity of the member around the solution is large enough, the temperature of the solution will become substantially the temperature of the same member.
In some embodiments, all or at least a portion of the member forming the flow channel may be formed of a material having a high thermal conductivity, may be formed of, for example, a metal such as copper, iron, stainless steel and the like or an alloy.
The optical measurement apparatus 300 of
In
Photodetector 322 has a photodiode in
In
In some embodiments, the apparatus may have a plurality of flow channels. Each flow channel may define a corresponding optical path.
In some embodiments, the apparatus may have a first flow channel and a second flow channel, wherein the first flow channel includes or defines a first optical path and the second flow channel includes or defines a second optical path. The first optical path and the second optical path are optical paths in which light emitted from the light source propagates. In some embodiments, the apparatus may include a first photodetector for detecting light that has passed through the flow channel and a second photodetector for detecting light that has passed through the second flow channel.
In some embodiments, the light source may include a plurality of light sources. In some embodiments, each of the different light sources may correspond to a respective flow channel. In some embodiments, the light source includes a first light source and a second light source, and the light path may include a first light path through which light emitted from the first light source propagates and a second light path through which light emitted from the second light source propagates. In some embodiments, the flow channel may include a first flow channel extending along the first optical path and a second flow channel extending along the second optical path. In some embodiments, the photodetector may include a first photodetector for detecting light that has passed through the first flow channel and a second photodetector for detecting light that has passed through the second flow channel.
In some embodiments, the first light source and the second light source may be the same light source. Light emitted from the same light source may be branched into a first optical path and a second optical path, respectively, using a beam splitter or the like.
In the flow channel housing 361 shown in
In some embodiments, the apparatus may further include a container to contain the solution. The container may be fluidly connected to the flow channel. The apparatus may be configured to deliver a container contained in the container to the flow channel. In some embodiments, the container may contain a solution to be mixed with the measurement target substance. Such a container may be configured to receive a solution including a measurement target substance with respect to a container storing in advance, and mix them inside the container. The container may be configured to deliver a further mixed solution to the flow channel.
In some embodiments, the container containing the solution may include a plurality of containers. In some embodiments, each of the plurality of flow channels may be arranged with a container containing a solution in fluid connection. In some embodiments, the apparatus may comprise a first container configured to be fluidly coupled to the first flow channel and a second container configured to be fluidly coupled to the second flow channel. In some embodiments, one of the first container and the second container may have an inlet (container inlet) for introducing the measurement target substance. In some embodiments, at least one of the first container and the second container may be configured to mix the already contained solution (mixed solution) with the introduced measurement target substance or the solution including the measurement target substance (original liquid or diluted solution of the original liquid) inside thereof.
In some embodiments, the apparatus may include a mixing mechanism for mixing a solution including a measurement target substance and a mixed solution. The mixing mechanism may be a mechanism for moving the whole such as shaking the container for mixing, and may be a mechanism for mechanically deforming a part or the whole of the container. The mixing mechanism may be disposed directly with respect to the container for mixing or in the vicinity thereof. The mixing mechanism may be a flow channel. Flow channel as a mixing mechanism may be configured to have a plurality of flow channels, may be curved linearly bent or curved, may have a diameter or cross-sectional area or cross-sectional shape which changes as it proceeds in the direction of the flow.
In some embodiments, the apparatus has a plurality of flow channels, wherein at least one flow channel is a flow channel containing a solution to be measured, and at least another flow channels may have a flow channel for performing a reference measurement or a flow channel for reference measurement. In some embodiments, the apparatus may further include a reference measurement flow channel including at least a portion of the reference measurement optical path and extending along the reference measurement optical path. In some embodiments, the reference measurement flow channel may be sealed. In some embodiments, the reference measurement flow channel may include an inlet and an outlet.
In some embodiments, the apparatus may further include a reference measurement optical system configured to propagate light emitted from the light emitter along a reference measurement optical path in the reference measurement flow channel and receive the light at the photodetector. The reference measurement optical system may include a beam splitter.
In some embodiments, it may include a reference measurement light source for propagating light along a reference measurement optical path in the reference measurement flow channel, and a reference measurement photodetector for detecting light emitted from the light source and having propagated in the reference measurement flow channel along the reference measurement optical path. In some embodiments, the apparatus may include a light source and a photodetector for a reference measurement, apart from the main optical system for measurement.
In some embodiments, a reference solution may already be filled in the reference measurement flow channel.
In some embodiments, the reference solution may be purified water for example, for measurement of a measurement target substance. In some embodiments, the reference measurement flow channel may be filled with air. In some embodiments, it may be a mixture of purified water and a luminescent material (for example, BCP) solution. The reference solution may be other solutions.
In some embodiments, the reference solution may be filled in the reference flow channel at the time of shipment or prior to shipment of the apparatus. In some embodiments, the reference solution may be stored in a reference solution container in the apparatus and configured to be mixed with the solution at a necessary timing.
In some embodiments, the reference measurement flow channel may have a substantially similar configuration as the flow channel. Thereby, for example, the accuracy of the reference measurement can be increased. By performing an optical measurement substantially the same as that for the target substance with respect to the reference solution in the flow channel for reference measurement, calibration of the absorbance measurement can be performed with relatively high accuracy.
In some embodiments, a chromogenic substance (hereinafter, including an indicator, a chromogenic reagent, a coloring reagent, and an absorbance standard substance) may be bonded to a measurement target substance. In some embodiments, the absorbance of the chromogenic substance (or the optical characteristics associated with the absorbance or the change thereof) may be measured, and the concentration of the measurement target substance may be specified from the same absorbance or the like. In some embodiments, a dye-binding method may be used.
