CN106175840A - A kind of method extracting tissue fluid - Google Patents
A kind of method extracting tissue fluid Download PDFInfo
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- CN106175840A CN106175840A CN201610509832.5A CN201610509832A CN106175840A CN 106175840 A CN106175840 A CN 106175840A CN 201610509832 A CN201610509832 A CN 201610509832A CN 106175840 A CN106175840 A CN 106175840A
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- skin
- electroporation
- tissue fluid
- ultrasound wave
- admittance
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
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- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
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Abstract
The invention discloses a kind of method extracting tissue fluid.It comprises the steps: that (1) uses chemical enhancers to process skin, forms water solublity passage in making keratodermatitis；(2) use ultrasound wave and electroporation that skin effect simultaneously is processed, provide additional motive power to chemical enhancers while improving skin permeability, expand osmotic effect further；(3) carry out ultrasound wave, electroporation to skin treatment while, the admittance to skin measures, and when admittance reaches the threshold value can extracted tissue fluid, utilizes reverses iontophoresis to carry out the extraction of tissue fluid.The method of the present invention is when extracting tissue fluid, and comparing the most methodical effect has had and be substantially improved, and the injury to skin significantly reduces.
Description
Technical field
The present invention relates to a kind of method extracting tissue fluid, extract the side of tissue fluid particularly to a kind of noinvasive or Wicresoft
Method.
Background technology
Detection to health index, such as glucose, lactic acid, sodium ion, the concentration of potassium ion, the most conventional detection hands
Section needs from vein (blood drawing) or after capillary tube (at acupuncture patient's finger fingertip) takes blood, then enters with blood analyser
Row measures.This kind of method not only brings pain, the danger that there is wound recovery difficulty, infect to patient, and this most all gives
Patient brings a pain and fear, and detects another kind of body fluid tissue fluid, is enriched substantial amounts of physiology equally with healthy
Information, and some index and blood middle finger indicate stable relations.Such as, Minn. research institution Mayo
The research that Clinic is done shows, blood glucose value measured from skin interstitial fluid is the most close with institute's measured value in blood.It addition, tissue
The extraction of liquid is extracted much easier than blood.
In the method extracting Skin tissue fluid, patent " Wicresoft of human blood glucose concentration, dynamic, continuous monitoring method "
(publication number: CN101214152A) proposes to use low frequency ultrasound to carry out pretreatment, then extracts Skin tissue fluid by the method for negative pressure.
But finding through research practice, the effect using single pretreating skin is unsatisfactory, and increases intensity and then may hinder
Evil is to skin.
Summary of the invention
In view of this, it is an object of the invention to provide a kind of new method extracting tissue fluid, the method for the present invention is carrying
When taking tissue fluid, comparing the most methodical effect has had and has been substantially improved, and the injury to skin significantly reduces.
To achieve these goals, the present invention provides a kind of method extracting tissue fluid, comprises the steps:
(1) use chemical enhancers that skin is processed, in making keratodermatitis, form water solublity passage；
(2) use ultrasound wave and electroporation that skin effect simultaneously is processed, to chemical while improving skin permeability
Penetrating agent provides additional motive power, expands osmotic effect further；
(3) carry out ultrasound wave, electroporation to skin treatment while, the admittance to skin detects, when admittance reaches
During to the threshold value that can tissue fluid be extracted, reverses iontophoresis is utilized to carry out the extraction of tissue fluid.
The present invention has a following beneficial effect:
The present invention proposes a kind of by improving the method that percutaneous permeability extracts tissue fluid: by chemical enhancers pair
Skin carries out pretreatment, then is further processed with ultrasound wave electroporation, makes skin (pass through after reaching certain permeability
Survey skin admittance and can draw skin permeation rates), finally use reverses iontophoresis that Skin tissue fluid is extracted.By chemistry
Penetrating agent, ultrasound wave, electroporation, the synergism of reverses iontophoresis, make the time of extraction tissue fluid be greatly shortened, than employing
Single mode is effective, and uses synergism to make the intensity of each single mode relative to using a kind of mode significantly to drop
Low, the damage to skin is significantly reduced.
