CN102058399B - Bionic pulse feeling system based on microfluidic chip - Google Patents
Bionic pulse feeling system based on microfluidic chip Download PDFInfo
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- CN102058399B CN102058399B CN2009102377425A CN200910237742A CN102058399B CN 102058399 B CN102058399 B CN 102058399B CN 2009102377425 A CN2009102377425 A CN 2009102377425A CN 200910237742 A CN200910237742 A CN 200910237742A CN 102058399 B CN102058399 B CN 102058399B
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Abstract
The invention discloses a bionic pulse feeling system based on a microfluidic chip, comprising the microfluidic chip, a microfluid driving device and a detection device, wherein the microfluidic chip is provided with a sensing film and a plurality of microflutes, the sensing film is covered on the microflutes and is used for conducting a pulse signal on a position of which the pulse to be felt to microfluids in the microflutes; the microfluid driving device is used for driving the microfluids to flow in the microflutes; and the detection device is used for detecting the flow, the flow rate or the pressure of the microfluids in the microflutes. Microflutes in the microfluidic chip better simulate vessels on the position of which the pulse is to be felt, so that the pulse signal can be better embodied in the microfluids in the microflutes to overcome the defects of limited detection point number and low detection sensitivity of the traditional single-point or composite multiple-point pressure sensors.
Description
Technical field
The present invention relates to a kind of bionical system of feeling the pulse, relate in particular to a kind of bionical system of feeling the pulse based on micro-fluidic chip.
Background technology
Pulse-taking is the important component part of the traditional Chinese medical science four diagnostic methods, and China just utilizes pulse condition information to diagnose the illness since ancient times and formed the pulse-taking system of the traditional Chinese medical science.Pulse-taking is most characteristic in a China's traditional medicine diagnostic method, is also extensively adopted by other national doctor, plays an important role in the diagnosis of disease and the context of detection of health.The exploration pulse wave spectrum objectifies, normalization method, is the important topic of tcm clinical practice research.Realize objectifying, standardizing of pulse-taking, key is to develop modern pulse condition information acquisition system, the internalise that overcomes the doctor individual is described, and finishes the awkward situation that the traditional Chinese medical science " has been prone at the heart, has referred to that difficulty is bright down ".
At present there are some problems in the great majority pulse condition information acquisition system that is used for clinical diagnosis and treatment and basic research, and for example the acquisition platform volume is bigger than normal, and portability, versatility are good inadequately; Mostly the pick off that is used for the pulse signal detection is liquid formula, photo-electric, strain-type and piezoelectric transducer; These pick offs receive factor affecting such as Fundamentals of Sensors, structural volume, sensing element performance, manufacturing process; The test point number is very limited; And interact between each test point and influence each other, reduced detection sensitivity, and the output of pick off and when feeling the pulse pulse beat and be difficult to have linear relationship between caused skin deformation; The pulse signal that obtains can not reflect the variation of skin surface space, the place each point of feeling the pulse careful and exactly, can't gather pulse condition information or the like comprehensively.
Therefore, need a kind of novel detection easily and analytical system to obtain pulse condition information more accurately.In recent years; Micro-fluidic chip has microminiaturization, automatization, advantage such as integrated, convenient and quick as a kind of novel analysis platform; Obtained to use widely, for example fields such as cytobiology, analytical chemistry, materialogy, organizational project and microelectronics in a lot of fields.Yet, utilize microflow control technique to simulate the traditional Chinese medical science diagnosis of feeling the pulse, obtain the analysis that comprehensive pulse condition information carries out physiological and pathological information, substantial breakthrough is not worldwide arranged as yet.
Summary of the invention
The objective of the invention is bigger than normal for the pulse condition information acquisition system volume that overcomes prior art, can not accurate defective of gathering pulse signal carefully, thereby the bionical system of feeling the pulse based on micro-fluidic chip that a kind of volume is small and can gather pulse signal exactly is provided.
The bionical system of feeling the pulse based on micro-fluidic chip provided by the invention comprises micro-fluidic chip, microfluid drive, checkout gear, microflute and sense film; This micro-fluidic chip has a plurality of above-mentioned microflute that is mounted with microfluid, and described sense film is covered on said a plurality of microflute, and is used for the feel the pulse pulse signal at position of waiting of obtaining of micro-fluidic chip is conducted the microfluid to said microflute; Described microfluid drive is built in the micro-fluidic chip, and this microfluid drive is used for driving microfluid and flows at said microflute; Described checkout gear is used for detecting flow, flow velocity or the pressure of the microfluid of said microflute.
