CN107525765A - Microfluidic circuit chip and corpse or other object for laboratory examination and chemical testing concentration measurement apparatus - Google Patents
Microfluidic circuit chip and corpse or other object for laboratory examination and chemical testing concentration measurement apparatus Download PDFInfo
- Publication number
- CN107525765A CN107525765A CN201710450415.2A CN201710450415A CN107525765A CN 107525765 A CN107525765 A CN 107525765A CN 201710450415 A CN201710450415 A CN 201710450415A CN 107525765 A CN107525765 A CN 107525765A
- Authority
- CN
- China
- Prior art keywords
- flow path
- wedge
- space
- corpse
- circuit chip
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/3103—Atomic absorption analysis
Landscapes
- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Optical Measuring Cells (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
The present invention provide can not from it is outside apply the effect of the kinematics such as centrifugal force in the case of separate from a micro corpse or other object for laboratory examination and chemical testing special component and the microfluidic circuit chip for the state that the special component of necessary amount is filled in determination part can be obtained with the short time and the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the concentration that can efficiently determine the special component in a corpse or other object for laboratory examination and chemical testing.The microfluidic circuit chip of the present invention is characterised by, it is by internally having first flow path, the plate body of second flow path and determination part is formed, the first flow path makes a corpse or other object for laboratory examination and chemical testing for liquid circulate, the second flow path forms and had from the first flow path branch width that special component is separated in the corpse or other object for laboratory examination and chemical testing that can be circulated from the first flow path and connected with the first flow path, the determination part connects with the second flow path and fills the special component separated from the corpse or other object for laboratory examination and chemical testing, wherein, the at least a portion in the space of the determination part is formed by being formed with the wedge-like space little by little to diminish and gap facing one direction.
Description
Technical field
The present invention relates to microfluidic circuit chip and the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the microfluidic circuit chip is used.In more detail and
Speech, relate to from the corpse or other object for laboratory examination and chemical testing such as the blood microfluidic circuit chip of the special component such as separation of plasma components and separated specific of measure
The corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the concentration of composition.
Background technology
In medical field, the composition (such as plasma fraction) of extraction microsize from a corpse or other object for laboratory examination and chemical testing (such as blood), and to institute
Obtained extract component or the concentration of the check object thing included in the extract component are measured.
In the past, as the method that plasma fraction is extracted from blood, it is known to following methods:By that will enclose in capillary
Blood processing is centrifuged, it is (literary referring for example to patent so as to which the plasma fraction in blood be separated with blood cell composition
Offer 1).
Prior art literature
Patent document
Patent document 1:Japanese Unexamined Patent Publication 6-43158 publications
The content of the invention
The technical problems to be solved by the invention
However, following problems be present:In order to from blood extract blood plasma and utilize centrifuge in the case of, it is necessary to than
Larger amount of blood, further, since using centrifugal separator, so becoming desirable for forming large-scale device.It is therefore desirable to be able to
Do not utilize centrifuge in the case of from micro blood separation of plasma components means.
Then, it is an object of the invention to provide can be in the case where not applying the effect of the kinematics such as centrifugal force from outside
Special component is separated from a micro corpse or other object for laboratory examination and chemical testing and the special component of necessary amount can be obtained with the short time and is filled in determination part
In state microfluidic circuit chip.
Another object of the present invention is to provide efficiently to determine in a corpse or other object for laboratory examination and chemical testing using above-mentioned microfluidic circuit chip
The corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the concentration of special component.
For solving the means of technical problem
The microfluidic circuit chip of the present invention is characterised by that it is by internally having first flow path, second flow path and determination part
Plate body form, above-mentioned first flow path makes a corpse or other object for laboratory examination and chemical testing for liquid circulate, and above-mentioned second flow path is formed from the first flow path branch
And connect with the width of separation special component in the corpse or other object for laboratory examination and chemical testing that can be circulated from above-mentioned first flow path and with the first flow path,
Said determination portion connects and filled the special component separated from an above-mentioned corpse or other object for laboratory examination and chemical testing with the second flow path, wherein, form said determination portion
Space at least a portion by being formed with the wedge-like space little by little to diminish and gap facing one direction.
In the microfluidic circuit chip of the present invention, when assuming that said one direction to be set to the xyz orthogonal coordinates in x directions,
Above-mentioned wedge-like space can be with a pair of wedges on the z directions shown under the vertical view from y directions toward each other
Shape space forming face forms the composition of the part of wedge-like.
In the chip of this composition, said determination portion has the cross sectional shape with the continuous yz sections in above-mentioned wedge-like space
For the constant volume product space of rectangular shape,
Angle formed by the continuous 2 constant volumes product space forming face shown in the yz sections of the constant volume product space is set to
γ, angle formed by above-mentioned a pair of wedge-likes space forming face shown under the vertical view from y directions in above-mentioned wedge-like space is set to α
When, above-mentioned wedge-like space, which preferably has, meets α<The spatial form of γ relation.
In addition, in the microfluidic circuit chip of the present invention, above-mentioned wedge-like space can be with aobvious under the vertical view from z directions
A pair of wedge-like space forming faces on existing y directions toward each other form the composition of the part of wedge-like.
In the chip of this composition, by above-mentioned a pair of the wedges shown under the vertical view from z directions in above-mentioned wedge-like space
When angle formed by the forming face of shape space is set to β, above-mentioned wedge-like space, which preferably has, meets β<The spatial form of γ relation.
And then in the microfluidic circuit chip of the present invention, size or z direction of the above-mentioned wedge-like space preferably with y directions
Size is the measure region of constant size.
The corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the present invention is characterised by that it possesses following form:
Microfluidic circuit chip, wherein, above-mentioned wedge-like space has the measure that the width in y directions or z directions is constant size
Use region;
Light source, it is to the said determination area illumination light in the microfluidic circuit chip;
Imaging member, it images the image in the region comprising the mensuration region in above-mentioned microfluidic circuit chip;And
Controlling organization, it has based on the view data obtained by the imaging member to calculate the dense of above-mentioned special component
The function of degree.
Invention effect
According to the microfluidic circuit chip of the present invention, second flow path, which has in the corpse or other object for laboratory examination and chemical testing that can be circulated from first flow path, to be separated
The width of special component, so spy can be separated from a corpse or other object for laboratory examination and chemical testing in the case where not applying the effect of the kinematics such as centrifugal force from outside
Determine composition.Also, pass through due to that can make to separate by second flow path to flow into the special component in determination part by wedge-like space
Caused capillary force is concentrated on the narrow and small direction in the wedge-like space, thus can be obtained with the short time necessary amount it is specific into
Divide the state being filled in determination part.
, can will be in microfluidic circuit core according to the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the invention for having used above-mentioned microfluidic circuit chip
(filling) is efficiently stored in mensuration region from the special component of the necessary amount of corpse or other object for laboratory examination and chemical testing separation in piece, so can obtain high
Check efficiency.In addition, the mensuration region for the microfluidic circuit chip that the light from light source is irradiated is because thickness is constant size, so
Optical path length can be made constant and the concentration of special component can be determined with high reliability.
Brief description of the drawings
Fig. 1 is the top view of the composition in an example for represent the microfluidic circuit chip of the present invention.
Fig. 2 is the explanation figure for representing the region surrounded by double dot dash line in Fig. 1, and (a) is top view, and (b) is side view.
Fig. 3 is the Section A-A end view drawing in Fig. 2 (a).
Fig. 4 is the section B-B end view drawing in Fig. 2 (a).
Fig. 5 is the explanation figure for the spatial form for showing schematically determination part, and (a) is stereogram, and (b) is in terms of z directions
Top view, (c) are the sectional views based on yz planes of constant volume product space, and (d) is from the side view in terms of y directions.
Fig. 6 is the explanation for showing schematically the state that the special component separated from a corpse or other object for laboratory examination and chemical testing is gradually filled in determination part
Figure.
Fig. 7 is the top view of the composition of the major part in another example for represent the microfluidic circuit chip of the present invention.
Fig. 8 is the top view of the composition in another example for represent the microfluidic circuit chip of the present invention.
Fig. 9 is the explanation figure of the composition in an example for show schematically the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the present invention.
Figure 10 is the explanation figure of the composition in another example for show schematically the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the present invention.
Figure 11 is to represent that the experiment fluid of each microfluidic circuit chip on being made in embodiment 1 and comparative example 1 is relative
In the figure of the rheological parameters' change with time of the storage length of determination part.