Accompanying drawing explanation
Fig. 1 is the schematic flow sheet that the present invention extracts the method for tissue fluid.
Fig. 2 is the flange ultrasound piezoelectric sheet positive and negative graphic example that the present invention uses.
Fig. 3 (A) and (B) are the electroporation output waveform examples that the present invention uses.
Fig. 4 be the present invention use ultrasound wave, electroporation, reverses iontophoresis coupling probe figure.
Detailed description of the invention
For making the object, technical solutions and advantages of the present invention clearer, below in conjunction with specific embodiment, and reference
Accompanying drawing, the present invention is described in further detail.
The present invention provides a kind of method extracting tissue fluid, comprises the steps:
(1) use chemical enhancers that skin is processed, in making keratodermatitis, form water solublity passage；
(2) use ultrasound wave and electroporation that skin effect simultaneously is processed, to chemical while improving skin permeability
Penetrating agent provides additional motive power, expands osmotic effect further；
(3) carry out ultrasound wave, electroporation to skin treatment while, the admittance to skin measures, when admittance reaches
During to the threshold value that can tissue fluid be extracted, reverses iontophoresis is utilized to carry out the extraction of tissue fluid.
Wherein, chemical enhancers described in step (1) is to meet not injure object two in skin and tissue fluid simultaneously
The chemical enhancers of condition.Described chemical enhancers can be a kind of chemical enhancers, it is also possible to two or more chemistry
The mixture of penetrating agent.
Specifically, described chemical enhancers, it is therefore an objective to remove the pollutant of skin surface, part in extraction horny layer
Lipid, or make horny layer inner lipid bimolecular disordering, form water solublity passage.The chemical enhancers used is to human body skin
Harmless material, it is common that the material that can be mutually dissolved, or one or more chemical enhancers are soluble in other one
Plant in chemical enhancers.
Preferably, described chemical enhancers is the combination of the menthol of the medical ethanol of 66wt% and 2.5wt%, or
The medical ethanol of 75wt% and the combination of 2.5wt% oleic acid.
In step (2), described ultrasound wave can be low-frequency ultrasonic waves, it is also possible to be low-frequency ultrasonic waves and high-frequency ultrasonic
Combination.The low-frequency ultrasonic waves used promotees the cavitation that the mechanism of infiltration is low-frequency ultrasonic waves, i.e. low-frequency ultrasonic waves causes Jie
Matter and intracellular gas molecule, the vibration of bubble, and bubble rupture formation space or empty pocket subsequently, and cavitation is formed
Gap be about 4 μm.Cavitation can change the ordered arrangement of skin lipid layer, causes the outer medium cavitation of skin to be formed, has
Help transdermal penetration.High-frequency ultrasonic promotees the mechanism of infiltration and promotes to permeate mainly by the heat that high frequency produces.It addition, it is ultrasonic
The mechanical vibration of ripple have facilitation to penetrating fluid.
Preferably, the frequency that described low-frequency ultrasonic waves uses is 20kHz, and the dutycycle of employing is 1:2.Described high frequency ultrasound
The frequency that ripple uses is 1MHz～16MHz, and the dutycycle of employing is 1:3.
Preferably, the intensity of described ultrasound wave is less than 2W/cm2, and during with electroporation circuit synergism, its intensity is the least
In 2W/cm2。
In step (2), described electroporation uses square-wave signal, and described square wave can be the square wave of single direction, also
Square wave that can be two-way.
The frequency of described square wave is typically larger than 1kHz and is less than 100kHz, and dutycycle can change, and dutycycle is less than or equal to
50%.
Preferably, described square wave acts on the Voltage Peak peak value on skin less than 200V.
Preferably, ultrasound probe and electroporation probe that step (2) is used are one and synthesize overall probe, described
Ultrasound wave is produced by the piezoelectric patches of supersonic generator, and described piezoelectric patches is the piezoelectric patches of flange, and described piezoelectric patches is positioned at contact
The electroporation probe of skin is following, sends ultrasound wave by resonance circuit, and described piezoelectric patches passes through insulating cement with electroporation probe
Bonding.