In some embodiments, the apparatus may have a chromogenic substance container comprising a chromogenic substance. In some embodiments, the apparatus may have an inlet for the measurement target substance and may have a mechanism for mixing the measurement target substance introduced from the inlet and the chromogenic substance. In some embodiments, the apparatus may have a mechanism for delivering a mixed solution of a measurement target substance and a chromogenic substance to a flow channel.
In certain embodiments, the measurement target substance may comprise albumin. The albumin contained in the measurement target may be albumin in blood or albumin in saliva or tear. In some embodiments, the chromogenic substance may be methyl violet, litmus, promocresol green, and may be methyl orange, bromocresol purple, phenol red. The chromogenic substance, in other examples, may be iodine which reacts with starch, ninhydrin which reacts with an amine or an amino acid, silver nitrate which reacts with chloride ions, and the like. The chromogenic substance is not limited to the above examples.
In some embodiments, it may be configured to mix an oxidizing agent with a measurement target substance or a solution including a measurement target substance. For example, an oxidizing agent may be mixed into tears. In some embodiments, the apparatus may have an oxidant container containing an oxidizing agent. Biomolecules in which there are oxidized and reduced forms may differ in the properties of modifications, such as chromogenic substances, between types. Therefore, exemplarily, by oxidizing before binding a chromogenic substance or the like, the amount of binding with the chromogenic substance can be reduced and furthermore measurement errors between biomolecules and between measurements can be reduced.
The flow channel member 460 forming the flow channel system of the apparatus 400 has an inlet 461. From this inlet 461, a solution 432 including an original liquid or a measurement target substance 431 is introduced. An openable and closable sealing lid 466 is connected to the inlet 461 in order to prevent backflow or leakage of the solution and penetration of impurities into the solution or the flow channel.
The flow channel member 460 has a mixing container 462, and a measurement solution 434 including a chromogenic substance 433 having a property of binding to the measurement target substance 431 is stored in advance. The introduced original liquid 432 is introduced into this mixing container 462, and the chromogenic substance 433 is bonded or adhered to the measurement target substance 431. The mixing container 462 is provided with a mixing mechanism 463 (details of which are not shown). The mixing mechanism 463 pushes the elastic membrane above the mixing container 462 up and down, thereby changing the volume or shape of the mixing container 462. Thereby, exemplarily, a reaction such as binding between the introduced measurement target substance 431 and the chromogenic substance 433 can be promoted and uniformly performed. A solution including the measurement target substance 431 to which the chromogenic substance 433 is bound by mixing is introduced into the first micro flow channel 411a from one end thereof.
The micro flow channel 411a for measuring the measurement target substance 431 is fluidically connected to a reservoir 464 at the other end thereof. For example, the solution which has passed through the flow channel 411a from the container 462 by pressing and has filled the micro flow channel 411a needs a place to escape. The storage container 464 may have its function. In addition, the reservoir 464 having a sufficient volume is effective when the solution reciprocates not only in one direction but also in the flow channel 411a. The reservoir 464 of
On the other hand, the second micro flow channel 411b is a flow channel for reference measurement. The space of the second micro flow channel 411b is sealed between the light entrance window 424 and the light exit window 425. The sealed space is previously filled with a reference measurement solution 435. The reference measurement solution 435 of
The apparatus 400 has a single light source 421 fixed to the main body 410, the amount of light is controlled using the adjustment photodetector 426. The light emitted from the light source 421 is first separated into two by the beam splitter 427 so as to be guided to the optical paths 423a,423b of the two flow channels 411a,411b, respectively. One of them directly travels straight, passes through the light entrance window 424, and travels along the optical path 423a in the micro flow channel 411a. The other light is further refracted by mirror 428 and travels along the optical path 423b in the micro flow channel 411b past the light entrance window 424.
At the other ends of the micro flow channels 411a,411b, photodetectors 422a,422b are fixed to the main body 410, respectively, the intensity of the emitted light can be measured. The internal shapes, dimensions, and inner wall properties of the micro flow channel 411a,411b are substantially the same, and the internal solutions occupying the respective flow channels 411a,411b are also the same. Therefore, by calculating the difference between the intensity at the photodetector 422a and the intensity at the photodetector 422b, the measurement error due to the solution or the wall of the flow channel can be arithmetically removed, and the absorbance or the like corresponding to the chromogenic substance 433 that was in the first micro flow channel 411a at the time of measurement can be more accurately obtained.
As shown in
In some embodiments, the absorbance measurement apparatus may include a plurality of absorbance measurement devices, may be combined with an apparatus of other measurement methods, may be configured to be connected or combined with other measurement devices or measurement apparatuses, and may be a combined system.
In some embodiments, the measurement apparatus may have a pretreatment solution or a container containing a pretreatment solution for performing pretreatment on a measurement target substance introduced into the apparatus or a solution including a measurement target substance (including an original liquid, a dilution solution thereof, and the like) In some embodiments, the measurement apparatus may have a plurality of measurement optical paths. In some embodiments, the measurement apparatus may have at least two measurement optical paths, one of which may be used as an optical path for the main measurement, and the other measurement optical path may be used to measure a comparison or a baseline (or background).