Symbol description
10 microfluidic circuit chips
11 chip basal bodies
12 first substrates
13a first flow path grooves
13b determination part recesses
15 second substrates
16 second flow path grooves
20 first flow path
The linear circuit portions of 20a
The linear circuit portions of 20b
21 corpse or other object for laboratory examination and chemical testing introduction parts
22 corpse or other object for laboratory examination and chemical testing reservoirs
23 first discharge unit
25 second flow paths
27 the 3rd streams
28 second discharge units
30 determination parts
30a upper bottom surfaces
30b bottom surfaces
31 constant volume product spaces
32a constant volume product space forming faces
32b constant volume product space forming faces
35 wedge-like spaces
36a wedge-likes space forming face
36b wedge-likes space forming face
38 mensuration regions
40 light sources
The light sources of 40a first
40b secondary light sources
41 power supplys
42 dichroscopes
45 optical filters
The optical filters of 46a first
The optical filters of 46b second
48 lens
49a lens
49b lens
50 imaging members
51 lens
60 controlling organizations
C crest lines
PL special components
Embodiment
Hereinafter, the embodiment of the microfluidic circuit chip of the present invention is illustrated.
Fig. 1 is the top view of the composition in an example for represent the microfluidic circuit chip of the present invention.Fig. 2 is represented in Fig. 1
By double dot dash line surround region explanation figure, (a) is top view, and (b) is side view.Fig. 3 is the Section A-A in Fig. 2 (a)
End view drawing, Fig. 4 are the section B-B end view drawings in Fig. 2 (a).
The microfluidic circuit chip 10 has the chip basal body 11 being made up of plate body, and above-mentioned plate body, which internally has, to be used to make
The first flow path 20 of the corpse or other object for laboratory examination and chemical testing circulation of liquid, for separation and Extraction special component in the corpse or other object for laboratory examination and chemical testing that is circulated from first flow path 20
The determination part 30 for the special component that multiple second flow paths 25 and filling separate from a corpse or other object for laboratory examination and chemical testing.
In the example in the figures, chip basal body 11 is that first substrate 12 is engaged and formed with second substrate 15, first-class
Road 20, the 2nd stream 25 and determination part 30 are formed along the plane vertical with the thickness direction of chip basal body 11 with two dimension.
State of the determination part 30 to extend along a direction in the face direction vertical with the thickness direction of chip basal body 11
Formed, be connected via the 3rd stream 27 with the second discharge unit 28.
First flow path 20 has the linear stream extended along determination part 30 in the position of the both sides of clamping determination part 30
Part 20a, 20b.The inspection that the upstream side of corpse or other object for laboratory examination and chemical testing circulating direction in first flow path 20 imports with storage from corpse or other object for laboratory examination and chemical testing introduction part 21
The corpse or other object for laboratory examination and chemical testing reservoir 22 of body connects.The downstream side of corpse or other object for laboratory examination and chemical testing circulating direction in first flow path 20 is connected with first discharge unit 23.
Multiple second flow paths 25 are each according to from the branch of first flow path 20 and along relative to the vertical side of the first flow path 20
Formed to the mode of extension.The upstream side of corpse or other object for laboratory examination and chemical testing circulating direction in second flow path 25 and the linear stream in first flow path 20
Road part 20a, 20b connection, the downstream side of corpse or other object for laboratory examination and chemical testing circulating direction connect with forming the space of determination part 30.In example illustrated
In, the whole region in the direction that multiple second flow paths 25 are each extended with the determination part 30 throughout determination part 30 is with equal intervals
The state left and arranged is formed.
First substrate 12 and 15 respective thickness of second substrate are not particularly limited, for example, more than 0.1mm and 5.0mm with
Under.
In the example in the figures, first flow path 20 is by being formed on the groove 13a of the first flow path in first substrate 12
Internal face and the subregion of second substrate 15 and formed.In addition, second flow path 25 by be formed in second substrate 15 second
The internal face and the subregion of first substrate 12 of stream groove 16 and formed.In addition, determination part 30 is by being formed on first substrate
The internal face and the subregion of second substrate 15 of determination part recess 13b in 12 and formed.In addition, first flow path groove 13a,
Times that can also be all formed in first substrate 12 and second substrate 15 of two stream grooves 16 and determination part recess 13b
In one.
Preferred pair first flow path 20, second flow path 25 and 30 respective internal face of determination part implement hydrophilicity-imparting treatment.Specifically
For, the contact angle of the water in 30 respective internal face of first flow path 20, second flow path 25 and determination part is preferably shorter than 90 °, more
Preferably less than 50 °.
First flow path 20 have can make the width that a corpse or other object for laboratory examination and chemical testing (such as blood) for liquid circulates.In the present invention, " the width of stream
Spend " refer to, the minimum width of the stream in the section vertical with the direction of stream extension in stream.In illustrated example
In first flow path 20 and second flow path 25, the width of the thickness direction of microfluidic circuit chip 10 is minimum width.
The width of this first flow path 20 is preferably more than 10 μm and less than 1000 μm, more preferably more than 50 μm and 100 μ
Below m.In the case where the width of first flow path 20 is too small, in first flow path 20, because of the flow path resistance change stream of a corpse or other object for laboratory examination and chemical testing greatly
Amount declines, it is possible to quantity delivered deficiency of the special component (such as plasma fraction) into second flow path 25.On the other hand, first
In the case that the width of stream 20 is excessive, it is possible to the amount increase of a required corpse or other object for laboratory examination and chemical testing.Additionally due to capillary force diminishes, so
The flow velocity of the corpse or other object for laboratory examination and chemical testing flowed in first flow path 20 diminishes, it is possible to when special component reaches determination part 30 and needs considerably long
Between.
In addition, do not limited especially from length of the upstream side of first flow path 20 untill with the branch point of second flow path 25
Determine, for example, more than 10mm and below 100mm.
Second flow path 25 has separation special component in the corpse or other object for laboratory examination and chemical testing (such as blood) that can be circulated from first flow path 20
The width of (such as plasma fraction).
The width of this second flow path 25 is preferably more than 0.1 μm and less than 5 μm, more preferably more than 1.0 μm and 3.0 μm
Below.In the case where the width of second flow path 25 is too small, the quantitative change that can be supplied to the special component in determination part 30 is few, has
The extraction of possible special component needs for quite a long time.On the other hand, in the case where the width of second flow path 25 is excessive, have
The composition (such as the blood cell composition such as red blood cell) in addition to special component in a possible corpse or other object for laboratory examination and chemical testing is mixed into without showing separation function.
In addition, the length of second flow path 25 is not particularly limited, for example, more than 0.1mm and below 1mm.
In addition, the number of second flow path 25 is, for example, more than 100 and less than 10000.
Determination part 30 by formed the determination part 30 space at least a portion with facing one direction and gap by
The wedge-like space that gradually diminishes and formed.
In the example in the figures, one end part in the direction of the determination part 30 extension in determination part 30 passes through wedge-like space
And formed.That is, determination part 30 as also illustrated that in Fig. 5, by wedge-like space 35 and with 35 continuous constant volume of wedge-like space
Product space 31 is formed.
Hereinafter, define and the direction of wedge-like space 35 (determination part 30) extension is set to " x directions ", by the thickness of chip basal body 11
Degree direction is set to the xyz orthogonal coordinates in " z directions ", and the spatial form of determination part 30 is specifically described.
Constant volume product space 31 in determination part 30 has spatial form roughly the same in the x direction, the section in yz sections
It is shaped as rectangular shape.Formed by the continuous 2 constant volumes product space forming face shown in the yz sections of constant volume product space 31
Angle γ is such as more than 45 ° and less than 90 °.
In the example in the figures, constant volume product space 31 passes through the upper bottom surface 30a and bottom surface that extend respectively along x/y plane
30b and formed relative to inclined a pair of constant volumes product space forming faces 32a, 32b of bottom surface 30b, there is cutting in yz sections
Face is shaped as the spatial form of trapezoidal shape.Also, on the y directions shown in the yz sections of constant volume product space 31 toward each other
A pair of constant volume product space forming faces 32a, 32b be, for example, relative to angle γ 1, γ 2 formed by the bottom surface 30b along x/y plane
More than 45 ° and less than 90 °.γ 1, γ 2 can be identical size each other, or different sizes.
Wedge-like space 35 is preferably with a pair of wedge-likes on the z directions shown under the vertical view from y directions toward each other
Space forming face forms the part of wedge-like and with a pair on the y directions shown under the vertical view from z directions toward each other
Wedge-like space forming face forms the spatial form of the part of wedge-like.