In step (3), it is that ultrasound wave and electroporation are carried out described in step (2) that the described admittance to skin measures
Carry out after a period of time, and described measurement is to carry out in the off time that ultrasound wave and electroporation do not act on, to prevent them
Interfering between circuit.
In step (3), the described admittance to skin measures and utilizes the extraction that reverses iontophoresis carries out tissue fluid
It is the process of a phase mutual feedback, while carrying out tissue fluid extraction, i.e. measures admittance, the size correspondence counter ion electricity of admittance
The size of the curtage that infiltration uses.
Preferably, electroporation probe and the reverse iontophoresis described in step (3) that described in step (2), electroporation is used
The reverses iontophoresis probe thoroughly used is the probe of a multiplexing, uses same electrode to export, and their output is by height
Speed analog switch is controlled switching.
The method been specifically described aboving the present invention, the method for the present invention has the effect of collaborative enhancing, is neither hindering
While evil skin, the permeability of skin can be improved again.In the method extracting Skin tissue fluid object, it is most commonly used that
Reverses iontophoresis, the method mainly applies suitable voltage or suitably constant current at the diverse location of epiderm skin, at electric field
Under effect, the momentum transfer that ion motion produces with solvent can cause an anode can promote to the clean convection current of negative electrode, this convection current
Enter the transport in the same direction of uncharged solute.The method uses constant current or constant voltage to extract, due to everyone skin
Impedance is different, voltage or electric current cross conference make skin produce burn, red and swollen side effect, make patient satisfaction decline, electric current or
The effect of voltage too small extraction tissue fluid is bad, it is impossible to reach the effect wanted, and the health that the most just cannot detect in tissue fluid refers to
Mark.Therefore, before the present invention proposes to carry out tissue fluid extraction, (admittance of skin and the permeability of skin exist steady in detection skin admittance
Fixed relation), according to the size i.e. situation of permeability of skin admittance, determine that counter ion permeates the curtage used
Size, thus will not hurt skin.
Embodiment 1
Referring to Fig. 1, it extracts the schematic flow sheet of method of tissue fluid for the present invention, mainly use chemical enhancers,
Ultrasound wave, electroporation and counter ion infiltration, it is achieved collaborative reinforced effects, and significantly reduce the wound to skin simultaneously.
The steps include:
1) use chemical enhancers that skin is carried out pretreatment, in making keratodermatitis, form water solublity passage；
2) use ultrasound wave and electroporation that skin effect simultaneously is processed, promote to chemistry while improving skin permeability
Penetration enhancer provides additional motive power, expands osmotic effect further；
3) carrying out ultrasound wave, electroporation to skin treatment simultaneously, the admittance to skin detects, and when admittance, reach can
During to carry out the threshold value extracted, i.e. may utilize reverses iontophoresis and carry out extracting tissue fluid.Electric current used by reverses iontophoresis
Or voltage adjusts at any time according to the size of admittance, when i.e. skin permeation rates is strong, the extraction electric current of employing is less, Cutaneous permeation
When rate is weak, the extraction curtage of employing is relatively big, but the electric current used and voltage are all to meet not injure under skin condition
Curtage.
Specifically, step 1) described in the medical ethanol that chemical enhancers is 66wt% and the group of menthol of 2.5%
Close, or the medical ethanol of 75wt% and the combination of 2.5wt% oleic acid.
Step 2) ultrasound wave that used can be low-frequency ultrasonic waves, it is also possible to it is the mixed of low frequency ultrasound and high frequency ultrasound
Close.Usually, the frequency that low-frequency ultrasonic waves uses is led to for about 20KHZ, and the dutycycle of employing is 1:2.The high frequency used surpasses
The frequency of sound wave is 1MHZ～16MHZ, and the dutycycle of employing is 1:3.
Step 2) intensity of ultrasound wave that used is typically smaller than 2W/cm2, and during with electroporation circuit synergism, by force
Degree is much smaller than 2W/cm2。
Step 2) piezoelectric patches of ultrasonic circuit that used is the piezoelectric patches of flange, as in figure 2 it is shown, piezoelectric patches shielding
Cable is connected with ultrasonic circuit.