Described sense film and said microflute covered surfaces mutually have a kind of in the 3-D nano, structure of three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges, array arrangement.
Said micro-fluidic chip comprises involution following chip together and goes up chip; Have a plurality of microflutes arranged side by side on the described down chip and be covered in the sense film on these a plurality of microflutes arranged side by side; The described chip of going up comprises being used to hold and waits to feel the pulse the opening groove at position; The bottom of this opening groove has open channel; This open channel be positioned at said sense film directly over, be used for making being contained in the said opening groove position of waiting to feel the pulse and contacting with said sense film.
The described chip of going up also comprises and is embedded in the described thin slice of going up in the chip open channel, and thin slice has respectively and the human body projection of corresponding three the class finger-like in cun,guan,chi zone of wrist radial artery at position of waiting to feel the pulse on the surface of sense film dorsad.
Described microfluid drive is to be built in the described chip down; Described microfluid drive is an electroosmotic pump.
Described chip down also has the signals collecting micropore; Said checkout gear is flow, flow velocity or the pressure that detects the microfluid in the single microflute in said a plurality of microflute arranged side by side through this signals collecting micropore, perhaps detects overlaying flow, flow velocity or the pressure of the microfluid in a plurality of microflutes in said a plurality of microflute arranged side by side.
Said micro-fluidic chip makes through following steps:
A, form a plurality of microflutes (can obtain), with as chip down through etching at substrate surface;
B, form opening groove and open channel at substrate surface, with as last chip, said opening groove is used to hold position to be felt the pulse, and open channel is positioned at the opening groove bottom;
C, sense film is carried out finishing; Form a kind of in three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges, the 3-D nano, structure that array is arranged on its surface, the one side of 3-D nano, structure that said sense film is formed with three-dimensional micrometer structure or the array arrangement of three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arrangement is covered on said a plurality of microflute;
D, the surface is had three thin slices with the projection of the corresponding type of finger-like in the cun,guan,chi of human body wrist radial artery zone be embedded in the said open channel of going up chip, and make its surface sense film dorsad with said projection; And
E, will descend chip and last chip involution, make the sense film that is covered on said a plurality of microflute be positioned at said open channel under.
System of the present invention also comprises the wiper seal chamber, is used for applying the pressure of feeling the pulse to position to be felt the pulse.
System of the present invention also comprises pressure-regulating device, and this pressure-regulating device is used to regulate the pressure of feeling the pulse that said wiper seal chamber applies for position said to be felt the pulse.
Sense film of the present invention is preferably piezoelectric membrane.
In the bionical system of feeling the pulse based on micro-fluidic chip provided by the invention; In the microflute of micro-fluidic chip, flowing simulate blood to pass through heartbeat through microfluid drive driving microfluid flows in blood vessel; By sense film the pulse signal of human body is passed to the microfluid that flows in microflute; Thereby convert the pulse signal of human body flow, flow velocity or the pressure signal of microfluid to, based on this flow, flow velocity or pressure signal physiological pathology of human body information is analyzed then.Because treating the blood vessel at the position of feeling the pulse, a plurality of microflutes in the micro-fluidic chip carried out emulation well; Thereby pulse signal can be embodied in the microfluid in the microflute well, and being arranged in parallel of a plurality of microflutes also overcome traditional single-point or compound multiple spot pressure transducer test point number is limited, detection sensitivity is not high defective.In addition, the bionical system of feeling the pulse based on micro-fluidic chip of the present invention have also that volume is little, good portability and highly sensitive advantage.
Description of drawings
Fig. 1 is the structural representation of the bionical system of feeling the pulse of the present invention.
Fig. 2 is the structural representation of following chip.
Fig. 3 a is the structural representation of last chip.
Fig. 3 b is the sectional view of last chip.
Fig. 4 is the structural representation of an embodiment of the bionical system of feeling the pulse of the present invention.
Fig. 5 is the structural representation of an embodiment again of the bionical system of feeling the pulse of the present invention.
Reference numeral
10. chip 10b. goes up chip under the micro-fluidic chip 10a.
20. microfluid drive 30. checkout gears 40. wiper seal chambeies
50.A/D transducer 60. little process chip 70. computers
110. microflute 120. sense films 130. microchannels
140. opening groove 150. open channels
160. thin slice 160a, 160b, 160c. projection
170. place, the single microchannel of signals collecting micropore 170a.
The junction of 170b, 170c, 170d, 170e. microchannel
180. microfluid circulation canal 190. drive channels 410. pressure-regulating devices
A. the array nano-wire array structure of arranging
B. the mastoid process shape array structure arranged of array
C. the gear shape array structure arranged of array
The specific embodiment
Be described in detail with reference to the attached drawings the present invention below.