Specifically, by angle formed by a pair of the wedge-like space forming faces shown under the vertical view from y directions (hereinafter referred to as
" the front end inclination angle in wedge-like space ") when being set to α, wedge-like space 35, which preferably has, meets α<γ1、α<The space of γ 2 relation
Shape.In addition, by angle formed by a pair of the wedge-like space forming faces shown under the vertical view from z directions, (hereinafter referred to as " wedge-like is empty
Between angular aperture ") when being set to β, wedge-like space 35, which preferably possesses, meets β<γ1、β<The sky of the spatial form of γ 2 relation
Between shape.
In the example in the figures, wedge-like space 35 is by the upper bottom surface 30a and bottom surface 30b along x/y plane and towards x
The side of direction one and closer to each other formed relative to inclined a pair of wedge-likes space forming faces 36a, 36b of bottom surface 30b.
Also, as shown in Fig. 5 (d), a pair of wedge-like space forming faces showing under the vertical view from y directions
The front end inclined angle alpha in wedge-like space 35 formed by 36a, 36b crest line C and bottom surface 30b is than constant volume product space forming face
32a, 32b are relative to bottom surface 30b inclination angle γ 1, γ 2 small state.In addition, as shown in Fig. 5 (b), from z
The angular aperture β in wedge-like space 35 formed by a pair of wedge-like space forming faces 36a, 36b shown under the vertical view in direction is than constant volume
Product space forming face 32a, 32b is relative to bottom surface 30b inclination angle γ 1, γ 2 small state.
In addition, the spatial form in wedge-like space 35 for example can also be corner taper.
The angular aperture α in wedge-like space 35 is for example preferably more than 15 ° and less than 45 °.In addition, the front end in wedge-like space 35 is inclined
Oblique angle β is for example preferably more than 5 ° and less than 45 °.
On the capillary force P as caused by wedge-like space 35, surface tension is being set to F, is being set to the contact angle of liquid
θ, when the radius of curvature of liquid level is set into R, calculated by P=2Fcos α+(θ/R) or P=2Fcos β+(θ/R).Therefore, hair
The size of the size for the angular aperture α that tubule power P passes through wedge-like space or the front end angle of inclination beta in wedge-like space determines.
By making wedge-like space 35 that there is spatial form as described above, can make to separate to flow into by second flow path 25
Special component in determination part 30 is reliably stored for along the narrow and small orientation preferentially in wedge-like space 35.
In addition, wedge-like space 35 is preferably the structure for the mensuration region for being constant size with the size on y directions or z directions
Into.
In the example in the figures, the size on z directions (thickness) is formed at wedge-like sky for the mensuration region 38 of constant size
Between in x directions another side part in 35.
By for this composition, in the concentration mensuration of the absorbance described later based on special component, due to can be by light
Road length is set as constant size, so the high concentration mensuration of reliability can be carried out to the special component in a corpse or other object for laboratory examination and chemical testing.
More than, the dimension D in the constant volume product space 31 of determination part 30 and the z directions in the mensuration region 38 in wedge-like space 35 is excellent
Elect such as more than 10 μm and less than 1000 μm as, more preferably more than 100 μm and less than 500 μm.In the situation that the dimension D is too small
Under, due to the optical path length of the size required for can not ensuring in absorbance measurement described later, so becoming to carry out specific
The concentration mensuration of composition.On the other hand, in the case where the dimension D is excessive, it is possible to the amount increase of a required corpse or other object for laboratory examination and chemical testing.In addition
Because capillary force diminishes, reaching determination part 30 it is possible to special component needs for quite a long time.
In addition, the size W1 in the face direction (y directions) in the constant volume product space 31 of determination part 30 is preferably 100 μm of more than m
And less than 1000 μm.
<The constituent material of chip basal body>
As form chip basal body 11 (first substrate 12 and second substrate 15) material, after being come from using transmissive
Material, such as resin material of the light in the light source portion in the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus stated.
As resin material, such as acrylic resin, polystyrene resin, COP resin (cyclic olefin polymers can be used
Resin) etc., preferably using resin combination as shown below.
The resin combination that constituent material as chip basal body 11 uses is preferably that temperature of deflection under load is more than 40 DEG C
And less than 100 DEG C and glass transition temperature are more than -40 DEG C and less than -20 DEG C of resin combination.
Wherein, the temperature of deflection under load of resin combination and glass transition temperature refer to by JIS K7191 and JIS
The temperature that method specified in K7121 determines.
As this resin combination, preferably using (hereinafter referred to as " specific containing polypropylene-based resin and block copolymer
Block copolymer ") the display that forms of hydrogenated derivatives (hereinafter referred to as " specific hydrogenated derivatives ") from melt bonded property
Resin combination (hereinafter referred to as " specific resin combination "), above-mentioned block copolymer is not by compatible with polypropylene-based resin
Polymer blocks X (hereinafter referred to as " polymer blocks X ") and elastomer using conjugated diene polymer blocks Y
(hereinafter referred to as " polymer blocks Y ") form.
<Polypropylene-based resin>
As polypropylene-based resin, the homopolymer or propylene and ethene or 1- butylene, 1- hexenes etc. of propylene can be used
The random copolymer of alpha-olefin in addition to propylene.It specifically can for example use commercially available " Microresico " (registrar
Mark) (Richell Corporation systems) etc..
<Specific block copolymer>
As long as specific block copolymer is embedding with the polymer of more than 1, preferably more than 1 and less than 5 respectively
Section X and polymer blocks Y block copolymer, specific structure can be (X-Y)nRepresented by (wherein, n=1~5)
Any one of structure represented by structure, Y-X-Y represented by structure, X-Y-X etc..
<Polymer blocks X>
In specific block copolymer, as polymer blocks X, as long as not compatible with polypropylene-based resin polymerize
Thing block is not particularly limited, such as can use vinyl aromatic monomers (such as styrene), ethene or methyl-prop
Polymer blocks obtained from the polymerization such as olefin(e) acid ester (such as methyl methacrylate).Example as specific polymer blocks X
Son, the block of polystyrene or the block of polyolefin can be included.
As the polymer blocks X of polystyrene example, can include by selected from styrene, α-methylstyrene,
In o-methyl styrene, a methyl styrene, p-methylstyrene, 2,4- dimethyl styrenes, vinyl naphthalene, vinyl anthracene
Polymer blocks obtained from one kind or two or more vinyl aromatic compounds polymerization.
In addition, another example of the polymer blocks X as polyolefin, it can include and be by ethene and carbon number
Polymer blocks obtained from 3~10 alpha-olefin copolymer.In the polymer blocks can also conjugated polymers have non-conjugated two
Alkene.
As the specific example of above-mentioned alpha-olefin, propylene, 1- butylene, 3-methyl-1-butene, 1- amylenes, 4- can be included
Methyl-1-pentene, 1- hexenes, 1- amylenes, 1- octenes, 1- decene etc..
As the specific example of above-mentioned non-conjugated diene, Isosorbide-5-Nitrae-hexadiene, 5- methyl isophthalic acids can be included, 5- hexadienes, 1,
4- octadienes, cyclohexadiene, cyclo-octadiene, cyclopentadiene, 5- ethylidene -2- ENBs, 5- fourth fork -2- ENBs, 2- are different
Acrylic -5- ENBs etc..
As the polymer blocks X of polyolefin specific example, can include ethylene-propylene copolymer block, ethene-
Butene-1 copolymer block, ethylene-l-octane copolymer block, ethylene-propylene -1,4- hexadienes copolymer block, ethene-the third
Alkene -5- ethylidene -2- norbornene copolymer blocks etc..
In specific block copolymer, polymer blocks X containing ratio is, for example, more than 10 mass % and 20 mass %
Below.
<Polymer blocks Y>
As polymer blocks Y, as the polymer blocks before hydrogenation, can include by by selected from by 2- butene-1s,
The polybutadiene block for the construction unit composition that at least one kind of group in 4- diyls and the group of vinyl ethylidene composition is formed,
By by selected from being made up of 2- methyl-2-butene -1,4- diyls, isopropenyl ethylidene and 1- methyl isophthalic acids-vinyl ethylidene
Group at least one kind of group formed construction unit form polyisoprene blocks.
And then as the polymer blocks Y before hydrogenation, it is by selected from by 2- methyl -2- that can include isoprene unit
Butene-1, at least one kind of group structure in the group of 4- diyls, isopropenyl ethylidene and 1- methyl isophthalic acids-vinyl ethylidene composition
Into construction unit and butadiene unit to pass through by 2- butene-1s, structure list that 4- diyls and/or vinyl ethylidene are formed
Isoprene/butadiene copolymer block that member is formed etc..Isoamyl two is derived from isoprene/butadiene copolymer block
The configuration of the construction unit of alkene and the construction unit from butadiene can be in random shape, block-wise, taper block-wise
Any form.