Step 2) used electroporation is square-wave signal, can be the square wave of single direction, it is also possible to two-way square wave.As
Being that electroporation exports square-wave signal shown in Fig. 3 (A) and (B), Fig. 3 (A) is the square-wave signal of single direction, and Fig. 3 (B) is just to have
The square-wave signal of negative direction.In the case of not injuring skin, using electroporation can form one at skin surface can wear
Cross the puddle of glucose molecule, lactic acid molecules.The relating to parameters such as electroporation effect and the amplitude of voltage, frequency, dutycycle.
Step 2) frequency of square wave that used is typically larger than 1KHZ less than 100KHZ, and dutycycle can change, dutycycle
Less than or equal to 50%.
Step 2) square wave that used act on skin Voltage Peak peak value less than 200V.
Step 2) ultrasound probe that used and electroporation probe be the overall probe of a synthesis.Ultrasonic piezoelectric patches position
Following in the electroporation probe of contact skin, send ultrasound wave by resonance circuit, ultrasonic piezoelectric patches passes through with electroporation probe
Insulating cement bonds, their dielectric strength about 500V.
Step 2) electroporation probe and step 3) counter ion infiltration probe be that the probe of a multiplexing is (such as Fig. 4 institute
Show), use same electrode to export, their output is controlled switching by high-speed analog switch.The output of this multiplexing probe
Being completed by the electrode of a series of even number numbers, they compartment of terrains connect together as an electrode, thus achieve two
The switching of electrode.All electrodes 1 of Fig. 4 probe are connected in inside to connect, and similarly, all electrodes 2 are also connected in inside
Connect.
Step 3) be in step 2 to the detection of skin admittance) ultrasound wave and electroporation carry out a period of time after carry out,
Usually, this time is less than 10 minutes.Admittance measurement to skin is the off time not acted at ultrasound wave and electroporation
Carrying out, now ultrasound wave and electroporation are all 0 without exporting output amplitude in other words, effectively prevent ultrasonic circuit and electroporation
Interfere between circuit.
Step 3) system that tissue fluid is a phase mutual feedback is extracted in the test of admittance and reverses iontophoresis, i.e. entering
Row tissue fluid surveys admittance when of extraction simultaneously, the curtage that the size correspondence reverses iontophoresis of admittance uses big
Little.As it is shown in figure 1, the admittance measurement unit shown in figure detects the admittance of skin immediately, feed back to central processing unit control, in
Central processor adjusts the size of the electric current that reverses iontophoresis is used immediately according to the size measuring admittance, is effectively prevented skin
Skin damages, it is ensured that safety.
Through putting into practice technical scheme, result shows that extracting tissue fluid with the inventive method compares traditional side
Method the most significantly shortens, and injury and sense of discomfort to skin substantially reduce, and substantially realizes noinvasive and extracts.
Separately it should be noted that, though the objective for implementation of technical scheme is human or animal, but the technical side of the present invention
Case is not related to diagnosis and the Therapeutic Method of disease, and it is only the initial link measuring some sign Indexes.
Particular embodiments described above, has been carried out the purpose of the present invention, technical scheme and beneficial effect the most in detail
Describe in detail bright it should be understood that the foregoing is only the specific embodiment of the present invention, be not limited to the present invention, all
Within the spirit and principles in the present invention, any modification, equivalent substitution and improvement etc. done, should be included in the protection of the present invention
Within the scope of.
Claims (10)
1. the method extracting tissue fluid, it is characterised in that comprise the steps:
(1) use chemical enhancers that skin is processed, in making keratodermatitis, form water solublity passage；
(2) use ultrasound wave and electroporation that skin effect simultaneously is processed, while raising skin permeability, give chemical enhancement
Agent provides additional motive power, expands osmotic effect further；
(3) carry out ultrasound wave, electroporation to skin treatment while, the admittance to skin measures, and when admittance, reach can
With tissue fluid is extracted threshold value time, utilize reverses iontophoresis to carry out the extraction of tissue fluid.