Fig. 1 is the structural representation of the bionical system of feeling the pulse of the present invention.As shown in Figure 1, the invention provides a kind of bionical system of feeling the pulse based on micro-fluidic chip, this system comprises: micro-fluidic chip 10, microfluid drive, checkout gear, microflute and sense film; This micro-fluidic chip 10 has a plurality of microflutes 110 and the sense film 120 that is mounted with microfluid; This sense film 120 is covered on said a plurality of microflute 110, is used for the feel the pulse pulse signal at position of waiting of obtaining of micro-fluidic chip is conducted the microfluid to said microflute 110; Described microfluid drive 20 is built in the micro-fluidic chip, and this microfluid drive is used for driving microfluid and flows at said microflute 110; Described checkout gear 30 is used for detecting flow, flow velocity or the pressure of the microfluid of said microflute 110.
Wherein, said microfluid can be a deionized water.The size of said micro-fluidic chip can be 40～60 * 40～60 * 2～5 (long * wide * thick).The a plurality of microflutes that comprise arrangement arranged side by side in the said micro-fluidic chip, the size of each microflute can be 10～30 * 0.2～0.6 * 0.2～0.6mm (long * wide * dark).Under the preferable case; Said micro-fluidic chip comprises 3 groups of microflutes; Correspond respectively to three positions of cun,guan,chi of human body wrist radial artery, every group of microflute comprises 12 microflutes, and each microflute is of a size of 20 * 0.4 * 0.4mm (long * wide * dark); The spacing that is between the microflute of same group of microflute can be 0.4mm, and each spacing of organizing between the microflute is 0.8mm.Certainly, the layout of microflute is not limited to this, for the pulse at other positions of human body wrist radial artery except that three positions of cun,guan,chi, can microflute be set with the corresponding position of other detected part.
Particularly, said micro-fluidic chip comprises chip 10a and last chip 10b down.Fig. 2 is the structural representation of following chip 10a; As shown in Figure 2; Have a plurality of microflutes 110 arranged side by side on the following chip 10a and be covered in the sense film 120 on these a plurality of microflutes 110 arranged side by side; The drive channels 190, microchannel 130, microflute 110, microchannel 130 and the microfluid circulation canal 180 that are communicated with successively have been shown among Fig. 2; The size of wherein said drive channels 190 can be 10 * 0.4 * 0.4mm (long * wide * dark), and the width and the degree of depth of microchannel 130 and microfluid circulation canal 180 can be respectively 0.2 * 0.2mm.
Fig. 3 a and 3b are respectively structural representation and the sectional view of chip 10b; Shown in Fig. 3 a and Fig. 3 b; Last chip 10b comprises being used to hold and waits to feel the pulse the opening groove 140 at position, and the length of this opening groove can be 4～5cm, and width can be 4～5cm; Thickness 2mm, 3mm, 4mm or 5mm corresponding to last chip; The degree of depth of this opening groove can be 1.8mm, 2.8mm, 3.8mm or 4.8mm, and the bottom of this opening groove 140 has open channel 150, and the size of this open channel 150 can be 3 * 1～3 * 0.02cm (long * wide * dark); This open channel 150 is positioned at directly over the said sense film 120 (size of this sense film 120 can 3 * 1～3 * 0.03～0.1cm (long * wide * thick)), is used for making being contained in opening groove 140 position of waiting to feel the pulse and contacting with said sense film 120.In the process of feeling the pulse; Position to be felt the pulse is placed in the said opening groove 140; The feasible position of waiting to feel the pulse contacts with sense film 120 through said open channel 150; Sense film 120 can will wait the to feel the pulse pulse signal at position passes to the microfluid that is arranged in the microflute 110 a plurality of arranged side by side under the sense film 120, thereby comes physiological pathology of human body information is analyzed through flow, flow velocity or the pressure that detects microfluid.
Preferably, said sense film 120 and said a plurality of microflutes 110 mutually covered surfaces have a kind of in the 3-D nano, structure of three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges, array arrangement.