In addition, polymer blocks Y can also be the polymer blocks that vinyl aromatic compounds copolymerization forms.It is used as this
Kind polymer blocks Y, the unit that can be used from vinyl aromatic compounds are selected from styrene, Alpha-Methyl benzene second
Alkene, o-methyl styrene, a methyl styrene, p-methylstyrene, 2,4- dimethyl styrenes, vinyl naphthalene, vinyl anthracene
In a kind of monomeric unit and conjugated diene unit be 2- butene-1s, 4- diyls and/or vinyl ethylidene copolymer block.
In addition, the configuration of the construction unit and the construction unit from conjugated diene from vinyl aromatic compounds can be
Any form in random shape, block-wise, taper block-wise.
<Specific hydrogenated derivatives>
Specific hydrogenated derivatives are as obtained from by above-mentioned specific block copolymer hydrogenation.Specific hydrogenation
The state of hydrogenation in derivative can be part hydrogenation, can also be to hydrogenate completely in addition.
As this specific hydrogenated derivatives, polymer blocks X is in specific block copolymer before the hydrogenation
Polystyrene block, polymer blocks Y are that the hydrogenation of the polyisoprene blocks of 1,2 bondings, 3,4 bondings and/or 1,4 bondings is spread out
The polybutadiene that biology or polymer blocks X are polystyrene block, polymer blocks Y is 1,2 bondings and/or 1,4 bondings
The hydrogenated derivatives of block can be readily available.
Further, since polystyrene block be difficult to polypropylene-based resin it is compatible, so using polystyrene block
In the case of the high specific hydrogenated derivatives of ratio, (specific hydrogenated derivatives are with gathering for the preparation of specific resin combination
Propylene resin mixes) need for a long time, it is therefore preferable that being sufficiently mixed in advance by carrying out masterbatching gel etc..
<The preparation of specific resin combination>
Specific resin combination is by the way that polypropylene-based resin is heated into the shape of melting with specific hydrogenated derivatives
State is mixed obtained from (mixing).In this specific resin combination, polypropylene-based resin is with polymer blocks X
State incompatible with each other.
Wherein, in specific resin combination polypropylene-based resin with whether polymer blocks X compatible to enter as follows
Row confirms.
In the case of polymer blocks X compositions not compatible with polypropylene-based resin, in specific resin combination
In, polymer blocks X-shaped is into micro- field of the size with its radius of inertia or so.This micro- field can be by with transmission-type
Electron microscope is observed or the scattering pattern for isolating field is measured using small angle X ray scattering, parsed come really
Recognize.
In addition, in the case of polymer blocks X polymer not compatible with polypropylene-based resin, polymer blocks X's
Glass transition temperature will not also change even if being mixed with polypropylene-based resin.This polymer blocks X vitrifying turns
The presence or absence of change of temperature can determine (DSC) or Measurement of Dynamic Viscoelasticity etc. by means of differential scanning calorimetry to confirm.
In the case of the polymer blocks Y compositions compatible with polypropylene-based resin, polymer blocks Y vitrifying turns
Temperature and polyacrylic glass transition temperature each change, and occur new vitrifying in temperature between them and turn
Temperature.
The presence or absence of change of this glass transition temperature can be confirmed by Measurement of Dynamic Viscoelasticity etc..
In the case where both polymer blocks X and polymer blocks be not compatible with polypropylene-based resin, specific
In resin combination, the polymer phase obtained by specific block copolymer is morphologically separated into (by polymer blocks X phase
The phase obtained with the polymer blocks Y micro- field structure mutually formed) and the polymer phase that is obtained by polypropylene-based resin.It is another
Aspect, in the case of the polymer blocks Y compositions compatible with polypropylene-based resin, in specific resin combination, gather
The mutual interval in compound block X micro- field becomes big, or polymer blocks X micro- field in polypropylene-based resin equably
It is scattered.
The change of forms of this polymer blocks Y with polypropylene-based resin when compatible can be by using transmission electron
Microscope is observed the mutual alignment in micro- field or distance micro- field is parsed using small angle X ray scattering
To confirm.
In specific resin combination, the ratio of specific hydrogenated derivatives is preferably relative to polypropylene-based resin
100 mass parts are the ratio more than 40 mass parts and below 50 mass parts.
In specific resin combination, various additives can also be contained as needed, such as polypropylene-based resin is used
Make core agent etc..Core agent is made as above-mentioned, the metal salt form (phosphorus for improving physical property or the transparency by coring effect can be used
Acid metal salt, carboxylic metallic salt) make core agent or make core by forming network to assign the benzal sorbitol-type of the transparency
Agent.The core agent of making of benzal sorbitol-type is made up of the condensation product of benzaldehyde and D-sorbite, in the molecule with hydroxyl.
<The manufacture method of microfluidic circuit chip>
Above-mentioned microfluidic circuit chip 10 can for example be manufactured by following the 1st method or the 2nd method.
《1st method》
First, make formed with for forming the first flow path groove 13a of first flow path 20 and for forming determination part
30 determination part recess 13b first substrate 12 and formed with the second flow path groove for forming second flow path 25
16 second substrate 15.
First substrate 12 and second substrate 15 for example can be by manufacturing microfluidic circuit chip manufacturing mould, and use this micro-
Fluidic chip die for manufacturing, such as above-mentioned resin material is molded to make by injection molding method.Microfluidic circuit chip system
Make for example can be by carrying out anisotropic etching processing or by inclining using photoresist with mould to silicon wafer
The material that oblique exposure or multistage technology obtain carries out electroforming processing to manufacture.In addition, first substrate 12 and second substrate 15 also may be used
To form first flow path groove 13a, determination part recess 13b, second flow path by being machined to baseplate material
Made of groove 16.
In the 1st method, preferably:To including first flow path with groove 13a and determination part recess in first substrate 12
The composition surface for including second flow path groove 16 in the composition surface on 13b surface and second substrate 15, implement surface-active
Change is handled.As surface activation processing method, can using be coated with hydrophilizing agent method, by irradiate vacuum ultraviolet and
The method that is surface-treated, the method being surface-treated by plasma etc., in them, preferably by irradiating vacuum purple
Outside line and the method being surface-treated., can be by the base of first substrate 12 and second by carrying out this surface activation processing
Plate 15 is more engaged firmly and with the short time.
In the case where carrying out surface activation processing by irradiating vacuum ultraviolet, if including vacuum ultraviolet
The specific example of irradiation condition, then using the Excimer lamp of xenon is sealed with as ultraviolet light source, using illumination as 30mW/cm2
Condition irradiate the vacuum ultraviolet that 10 minutes wavelength are 172nm.
Afterwards, it is overlapping and contact first substrate 12 with the state to good position on the composition surface of second substrate 15.
Then, by the way that first substrate 12 and second substrate 15 are heated simultaneously, by first substrate 12 and second substrate
15 utilizations engage from melt bonded property.
In addition, the heating-up temperature of first substrate 12 and second substrate 15 is the composition than first substrate 12 and second substrate 15
The low-melting temperature of material and the temperature higher than the glass transition temperature of first substrate 12 and the constituent material of second substrate 15
Degree.Particularly heating-up temperature is preferably from more than 80 DEG C lower than the fusing point of this composition material of temperature and than the glass of this composition material
The scope selection for the temperature that high more than 60 DEG C of glass transition temperature.
If showing the specific heating-up temperature of first substrate 12 and second substrate 15, for example, more than 50 DEG C and 70 DEG C with
Under.In addition, if be shown, in the situation that heating-up temperature is 60 DEG C the specific heat time of first substrate 12 and second substrate 15
Under, for example, more than 1 hour and less than 2 hours.
《2nd method》
First, first substrate 12 and second substrate 15 are made in the same manner as the 1st method.
Then, connecing to the surface comprising first flow path groove 13a and determination part recess 13b in first substrate 12
The composition surface for including second flow path groove 16 in conjunction face and second substrate 15, is implemented by irradiating vacuum ultraviolet
Surface activation processing.
If the specific example of the irradiation condition of the vacuum ultraviolet in surface activation processing is included, using being sealed with
The Excimer lamp of xenon is as ultraviolet light source, using illumination as 30mW/cm2Condition to irradiate 10 minutes wavelength be the true of 172nm
Empty ultraviolet.
Then, it is overlapping and contact first substrate 12 with the state to good position on the composition surface of second substrate 15, pass through
Placed at normal temperatures in the case of no heating, first substrate 12 is engaged with second substrate 15.
According to this 1st method or the 2nd method, by first substrate 12 and second substrate 15 with the constituent material than them
Low-melting temperature is engaged, so the heating when engagement first substrate 12 and second substrate 15 will not be caused to become
Shape.Therefore, even if the microfluidic circuit chip to be manufactured is the core for the fine second flow path 25 for being for example less than 5 μm with width
Piece, it also can reliably manufacture desired microfluidic circuit chip 10.
