CN110501403A - Single pixel noninvasive dynamics monitoring device - Google Patents
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- CN110501403A CN110501403A CN201810482745.4A CN201810482745A CN110501403A CN 110501403 A CN110501403 A CN 110501403A CN 201810482745 A CN201810482745 A CN 201810482745A CN 110501403 A CN110501403 A CN 110501403A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
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- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/308—Electrodes, e.g. test electrodes; Half-cells at least partially made of carbon
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3273—Devices therefor, e.g. test element readers, circuitry
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
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- G01N27/3274—Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
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- G01N27/3275—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
- G01N27/3278—Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction involving nanosized elements, e.g. nanogaps or nanoparticles
Abstract
The present invention relates to single pixel noninvasive dynamics monitoring devices.According to an embodiment, a kind of single pixel noninvasive dynamics monitoring device can include: single sensor pixel is arranged on the first substrate, for attaching to user's skin；And alignment device, at least one hair follicle for being directed at the sensor pixel on user's skin.The single sensor pixel is registered at least one hair follicle only with single sensor pixel, and using alignment device by noninvasive dynamics monitoring device of the invention, can quickly and efficiently carry out noninvasive dynamics monitoring.
Description
Technical field
Present invention relates in general to blood sugar test fields, more specifically it relates to a kind of single pixel noninvasive dynamics monitoring device.
Background technique
Diabetes are inner-sphere reorganization energies most commonly seen in the world." Chinese residents nourishment and chronic disease status report
(2015) " it shows, 18 years old or more maturity-onset diabetes illness rate is 9.7%.China becomes incontrovertible the first big country of diabetes,
And have the tendency that rising year by year.
In diabetes patient, there is the number of invasive blood sugar instrument more than 50,000,000 people using tradition, blood glucose meter test paper is per capita
Yearization usage amount about 180, needing the blood glucose meter test paper consumed every year is about 9,000,000,000.At present since social life pressure is big,
Eating good things, it is few to move, and often stays up late, the pollution of excessive Smoking And Drinking and ecological environment, causes the presence of a large amount of sugar in compatriots
Urinate sick potential patient.Therefore, correct diagnosing and treating diabetes have a very important significance.
Diabetic will often carry out blood sugar concentration chemical examination during diagnosis and treatment, so that medical worker is well understood in time
The effect for the treatment of.But continually blood drawing has many drawbacks, has not only increased the danger of infection, but also cause suffering to patient, has returned doctor
Business personnel bring certain pressure.
Therefore, how to realize that noninvasive dynamics monitoring becomes the direction of researcher's effort for it.In order to change this situation,
The non-damage determination method of blood sugar concentration is actively studied in recent years, including uses near infrared spectrum and Raman spectrum skill
Art carries out blood sugar monitoring.These method spectral signal-noise ratios are low, thus low using the accuracy of above method measurement blood glucose value.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of single pixel noninvasive dynamics monitoring device, it is noninvasive to realize
The purpose of blood sugar test.
According to the one aspect of the application, a kind of single pixel noninvasive dynamics monitoring device is provided, comprising: single sensor
Pixel is arranged on the first substrate, for attaching to user's skin；And alignment device, it is used for the sensor pixel
At least one hair follicle being aligned on user's skin.
In some embodiments, the alignment device includes the alignment mark being formed on first substrate, the biography
Sensor pixel is on first substrate at the centring of the alignment mark.
In some embodiments, the alignment device includes: the second substrate；And opening, second substrate is penetrated,
In, the alignment device is configured to when second substrate is attached on user's skin, and the opening is aligned and exposure institute
State at least one hair follicle.
In some embodiments, the alignment device further include: alignment mark is formed on second substrate, wherein
The opening is on second substrate at the centring of the alignment mark.
In some embodiments, the opening has the shapes and sizes essentially identical with the sensor pixel.
In some embodiments, first substrate and second substrate are flexible substrates.
In some embodiments, first substrate and second substrate are transparent substrates.
In some embodiments, the alignment mark includes multi-color cord part, crown line part, recess line part, laser
Etching line part, bold portion, dotted portion or their any combination.
In some embodiments, the alignment mark includes concentric circles, cruciform pattern, M shape pattern, box
Pattern, circular pattern or their any combination.
In some embodiments, the sensor pixel includes: extraction electrode, is formed on first substrate, is used for
It is permeated by reverse ion through user's skin extraction glucose；Detecting electrode is formed on first substrate, for passing through electricity
Chemical method detects the concentration of extracted glucose；And reaction chamber, for receiving extracted glucose.
In some embodiments, the extraction electrode includes anode and cathode, for formed in user's skin reversely from
Sub- infiltration lane is to extract glucose, and wherein, the detecting electrode includes reference electrode, working electrode and to electrode, is used for
The concentration of extracted glucose is detected by electrochemical reaction.
In some embodiments, the anode includes Ag, the cathode, the reference electrode and described to each of electrode
Including Ag/AgCl.
In some embodiments, the working electrode includes: layer of precious metal；And catalyst granules, it is attached to described expensive
Metal layer towards the decomposition reaction on the surface of the reaction chamber, for catalyzing hydrogen peroxide.