According to the present invention; The three-dimensional micrometer structure that the three-dimensional micron that said array is arranged and three-dimensional manometer hierarchy, array are arranged, the 3-D nano, structure of array arrangement can be in nano-wire array structure, triangular array structure, mastoid process shape array structure, bar-shaped shape array structure, column shape array structure and the gear shape array structure etc. one or more.As shown in Figure 2, wherein, a is the nano-wire array structure that array is arranged, and b is the mastoid process shape array structure that array is arranged, and c is the gear shape array structure that array is arranged.Specifically; Three-dimensional micron that said array is arranged and the micrometer structure in the three-dimensional manometer hierarchy refer to its array main body (height and width of boss all are microns) structure and are of a size of micron; There is nanostructured on the surface of its array agent structure, and/or is of a size of micron or nanometer (recess position) size between its array agent structure; For example the mastoid process in the mastoid process shape array is micron (height and width all are microns) size, and there is nanostructured (like the little mastoid process of nanoscale) on the surface of mastoid process, is of a size of micron or nano-scale between the mastoid process; Gear in the gear shape array is micron (height and width all are microns) size, and gear surface has nanostructured, is of a size of micron or nanometer between the gear; Nano wire in the nanometer linear array is micron (height and width all are microns) size, and the nanowire surface of vertically arranging has nanostructured, is of a size of micron or nanometer between the nano wire; Therefore just be called the combination of micrometer/nanometer hierarchy.Micrometer structure in the three-dimensional micrometer structure of the polymer that said array is arranged refers to its array main body (height and width of boss all are microns) structure and is of a size of micron, is of a size of micron or nanometer (recess position) size between its array agent structure; Nanostructured in the 3-D nano, structure of the polymer that said array is arranged refers to its array main body (height and width of boss all are nanometers) structure and is of a size of nanometer, is of a size of micron or nanometer (recess position) size between its array agent structure.
Thus; The 3-D nano, structure that three-dimensional micrometer structure that the three-dimensional micron that above-mentioned array is arranged and three-dimensional manometer hierarchy, array are arranged or array are arranged can amplify pulse signal; Pulse signal is embodied on the microfluid that flows in the microflute well, improves the sensitivity and the resolution of pulse signal.
According to the present invention; The 3-D nano, structure that three-dimensional micrometer structure that the three-dimensional micron that said array is arranged and three-dimensional manometer hierarchy, array are arranged or array are arranged preferably is made up of at the array below 5 microns diameter (or neutrality line), and array pitch is tens to hundred nanometers.
Generally speaking, cun,guan,chi three subregions that the position all gets the human body wrist radial artery of waiting to feel the pulse.For anthropomorphic dummy's job number arteries and veins mode better; Preferably; The said chip 10b that goes up also comprises thin slice 160; This thin slice 160 is embedded in the said open channel 150 of going up chip 10b, and it has respectively the projection (160a, 160b and 160c) with corresponding three the class finger-like in cun,guan,chi zone of human body wrist radial artery in surface of sense film 120 dorsad.Said thin slice 160 can be PDMS (polydimethylsiloxane) thin slice, PMMA (polymethyl methacrylate) thin slice, PC (Merlon) thin slice, silicon chip or piezoid.When will position felt the pulse being placed in the said opening groove 140; The projection (160a, 160b and 160c) that is embedded in three class finger-like of the thin slice 160 in the said open channel 150 just can be simulated the doctor and be pressed in three fingers of cun,guan,chi three subregions of wrist radial artery in feeling the pulse, thereby obtains the pulse signal of cun,guan,chi three subregions better.Certainly, the bionical system of feeling the pulse of the present invention not merely is applicable to gathers the pulse signal of cun,guan,chi three subregions of wrist radial artery, can also gather the pulse signal at other positions of human body.
Wherein, said micro-fluidic chip 10 can make through following steps:
A, form a plurality of microflutes 110, with as chip 10a down at substrate surface;
B, form opening groove 140 and open channel 150 at substrate surface, with as last chip 10b, said opening groove 140 is used to hold position to be felt the pulse, and open channel 150 is positioned at opening groove 140 bottoms;
C, sense film 120 is covered on said a plurality of microflute 110; And
E, will descend chip 10a and last chip 10b involution, make the sense film that is covered on said a plurality of microflute 110 be positioned at said open channel 150 under.
Preferably; Said step C can be: sense film 120 is carried out finishing; Form a kind of in the three-dimensional micrometer structure have three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array and to arrange, the 3-D nano, structure that array is arranged on its surface, the one side that said sense film 120 is formed with the 3-D nano, structure of three-dimensional micrometer structure with three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arrangement or array arrangement is covered on said a plurality of microflute 110.