One of the divided solutions is introduced into a container 702 containing a chromogenic substance solution, where the measurement target substance after the pretreatment and the solution of the chromogenic substance are mixed. In
The other of the divided solution is sent to a second measurement path 707 without being bound with the chromogenic substance. In the second measurement light path 707, the optical influence by the pretreatment solution can be measured substantially without the influence of the chromogenic substance. In other words, in the second measurement optical path 707, the baseline is measured.
The difference between the information obtained in the main measurement in the first measurement light path 704 and the information obtained in the baseline measurement of the second measurement light path 707 can be taken as a substantial optical measurement result for the chromogenic substance.
In the measurement apparatus 700 as shown in
Thereafter, the solution is introduced into the container 802 containing the chromogenic substance solution, where the measurement target substance after the pretreatment and the solution of the chromogenic substance are mixed. In
Then, the difference between the information obtained in the baseline measurement performed first and the information obtained in the baseline measurement performed next can be taken as a substantial optical measurement result for the chromogenic substance.
In the measurement apparatus, as shown in
First, the flow channel 911a for main measurement will be described. A solution including a measurement target substance (or an original liquid such as a diluted solution thereof or the like) is introduced into the apparatus 900 from the inlet 912. The solution including the introduced measurement target substance enters the container 931a containing the pretreatment liquid, and is mixed, and the pretreatment is performed. The solution after the pretreatment is introduced into the measurement flow channel 911a, and fills the flow channel portion 911a in which the optical path is defined. Thereafter, measurements are performed in two wavelength regions emitted from two light sources 921a,921b. The light sources may be turned on sequentially or alternately so that light from one light source passes through the flow channel at a point of time.
After the measurement of the solution after the pretreatment is completed, the solution is pushed and introduced into the container 941a containing the solution of the chromogenic substance. The measurement substance and the chromogenic substance are bound. The pressure as the solution is extruded can be released to the outside through the air vent 913. When the measurement substance and the chromogenic substance are sufficiently bound, the solution is sent in the reverse direction and introduced into the flow channel 911a again. Then, the measurement is performed on the chromogenic substance.
Next, a buffer measurement flow channel 911b and a reference solution measurement flow channel 911c will be described. In either case, the measurement target substance is not introduced. The solutions contained in the buffer container 932b and the reference solution 932c are introduced into the containers 931b,931c containing the pretreatment liquid, respectively, and mixed, and the pretreatment is performed.
The buffer solution is a solution not including the measurement target substance. Thereby, the measurement corresponding to the concentration zero can be performed.
The solution for reference measurement is a solution including the same or equivalent measurement target substance at a known concentration. In some embodiments, a measurement target substance having a concentration corresponding to a concentration region of a measurement target substance assumed in the main measurement may be contained in the solution for reference measurement. In some embodiments, a measurement target substance having a concentration sufficiently different from the concentration region of the measurement target substance assumed in the main measurement may be contained in the solution for reference measurement.
Thereafter, the operation is the same as that of the main measurement flow channel. In other words, the solution after the pretreatment is introduced into the measurement flow channels 911b,911c, respectively, and fills the flow channel portions 911b,911c in which the optical path is defined. Thereafter, measurements are performed in the two wavelength regions emitted from the two light sources 921a,921b. After the measurement of the solution after the pretreatment is completed, the solution is pushed and introduced into the containers 941b,941c containing the solution of the chromogenic substance. The measurement substance and the chromogenic substance combine. The pressure as the solution is extruded can be released to the outside through the air vent 913. After a period of time similar to the binding of the measurement substance and the chromogenic substance in the flow channel for measurement, the solution is sent in the reverse direction and introduced into the flow channels 911b,911c again. Then, the same optical measurement is performed.
The measurement results (information) obtained from these six measurements can be calculated as follows to calculate the concentration of the chromogenic substance to be determined.
In each flow channel, post-pretreatment measurements (baseline measurements) provide a baseline. The information obtained in the measurement of the target substance to which the chromogenic substance (the main measurement) is bound is the sum of the information of the desired chromogenic substance and the information based on the baseline. Therefore, the measurement information of the desired substance is the information obtained by subtracting the information obtained by baseline measurement from the information obtained by the main measurement.
The difference may be taken if the baseline measurement is V1 and the main measurement is V2. That is,
ΔV=V2−V1
For this ΔV, the value ΔVb (or ΔV0) from the measurement value in the buffer flow channel 911b corresponds to zero concentration (C=0 or C0) of the target substance. The value ΔVc (or ΔVref) from the measured value in the buffer flow channel 911c corresponds to the reference concentration (C=Cref) of the target substance. Since these four values, {ΔV0, C0}{ΔVref, Cref} correspond to two points in the space of {measurement V (or ΔV), concentration C}, the relation of {measurement V, concentration C} can be represented by a straight line passing through these two points, or other one-to-one corresponding curves. Based on this relationship, the concentration (CT) in the flow channel 911a of the chromogenic substance to be determined can be determined from the measured value ΔVa (ΔVT) in the flow channel 911a. See
According to the present disclosure, an optical measurement apparatus (such as a GA level measurement apparatus) having a footprint (or occupied area, device size) of several centimeters by several centimeters or smaller can be manufactured on the basis of a micro flow channel. The footprint may be smaller than or equal to a value such as 25 cm2, 20 cm2, 16 cm2, 15 cm2, 12 cm2, 10 cm2, 9 cm2, 8 cm2, 6 cm2, and 4 cm2.