In some embodiments, the surface towards the reaction chamber of the layer of precious metal is roughened surface.
In some embodiments, the layer of precious metal includes layer gold, and the catalyst granules includes Prussian blue.
In some embodiments, the working electrode includes: graphene layer；And catalyst nano-particles, it is attached to institute
State graphene layer towards the decomposition reaction on the surface of the reaction chamber, for catalyzing hydrogen peroxide.
In some embodiments, the catalyst nano-particles include at least one in Pt nanoparticle and gold nano grain
Kind.
In some embodiments, the working electrode includes transition metal oxide layer.
In some embodiments, the transition metal oxide layer includes the compound of transition metal oxide.
In some embodiments, the compound of the transition metal oxide includes nickel oxide, tin oxide and indium oxide.
In some embodiments, the transition metal oxide layer has porous structure.
In some embodiments, gelinite is accommodated in the reaction chamber.
In some embodiments, glucose oxidase is also accommodated in the reaction chamber, for being catalyzed extracted grape
The oxidation reaction of sugar is to generate hydrogen peroxide.
In some embodiments, alkaline matter is also accommodated in the reaction chamber.
In some embodiments, the cathode and it is described be same electrode to electrode.
In some embodiments, the area of the working electrode is greater than any one electrode in other electrodes.
In some embodiments, the area of the working electrode is greater than the sum of the area in other electrodes.
In some embodiments, the working electrode occupies the central area of the sensor pixel, the setting of other electrodes
Around the working electrode.
In some embodiments, the reaction chamber at least exposes the working electrode.
In some embodiments, the reaction chamber exposure detecting electrode.
In some embodiments, the area of the reaction chamber is less than both the extraction electrode and described detecting electrode and occupies
Area.
In some embodiments, the sensor pixel is configured to when being attached on user's skin, the detecting electrode
Cover at least one described hair follicle.
In some embodiments, the sensor pixel is configured to when being attached on user's skin, and the reaction chamber covers
Cover at least one described hair follicle.
In some embodiments, the area of the sensor pixel is in 0.0025mm2To 80mm2Between, preferably exist
0.0025mm2To 30mm2Between, more preferably in 0.0025mm2To 10mm2Between, more preferably in 0.0025mm2To 3mm2Between,
More preferable 0.0025mm2To 1mm2Between.
In some embodiments, the volume of the reaction chamber is less than 20 μ L, preferably smaller than 10 μ L, more preferably less than 2 μ L.
In some embodiments, the thickness of the reaction chamber is preferably arrived in 0.05mm between 0.03mm to 0.4mm
Between 0.2mm.
In some embodiments, the single pixel noninvasive dynamics monitoring device further include: data processing unit, for institute
The detection signal for stating sensor pixel generation is handled with the concentration of the extracted glucose of determination.
In some embodiments, the data processing unit includes: memory, and storage is defined concentration of glucose and detection
The calibration curve of relationship between electric current；Controller determines grape corresponding with the detection signal based on the calibration curve
Sugared concentration；And output unit, for exporting identified concentration of glucose.
It can be seen from the above technical proposal that the embodiment of the invention provides a kind of single pixel noninvasive dynamics monitoring devices.
The sensor pixel is directed at the hair follicle of human body by the alignment device by the single pixel noninvasive dynamics monitoring device, is utilized
The sensor pixel passes through Reverse iontophoresis and from human body glucose to skin surface and passes through by human body hair follicle
Electrochemical reaction obtains current signal relevant to blood glucose in human skin surface's detecting glucose concentration, so that it is dense to obtain blood glucose
Degree.By above-mentioned workflow it can be found that the single pixel noninvasive dynamics monitoring device does not need to damage object to be measured
The detection for carrying out object blood glucose to be measured, realizes the purpose of noninvasive dynamics monitoring.
In addition, the single pixel noninvasive dynamics monitoring device utilizes Reverse iontophoresis, glucose is extracted into skin table
Face, whole process will not damage object to be measured, the noninvasive purpose of realization.The single pixel noninvasive dynamics monitoring device utilizes electrochemistry
It reacts to detect glucose, glucose has specificity, eliminates a large amount of interference in detection process.Therefore, the Woundless blood sugar
Instrument is realized in the case where not damaging object to be measured, carries out accurately blood sugar test.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Fig. 1 is the operation chart according to the single pixel noninvasive dynamics monitoring device of one embodiment of the application；
Fig. 2 is the detection schematic diagram according to the single pixel noninvasive dynamics monitoring device of one embodiment of the application；
Fig. 3 to Figure 11 is according to the alignment device in the single pixel noninvasive dynamics monitoring device of some embodiments of the application
Structural schematic diagram；
Figure 12 is the structural schematic diagram according to the sensor pixel of one embodiment of the application；
Figure 13 is the structural schematic diagram according to the sensor pixel of another embodiment of the application；
Figure 14 A and Figure 14 B are the structural representation according to the single pixel noninvasive dynamics monitoring device of another embodiment of the application
Figure；
Figure 15 is the wearing schematic according to the single pixel noninvasive dynamics monitoring device of one embodiment of the application.