Wherein, It is known in those skilled in the art with the method that forms the 3-D nano, structure with three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges or array arrangement on its surface that sense film 120 is carried out finishing; For example can adopt conventional the whole bag of tricks on base material, (can be selected from high molecular polymer (polymethyl methacrylate, Merlon, polyamide, polyethylene, polypropylene, polystyrene, polydimethylsiloxane) or the metal material (copper, aluminum, rustless steel, nickel) one or more) to form earlier the three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges or the 3-D nano, structure of array arrangement like base material; For example; Can pass through physical method; Mill processing methods such as quarter, mask, soft lithographic technique like numerical control, preparation triangular array, mastoid process shape array and gear shape array etc.; Also can pass through chemical method, the preparation nano-wire array, for example, zinc oxide nano-wire array, TiOx nano linear array, tin oxide nano linear array, carbon nano pipe array, metal nanometer line array, silicon nanowire array etc.; The method for preparing of said nano-wire array can adopt the conventional method in this area to carry out; The example that is prepared as with zinc oxide nano-wire array; Its preparation process is following: ZnO colloidal sol evenly is applied to sense film 120 (like native gold); After high temperature (200～400 ℃) is handled, form the crystal seed film of one deck 100～200 nanometer thickness; Then the sense film that is formed with the crystal seed film on it is immersed in the aqueous solution of zinc nitrate hexahydrate (0.025M) and hexamethylenetetramine (0.025M), heated 15 hours down at 85 ℃; At last, use washed with de-ionized water,, obtain zinc oxide nano-wire array 85 ℃ of oven dry down.
Preferably; Can also comprise step D between said step C and the step e: the surface is had three polydimethylsiloxane thin slices with the projection of the corresponding type of finger-like in cun,guan,chi zone of human body wrist radial artery be embedded in the open channel 150 of the said chip 10b of going up, and make its surface sense film 120 dorsad with said projection.
Wherein, said base material can be quartz, glass, silicon materials, high molecular polymer or metal material.Forming microflute 110, opening groove 140 and open channel 150 at substrate surface realizes through one in the following method or many persons: quarter, laser ablation, LIGA technology, method of molding, pressure sintering, chemical attack and soft lithography are milled in numerical control.Said sense film 120 be so long as can produce the thin-film material of deformation and get final product, and for example can be metallic film, polydimethylsiloxane thin film, latex thin film, polyethylene film, conductive film or gathers inclined to one side tetrafluoroethene piezoelectric membrane.The three-dimensional micrometer structure that the three-dimensional micron that said array is arranged and three-dimensional manometer hierarchy, array are arranged, the 3-D nano, structure that array is arranged preferably are formed at zinc oxide nano-wire array, TiOx nano linear array, tin oxide nano linear array, carbon nano pipe array, nanowires of gold array or the silicon nanowire array on said sense film 120 surfaces or the like.
Provide three kinds of embodiments of the manufacture method of micro-fluidic chip below:
First embodiment
Utilize photoetching-chemical corrosion method to go out the pattern that is had on chip and the following chip on above-mentioned, two sheet glass chips about obtaining in the surface etch of two sheet glass respectively.After two sheet glass chips cleaned with ethanol, deionized water, acetone, ethanol one by one up and down, room temperature was dried.
Piezoelectricity PVDF thin film is carried out surface chemical modification, form the array zinc oxide nano-wire array on its surface, the diameter of this zinc oxide nanowire is tens to hundreds of nanometers, and length can arrive several microns.The one side that piezoelectricity PVDF thin film is formed with the array zinc oxide nanowire is covered on the microflute a plurality of arranged side by side of lower-glass chip.
The surface is had three PDMS thin slices with the projection of the corresponding type of finger-like in cun,guan,chi zone of human body wrist radial artery be embedded in the open channel of upper glass chip, and make its surface piezoelectricity PVDF thin film dorsad with said projection.
Utilize double pressure adhesive membrane (
8890) two sheet glass chip involutions up and down under pressure, make the piezoelectricity PVDF thin film that is covered on said a plurality of microflute arranged side by side be positioned at said open channel under.
Second embodiment
Utilize the quasi-molecule laser etching machine to go out the pattern that is had on chip and the following chip on above-mentioned, two polymethyl methacrylate chips about obtaining at two polymethyl methacrylate base material surface etchings respectively.After two polymethyl methacrylate chips clean with ethanol, deionized water, ethanol one by one up and down, dry naturally.
Form the array mastoid process through mask, chemical attack and replica on the surface of polydimethylsiloxane thin film (PDMS), the length and width of this array mastoid process can be that the hundreds of nanometer is to several microns with height.The one side that the polydimethylsiloxane thin slice is formed with the array mastoid process is covered in down on the microflute a plurality of arranged side by side of polymethyl methacrylate chip.
The surface is had three PDMS thin slices with the projection of the corresponding type of finger-like in cun,guan,chi zone of human body wrist radial artery be embedded in the open channel of polymethyl methacrylate chip, and make the soft dorsad polyethylene film in its surface with said projection.