The photodetector 922a,922b,922c of the measurement apparatus of
The measurement substance may be an inorganic substance and may be an organic substance. In some embodiments, the measurement target substance may be a biomolecule. In some embodiments, the measurement target substance may be a protein included in a body fluid. In some embodiments, the solution (or diluent, original liquid) including the measurement target substance may be a bodily fluid. The “body fluid” may be blood, serum, plasma, lymph fluid, tissue fluids such as interstitial fluid, intercellular fluid, interstitial fluid, and the like, and may be body cavity fluid, serosal fluid, pleural fluid, ascites fluid, pericardial fluid, cerebrospinal fluid, joint fluid (synovial fluid), and aqueous humor of the eye (aqueous). The body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, intestinal fluid, and the like, and may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, milk, and the like. The body fluid may be a body fluid of an animal and may be a body fluid of a human. The “body fluid” may be a solution. The solution may include a buffer solution such as phosphate buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES) including a measurement target substance. The solution is not particularly limited as long as the measurement target substance is included.
The solution may include a measurement target substance. For example, the solution may be tear and the measurement target substance may be albumin or glycoalbumin included in tears. Alternatively, the measurement target substance may be albumin, glycoalbumin, hemoglobin, glycohemoglobin in blood or serum, may be albumin, glycoalbumin in interstitial fluid, may be albumin, glycoalbumin in tears, and may be albumin, glycoalbumin in urine, or the like.
In some embodiments, the measurement target substance is albumin, and the original liquid may be tear or saliva. In some embodiments, the pretreatment liquid may be an oxidizing agent. In some embodiments, the chromogenic substance may be BCP (bromocresol purple). In some embodiments, the wavelengths of the light sources 921a,921b may be 600 nm and 660 nm or wavelengths in the vicinity thereof, respectively.
In some embodiments, the measurement apparatus may include a plurality of measurement units, each of which is composed of a main measurement flow channel system, a buffer measurement flow channel system, and a reference solution measurement flow channel system, as one measurement unit. In some embodiments, multiple measurement units may perform same or similar measurements multiple times simultaneously, synchronously, at varying times, or asynchronously. In some embodiments, at least two of the plurality of measurement units may perform different measurements.
The measurement unit 1010 is the same measurement unit as in
On the other hand, the other measurement unit 1050 of
The original liquid introduced from the inlet 1012 is divided into a flow channel system of the main measurement flow channel 1011a of the measurement unit 1010 and a flow channel system of the main measurement flow channel 1061a of the measurement unit 1050. The pressure in the flow channel which is generated in this case can be released from the air vent 1013.
In the measurement unit 1050, containers 1081a,1081b,1081c containing a solution including the first treatment solution are disposed upstream of the flow channels 1061a,1061b,1061c, respectively, and containers 1091a,1091b,1091c containing a solution including the first treatment solution are disposed downstream of the flow channels 1061a,1061b,1061c, respectively. Two light sources 1071a,1071b are disposed, and the light emitted from each passes through the flow channels 1061a,1061b,1061c, is received by the photodetectors 1072a,1072b,1072c disposed on the opposite side of the respective flow channels.
The operation of the measurement units 1010, 1050 shown in
The measurement apparatus of
An oxidizing agent may be contained as a pretreatment solution in the containers 1031a,1031b,1031c of pretreatment liquid of the measurement unit 1010. The containers 1041a,1041b, 1041c for the chromogenic substance of the measurement unit 1010 may contain BCP as the chromogenic substance. Then, a predetermined buffer solution may be contained in the buffer solution container 1031b, and a solution including albumin of a known concentration may be contained in the reference solution 1031c. For example, in the above configuration, the measurement unit 1010 can be used to derive the concentration of albumin as the measurement target substance in the original liquid from the optical measurement.
A ketone amine oxidase and a peroxidase (HRP) may be contained in the containers 1081a,1081b,1081c for the first treatment solution of the measurement unit 1050. A protease may be contained in the container 1091a,1091b,1091c for the second treatment solution. Then, a predetermined buffer solution may be contained in the container 1031b of the buffer solution, and a solution including glycoalbumin of a known concentration may be contained in the solution 1031c of the reference solution.
As an example, the concentration of albumin can be determined as follows. The buffer solution of the buffer container 1032b of
On the other hand, the concentration of glycoalbumin (GA) can be determined from the absorbance measured in the measurement flow channels 1061a,1061b,1061c in the same manner as the concentration of albumin described above. For example, in a reference solution, fructosyl lysine included in 80 mg/dL of albumin of 20% GA is known (for example, it is known to be 5 μM). Thus, the concentration of GA can eventually be determined.
The ketoamine oxidase may be a dehydrogenase, may be a kinase, and may be an oxidase. The ketoamine oxidase may be fructosyl amino acid oxidase (FAOD), fructosyl peptide oxidase, fructosyl valylhistidine oxidase, fructosylamine oxidase, amadriase, fructosylamine deglyase or modified forms thereof.
In some embodiments, the ketoamine oxidase may be an oxidase which acts on an amino acid or peptide in which the ε-amino group is glycated. The amino acid may be lysine. By using an oxidase which selectively acts on an amino acid or peptide in which an ε-amino group is glycated, a glycoalbumin sensor can be constructed.
In some embodiments, the ketoamine oxidase may be an oxidase which acts on an amino acid or peptide in which the α-amino group is glycated. The amino acid may be valine. By using an oxidase that acts on an amino acid or peptide in which an α-amino group is glycated, a glycohemoglobin sensor or a glycohemoglobin A1c (HbA1c) sensor can be constructed.