Figure 16 is the structural block diagram according to the data processing unit of one embodiment of the application.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Fig. 1 is the operation chart according to the single pixel noninvasive dynamics monitoring device 100 of one embodiment of the application.Such as Fig. 1
Shown, single pixel noninvasive dynamics monitoring device 100 includes substrate 110, alignment device 120 and sensor pixel 130.
Substrate 110 can be flexible transparent substrate, such as it can be made of the plastic film of such as PET etc, with
In the alignment device 120 and sensor pixel 130 of bearing thereon.Alignment device 120 can be various alignment marks, such as colored
Line part, crown line part, recess line part, laser-induced thermal etching line part, bold portion, dotted portion etc., and can have
Various shape or pattern, will be discussed in further detail below.Alignment device 120 can be formed in the upper surface of substrate 110
It on upper and lower surfaces, or can be embedded in substrate 110, as long as it is able to carry out the alignment function being described below in detail.
Sensor pixel 130 is formed in will the attaching on the surface on skin of substrate 110, is shown in Figure 1 for lower surface.It should infuse
It anticipates, substrate 110 and sensor pixel 130 is separately depicted in order to clearly show that in Fig. 1, but actually sensor pixel
130 may be formed on the lower surface of substrate 110, moreover, sensor pixel 130 is located at the centring of alignment device 120.It passes
The specific structure of sensor pixel 130 will be discussed in more detail below.Although it is not shown, being connected to leading for sensor pixel 130
Electrical wiring can extend on substrate 110 and can penetrate substrate 110 and extend on opposing surfaces.
User is in use, as shown in Figure 1, can will be located at pair of alignment device 120 under the auxiliary of alignment device 120
Sensor pixel 130 at true centric position is aligned and attaches on hair follicle 410 on human skin.In some embodiments
In, sensor pixel 130 can have lesser size, therefore referred to herein as " pixel ".By and large, sensor picture
The size of element 130 can be roughly the same with the size of hair follicle on human skin, is specifically described below.Due to hair follicle
410 and sensor pixel 130 all have lesser size, it may be difficult to the two is aligned, therefore in some implementations of the invention
In example, alignment device 120 is provided, can be various forms of alignment marks, and is formed as various alignment patterns, passed
Sensor pixel 130 can be located at the center position of the alignment pattern of alignment device 120.In this way, for example old for dysphotia person
For year people, the position of sensor pixel 130 can be readily determined by means of alignment device 120.Moreover, because substrate 110
Be it is transparent, substrate 110 can be passed through and see hair follicle 410, and under the auxiliary of alignment device 120, by sensor pixel 130
It is registered to 410 top of hair follicle, so that sensor pixel 130 accurately be covered on hair follicle 410.It should be understood that although Fig. 1 only shows
A hair follicle 410 is gone out, but has been also possible to two or more hair follicles on skin and is very close to each other, at this time sensor pixel
130 can also cover two or more hair follicles.
Fig. 2 is the detection schematic diagram according to the single pixel noninvasive dynamics monitoring device of one embodiment of the application.Such as Fig. 2
Shown, the sensor pixel 130 of single pixel noninvasive dynamics monitoring device 100 includes extracting electrode 131 and detecting electrode 133, is mentioned
Take electrode 131 for extracting glucose through corresponding hair follicle 410 by reverse ion infiltration, detecting electrode 133 is for passing through
Electrochemical method detects the concentration of extracted glucose.In the embodiment shown in Figure 2, extracting electrode 131 may include anode
132 and cathode 134, the channel of Reverse iontophoresis is established in user's skin, to extracting glucose to skin surface.
Anode 132 can be Ag electrode, and cathode 134 can be Ag/AgCl electrode, and Ag/AgCl electrode includes the mixture of Ag and AgCl.
Detecting electrode 133 may include to electrode 134, working electrode 136 and reference electrode 138, they constitute three electricity of electrochemical reaction
Electrode systems, to be detected by concentration of glucose of the electrochemical method to extraction to skin surface.To electrode 134 and reference
Electrode 138 or Ag/AgCl electrode.It should be noted that electrode 134 be also used as cathode when extracting and when detection to electrode,
That is cathode and be same electrode to electrode cathode and is also possible to individually electrode however, it is understood that in further embodiments
Electrode.
Working electrode 136 may include conductive layer and the catalyst granules that is arranged on the conductive layer.For example, in some realities
It applies in example, working electrode 136 may include graphene layer conductive layer, (is described later on) on the surface of side towards reaction chamber 135
Nano particle of noble metal catalyst, such as Pt nanoparticle, gold nano grain etc. can be attached with.Here, graphene layer can
To be single-layer graphene or multi-layer graphene, with excellent electric conductivity and flexibility, therefore it is used as the excellent of working electrode 136
Material selection may be implemented the perfection with human skin and attach.In further embodiments, working electrode 136 may include noble metal
Layer such as layer gold.Layer gold can form relatively thin, to also have good flexibility.Working electrode 136 may also include setting and exist
Catalyst granules on the surface towards 135 side of reaction chamber of layer of precious metal.For example, layer of precious metal can by specially treated with
With roughened surface, thus for example Prussian blue roughening table that can be attached to layer of precious metal well of catalyst granules
On face.