Utilize double pressure adhesive membrane (
8890) two polymethyl methacrylate chip involutions up and down under pressure, make the soft polyethylene film that is covered on said a plurality of microflute arranged side by side be positioned at said open channel under.
The 3rd embodiment
Utilize numerical control to mill and go out the pattern that is had on chip and the following chip on above-mentioned, two Merlon chips about obtaining at two polycarbonate substrate surface etchings respectively quarter.After two Merlon chips clean with deionized water, ethanol, deionized water, ethanol one by one up and down, dry naturally.
Form the array gear through mask, chemical attack and replica on the surface of polydimethylsiloxane thin film (PDMS), the length and width of this array gear can be that the hundreds of nanometer is to several microns with height.The one side that this PDMS thin slice is formed with the array gear is covered in down on the microflute a plurality of arranged side by side of Merlon chip.
The surface is had three PDMS thin slices with the projection of the corresponding type of finger-like in cun,guan,chi zone of human body wrist radial artery be embedded in the open channel of Merlon chip, and make its surface soft polyurethane ester film dorsad with said projection.
Utilize double pressure adhesive membrane (
8890) two Merlon chip involutions up and down under pressure, make the soft polyurethane ester film that is covered on said a plurality of microflute arranged side by side be positioned at said open channel under.
Preferably; As shown in Figure 2; Said chip 10a down also has signals collecting micropore 170; This signals collecting micropore 170 can be positioned at place, single microchannel, and (for example, 170a), the junction that also can be positioned at a plurality of microchannels (for example; Be arranged in the 170b-170e at Fig. 2 expression S place), flow, flow velocity or the pressure that said checkout gear 30 detects the microfluid in single microchannel (that is the single microflute in said a plurality of microflute arranged side by side) through this signals collecting micropore 170 is overlaying flow, flow velocity or the pressure of the microfluid in a plurality of microchannels (that is a plurality of microflutes in said a plurality of microflute arranged side by side) perhaps.Can gather the information of microfluid in the microchannel selectively like this, improve the motility of information gathering.From the angle of data acquisition, the quantity of information of being gathered is many more, and the effect of interfere information is just more little, thereby the information that obtains is just accurate more, and therefore gathering overlaying flow, flow velocity and pressure will improve the degree of accuracy of information gathering greatly.Need to prove, need paste piezoelectric membrane (for example, the PVDF thin film) at signals collecting micropore 170, gather the pressure of microfluid through this piezoelectric membrane through the pressure information of microfluid in the signals collecting micropore 170 detection microchannels 130.The collection of flow, flow rate information then only need get final product at flow, the flow rate detection device of signals collecting micropore 170 join dependencys.At this, said checkout gear 30 is and is used for gathering the device of the pressure information of microfluid, or gathering the flow of microfluid and flow detector, the flow rate detection device of flow velocity through signals collecting micropore 170 through being affixed on piezoelectric membrane on the signals collecting micropore 170.
Wherein, said microfluid drive 20 can be for driving microfluid mobile any device, for example electroosmotic pump in said a plurality of microflutes 110.For the volume and simplification line layout that reduces the whole bionical system of feeling the pulse; Preferably; As shown in Figure 2; Said microfluid drive (electroosmotic pump) 20 can be built among the said chip 10a down, and this microfluid drive (electroosmotic pump) 20 is connected with drive channels 190, is used to drive microfluid and circulates through drive channels 190, microchannel 130, a plurality of microflute arranged side by side 110, microchannel 130, microfluid circulation canal 180 and drive channels 190 successively.
In order to simulate the pressure of feeling the pulse of applying for position to be felt the pulse when the doctor feels the pulse, preferably as shown in Figure 4, said system also comprises wiper seal chamber 40, is used for applying the pressure of feeling the pulse to position to be felt the pulse.Under the situation with wiper seal chamber, the said bionical system of feeling the pulse can also comprise pressure-regulating device 410, and this pressure-regulating device 410 is used to regulate said wiper seal chamber 40 and applies the pressure of feeling the pulse for position said to be felt the pulse.The structure of above-mentioned wiper seal chamber 40 and pressure-regulating device 410 can be similar to employed arm band and inflatable ball in the sphygomanometer, and its structure is not limited to this certainly, can also be other structure that can realize above-mentioned functions.From Fig. 4, can find out; Wiper seal chamber 40 is shown as with micro-fluidic chip 10 and is connected; This is not to mean that both certainly exist connection physically, exert pressure can for position to be felt the pulse with the wiper seal chamber 40 of micro-fluidic chip 10 no any annexations yet.
Preferably; Said sense film 120 is a piezoelectric membrane; Said wiper seal chamber 40 gives that position to be felt the pulse applies, and the pressure of feeling the pulse can come out through the pressure-voltage of this piezoelectric membrane 120 is specific and measured; Thereby can utilize 40 applied pressures in 410 pairs of wiper seal chambeies of pressure-regulating device accurately to regulate and control continuously according to the suffered pressure of piezoelectric membrane.
Certainly, as shown in Figure 5, the said bionical system of feeling the pulse can also comprise A/D converter 50, little process chip 60 and computer 70.Pulse signal is after the micro-/ nano hierarchy of sense film amplifies; Change into the variation of flow, flow velocity or the pressure of the microfluid in the micro-fluidic chip 10; Said checkout gear 30 detects flow, flow velocity or the pressure signal of the microfluid in the said microflute 110; These continuous analog signals that collect are passed to A/D converter 50; A/D converter 50 is digital signal with these continuous analog conversion of signals and is stored in the relief area, and the signal after will changing offers little process chip 60, through USB interface said digital signal offered computer 70 by little process chip 60; 70 pairs of said digital signals of computer are eliminated noise processed; And generate flow, flow velocity or the time dependent waveform of pressure according to the digital signal that removes after making an uproar, the characteristic of the waveform of various relevant flow, flow velocity or the pressure stored in the principal character (for example, crest, trough and flex point etc.) of the waveform that is generated and the pulse wave expert database is compared; Thereby obtain and the corresponding physiological pathology of human body information of waveform that is generated, thereby realize the computer-controlled bionical system of feeling the pulse of feeling the pulse based on the simulation traditional Chinese medical science of micro-fluidic chip.Wherein, store in advance in the said pulse wave expert database and the corresponding waveform about flow, flow velocity or pressure of various physiological pathology of human body information, these information corresponding and waveform all obtain through gathering a large amount of case accumulations.
Introduce the concrete use of the above-mentioned bionical system of feeling the pulse below.Human body wrist is put into the opening groove 140 of micro-fluidic chip, the cun,guan,chi zone that makes the human body wrist radial artery respectively with thin slice 160 on three class digitations contact; Open microfluid drive 20, drive microfluid and in said microflute 110, flow; The pulse signal in the cun,guan,chi zone of human body wrist radial artery conducts to the microfluid in the microflute 110 after sense film 120 amplifies; Checkout gear 30 detects flow, flow velocity or the pressure signal of the microfluid in the microflute 110; And these continuous analog signals that detected are passed to A/D converter 50; A/D converter 50 is a digital signal with these continuous analog conversion of signals; And the signal after will changing offers little process chip 60; Through USB interface said digital signal is offered computer 70 by little process chip 60; 70 pairs of said digital signals of computer are eliminated noise processed, and generate flow, flow velocity or the time dependent waveform of pressure according to the digital signal that removes after making an uproar, with the principal character of the waveform that is generated (for example; Crest, trough and flex point etc.) with the pulse wave expert database in the characteristic of waveform of various relevant flow, flow velocity or the pressure stored compare, thereby obtain and the corresponding physiological pathology of human body information of waveform that is generated.
The bionic system that the simulation traditional Chinese medical science based on micro-fluidic chip that the present invention proposes is felt the pulse; Have simple to operate, applied widely, degree of accuracy is high, convenience is high, cost performance is high and the high characteristics of integrated level; Can realize the collection of human pulse information on this basis, and analyze physiological and pathological information wherein.This system provides important foundation and technological break-through for realizing the traditional Chinese medical science feeling the pulse diagnosis on the chip.
Claims (9)
1. bionical system of feeling the pulse based on micro-fluidic chip, this system comprises: micro-fluidic chip, microfluid drive, checkout gear, microflute and sense film; Wherein: this micro-fluidic chip has a plurality of said microflute that is mounted with microfluid, and described sense film is covered on said a plurality of microflute, and is used for the pulse signal at the position of waiting to feel the pulse is conducted the microfluid to said microflute;
Described microfluid drive, this microfluid drive are used for driving microfluid and flow at said microflute;
Described checkout gear is used for detecting flow, flow velocity or the pressure of the microfluid of said microflute;
Said micro-fluidic chip comprises involution following chip together and goes up chip;
Have a plurality of microflutes arranged side by side on the described down chip and be covered in the sense film on these a plurality of microflutes arranged side by side;
The described chip of going up comprises being used to hold and waits to feel the pulse the opening groove at position; The bottom of this opening groove has open channel; This open channel be positioned at said sense film directly over, be used for making being contained in the said opening groove position of waiting to feel the pulse and contacting with said sense film.