Further, since can be by first substrate 12 and second substrate 15 with the temperature of the fusing point of the constituent material less than them
Engaged, so when first substrate 12 and second substrate 15 are engaged, can by first substrate 12 and second substrate 15 with
The heating for comparing low temperature is engaged.Accordingly it is possible to prevent it is formed at the fine second flow path groove in second substrate 15
16 occur thermal deformations and damage by pressure.
, should by the way that a corpse or other object for laboratory examination and chemical testing for liquid such as blood is imported from corpse or other object for laboratory examination and chemical testing introduction part 21 in above-mentioned microfluidic circuit chip 10
A corpse or other object for laboratory examination and chemical testing is stored in corpse or other object for laboratory examination and chemical testing reservoir 22.The corpse or other object for laboratory examination and chemical testing in corpse or other object for laboratory examination and chemical testing reservoir 22 is stored in by capillarity in first flow path
Circulated in 20, reach the branch point with second flow path 25.Then, at the branch point, ratio second flow path 25 in a corpse or other object for laboratory examination and chemical testing it is wide
The composition of big size, such as blood cell composition are spent due to cannot be introduced into second flow path 25, so the court in first flow path 20
Downstream effluent leads to.On the other hand, the special component of the small size of the width of the ratio second flow path 25 in a corpse or other object for laboratory examination and chemical testing, such as blood plasma into
Divide due to that can enter in second flow path 25, so being circulated in second flow path 25, flow into determination part 30.As shown in Figure 6
As, the special component PL flowed into determination part 30 by the capillary force as caused by the wedge-like space 35 in determination part 30,
Flowed along the inwall of the formation determination part 30 in chip basal body 11 towards the narrow and small direction in wedge-like space 35.Therefore, it is specific into
PL is divided to concentrate in wedge-like space 35, be preferentially filled from wedge-like space 35.
As described above, according to above-mentioned microfluidic circuit chip 10, substantially second flow path 25 is due to can be from
The width of special component is separated in the corpse or other object for laboratory examination and chemical testing to be circulated in one stream 20, so the kinematics such as centrifugal force can not be being applied from outside
In the case of effect special component is separated from a micro corpse or other object for laboratory examination and chemical testing.
Also, according to above-mentioned microfluidic circuit chip 10, it can make to separate by second flow path 25 to flow into determination part 30
Special component concentrated on by the capillary force as caused by wedge-like space 35 on the narrow and small direction in the wedge-like space 35.That is, exist
In chip of the spatial form of determination part 30 for the composition of such as prism-shaped, the special component flowed into determination part 30 passes through even
Capillary force caused by the boundary member of continuous 2 determination part forming faces (such as bottom surface and side wall), is maintained at determination part
Forming face neighbouring position.That is, because special component is filled gradually from determination part forming face neighbouring position, thus for example in order to
The special component measured needed for concentration mensuration is filled in, the extracted amount of special component becomes huge, it is necessary to the prolonged time.This
Outside, special component crosses determination part forming face and also reaches discharge unit (the second discharge unit 28), hinders air in determination part 30
Discharge.
However, formed by making to form the part in the space of determination part 30 by wedge-like space 35, according to above-mentioned miniflow
Road chip 10, the special component of necessary amount can efficiently be extracted from a corpse or other object for laboratory examination and chemical testing, can obtained can ensure that rear with the short time
Optical path length required in the concentration mensuration based on absorbance stated (is filled in exemplified by the thickness of the special component in determination part 30
Such as 100 μm) state.
More than, the embodiment of microfluidic circuit chip of the present invention is illustrated, but the present invention be not limited to it is above-mentioned
Embodiment, various changes can be subject to.
For example, in above-mentioned microfluidic circuit chip, second flow path is not necessarily to the determination part extension in determination part
Direction whole region and formed, such as can also be made as shown in Fig. 7 (a) and Fig. 7 (b) and be only formed at survey
Determine the composition in the part of the constant volume product space 31 in portion 30.By this composition, it can also make the spy in inflow determination part 30
Determine composition to concentrate on the narrow and small direction in wedge-like space 35.In addition, internal face (the wedge-like in the formation wedge-like space in chip basal body
Space forming face) It is not necessary to be tabular surface, can also be as shown in Fig. 7 (b), inner surface configuration is with stepped shape
Into.And then the one of the determination part 30 that second flow path 25 is only formed on the direction of face as shown in Figure 8, can also be made
The composition of side, it is simply formed with making the linear circuit portion 20a positioned at corpse or other object for laboratory examination and chemical testing circulating direction upstream side in first flow path 20
The composition of the second flow path 25 connected with determination part 30.
And then in above-mentioned microfluidic circuit chip, it is formed in one end of the determination part along the face direction extension of chip basal body
Composition formed with wedge-like space in part, but the spatial form of determination part is not particularly limited, and wedge-like space for example can also
By in along the plane direction either direction extension in the way of formed, in addition can also by through-thickness extend in the way of shape
Into.
And then chip basal body can also be that multiple substrates are engaged and formed, and first flow path, the 2nd stream and determination part is made
With three-dimensionally formed composition.
Hereinafter, the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the invention formed to possessing above-mentioned microfluidic circuit chip illustrates.
Fig. 9 is the explanation figure of the composition in an example for represent the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the present invention.
The corpse or other object for laboratory examination and chemical testing concentration measurement apparatus is that separation includes check object composition i.e. courage in blood e.g. from a corpse or other object for laboratory examination and chemical testing for liquid
The blood plasma of red pigment and the device for determining the concentration of bilirubin.
Check object measure device shown in Fig. 9 possesses Fig. 1 to the microfluidic circuit chip 10, right of the composition shown in Fig. 5
The light source of thickness direction irradiation light of the mensuration region 38 along the microfluidic circuit chip 10 in the determination part 30 of the microfluidic circuit chip 10
40th, image the imaging member 50 of the image in the region comprising the determination part 30 in microfluidic circuit chip 10 and taken the photograph with being based on passing through
The controlling organization 60 of the function of the concentration of check object composition is calculated as the view data for the image that component 50 images.
In light path between light source 40 and microfluidic circuit chip 10, the filter of the wavelength region of restricted transmitted light is configured
Mating plate 45.Between optical filter 45 and microfluidic circuit chip 10, the lens 48 that incident light is carried out to parallelization are configured with.Micro-
Between fluidic chip 10 and imaging member 50, it is configured with that the light image being made up of the light radiated from light source 40 is amplified and projected to and takes the photograph
As the lens 51 on component 50.In addition, light source 40 electrically connects with supplying the power supply 41 of electricity to the light source 40.The power supply 41 and control
Mechanism 60 electrically connects.
As light source 40, included using radiation to determine the light of the wavelength region required for the concentration of check object composition
Light source.In this example embodiment, using radiation comprising attached in order to determine in blood plasma 455nm required for the concentration of contained bilirubin
The light source 40 of the light of wavelength region near near wavelength region and 575nm.
As the specific example of this light source 40,2 kinds of the light by radiating mutually different wavelength region can be included
The LED element and peak emission wavelength that LED element, such as peak emission wavelength are 450nm are formed for 570nm LED element
Light source.
As optical filter 45, using the wavelength region of the light transmitted is limited in order to determine the dense of check object composition
The bandpass filter of wavelength region required for degree.In this example embodiment, as optical filter 45, using by the wavelength of the light transmitted
Region is limited to determine the wavelength region and 575nm near the 455nm required for the concentration of the bilirubin included in blood plasma
The multi-bandpass filter of neighbouring wavelength region.The ripple near wavelength region and 575nm near the 455nm of transmission filter 45
The bandwidth in long region is calculated as more than 10nm and below 15nm with half breadth respectively.
As imaging member 50, regarded using the region for possessing the determination part 30 using in comprising microfluidic circuit chip 10 as shooting
The imaging member of wild photographing element.Specifically, the shooting visual field of the photographing element of imaging member 50 is microfluidic circuit chip 10
The another side opposite with photographing element in determination part 30 residing for region and its neighboring area.In the example in the figures, with
Determination part 30 also includes a part and multiple second flow paths 25 for linear circuit portion 20a, 20b in first flow path 20 together
Respective region is the shooting visual field of photographing element, and light source 40 is come to forming the whole region radiation in region in the shooting visual field
Light.
As imaging member 50, such as use the cmos camera for possessing CMOS photographing elements.The cmos camera
The shooting visual field of CMOS photographing elements, the picture size obtained in cmos camera are 640 × 480 pixels (equivalent to miniflow
The region of 1090 × 820 μm of size in length and breadth in road chip 10).