As shown in Fig. 2, sensor pixel 130 further includes that the reaction extracted below electrode 131 and detecting electrode 133 is arranged in
Chamber 135.Reaction chamber 135 can be surrounded as insulating materials such as PDMS made of chamber, the chamber at least expose working electrode
136, such as detecting electrode 133 can be exposed, such as can expose and extract both electrode 131 and detecting electrode 133.Preferably,
Reaction chamber 135 exposes detecting electrode 133, but can not expose and extract electrode 131, as will be described below, lesser
Reaction chamber 135 is advantageous for improving detection efficiency.In some embodiments, area occupied by reaction chamber 135 can be small
In the area of sensor pixel 130, i.e. area occupied by extraction electrode 131 and 133 the two of detecting electrode.Reaction chamber 135 can
The essentially identical shape in the region covered with the extraction electrode 131 and detecting electrode 133 with top, it is possible to have different
Shape.Gelinite can be accommodated in reaction chamber 135, with for absorbing the glucose extracted through hair follicle 410, and absorbed
In reaction chamber 135 electrochemical reaction can occur for glucose.
It in some embodiments, can also include glucose oxidase, Portugal in reaction chamber 135 other than gelinite
Grape carbohydrate oxidase can be catalyzed the oxidation reaction of glucose to generate hydrogen peroxide, and hydrogen peroxide again can be by working electrode 136
On catalyst nano-particles catalytic decomposition.In above-mentioned electrochemical reaction process, the concentration with extracted glucose is generated
Relevant detection electric current may thereby determine that the intracorporal blood sugar concentration of people.Although there has been described glucose oxidases to be located at instead
It answers in chamber 135, but in further embodiments, the particle of glucose oxidase can also be arranged in together with catalyst granules
On the surface of the conductive layer of working electrode 136, this modification should also be contained by the scope of the present invention defined in the appended claims
Lid.
In further embodiments, working electrode 136 may also comprise transition metal oxide electrode.Transition metal oxide
Electrode may include the transition metal oxide of such as nickel oxide, copper oxide etc, also may include answering for transition metal oxide
Close the mixture of object, such as nickel oxide, tin oxide and indium oxide etc..Such transition metal oxide electrode has porous knot
Structure can directly be catalyzed the electrochemical reaction of glucose with high specific area.In the sensor using the working electrode 136
In pixel 130, it may not be necessary to use glucose oxidase, therefore simpler in structure, and it is glycoxidative to can solve grape
Enzyme is easy the problem of inactivation, can keep detection activity for a long time, is conducive to long-term lasting detection.It should be understood that in this reality
It applies in example, working electrode 136 may also include the substrate for carrying transition metal oxide, which, which can be, is not yet oxidized
Transition metal material.Such working electrode 136 is preferred for including OH-Alkaline environment in, therefore in reaction chamber 135
Alkaline matter can be accommodated to provide such alkaline environment.
As shown in Fig. 2, in human body, glucose in blood vessel and tissue fluid by resorption process and can refilter process
It exchanges each other, concentration is of substantially equal.Traditional non-invasive blood sugar instrument is by skin extraction glucose, and then detection is extracted
Glucose, but, generally takeing a long time such as 20 minutes or more just can make extracted glucose reach steady
Fixed concentration, to complete to detect.Through research, the inventor has found that the percutaneous extraction channel of blood sugar for human body includes a variety of, allusion quotation
It include type across cell channel, intercellular channel and hair follicle channels, the extractability in different channels is widely different.Hair follicle is made
For the cuticula, epidermis and corium for penetrating skin, the natural lane for the hypodermal layer that goes directly, there is excellent glucose extractability,
Much larger than across cell channel and intercellular channel.Moreover, each hair follicle all has similar structure, therefore the same area substantially
Hair follicle has essentially identical glucose extractability.It is found in view of the studies above, noninvasive dynamics monitoring device quilt of the invention
It is designed as sensor pixel 130 being directed at hair follicle non-invasively to extract and detect the intracorporal blood glucose of people.
On the other hand, the present inventor the study found that the sensor of traditional non-invasive blood sugar instrument be all designed to have it is biggish
Area is not only extracted by hair follicle when the area of sensor is very big, but also is passed through in the area bigger than hair follicle
Across cell channel and intercellular channel extract.The extractability of across cell channel and intercellular channel is far below hair follicle
Extractability, thus by hair follicle extract concentration of glucose be diluted, need long time complete extract and detect,
Cause detection efficiency low, and detection accuracy is not high.On the contrary, in the present invention by the way that sensor pixel 130 is designed face
Product it is sufficiently small, only with single sensor pixel, and make the single sensor pixel extracted mainly for hair follicle and
Detection rapidly and efficiently can be completed to rate glucose and be extracted and detected due to the excellent glucose extractability of hair follicle channels,
And it can reduce and interfered by other Path Migration brings, to effectively promote the signal-to-noise ratio of measurement, obtain detection accuracy
Greatly improve, can compare favourably with conventional finger blood detection mode.Certainly, the area of sensor pixel 110 can not be too small, no
Hair follicle cannot be then covered, nor is conducive to production.