Method the most according to claim 1, it is characterised in that described in step (1), chemical enhancers is to meet not simultaneously
The chemical enhancers of two conditions of object in injury skin and tissue fluid.
Method the most according to claim 1, it is characterised in that described chemical enhancers be 66wt% medical ethanol and
The combination of the menthol of 2.5wt%, or the medical ethanol of 75wt% and 2.5wt% oleic acid combination.
Method the most according to claim 1, it is characterised in that in step (2), described ultrasound wave is low-frequency ultrasonic waves,
Or low-frequency ultrasonic waves and the combination of high-frequency ultrasonic；
Preferably, the frequency that described low-frequency ultrasonic waves uses is 20kHz, and the dutycycle of employing is 1:2；Described high-frequency ultrasonic is adopted
Frequency be 1MHz～16MHz, the dutycycle of employing is 1:3.
Method the most according to claim 1, it is characterised in that the intensity of described ultrasound wave is less than 2W/cm2。
Method the most according to claim 1, it is characterised in that in step (2), described electroporation uses square wave letter
Number；
Described square wave acts on the Voltage Peak peak value on skin less than 200V.
Method the most according to claim 1, it is characterised in that ultrasound probe and electroporation that step (2) is used are visited
Head is the probe that a synthesis is overall, and described ultrasound wave is produced by the piezoelectric patches of supersonic generator, and described piezoelectric patches is flange
Piezoelectric patches, described piezoelectric patches be positioned at contact skin electroporation probe following, send ultrasound wave, described pressure by resonance circuit
Electricity sheet is bonded by insulating cement with electroporation probe.
Method the most according to claim 1, it is characterised in that in step (3), the described admittance to skin measures and is
Described in step (2), ultrasound wave and electroporation are carried out after carrying out a period of time, and described measurement is to wear at ultrasound wave and electricity
The off time that hole does not acts on is carried out.
Method the most according to claim 1, it is characterised in that in step (3), the described admittance to skin measure and
The extraction utilizing reverses iontophoresis to carry out tissue fluid is the process of a phase mutual feedback, i.e. while carrying out tissue fluid extraction
Measure admittance, the size of the curtage that the size correspondence reverses iontophoresis of admittance uses.
Method the most according to claim 1, it is characterised in that the electroporation probe employed in step (2) and step
(3) the reverses iontophoresis probe employed in is the probe of a multiplexing, uses same electrode to export, and their output is passed through
High-speed analog switch is controlled switching.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610509832.5A CN106175840A (en) | 2016-07-01 | 2016-07-01 | A kind of method extracting tissue fluid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610509832.5A CN106175840A (en) | 2016-07-01 | 2016-07-01 | A kind of method extracting tissue fluid |
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| Publication Number | Publication Date |
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| CN106175840A true CN106175840A (en) | 2016-12-07 |
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| CN201610509832.5A Pending CN106175840A (en) | 2016-07-01 | 2016-07-01 | A kind of method extracting tissue fluid |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111107679A (en) * | 2019-12-02 | 2020-05-05 | 天津大学 | Flexible temperature control system |
| CN111803789A (en) * | 2020-06-28 | 2020-10-23 | 王瑾 | Noninvasive lip beautifying method |
| WO2023179806A3 (en) * | 2023-07-06 | 2024-05-16 | 杭州柔谷科技有限公司 | Biochemical substance measurement system and method, and storage medium |
-
2016
- 2016-07-01 CN CN201610509832.5A patent/CN106175840A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111107679A (en) * | 2019-12-02 | 2020-05-05 | 天津大学 | Flexible temperature control system |
| CN111107679B (en) * | 2019-12-02 | 2021-06-04 | 天津大学 | Flexible temperature control system for extraction of reverse iontophoresis |
| CN111803789A (en) * | 2020-06-28 | 2020-10-23 | 王瑾 | Noninvasive lip beautifying method |
| WO2023179806A3 (en) * | 2023-07-06 | 2024-05-16 | 杭州柔谷科技有限公司 | Biochemical substance measurement system and method, and storage medium |
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Application publication date: 20161207 |