2. the bionical system of feeling the pulse according to claim 1, wherein: described sense film and said microflute covered surfaces mutually have a kind of in the 3-D nano, structure of three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges, array arrangement.
3. the bionical system of feeling the pulse according to claim 1; Wherein: the described chip of going up also comprises and is embedded in the described thin slice of going up in the chip open channel, and thin slice has respectively and the human body projection of corresponding three the class finger-like in cun,guan,chi zone of wrist radial artery at position of waiting to feel the pulse on the surface of sense film dorsad.
4. the bionical system of feeling the pulse according to claim 1, wherein, described microfluid drive is to be built in the described chip down; Described microfluid drive is an electroosmotic pump.
5. the bionical system of feeling the pulse according to claim 1, wherein, described chip down also has the signals collecting micropore;
Said checkout gear is flow, flow velocity or the pressure that detects the microfluid in the single microflute in said a plurality of microflute arranged side by side through this signals collecting micropore, perhaps detects overlaying flow, flow velocity or the pressure of the microfluid in a plurality of microflutes in said a plurality of microflute arranged side by side.
6. the bionical system of feeling the pulse according to claim 3, wherein, said micro-fluidic chip makes through following steps:
A, form a plurality of microflutes, with as chip down at substrate surface;
B, form opening groove and open channel at substrate surface, with as last chip, said opening groove is used to hold position to be felt the pulse, and open channel is positioned at the opening groove bottom;
C, sense film is carried out finishing; Form a kind of in three-dimensional micrometer structure that three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arranges, the 3-D nano, structure that array is arranged on its surface, the one side of 3-D nano, structure that said sense film is formed with three-dimensional micrometer structure or the array arrangement of three-dimensional micron that array arranges and three-dimensional manometer hierarchy, array arrangement is covered on said a plurality of microflute;
D, the surface is had three thin slices with the projection of the corresponding type of finger-like in the cun,guan,chi of human body wrist radial artery zone be embedded in the said open channel of going up chip, and make its surface sense film dorsad with said projection; And
E, will descend chip and last chip involution, make the sense film that is covered on said a plurality of microflute be positioned at said open channel under.
7. the bionical system of feeling the pulse according to claim 1, wherein, said system also comprises the wiper seal chamber, is used for applying the pressure of feeling the pulse to position to be felt the pulse.
8. the bionical system of feeling the pulse according to claim 7, wherein, said system also comprises pressure-regulating device, this pressure-regulating device is used to regulate the pressure of feeling the pulse that said wiper seal chamber applies for position said to be felt the pulse.
9. the bionical system of feeling the pulse according to claim 8, wherein, said sense film is a piezoelectric membrane.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102266220B (en) * | 2011-07-21 | 2013-04-10 | 邵光震 | Biomimetic wrist |
| JP6429794B2 (en) | 2013-01-03 | 2018-11-28 | ブリガム・アンド・ウイミンズ・ホスピタル・インコーポレイテッド | Biomimetic fluid process systems and methods |
| CN103330550B (en) * | 2013-03-04 | 2016-08-31 | 北京中医药大学 | MEMS hydraulic passes three the nine marquis's automatic acquisition of scientific informations of diagnosis by feeling the pulse touched and identifies device and method |
| WO2015153451A1 (en) | 2014-03-31 | 2015-10-08 | Brigham And Women's Hospital, Inc. | Systems and methods for biomimetic fluid processing |
| CN104605837B (en) * | 2014-12-23 | 2016-08-24 | 电子科技大学 | A kind of monitoring of pulse system based on microfluid sensor |
| CN104888675A (en) * | 2015-06-08 | 2015-09-09 | 南京理工大学 | Microfluidic reactor integrated with heat transfer unit and detection unit |
| CN104931558A (en) * | 2015-06-30 | 2015-09-23 | 上海奥普生物医药有限公司 | Universal POCT (point-of-care testing) apparatus based on intelligent cellphone platform and test method thereof |
| CN110772236B (en) * | 2019-10-08 | 2021-04-20 | 华中科技大学 | Pulse feeling sensor based on directional coupler and pulse condition measuring device |
| CN111939991A (en) * | 2020-07-09 | 2020-11-17 | 南京元感微电子有限公司 | Microfluidic system and preparation method thereof |
| CN111872460A (en) * | 2020-08-17 | 2020-11-03 | 山东大学 | Discontinuous micro-blade micro-milling cutter |
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