To achieve the goals above, the present inventor has carried out meticulous design to sensor pixel 130.In general, people
Range of the diameter of chaeta capsule in 0.02-0.05mm.In some embodiments, the area of sensor pixel 130 can be
0.0025mm2To 80mm2Between, preferably in 0.0025mm2To 30mm2Between, more preferably in 0.0025mm2To 10mm2It
Between, more preferably in 0.0025mm2To 3mm2Between, such as can be in 0.0025mm2To 1mm2Between.The present inventor passes through reality
It issues after examination and approval now, the area of sensor pixel 130 is in such as 10mm2It when left and right, needs extract to complete glucose within 3-6 minutes, and works as
The area of sensor pixel 130 drops to such as 1mm2When following, glucose extraction operation only can be completed within 1 minute.
Therefore, the area of sensor pixel 130 is in 1mm2It is most preferred below.
It is also related to the volume of reaction chamber 135 that glucose extracts the time.In some embodiment of the invention, reaction chamber 135
Can have the area with region occupied by electrode above, i.e. the area of sensor pixel 130 is compared, it is essentially identical or
The thickness (depth in other words) of smaller area, reaction chamber 135 can preferably be arrived in 0.05mm between 0.03mm to 0.4mm
Between 0.2mm.The volume of reaction chamber 135 can be in the range less than 20 μ L, preferably less than 10 μ L, even more preferably less than 2 μ L.
It shall yet further be noted that when detecting, the oxidation reaction of the glucose oxidase catalysis glucose in reaction chamber 135 generates
Hydrogen peroxide, the decomposition reaction of 136 catalyzing hydrogen peroxide of working electrode in detecting electrode 133, to generate dense with glucose
Spend corresponding detection electric current.Therefore in some embodiment of the invention, reaction chamber 135 is set as exposing working electrode 136, or
Preferably exposure includes the detecting electrode 133 to electrode 134, working electrode 136 and reference electrode 138, or can also be exposed
Extract both electrode 131 and detecting electrode 133.Preferably, working electrode 136 may be designed as having than other any electrodes bigger
Area, such as working electrode 136 can be designed as to area of its area greater than the every other electrode in sensor pixel
The sum of.And it is possible to which working electrode 136 is made to be located at the central area of sensor pixel 130, other electrodes are centered around working electrode
Around 136, and it can make working electrode 136 that there is the chamfered shape roughly the same with sensor pixel 130.In this way, when passing
When sensor pixel 130 is directed at hair follicle 410, working electrode 136 and reaction chamber 135 below are just targeted by hair follicle 410, so as to
The enough glucose that quickly and efficiently executes is extracted and is detected.
Since sensor pixel 130 and hair follicle 410 all have lesser area, in order to which sensor pixel 130 is registered to
Hair follicle 410, as previously mentioned, providing alignment device 120 around sensor pixel 130.It on the other hand, can be by substrate 110
The upper surface of part corresponding with alignment device 120 be formed to have the shape of convex lens sample, lower surface still can be flat
To form sensor pixel 130, and convenient for attaching on skin surface.It is put in this way, the part of transparent substrates 110 has
The function of big mirror can observe and be aligned hair follicle 410 convenient for user.
Alignment device 120 may include various alignment marks, such as multi-color cord part, crown line part, recess line part, swash
Photetching groove part, bold portion, dotted portion etc., and various shape or pattern can be formed.For example, alignment device 120
It is formed as concentric circles, cruciform pattern, M shape pattern, box pattern, circular pattern and their various combinations
With modification etc..Fig. 3 to Figure 11 shows the example of various alignment devices 120, it should be appreciated that for the sake of clarity, sensing is not shown
Device pixel 130, but actually sensor pixel 130 is located at the centring of alignment device 120.
Referring to attached drawing, Fig. 3 shows a kind of example of alignment device 120 comprising cross-shaped alignment marks and surrounds
The circular pattern of cross-shaped alignment marks, the circular pattern substantially define the boundary of alignment device 120, and cross-shaped alignment marks are then
Define the centring of alignment device 120.In another example shown in Fig. 4, cross figure is replaced with multiple concentric circles
Case is used as alignment mark, wherein the smallest circle can be around the periphery of sensor pixel 130 and adjacent thereto；It is shown in Fig. 5
Example in, then use cruciform pattern and concentric circles combination.M shape alignment figure is used in the example of fig. 6
Case uses the combination of M shape pattern and concentric circles in the example in figure 7.In the example of fig. 8, cross is used
The modification of pattern, i.e., the arrow at four direction centers, and further include the circular pattern around central area.In the example of Fig. 9
In, alignment device 120 includes the M shape pattern as the rectangle frame of outer perimeter and in rectangle frame, and the example of Figure 10 includes
The combination of M shape pattern in rectangular outer frame and concentric circles, the example of Figure 11 include M shape pattern and multiple same
The combination of central rectangular block diagram case.It should be understood that alignment device 120 also may include many other patterns.
Figure 12 is the structural schematic diagram according to the sensor pixel 130 of another embodiment of the application.As shown in figure 12, it senses
Device pixel 130 includes that anode 132, cathode (to electrode) 134, working electrode 136 and reference electrode 138, each electrode pass through cloth
Line 137 is connected to external circuit.Although the example with Fig. 2 includes identical electrode, its layout is different.Fig. 2's
In example, working electrode 136 is substantially rectangular, and cathode 134 and reference electrode 138 are around the periphery of working electrode 136, anode
132 are arranged in the outside of cathode 134 with cathode 134 substantially in parallel.In the illustration in fig 12, working electrode 136 has circle
Shape, anode 132, cathode 134 and reference electrode 138 surround the circumference of working electrode 136.Anode 132 and cathode 134 can enclose
Around the major part of the circumference of working electrode 136, in order to carry out glucose extraction, and reference electrode 138 can be only around work
Make the smaller portions of the circumference of electrode 136.The advantage of this structure is working electrode 136 occupies the center of sensor pixel 130
Region and the most of area for occupying sensor pixel 130, so as to easily by working electrode 136 and below anti-
Chamber 135 (Figure 12 is not shown) is answered to be aligned with hair follicle 410.
Figure 13 is the structural schematic diagram according to the sensor pixel 130 of another embodiment of the application.As shown in figure 13, it senses
Device pixel 130 includes anode 132, cathode (to electrode) 134, working electrode 136 and reference electrode 138.Working electrode 136 is located at
The center of sensor pixel 130 has rectangular patterns, and anode 132, cathode (to electrode) 134 and reference electrode 138 are centered around work
Make around electrode 136, Anodic 132 and cathode 134 extend along the long side of working electrode 136, and status relative to each other
In the two sides of working electrode 136, reference electrode 138 extends along the short side of working electrode 136.
Figure 14 A and Figure 14 B are the structural representation according to the single pixel noninvasive dynamics monitoring device of another embodiment of the application
Figure, wherein Figure 14 A is top view, and Figure 14 B is side view.As shown in figs. 14 a-b, single pixel noninvasive dynamics monitoring device 200
Including the first substrate 210, alignment device 220 and sensor pixel 230, sensor pixel 230 be can be set in the first substrate
On 210.Alignment device 220 may include the second substrate 222, and the first substrate 210 and the second substrate 222 can be and 110 phase of substrate
Same substrate, i.e. transparent flexible substrate.Alignment device 220 may also include the alignment mark 224 being formed on the second substrate 222,
It defines centring, and the opening 226 for penetrating the second substrate 222 is formed at the centring, and opening 226 can have and pass
The essentially identical shapes and sizes of sensor pixel 230, for accommodating sensor pixel 230.In use, user can first will be right
Standard apparatus 220 attaches on user's skin, and under the auxiliary of the alignment mark of alignment device 220 224, makes 226 pairs of opening
Quasi- hair follicle 410.Due to blocking for not no sensor pixel, user can easily will 226 alignment hair follicles 410 of opening, such as can
So that hair follicle 410 is located substantially at the center of opening 226.Then, the first substrate 210 can be attached to alignment device 220 by user
The second substrate 222 on, and be located at sensor pixel 230 on the first substrate 210 in opening 226.In this way, being achieved that
Sensor pixel 230 is accurately aimed at hair follicle 410.
In some embodiments, it can also be not provided with alignment mark 224 on the second substrate 222, because opening 226 is inherently
It may be used as alignment mark.For example, user can make hair follicle 410 be located at opening 226 directly by 226 alignment hair follicle 410 of opening
Center.
In some embodiments, alignment device, such as previously described alignment also can be set on the first substrate 210
Device 120 to assist determining the position of sensor pixel 230, and sensor pixel 230 is registered in opening 226.
Figure 15 shows the wearing schematic of the single pixel noninvasive dynamics monitoring device according to one embodiment of the application.Such as figure
Shown in 15, aforementioned single pixel noninvasive dynamics monitoring device 100 (200) can be attached on the human body such as skin surface of arm 400,
Each electrode of single pixel noninvasive dynamics monitoring device 100 can be wired to data processing unit 300, it should be appreciated that number
A part of single pixel noninvasive dynamics monitoring device of the invention can also be considered as according to processing unit 300.Although Figure 15 is shown
Sensor pixel is connected to data processing unit 300 by Wireline, but in further embodiments, it can also detect
100 side of device provides necessary circuit, and signal is wirelessly transmitted to data processing unit 300.Data processing unit 300 can be with
It is the portable electronic device of user's body-worn or carrying, such as is desirably integrated into the mobile phone of user.In other implementations
In example, together with detection device 100 also can integrate with data processing unit 300, a wearable device is formed, is directly worn on
On such as arm 400 of user.
Figure 16 shows the structural block diagram of data processing unit 300.Data processing unit 300 is used to examine detection device 100
The detection signal generated when surveying extracted glucose is handled, with the concentration of the extracted glucose of determination.Specifically,
The detection signal that detection device 100 generates, such as detection electric current, it is proportional to the concentration of glucose.In data processing unit 300
It may include having memory 310, such as ROM, EEPROM, flash memory etc., can store a calibration curve, calibration curve description
Relationship between concentration of glucose and detection electric current, is generally linear relationship.Data processing unit 300 further includes having controller
320, the glucose that controller 320 can control detection device 100 extracts and detection operation, and also bent based on such alignment
Line determines concentration of glucose corresponding to the detection signal of the generation of detection device 100, so that it is determined that the blood sugar concentration of user.Number
May also include according to processing unit 300 has output unit 330, is used for output test result, the i.e. blood sugar concentration of user.Output unit
330 can be such as display, loudspeaker, be also possible to communication unit such as bluetooth, WiFi etc. is will test result transmission
To other equipment, such as the information management system of hospital or the data system of patient doctor are sent to by internet.One
In a little embodiments, data processing unit 300 may also include alarm unit 340, when blood glucose value is more than certain level, alarm unit
340 can trigger various forms of alarm signals, such as instruction modulating signal, buzzerphone etc..
In conclusion the embodiment of the present application provides a kind of single pixel noninvasive dynamics monitoring device.The single pixel is noninvasive
Blood sugar detection apparatus is using the sensor pixel by Reverse iontophoresis and by human body hair follicle from human body glucose
Electric current letter relevant to blood glucose is obtained in human skin surface's detecting glucose concentration to skin surface and by electrochemical reaction
Number, to obtain blood sugar concentration.By above-mentioned workflow it can be found that the single pixel noninvasive dynamics monitoring device does not need
The detection of object blood glucose to be measured can be carried out by damaging object to be measured, realize the purpose of noninvasive dynamics monitoring.
In addition, the single pixel noninvasive dynamics monitoring device utilizes Reverse iontophoresis, glucose is extracted into skin table
Face, whole process will not damage object to be measured, the noninvasive purpose of realization.The single pixel noninvasive dynamics monitoring device utilizes electrochemistry
It reacts to detect glucose, glucose has specificity, eliminates a large amount of interference in detection process.Therefore, the Woundless blood sugar
Instrument is realized in the case where not damaging object to be measured, carries out accurately blood sugar test.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
Claims (38)
1. a kind of single pixel noninvasive dynamics monitoring device, comprising:
Single sensor pixel is arranged on the first substrate, for attaching to user's skin；And
Alignment device, at least one hair follicle for being directed at the sensor pixel on user's skin.
2. single pixel noninvasive dynamics monitoring device as described in claim 1, wherein the alignment device is described including being formed in
Alignment mark on first substrate, the sensor pixel are located at the centring of the alignment mark on first substrate
Place.
3. single pixel noninvasive dynamics monitoring device as described in claim 1, wherein the alignment device includes:
Second substrate；And
Opening, penetrates second substrate,
Wherein, the alignment device is configured to when second substrate is attached on user's skin, opening alignment and
At least one described hair follicle of exposure.
4. single pixel noninvasive dynamics monitoring device as claimed in claim 3, wherein the alignment device further include:
Alignment mark is formed on second substrate,
Wherein, the opening is on second substrate at the centring of the alignment mark.
5. single pixel noninvasive dynamics monitoring device as claimed in claim 3, wherein the opening has and the sensor picture
The essentially identical shapes and sizes of element.
6. single pixel noninvasive dynamics monitoring device as claimed in claim 3, wherein first substrate and second substrate
It is flexible substrate.
7. single pixel noninvasive dynamics monitoring device as claimed in claim 3, wherein first substrate and second substrate
It is transparent substrates.
8. single pixel noninvasive dynamics monitoring device as claimed in claim 2 or 4, wherein the alignment mark includes multi-color cord
Partially, crown line part, recess line part, laser-induced thermal etching line part, bold portion, dotted portion or their any combination.
9. single pixel noninvasive dynamics monitoring device as claimed in claim 2 or 4, wherein the alignment mark includes concentric circles
Pattern, cruciform pattern, M shape pattern, box pattern, circular pattern or their any combination.
10. single pixel noninvasive dynamics monitoring device as described in claim 1, wherein the sensor pixel includes:
Electrode is extracted, is formed on first substrate, for being permeated by reverse ion through user's skin extraction glucose；
Detecting electrode is formed on first substrate, for detecting the concentration of extracted glucose by electrochemical method；
And
Reaction chamber, for receiving extracted glucose.
11. single pixel noninvasive dynamics monitoring device according to claim 10, wherein the extraction electrode include anode and
Cathode, for reverse ion infiltration lane being formed in user's skin to extract glucose, and
Wherein, the detecting electrode includes reference electrode, working electrode and to electrode, for by electrochemical reaction to detect
The concentration of the glucose of extraction.
12. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the anode includes Ag, the yin
Pole, the reference electrode and described Ag/AgCl is each included to electrode.
13. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the working electrode includes:
Layer of precious metal；And
Catalyst granules, be attached to the layer of precious metal towards on the surface of the reaction chamber, for catalyzing hydrogen peroxide
Decomposition reaction.
14. single pixel noninvasive dynamics monitoring device according to claim 13, wherein described in the direction of the layer of precious metal
The surface of reaction chamber is roughened surface.
15. single pixel noninvasive dynamics monitoring device according to claim 13, wherein the layer of precious metal includes layer gold,
The catalyst granules includes Prussian blue.
16. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the working electrode includes:
Graphene layer；And
Catalyst nano-particles, be attached to the graphene layer towards on the surface of the reaction chamber, for being catalyzed peroxidating
The decomposition reaction of hydrogen.
17. single pixel noninvasive dynamics monitoring device according to claim 16, wherein the catalyst nano-particles include
At least one of Pt nanoparticle and gold nano grain.
18. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the working electrode includes transition gold
Belong to oxide skin(coating).
19. single pixel noninvasive dynamics monitoring device according to claim 18, wherein the transition metal oxide layer packet
Include the compound of transition metal oxide.
20. single pixel noninvasive dynamics monitoring device according to claim 19, wherein the transition metal oxide is answered
Closing object includes nickel oxide, tin oxide and indium oxide.
21. single pixel noninvasive dynamics monitoring device according to claim 19, wherein the transition metal oxide layer tool
There is porous structure.
22. single pixel noninvasive dynamics monitoring device according to claim 1, wherein accommodate gel in the reaction chamber
Body.
23. single pixel noninvasive dynamics monitoring device according to claim 22, wherein also accommodate Portugal in the reaction chamber
Grape carbohydrate oxidase, for being catalyzed the oxidation reaction of extracted glucose to generate hydrogen peroxide.
24. single pixel noninvasive dynamics monitoring device according to claim 22, wherein also accommodate alkali in the reaction chamber
Property substance.
25. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the cathode and described be to electrode
Same electrode.
26. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the area of the working electrode is greater than
Any one electrode in other electrodes.
27. single pixel noninvasive dynamics monitoring device according to claim 26, wherein the area of the working electrode is greater than
The sum of area in other electrodes.
28. single pixel noninvasive dynamics monitoring device according to claim 11, wherein the working electrode occupies the biography
The central area of sensor pixel, other electrodes are arranged in around the working electrode.
29. single pixel noninvasive dynamics monitoring device according to claim 11, wherein described in the reaction chamber at least exposes
Working electrode.
30. single pixel noninvasive dynamics monitoring device according to claim 29, wherein the reaction chamber exposure detection
Electrode.
31. single pixel noninvasive dynamics monitoring device according to claim 30, wherein the area of the reaction chamber is less than institute
It states and extracts the area that both electrode and the detecting electrode occupy.
32. single pixel noninvasive dynamics monitoring device according to claim 10, wherein the sensor pixel is configured to work as
When being attached on user's skin, the detecting electrode covers at least one described hair follicle.
33. single pixel noninvasive dynamics monitoring device according to claim 10, wherein the sensor pixel is configured to work as
When being attached on user's skin, the reaction chamber covers at least one described hair follicle.
34. single pixel noninvasive dynamics monitoring device according to claim 1, wherein the area of the sensor pixel exists
0.0025mm2To 80mm2Between, preferably in 0.0025mm2To 30mm2Between, more preferably in 0.0025mm2To 10mm2Between, more
It is preferred that in 0.0025mm2To 3mm2Between, more preferable 0.0025mm2To 1mm2Between.
35. single pixel noninvasive dynamics monitoring device according to claim 1, wherein the volume of the reaction chamber is less than 20 μ
L, preferably smaller than 10 μ L, more preferably less than 2 μ L.
36. single pixel noninvasive dynamics monitoring device according to claim 1, wherein the thickness of the reaction chamber exists
Between 0.03mm to 0.4mm, preferably between 0.05mm to 0.2mm.
37. single pixel noninvasive dynamics monitoring device according to claim 1, further includes:
Data processing unit, the detection signal for generating to the sensor pixel are handled with the extracted grape of determination
The concentration of sugar.
38. the single pixel noninvasive dynamics monitoring device according to claim 37, wherein the data processing unit includes:
Memory, storage are defined concentration of glucose and detect the calibration curve of the relationship between electric current；
Controller determines concentration of glucose corresponding with the detection signal based on the calibration curve；And
Output unit, for exporting identified concentration of glucose.
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| KR20080030376A (en) * | 2006-09-30 | 2008-04-04 | 케이엠에이치 주식회사 | A patch for extracting an interstitial glucose and an apparatus for measuring an interstitial glucose containing the same |
| CN105445339A (en) * | 2014-07-31 | 2016-03-30 | 天津大学 | Flexible differential array electrochemical glucose sensor and use method thereof |
| CA3021886A1 (en) * | 2016-04-26 | 2017-11-02 | The University Of Bath | Multiplexed transdermal extraction and detection devices for non-invasive monitoring of substances and methods of use |
| CN208736824U (en) * | 2018-05-18 | 2019-04-12 | 潘新宇 | Single pixel noninvasive dynamics monitoring device |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20080030376A (en) * | 2006-09-30 | 2008-04-04 | 케이엠에이치 주식회사 | A patch for extracting an interstitial glucose and an apparatus for measuring an interstitial glucose containing the same |
| CN105445339A (en) * | 2014-07-31 | 2016-03-30 | 天津大学 | Flexible differential array electrochemical glucose sensor and use method thereof |
| CA3021886A1 (en) * | 2016-04-26 | 2017-11-02 | The University Of Bath | Multiplexed transdermal extraction and detection devices for non-invasive monitoring of substances and methods of use |
| CN208736824U (en) * | 2018-05-18 | 2019-04-12 | 潘新宇 | Single pixel noninvasive dynamics monitoring device |
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