“Protease” is a generic term for peptide bond hydrolyzing enzymes that hydrolyze and catabolize proteins and polypeptides. The protease may be an enzyme that degrades a protein into peptide fragments. When a protein includes a glycated amino acid residue, among the peptide fragments generated in the action of the protease, there may be peptide fragments including a glycated amino acid residue and peptide fragments not glycated at all.
“Protease” may be a protease derived from an animal, may be a protease derived from a plant, and may be a protease derived from a microorganism. The protease may be an exopeptidase and may be an endopeptidase. The protease may be an aspartic protease, a metal protease, a serine protease, or a thiol protease.
“Protease” may include a plurality of types or kinds of proteases and may include one type or kind of protease. For example, a protease may include one of a proteinase and a peptidase, and may include both. Mixing multiple proteases may increase the efficiency of degradation.
The animal-derived protease may be trypsin, chymotrypsin, elastase, bovine pancreatic protease, cathepsin, calpain, protease type-I, protease type-XX, aminopeptidase-N, carboxypeptidase, pancreatin (a mixture of multiple enzymes such as proteases and amylases), and the like.
The plant-derived protease may be papain, bromelain, gingipain, kallikrein, ficin, chymopapain, and the like.
The microbiota-derived protease may include Bacillus-derived proteases, Aspergillus-derived proteases, Penicillium-derived proteases, Streptomyces-derived proteases, Lysobacter-derived proteases, Yeast-derived proteases, Tritilatium-derived proteases, Thermus-derived proteases, Pseudomonas-derived proteases, Acromobacter-derived proteases, and the like.
The measurement apparatus shown in
In some embodiments, the measurement apparatus may be a protein measurement device or apparatus. In some embodiments, the measurement apparatus may be an albumin measurement device or apparatus.
The present disclosure includes a GA level measurement system. A GA level measurement system according to an embodiment may include an albumin measurement device and a glycated albumin measurement device. The albumin measurement device may include an absorbance measurement instrument of the present disclosure and may be configured to be connected to an absorbance measurement instrument. In some embodiments, the GA level measurement system may measure the albumin concentration in a solution using an albumin measurement device, measure the glycated albumin concentration using a glycated albumin measurement device, and calculate the GA level from the obtained albumin concentration and glycated albumin concentration. In some embodiments, the GA level measurement system may have an arithmetic processing unit that calculates a GA level from the obtained albumin concentration and glycated albumin concentration.
In some embodiments, the GA level measurement system may be configured to determine an albumin concentration and a glycated albumin concentration of tears.
The present disclosure includes a blood glucose level management system or a health management system. In some embodiments, a blood glucose management system or the like may include a GA measurement system. In some embodiments, the review control system may include a testing system, such as a CGM (Continuous Glucose Measurement (Continuous Glucose Monitoring)) apparatus or system.
In some embodiments, the blood glucose level management system may be configured to be connected to a GA level measurement system.
2. Measurement Method
In some embodiments of the present disclosure, a method of measuring the concentration of a substance in a solution using an optical method such as an absorbance spectroscopy is provided. A measurement method using the measurement instrument of the present disclosure will be described in a non-limiting or exemplary manner.
An original liquid including the measurement target substance is provided or prepared (S102). In some embodiments, a measurement target substance may be provided. The solution including the measurement target substance may be used for detection or measurement in a state at the time of acquisition, and processing such as dilution or replacement of the solution may be performed before introduction into the apparatus.
In some embodiments, the measurement target substance may be a biological substance such as a biomolecule, may be a chemical substance, and may be a mixture thereof. The measurement target substance may be a protein molecule present in a living body. The measurement target substance may be albumin. The original liquid including the measurement target substance may be tears or saliva or other body fluid. The measurement target substance may be albumin contained in tears or saliva.
Providing an original liquid including a measurement target substance may include obtaining tears or saliva of a human or other animal.
In
Next, the original solution including the measurement target substance is introduced into the micro flow channel of an absorbance measurement apparatus (S103). In some embodiments, the acquired solution may not be processed as it is, but may be introduced into an absorbance measurement apparatus. In some embodiments, after acquisition, the solution may be diluted, mixed with other solutions, physical filters, temperature treatment, chemical treatment, electrochemical treatment, electromagnetic wave treatment, or other treatments. The treatment for the solution may be performed before introduction into the absorbance measurement apparatus, may be performed after introduction into the absorbance measurement apparatus, may be performed before measurement, may be performed during measurement, and may be performed between a plurality of measurements. In some embodiments, the same, same types or different types of treatments may be performed at multiple timings.
Using an absorbance measurement apparatus, the absorbance of the measurement target substance introduced into the micro flow channel is measured or measured (S104).
The concentration of the measurement target substance in the micro flow channel can be determined from the absorbance (S105). If the concentration in the micro flow channel and the concentration before the introduction into the micro flow channel are substantially the same or substantially the same, the concentration determined directly by the measurement is the concentration of the measurement target substance in the original solution to be determined. If there is a relationship between the concentrations, the concentration of the measurement target substance in the original solution may be determined from the measured concentration based on the relationship. The relationship may be confirmed in advance by another measurement before the measurement.
In some embodiments, the absorbance of the measurement target substance in the micro flow channel may be determined, and the concentration of the measurement target substance in the original solution may be determined from the determined absorbance by conversion or another method. In some embodiments, the concentration of the measurement target substance in the original solution may be determined based on the output of the photodetector without calculating the absorbance of the measurement target substance in the micro flow channel as a value.
In some embodiments, a chromogenic substance may be used. In some embodiments, a chromogenic substance may be bound to the measurement target substance to be measured for concentration, and the absorbance of the chromogenic substance bound to the measurement target substance may be measured.