As lens 51, such as using achromatic lens, the enlargement ratio using the light image of the lens 51 is, for example, 5 times.
There is controlling organization 60 view data by the image for imaging the photographing element being related to by imaging member 50 to enter
Row image procossing, so as to determine the brightness of the position (location of pixels) of the determination part 30 in image and calculate the extinction of plasma fraction
The function of degree.In addition, the function of the power supply 41 of electricity is supplied to light source 40 with control.
In this example embodiment, picture number obtained from carrying out image procossing based on the image as will be imaged as imaging member 50
According to blue brightness value calculate absorbance A under wavelength 455nm455, while the green brightness value based on the view data is calculated
The absorbance A gone out under wavelength 575nm575.Wherein, absorbance A455The absorbance for the bilirubin that can be considered as under wavelength 455nm and
The sum of the absorbance of haemolysis hemoglobin.On the other hand, A575The extinction for the haemolysis hemoglobin that can be considered as under wavelength 575nm
Degree.Also, because the absorbance of the haemolysis hemoglobin under wavelength 575nm is and the haemolysis hemoglobin under wavelength 455nm
Absorbance is approximately worth, it is possible to will be by absorbance A455Subtract absorbance A575Obtained from be worth (A455-A575) it is considered as wavelength
The absorbance of bilirubin under 455nm.And then using absorbance relation (langbobier law) proportional to concentration, by advance
The standard curve and A of acquirement455-A575Value calculate the concentration of bilirubin.
In this corpse or other object for laboratory examination and chemical testing concentration measurement apparatus, as described above, (wedge-like is empty for the determination part 30 in microfluidic circuit chip 10
Between 35) in be filled with the special component of the separation from the corpse or other object for laboratory examination and chemical testing (be blood in the example) of liquid (be to include check object in the example
Composition is the blood plasma of bilirubin).
Then, it is filled with the state of special component in the determination part 30 of microfluidic circuit chip 10, is radiated from light source 40
Light is exposed in the mensuration region 38 in microfluidic circuit chip 10 via optical filter 45 and lens 48.The light of transmission filter 45, i.e.
It is attached that the wavelength region of light in the mensuration region 38 exposed in microfluidic circuit chip 10 by the optical filter 45 is restricted to 455nm
Wavelength region near near wavelength region and 575nm.Afterwards, by the light shape of the mensuration region 38 in transmission microfluidic circuit chip 10
Into light image imaged by imaging member 50.Then, based on the view data obtained by imaging member 50, inspection pair is calculated out
As composition is the concentration of bilirubin.
, can be by the spy of the necessary amount separated in microfluidic circuit chip 10 from a corpse or other object for laboratory examination and chemical testing according to above-mentioned corpse or other object for laboratory examination and chemical testing concentration measurement apparatus
Determine composition and the mensuration region 38 of (filling) in determination part 30 is efficiently stored by the capillary force as caused by wedge-like space 35
In, so high inspection efficiency can be obtained.In addition, the mensuration region for the microfluidic circuit chip 10 that the light from light source 40 is irradiated
38 because thickness is constant size, so optical path length can be made constant, can be with the concentration of high reliability determination special component.
The corpse or other object for laboratory examination and chemical testing concentration measurement apparatus of the present invention is not limited to the device of above-mentioned composition, can also be as shown in Figure 10
Like that, be made be provided separately for example possess emission peak emission wavelength be 450nm light LED element the first light source 40a,
Such as possesses the secondary light source 40b of the LED element for the light that emission peak emission wavelength is 570nm composition.It is dense in the corpse or other object for laboratory examination and chemical testing
In degree measure device, the first light source 40a configures according to the mode opposite with the determination part 30 in microfluidic circuit chip 10, secondary light source
40b is configured with direction relative to the state in the vertical direction of the light path of the light from the first light source 40a.First light source 40a and
Two light source 40b electrically connect with power supply 41.In the light path and the light of the light from secondary light source 40b of the light from the first light source 40a
The position of intersecting point on road, with relative to the light path of the light from the first light source 40a and the light path of the light from secondary light source 40b each
Tilt what state at 45 ° was configured with the light transmission from the first light source 40a and reflected the light from secondary light source 40b
Dichroscope 42.
In light path between the first light source 40a and dichroscope 42, the wavelength region of restricted transmitted light is configured
The first optical filter 46a.Between the first optical filter 46a and dichroscope 42, it is configured with and incident light is subjected to parallelization
Lens 49a.In light path between secondary light source 40b and dichroscope 42, the wavelength zone of restricted transmitted light is configured
The second optical filter 46b in domain.Between the second optical filter 46b and dichroscope 42, it is configured with incident light progress is parallel
The lens 49b of change.Other compositions in corpse or other object for laboratory examination and chemical testing concentration measurement apparatus shown in Figure 10 and the corpse or other object for laboratory examination and chemical testing concentration mensuration shown in Fig. 9
Composition in device is same.
In the corpse or other object for laboratory examination and chemical testing concentration measurement apparatus, to the determination part 30 of microfluidic circuit chip 10, it can carry out simultaneously by the first light
The action and the action by secondary light source 40b irradiation lights of source 40a irradiation lights, it can also be carried out another after any action is carried out
Action.
Embodiment
<Embodiment 1>
(1) manufacture of first substrate and second substrate
By by acrylic resin (Japan Polypropylene Corporation systems " Novak (R) PP ") 50 mass
Part and hydrogenated styrene isoprene-butadiene block copolymer (KURARAY CO., LTD. system " HYBRAR 7311 ", polyphenyl
The mass % of the containing ratio of ethylene block=12) 50 mass parts carry out heating mixing, prepare specific resin combination.Resulting
The fusing point of specific resin combination is 142 DEG C, and temperature of deflection under load is 43 DEG C, and glass transition temperature is -35 DEG C.
Then, by the way that prepared specific resin combination carried out into injection molding, manufacture is on the surface formed with the
The first substrate of one stream groove and determination part recess and on the surface the second base formed with second flow path groove
Plate.
In resulting first substrate, first flow path is from corpse or other object for laboratory examination and chemical testing introduction part (21) to first discharge unit (23) with groove
Total length only is 50mm (reference picture 1), and the width (depth) of the thickness direction of first substrate is 100 μm, the face side of first substrate
To width be 300 μm.
If determination part recess reference picture 2 to Fig. 4, total length (length for forming the part of multiple second flow paths) is
15mm, the length (L1) of wedge-like space (35) is 1mm, and the length (L2) of mensuration region is 0.5mm.In addition, it is empty to form constant volume
Between (31) part in first substrate thickness direction size (D) be 100 μm, the face side of the first substrate in open end
To size (W1) be 200 μm, formed constant volume formed space a pair of constant volume product space forming faces (32a, 32b) relative to survey
Angle formed by the bottom surface of portion's recess (γ 1, γ 2) is determined for 85 °.In addition, the front end inclination angle (α) of wedge-like space (35) is 45 °,
The angular aperture (β) in wedge-like space (35) is 11.4 °, the in the open end of one end opening position of the length direction of mensuration region
The size (W2) in the face direction of one substrate is 20 μm.
In addition, in resulting second substrate, second flow path is 0.5mm with the length of groove, the thickness of second substrate
The width (depth) in direction is 2 μm, and the width in the face direction of second substrate is 50 μm, and the number of second flow path groove is 300.
Between adjacent second flow path groove at intervals of identical size (at equal intervals).
(2) surface activation of first substrate and second substrate is handled
Composition surface to the surface comprising first flow path groove and determination part recess in resulting first substrate,
And the composition surface for including second flow path groove in second substrate, carry out surface activation by irradiating vacuum ultraviolet
Processing.Surface to implementing surface activation processing, determines the contact angle of water, is as a result 45 °.
More than, the surface activation processing carried out using the irradiation of vacuum ultraviolet is by using the standard point for being sealed with xenon
Sub- lamp is as ultraviolet light source, using illumination as 30mW/cm2Condition irradiate the vacuum ultraviolet that 10 minutes wavelength are 172nm and come
Carry out.
(3) manufacture of microfluidic circuit chip
It is overlapping and contact first substrate with the state to good position on the composition surface of second substrate.Then, by by
One substrate and second substrate are heated at 60 DEG C, and first substrate is utilized from melt bonded property with second substrate and engaged,
Thus, microfluidic circuit chip is manufactured.
In resulting microfluidic circuit chip, from the upstream side of first flow path to in the most upstream side of the first flow path
Length untill the branch point of the second flow path of branch is 5mm.