An original liquid including the measurement target substance is provided or prepared (S202). In
A chromogenic substance is bound to the measurement target substance (S203). In some embodiments, a solution including a bundle target substance and a solution including a chromogenic substance may be mixed.
The measurement solution is introduced into the micro flow channel of the apparatus (S204). Binding the chromogenic substance to the measurement target substance may be performed before introducing the measurement solution into the apparatus, and may be performed in the apparatus after introducing the measurement solution into the apparatus, and may be performed at other timings.
The absorbance of the chromogenic substance in the micro flow channel is measured using the absorbance spectroscopy (S205).
The concentration of the measurement target substance in the measurement solution (S206) is determined from the measured absorbance of the chromogenic substance. In some embodiments, the absorbance of the chromogenic substance in the micro flow may be determined, and the concentration of the measurement target substance in the original solution may be determined from the determined absorbance by conversion or another method. In some embodiments, the concentration of the measurement target substance in the original solution may be determined based on the output of the photodetector without calculating the absorbance of the chromogenic substance in the micro flow as a value. In some embodiments, the concentration of the measurement target substance in the corresponding original solution may be determined by conversion from the determined concentration during the measurement. In some embodiments, the measurement method may be an analysis of a protein by a dye-binding method, and may be a concentration measurement of a protein by a dye-binding method.
In some embodiments, the measurement target substance is or includes albumin, and the concentration of albumin in the original solution may be determined by measurement. In some embodiments, the chromogenic substance is or may include bromocresol purple. Bromocresol purple or a solution thereof and an original solution including albumin may be mixed. By this mixing, a solution including the albumin to which bromocresol purple is bound can be prepared as a measurement solution. In some embodiments, the absorbance of the bromocresol purple in the micro flow channel may be measured using an absorbance spectroscopy. In some embodiments, the concentration of the albumin in the measurement solution may be determined from the measured absorbance of the bromocresol purple.
In some embodiments, the absorbance may be measured at multiple wavelengths. In some embodiments, a wavelength characterizing the chromogenic substance (main wavelengths) and a wavelength in the wavelength region where the effect of absorption by the chromogenic substance is small or in the wavelength region of the background (sub-wavelengths) may be used. In some embodiments, bromocresol purple may be used as the chromogenic substance and measured at a main wavelength of 600 nm and a sub wavelength of 660 nm.
In some embodiments, the original solution and the oxidizing agent may be mixed prior to mixing the bromocresol purple or a solution thereof with the original solution. The oxidizing agent may be any agent that oxidizes albumin, disulfide: 5,5′-dithiobis(2-nitrobenzoic acid)(DTNB), 2,2′-dithiobis(5-nitropyridine)(NPDS), 2,2′-dithiodipyridine(2-PDS), 4,4′-dithiodipyridine(4-PDS), 4,4′-dithiobis(1-azidobenzene)(DTBPA), oxidized glutathione, and the like, oxidizing agent: iodine, ferricyanide, iodosobenzoic acid, iodate, salts of chloroacetate, mercury, zinc, and the like, alkylating agents: iodoacetic acid, chloroacetic acid, iodoacetamide, phenacyl chloride, and the like, Maleimide and its derivatives: maleimide, N-methylmaleimide, N-ethylmaleimide, N,N′-p-phoenix maleimide, and the like, thiophthalimide, and the like, among these, a disulfide such as DTNB, 2-PDS, 4-PDS, a maleimide, a maleimide derivative such as N-ethylmaleimide, or the like are preferably used. Further, these may be used alone or in combination as appropriate. Albumin exists in oxidized type and reduced type, and the specificity of BCP is altered depending on the type, which can lead to large errors. Therefore, by oxidizing all of the albumin using an oxidizing agent in advance, the accuracy of measurement can be increased.
In some embodiments, the concentration of albumin in the original solution may be determined from the concentration of albumin obtained in the measurement solution.
In some embodiments, the concentration of glycated albumin may be further determined. In some embodiments, a GA level may be determined based on the calculated albumin concentration and the calculated glycated albumin concentration. In some embodiments, a value obtained by dividing the calculated glycated albumin concentration by the calculated albumin concentration may be defined as a GA level. The calculation of the glycated albumin concentration is not limited in the present disclosure as there are various methods.
The present disclosure includes methods of disease state management, including glycemic management, methods of health management of preliminary or healthy persons with disease states, methods of disease prevention, and other methods of health care management. In some embodiments, these healthcare management methods may comprise determining albumin concentration using an optical measurement apparatus having a micro flow channel. In some embodiments, the healthcare management method may be a method of providing healthcare information, a non-invasive diabetes risk management method, a diabetic complication prevention method, or the like.
The present disclosure also includes the following embodiments. A01
An apparatus for measuring a substance in a solution, comprising:
a light source;
a micro flow channel including at least a portion of an optical path of light emitted from the light source and extending along the optical path; and
a photodetector for detecting light passed through the micro flow channel.
An apparatus for measuring a concentration of a substance in a solution by absorption spectrophotometry, comprising:
a flow channel being configured to contain a solution, defining an optical path and having a volume of 20 μL or smaller;
a light source; and
a photodetector for detecting an electromagnetic wave emitted from the light source and having passed through the optical path defined in the flow channel.
The apparatus according to embodiment A01,
wherein the micro flow channel has a volume of 20 μL or smaller.
The apparatus according to embodiment A02,
wherein the micro flow channel has a volume of 10 μL or smaller.
The apparatus according to embodiment A03,
wherein the micro flow channel has a volume of 5 μL or smaller.
The apparatus according to any one of embodiments A01 to A04,
wherein a cross-sectional dimension of the optical path of the micro flow channel is 3 mm or smaller.
The apparatus according to embodiment A05,
wherein the cross-sectional dimension of the optical path of the micro flow channel is 2 mm or smaller.
The apparatus according to embodiment A06,
wherein the cross-sectional dimension of the optical path of the micro flow channel is 1 mm or smaller.
The apparatus according to any one of embodiments A01 to A07, further comprising:
a second photodetector configured to measure light emitted by the light source outside the light path (an adjustment photodetector); and
a second photodetector controller for receiving information related to the luminance of the light measured by the second photodetector and controlling the light emission amount of the light source so as to be substantially constant in time.
The apparatus according to any one of embodiments A01 to A08, comprising a photodetector controller configured to receive information related to the luminance measured by the photodetector (first photodetector, measurement photodetector), and to make the light emitting amount of the light source to be substantially constant in time.
The apparatus according to any one of embodiments A01 to A09, further comprising a temperature controller for regulating the temperature of the solution in the micro flow channel.
The apparatus according to any one of embodiments A01 to A09, further comprising a heater disposed proximate the micro flow channel and configured to control the temperature of the solution.
The apparatus according to any one of embodiments A01 to A11, wherein at least a portion of the member forming the micro flow channel has a higher heat capacity than the solution in the micro flow channel.
The apparatus according to any one of embodiments A01 to A12, further comprising a shield configured to substantially prevent light from other than the light source from being detected by the photodetector.
The apparatus according to any one of embodiments A01 to A13, wherein the member forming the micro flow channel includes a shielding material.
The apparatus according to any one of embodiments A01 to A14, wherein the inner wall of the micro flow channel is hydrophilic.
The apparatus according to any one of embodiments A01 to A15, wherein the micro flow channel has an inlet and an outlet for the solution.
The apparatus according to embodiment A16, wherein the inlet and the outlet are arranged so that air bubbles are not substantially formed in the micro flow channel when the solution is introduced.
The apparatus according to embodiment A16, wherein the inlet and the outlet are disposed at a position of the entrance end and the exit end of the optical path in the micro flow channel.
The apparatus according to embodiment A16, wherein the inlet and the outlet are arranged such that no dead space is substantially formed in the micro flow channel.
The apparatus according to embodiments A01 to A19, wherein the light source has a plurality of peak wavelengths.
The apparatus according to embodiment A31, wherein the light source includes a plurality of light sources each having a different peak wavelength.
The apparatus according to embodiment A32, further comprising a light source control mechanism for introducing light from only one light source of the plurality of light sources into the light path.
The apparatus according to embodiment A32, further comprising a drive control apparatus for controlling an emission of the plurality of light sources.
The apparatus according to embodiment A33, wherein the light source control mechanism includes a drive control apparatus for controlling the emission of the plurality of light sources.
The apparatus according to any one of embodiments A01 to A35, further comprising a reference measurement flow channel including at least a portion of the reference measurement optical path and extending along the reference measurement optical path.
The apparatus according to embodiment A51, further comprising a reference measurement optical system configured to propagate light emitted from the light emitter along the reference measurement optical path in the reference measurement flow channel and receive light by the photodetector.
The apparatus according to embodiment A51, comprising:
a reference measurement light source for propagating light along the reference measurement optical path in the reference measurement flow channel; and
a reference measurement photodetector for detecting light emitted from the light source and propagating in the reference measurement flow channel along the reference measurement optical path.
The apparatus according to any one of embodiments A51 to A53, wherein a reference solution is contained in the reference measurement flow channel.
The apparatus according to any one of embodiments A01 to A54, wherein the apparatus is an absorbance optical apparatus by absorbance spectroscopy.
The apparatus according to embodiment A01,
wherein the optical path includes:
a first optical path in which light emitted from the light source propagates, and
a second optical path in which light emitted from the light source propagates, wherein the micro flow channel includes a first micro flow channel extending along the first optical path and a second micro flow channel extending along the second optical path, and
wherein the photodetector includes a first photodetector for detecting light passed through the first micro flow channel and a second photodetector for detecting light passed through the second micro flow channel.
The apparatus according to embodiment A01,
wherein the light source includes a first light source and a second light source, wherein the optical path includes a first optical path in which light emitted from the first light source propagates, and a second optical path in which light emitted from the second light source propagates,
wherein the micro flow channel includes a first micro flow channel extending along the first optical path and a second micro flow channel extending along the second optical path, and
wherein the photodetector includes a first photodetector for detecting light passed through the first micro flow channel and a second photodetector for detecting light passed through the second micro flow channel.
An apparatus for measuring a substance in a solution, comprising:
a first light source;
a second light source;
a first micro flow channel including at least a portion of a first optical path of light emitted from the first light source and extending along the first optical path;
a second micro flow channel including at least a portion of a second optical path of light emitted from the second light source and extending along the second optical path;
a first photodetector for detecting light passed through the first micro flow channel; and
a second photodetector for detecting light passed through the second micro flow channel.
The apparatus according to any one of embodiments A61 to A63, further comprising:
a first container being configured to be fluidly coupled to the first flow channel, having an inlet for introducing a measurement target substance, and containing a solution to be mixed with the measurement target substance; and
a second container being configured to be fluidly coupled to the second flow channel, and containing a solution to be mixed with the measurement target substance.
The apparatus according to embodiment A64, further comprising a mixing mechanism for mixing the measurement target substance and the solution to be mixed with the measurement target substance.
The apparatus according to any one of embodiments A01 to A65, further comprising:
a chromogenic substance container containing a chromogenic substance;
an inlet for the measurement target substance;
a mechanism for mixing the measurement target substance and the chromogenic substance introduced from the inlet; and
a mechanism for feeding the mixed solution of the measurement target substance and the chromogenic substance to the micro flow channel.
The apparatus according to embodiment A101,
wherein the measurement target substance includes albumin, and
wherein the chromogenic substance includes bromocresol purple.
The apparatus according to embodiment A102,
wherein the measurement target substance is albumin in a tear fluid.
The apparatus according to embodiment A102 or A103, further comprising an oxidant container containing an oxidizing agent.
The apparatus according to embodiment A104, further comprising a mechanism for mixing the tear fluid and the oxidizing agent.
A GA level measurement system comprising:
an albumin measurement device according to any one of embodiments A101 to A105;
a glycated albumin measurement device; and
a processing unit capable of calculating a GA level based on an albumin concentration obtained using the albumin measurement device and a glycated albumin concentration obtained using the glycated albumin measurement device.
The GA level measurement system according to embodiment A201, configured to determine the albumin concentration of tear fluid and the glycated albumin concentration. A203
A blood glucose level management system comprising the GA level measurement system according to embodiment A201 or A202. A204
A blood glucose level management system configured to be connected to the GA level measurement system according to embodiment A201 or A202. B01
A method for measuring a concentration of a substance in a solution, comprising
providing the apparatus according to any one of embodiments A01 to A204;
providing a solution including a measurement target substance;
introducing the solution including the measurement target substance into the micro flow channel of the apparatus;
measuring the absorbance of the substance in the micro flow channel using absorbance spectroscopy; and
determining the concentration of the measurement target substance in the solution from the measured absorbance associated with the substance.
A method for measuring a concentration of a substance in a solution, comprising:
providing the apparatus according to any one of embodiments A01 to A204;
providing a solution including a measurement target substance;
introducing the solution including the measurement target substance into the micro flow channel of the apparatus;
performing an optical measurement on the solution in the micro flow channel; and
determining from the measurement, the concentration of the measurement target substance in the solution.
A method for measuring the concentration of a substance in a solution, comprising:
providing the apparatus according to any one of embodiments A01 to A204;
providing an original solution including a measurement target substance;
binding a chromogenic substance to the measurement target substance;
providing a measurement solution including the measurement target substance to which the chromogenic substance is bonded;
introducing the measurement solution into the micro flow channel of the apparatus;
measuring the absorbance of the chromogenic substance in the micro flow channel using absorbance spectroscopy; and
determining from the measured absorbance of the chromogenic substance the concentration of the measurement target substance in the measurement solution.
A method for measuring a concentration of a substance in a solution, comprising providing the apparatus according to any one of embodiments A01 to A204;
providing an original solution including a measurement target substance;
binding a chromogenic substance to the measurement target substance;
providing a measurement solution including the measurement target substance to which the chromogenic substance is bonded;
introducing the measurement solution into the micro flow channel of the apparatus;
performing an optical measurement on the solution in the micro flow channel;
determining from the measurement the concentration of the measurement target substance in the solution; and
determining from the measurement the concentration of the measurement target substance in the measurement solution.
The method according to embodiment B02b, further comprising:
determining the concentration of the measurement target substance in the corresponding original solution by conversion from the concentration determined in the measurement.
A method for measuring a concentration of albumin, comprising:
providing the apparatus according to any one of embodiments A01 to A204;
providing an original solution including albumin;
mixing bromocresol purple with the original solution including the albumin, to bind it to the albumin;
preparing a measurement solution including the albumin to which the bromocresol purple is bound;
introducing the measurement solution into the micro flow channel of the apparatus;
performing an optical measurement on the solution in the micro flow channel;
measuring from the measurement the concentration of the bromocresol purple in the micro flow channel; and
determining from the measured concentration of bromocresol purple the concentration of the albumin in the measurement solution.
The method according to embodiment B04, wherein the original solution including the albumin is tear fluid or saliva.
The method according to embodiment B04 or B05, further comprising mixing the original solution and an oxidizing agent, prior to said mixing the bromocresol purple and the original liquid.
The method according to any one of embodiments B04 to B06, further comprising determining from the concentration of the albumin in the measurement solution the concentration of the albumin in the original solution.
A GA level measurement method comprising:
calculating a concentration of albumin using the method according to any one of embodiments B04 to B06;
calculating a concentration of glycated albumin;
determining a GA level based on the calculated albumin concentration and the calculated glycated albumin concentration.
A blood glucose level management method comprising determining the GA level using the GA level measurement method according to embodiment B11.
While several embodiments and examples of the present disclosure have been described above, these embodiments and examples illustrate the present disclosure. For example, each of the embodiments described above has been described in detail in order to explain the present disclosure in an easy-to-understand manner, and dimensions, configurations, materials, and circuits may be additionally changed as necessary. Embodiments in which one or more features of the present disclosure described above are arbitrarily combined are also included in the scope of the present disclosure. It is intended that the appended claims cover numerous modifications to the embodiments without departing from the spirit and scope of the present disclosure. Accordingly, the embodiments and examples disclosed herein have been shown by way of illustration and should not be considered as limiting the scope of the present disclosure.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2018-189758 | Oct 2018 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2019/038151 | 9/27/2019 | WO | 00 |