In addition, using the second flow path of the microfluidic circuit chip obtained by micro- sem observation, it is different as a result not see deformation etc.
Often.
(4) test
Water is imported into above-mentioned microfluidic circuit chip as experiment fluid, investigates the experiment stream relative to the elapsed time
Loading (storage length) of the body into determination part.Result is represented with curve a (plottings of square symbols) in fig. 11.This
In, the experiment in determination part refers to the measure from the boundary position of wedge-like space and constant volume product space with the storage length of fluid
Length on the direction of the extension in portion.
<Comparative example 1>
It is (empty without wedge-like with recess except forming the determination part with spatial form substantially certain on length direction
Between, the determination part recess that is only made up of constant volume product space) beyond, make with the first substrate phase with being made in embodiment 1
With the first substrate of the comparison formed.The total length of determination part recess in the first substrate compared (forms multiple the
The length of the part of two streams) it is 20mm, the size of the thickness direction of first substrate is 100 μm, the first base in open end
The size in the face direction of plate is 200 μm, and relative to determination part, the angle formed by the bottom surface of recess is a pair of determination part forming faces
85°。
In addition to the first substrate compared using this, the microfluidic circuit chip of comparison similarly to Example 1,
Water is imported into microfluidic circuit chip as experiment fluid, investigates the experiment fluid relative to the elapsed time into determination part
Loading (storage length).Result is represented with curve b (plotting of circle symbol) in fig. 11.
Results verification more than is to according to the microfluidic circuit chip of embodiment 1, can filling experiment fluid high-effective
In determination part.Therefore, can expect can be by the check object composition of required amount in the corpse or other object for laboratory examination and chemical testing concentration mensuration of reality
Extracted with the short time from a corpse or other object for laboratory examination and chemical testing.
In addition, importing the μ L of blood 5 of people in the microfluidic circuit chip made into embodiment 1, after placing 10 minutes, measure is micro-
The light splitting absorption spectrum for the liquid filled in the determination part of fluidic chip, results verification arrive:The liquid filled in determination part is blood
Composition is starched, plasma fraction is isolated from blood.
Claims (7)
1. a kind of microfluidic circuit chip, it is characterised in that it is by the internal plate body with first flow path, second flow path and determination part
Form, the first flow path makes a corpse or other object for laboratory examination and chemical testing for liquid circulate, and the second flow path is formed and had from the first flow path branch
The width of special component is separated in the corpse or other object for laboratory examination and chemical testing that can be circulated from the first flow path and is connected with the first flow path, the survey
Determine portion to connect with the second flow path and fill the special component separated from the corpse or other object for laboratory examination and chemical testing, wherein,
At least a portion for forming the space of the determination part passes through with the wedge little by little to diminish and gap facing one direction
Shape space and formed.
2. microfluidic circuit chip according to claim 1, it is characterised in that assuming that one direction is set into x directions
Xyz orthogonal coordinates when,
There are a pair of wedge-like spaces on the z directions shown under the vertical view from y directions toward each other to be formed in the wedge-like space
Face forms the part of wedge-like.
3. microfluidic circuit chip according to claim 2, it is characterised in that the determination part has to be connected with the wedge-like space
The cross sectional shape in continuous yz sections is the constant volume product space of rectangular shape,
Angle formed by the continuous 2 constant volumes product space forming face shown in the yz sections of the constant volume product space is set to γ,
When angle formed by the pair of wedge-like space forming face shown under the vertical view from y directions in the wedge-like space is set into α,
The wedge-like space, which has, meets α<The spatial form of γ relation.
4. microfluidic circuit chip according to claim 3, it is characterised in that the wedge-like space has in bowing from z directions
A pair of wedge-like space forming faces on the y directions shown depending under toward each other form the part of wedge-like.
5. microfluidic circuit chip according to claim 4, it is characterised in that by the wedge-like space in bowing from z directions
When angle formed by the pair of wedge-like space forming face shown depending under is set to β, the wedge-like space, which has, meets β<γ pass
The spatial form of system.
6. the microfluidic circuit chip according to any one of claim 2 to claim 5, it is characterised in that the wedge-like is empty
Between have y directions size or z directions size be constant size measure region.
7. a kind of corpse or other object for laboratory examination and chemical testing concentration measurement apparatus, it is characterised in that it possesses following form:
Microfluidic circuit chip described in claim 6,
Light source, its to the measure area illumination light in the microfluidic circuit chip,
Imaging member, it images the image in the region comprising the mensuration region in the microfluidic circuit chip, and
Controlling organization, it has based on the view data obtained by the imaging member to calculate the concentration of the special component
Function.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016-118765 | 2016-06-15 | ||
JP2016118765A JP6729026B2 (en) | 2016-06-15 | 2016-06-15 | Micro channel chip and sample concentration measuring device |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107525765A true CN107525765A (en) | 2017-12-29 |
CN107525765B CN107525765B (en) | 2021-09-07 |
Family
ID=60687954
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710450415.2A Active CN107525765B (en) | 2016-06-15 | 2017-06-15 | Microchannel chip and sample concentration measuring device |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP6729026B2 (en) |
CN (1) | CN107525765B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111886075A (en) * | 2018-03-27 | 2020-11-03 | 罗伯特·博世有限公司 | Method and microfluidic device for dividing a sample liquid using a sealing liquid, method for producing a microfluidic device, and microfluidic system |
CN112076806A (en) * | 2019-06-14 | 2020-12-15 | 中国科学院青岛生物能源与过程研究所 | Centrifugal enrichment microfluidic chip for low-concentration liquid sample |
CN113454437A (en) * | 2019-02-27 | 2021-09-28 | 京瓷株式会社 | Particle separation measuring device and particle separation measuring apparatus |
Citations (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030180965A1 (en) * | 2002-03-25 | 2003-09-25 | Levent Yobas | Micro-fluidic device and method of manufacturing and using the same |
JP2005265634A (en) * | 2004-03-18 | 2005-09-29 | National Food Research Institute | Microchannel array made of resin, its manufacturing method and blood measuring method using microchannel array |
EP1360931B1 (en) * | 2002-05-09 | 2006-01-04 | Lifescan, Inc. | Physiological sample collection devices |
JP2006058280A (en) * | 2004-03-16 | 2006-03-02 | Fuji Photo Film Co Ltd | Assay chip |
CN1997453A (en) * | 2004-03-17 | 2007-07-11 | 迈克罗泰克微技术有限公司 | Microfluidic chip |
CN101137908A (en) * | 2005-03-07 | 2008-03-05 | 可乐丽股份有限公司 | Microchannel array and method for producing the same, and blood measuring method employing it |
EP1926010A2 (en) * | 2006-11-22 | 2008-05-28 | FUJIFILM Corporation | Temperature regulation method of microfluidic chip, sample analysis system and microfluidic chip |
JP2008151772A (en) * | 2006-11-22 | 2008-07-03 | Fujifilm Corp | Method for controlling temperature of microfluidic chip, specimen analysis system, and microfluidic chip |
CN101454664A (en) * | 2006-05-24 | 2009-06-10 | 国立大学法人京都大学 | Microchannel for separating blood plasma |
KR100903458B1 (en) * | 2002-02-28 | 2009-06-18 | 외르리콘 어셈블리 이큅먼트 아게, 슈타인하우젠 | Method and device for measuring the amplitude of a freely oscillating capillary of a wire bonder |
CN101923053A (en) * | 2010-07-19 | 2010-12-22 | 杭州师范大学 | Device and method for continuously analyzing single-cell contents by miniflow control chip at high speed |
KR20110005963A (en) * | 2009-07-13 | 2011-01-20 | 주식회사 나노엔텍 | A microfluidic chip for separating plasma or serum from blood |
CN101959602A (en) * | 2008-02-27 | 2011-01-26 | 贝林格尔英格海姆米克罗帕茨有限责任公司 | The equipment of separated plasma |
CN102947701A (en) * | 2010-04-15 | 2013-02-27 | 西托根有限公司 | Microfluidic device and method for isolating target using same |
CN103285949A (en) * | 2013-05-27 | 2013-09-11 | 苏州扬清芯片科技有限公司 | Micro-fluidic serum extracting chip |
WO2014001781A1 (en) * | 2012-06-26 | 2014-01-03 | Imperial Innovations Limited | Microfluidic device for droplet generation |
CN103826690A (en) * | 2011-08-01 | 2014-05-28 | 亚克安娜生命科学有限公司 | Microfluidic drug delivery devices |
CN103930210A (en) * | 2011-09-19 | 2014-07-16 | 国家科学研究中心 | Microfluidic system |
CN104918551A (en) * | 2012-12-03 | 2015-09-16 | Pepex生物医药有限公司 | Sensor module and method of using a sensor module |
CN105300524A (en) * | 2014-05-27 | 2016-02-03 | 优志旺电机株式会社 | Polarization axis detector, polarization measurement device and method, and polarized light irradiation device |
CN105518464A (en) * | 2013-07-05 | 2016-04-20 | 华盛顿大学商业中心 | Methods, compositions and systems for microfluidic assays |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004042012A (en) * | 2001-10-26 | 2004-02-12 | Nec Corp | Separation apparatus, analysis system, separating method, and method of manufacturing the apparatus |
TW200702292A (en) * | 2005-02-28 | 2007-01-16 | Careside Medical Llc | A micro-fluidic fluid separation device and method |
JP2010071857A (en) * | 2008-09-19 | 2010-04-02 | Sekisui Chem Co Ltd | Plasma separation device |
-
2016
- 2016-06-15 JP JP2016118765A patent/JP6729026B2/en active Active
-
2017
- 2017-06-15 CN CN201710450415.2A patent/CN107525765B/en active Active
Patent Citations (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100903458B1 (en) * | 2002-02-28 | 2009-06-18 | 외르리콘 어셈블리 이큅먼트 아게, 슈타인하우젠 | Method and device for measuring the amplitude of a freely oscillating capillary of a wire bonder |
US20030180965A1 (en) * | 2002-03-25 | 2003-09-25 | Levent Yobas | Micro-fluidic device and method of manufacturing and using the same |
EP1360931B1 (en) * | 2002-05-09 | 2006-01-04 | Lifescan, Inc. | Physiological sample collection devices |
JP2006058280A (en) * | 2004-03-16 | 2006-03-02 | Fuji Photo Film Co Ltd | Assay chip |
CN1997453A (en) * | 2004-03-17 | 2007-07-11 | 迈克罗泰克微技术有限公司 | Microfluidic chip |
JP2005265634A (en) * | 2004-03-18 | 2005-09-29 | National Food Research Institute | Microchannel array made of resin, its manufacturing method and blood measuring method using microchannel array |
CN101137908A (en) * | 2005-03-07 | 2008-03-05 | 可乐丽股份有限公司 | Microchannel array and method for producing the same, and blood measuring method employing it |
CN101454664A (en) * | 2006-05-24 | 2009-06-10 | 国立大学法人京都大学 | Microchannel for separating blood plasma |
EP1926010A2 (en) * | 2006-11-22 | 2008-05-28 | FUJIFILM Corporation | Temperature regulation method of microfluidic chip, sample analysis system and microfluidic chip |
JP2008151772A (en) * | 2006-11-22 | 2008-07-03 | Fujifilm Corp | Method for controlling temperature of microfluidic chip, specimen analysis system, and microfluidic chip |
CN101959602A (en) * | 2008-02-27 | 2011-01-26 | 贝林格尔英格海姆米克罗帕茨有限责任公司 | The equipment of separated plasma |
KR20110005963A (en) * | 2009-07-13 | 2011-01-20 | 주식회사 나노엔텍 | A microfluidic chip for separating plasma or serum from blood |
CN102947701A (en) * | 2010-04-15 | 2013-02-27 | 西托根有限公司 | Microfluidic device and method for isolating target using same |
CN101923053A (en) * | 2010-07-19 | 2010-12-22 | 杭州师范大学 | Device and method for continuously analyzing single-cell contents by miniflow control chip at high speed |
CN103826690A (en) * | 2011-08-01 | 2014-05-28 | 亚克安娜生命科学有限公司 | Microfluidic drug delivery devices |
CN103930210A (en) * | 2011-09-19 | 2014-07-16 | 国家科学研究中心 | Microfluidic system |
WO2014001781A1 (en) * | 2012-06-26 | 2014-01-03 | Imperial Innovations Limited | Microfluidic device for droplet generation |
CN104918551A (en) * | 2012-12-03 | 2015-09-16 | Pepex生物医药有限公司 | Sensor module and method of using a sensor module |
CN103285949A (en) * | 2013-05-27 | 2013-09-11 | 苏州扬清芯片科技有限公司 | Micro-fluidic serum extracting chip |
CN105518464A (en) * | 2013-07-05 | 2016-04-20 | 华盛顿大学商业中心 | Methods, compositions and systems for microfluidic assays |
CN105300524A (en) * | 2014-05-27 | 2016-02-03 | 优志旺电机株式会社 | Polarization axis detector, polarization measurement device and method, and polarized light irradiation device |
Non-Patent Citations (4)
Title |
---|
ZHU PINGAN: "Tip-multi-breaking in Capillary", 《SCIENTIFIC REPORTS》 * |
弓建红: "《现代仪器分析技术》", 30 September 2011 * |
张凯, 等: "微流控芯片中微液滴的操控及其应用", 《分析化学》 * |
秦建华: "微流控技术研究的若干进展", 《色谱》 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111886075A (en) * | 2018-03-27 | 2020-11-03 | 罗伯特·博世有限公司 | Method and microfluidic device for dividing a sample liquid using a sealing liquid, method for producing a microfluidic device, and microfluidic system |
CN111886075B (en) * | 2018-03-27 | 2021-11-30 | 罗伯特·博世有限公司 | Method for dividing a sample liquid using a sealing liquid, microfluidic device, method for producing the same, and microfluidic system |
US11565261B2 (en) | 2018-03-27 | 2023-01-31 | Robert Bosch Gmbh | Method and microfluidic device for aliquoting a sample liquid using a sealing liquid, method for producing a microfluidic device and microfluidic system |
CN113454437A (en) * | 2019-02-27 | 2021-09-28 | 京瓷株式会社 | Particle separation measuring device and particle separation measuring apparatus |
CN113454437B (en) * | 2019-02-27 | 2024-03-15 | 京瓷株式会社 | Particle separation device and particle separation measuring device |
CN112076806A (en) * | 2019-06-14 | 2020-12-15 | 中国科学院青岛生物能源与过程研究所 | Centrifugal enrichment microfluidic chip for low-concentration liquid sample |
CN112076806B (en) * | 2019-06-14 | 2022-12-30 | 中国科学院青岛生物能源与过程研究所 | Centrifugal enrichment microfluidic chip for low-concentration liquid sample |
Also Published As
Publication number | Publication date |
---|---|
JP2017223532A (en) | 2017-12-21 |
CN107525765B (en) | 2021-09-07 |
JP6729026B2 (en) | 2020-07-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107525765A (en) | Microfluidic circuit chip and corpse or other object for laboratory examination and chemical testing concentration measurement apparatus | |
US8389960B2 (en) | Microfluidic devices and methods | |
JP7029175B2 (en) | Particle separation device and particle separation method | |
Hourlier-Fargette et al. | Role of uncrosslinked chains in droplets dynamics on silicone elastomers | |
KR101561718B1 (en) | Three-dimensional microfluidic devices | |
KR100742783B1 (en) | Cell separation chip | |
JP2008538282A (en) | Device and method for enrichment and modification of circulating tumor cells and other particles | |
EP2819783B1 (en) | Sample processing device with detachable slide | |
CN106754245A (en) | Based on the digital pcr chip of algin drop and its application | |
JP2014518509A (en) | A microfluidic system that controls the concentration of molecules that stimulate the target | |
DE102014209188B4 (en) | Apparatus and method for processing a biological sample and analysis system for analyzing a biological sample | |
Männel et al. | Combining hydrophilic and hydrophobic materials in 3D printing for fabricating microfluidic devices with spatial wettability | |
CN209210833U (en) | Digital PCR system | |
CN107519957A (en) | Microfluidic circuit chip | |
US10174313B2 (en) | Methods and devices for micro-isolation, extraction, and/or analysis of microscale components in an array | |
US10406521B2 (en) | Micro-droplet array for multiple screening of a sample | |
EP1862542A1 (en) | Detecting chip and method of detecting substance using the same | |
US20210363493A1 (en) | Target capturing apparatus and manufacturing method thereof, and target detecting method | |
JP7165346B2 (en) | particle detector | |
US20150370060A1 (en) | Microscope slide with etched shapes | |
KR102214461B1 (en) | Apparatus for testing drug-responsibility | |
Li et al. | A microfluidic platform for osmotic fragility test of red blood cells | |
WO2017097788A1 (en) | 3d spatially organized cultured tissue by means of stacking beads comprising hydrogel encapsulated cells | |
WO2020034479A1 (en) | Digital pcr system and digital pcr droplet forming method | |
Brettschneider | Combining polymer microfluidics with electrical functionality:: novel perspectives for the Bosch lab-on-chip platform |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |