CN104162391B - A kind of irregular microgel preparation method based on liquid bridge phenomenon - Google Patents
A kind of irregular microgel preparation method based on liquid bridge phenomenon Download PDFInfo
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Abstract
Based on an irregular microgel preparation method for liquid bridge phenomenon, adopt the elevation and subsidence mechanical platform of controllable height, select the different surfacing of parent/hydrophobicity to be fixed on stiff end and the liftable end of mechanical platform respectively.Using micropipettor to measure the hydrogel precursor solution of certain volume, drip between two surfacings, by stretching or pressurized water gel precursors drop, forming liquid bridge.By adjusting the spacing on the shape of two surfacings and drop contact position, material behavior and two surfaces, the liquid bridge of different target shape can be obtained.For the hydrogel precursor drop of different qualities, different physics and chemistry cross-linking method can be taked to make it solidify.The method is simple and efficient, do not limit by material, controlled shape, and improved by simple technique and directly can form the liquid bridge that high flux and inside exist gradient, be a kind of preparation method of very potential irregular microgel, for future, the preparation of organizational project infrastructure element provides strong support.
Description
Technical field
The present invention relates to microgel preparing technical field, be specifically related to a kind of irregular microgel preparation method based on liquid bridge phenomenon.
Background technology
At present, microgel has been widely used in the fields such as drug delivery, organizational project, bio-sensing, bio-barcode.The shape of microgel, can affect its function significantly as an important parameter.In order to the difform micro-structural repetitive existed a large amount of in better simulating nature circle, irregular microgel is a desirable solution.In fact, human body inherently has a lot of irregular constitutional repeating unit, as all there is a large amount of irregular repetitive in liver, kidney, lung, by certain combination, achieves complicated function.Similar with it, build the microgel matrix of a careful design, a lot of biologic applications is benefited to some extent.
At present, many methods have been had to prepare for asymmetric microgel, as pulling method (LelePPetal.2009), template (RollandJPetal.2005), microfluid (DendukuriDetal.2005) and photo mask method (DuYNetal.2008) etc.Although these methods partly can realize the accurate control or easy to operation of high flux, shape, but still there is respective limitation.Such as, utilize stretching circular granular can obtain the dumbbell shape of asymmetry or oval microgel, but this method require that the material of synthesis microgel is to responsive to temperature, makes it easy to reach vitrification point; When utilizing template synthesis microgel, when being separated with template by microgel, be easy to the structure of destroy microgels, require higher to the technology of preparing of template, and not all laboratory all can realize simultaneously; Although the microgel shape utilizing microfluid to prepare can obtain more accurately controlling, the microgel of synthesis is owing to being wrapped in oil, and this is further used for biologic applications by limiting it; Utilize photo mask method, then require that microgel material is necessary for photaesthesia type, realize crosslinked by ultraviolet light, but due to the refraction of trimmed book body and scattering, the microgel finite thickness causing photo mask method to synthesize, and there is uncontrollability.Therefore, the method for the microgel that a kind of biologic applications of invention has good prospects is needed badly.
When liquid is present between two surfaces of solids, liquid will form liquid bridge, connect two surfaces of solids.This phenomenon is extensively present in occurring in nature.Such as, the liquid that many insects (as beetle and blowfly) utilize oneself to secrete forms liquid bridge between oneself limbs and wall-attached surface, thus strengthens attaching power.This phenomenon is also used to industrial circle at present.Such as, printing industry utilizes liquid bridge transfer ink, and packaging industry utilizes this phenomenon to remove photoresist.But liquid bridge phenomenon is not also used to the preparation of microgel.
Summary of the invention
The object of the present invention is to provide a kind of irregular microgel preparation method based on liquid bridge phenomenon, the method possesses the advantages such as cost is low, preparation method simply, not limits by material, obtained microgel size is controlled, pattern is adjustable.
In order to achieve the above object, the technical scheme that the present invention takes is:
Based on an irregular microgel preparation method for liquid bridge phenomenon, comprise the following steps:
Step 1: liftable end first surface material being fixed on elevation and subsidence mechanical platform, is fixed on the stiff end of elevation and subsidence mechanical platform by second surface material;
Step 2: use micropipettor to draw and can form the hydrogel precursor solution of liquid bridge, drop to be fixed on elevation and subsidence mechanical platform stiff end second surface material on, second surface material is formed the hydrogel precursor drop that can form liquid bridge;
Step 3: adjustment elevation and subsidence mechanical platform, make first surface material near second surface material, until first surface material contacts with hydrogel precursor drop, liquid bridge is formed between first, second surfacing, then adjustment elevation and subsidence mechanical platform is continued, make first surface material away from or near second surface material, until the shape of liquid bridge is required irregular microgel shape;
Step 4: according to kind and the character of hydrogel precursor drop, adopts corresponding chemical reaction or physical means to make the hydrogel in liquid bridge crosslinked fixing, obtains the irregular microgel of required form.
Described first surface material and second surface material close hydrophobicity scope be from super hydrophilic to super-hydrophobic.
Described first surface material and the material of second surface material comprise glass, metal, PMMA plate and the glass through super-hydrophobic agent treatment.
Described first surface material and second surface material are arbitrary shape, first surface material is parallel with the relative position of second surface material or becomes the angle of 0 ° ~ 45 °, and the distance between first surface material and second surface material is any distance that can form liquid bridge.
The volume of described hydrogel precursor drop is 0.05 μ l ~ 2 μ l.
Described hydrogel precursor solution is the hydrogel precursor solution that can be solidified by heating and cooling, UV-irradiation or chemical catalysis cross-linking reaction.
Described hydrogel precursor solution comprises the PEG solution containing 2-hydroxyl-2 methyl phenyl ketone, the mixed solution of acrylamide, methylene diacrylamide, ammonium persulfate and N, N, N', N'-tetramethyl diethylamine, gelatin solution, and the PEG solution containing cell.
When preparing irregular microgel array, on second surface material, print hydrogel precursor droplet array with cell printing machine or the volley of rifle fire, then adjust elevation and subsidence mechanical platform, first surface material is near second surface material and form liquid bridge, after crosslinking curing, obtain irregular microgel array.
When preparation has the irregular microgel of inner gradient, first surface material and second surface material drip hydrogel precursor drop respectively, and cell containing variable concentrations or heterogeneity in the hydrogel precursor drop on first surface material and the hydrogel precursor drop on second surface material and/or chemical substance; Then adjust elevation and subsidence mechanical platform, make first, second surfacing close to each other and form liquid bridge, after crosslinking curing, obtaining the irregular microgel that inside has cell gradient, chemical gradient and/or hardness gradient.
Simulate by setting up the shape of mathematical model to the irregular microgel of preparation,
Wherein z is the vertical direction coordinate of the interface each point of liquid bridge, the axial coordinate that R (z) is z, R is writing a Chinese character in simplified form of R (z), Δ P be liquid bridge interface inside and outside pressure difference, γ is the surface tension coefficient of liquid bridge, and ρ is the density of liquid bridge, g is gravity constant, by gal the Liao Dynasty's above-mentioned equation of golden finite element method and the boundary condition of interface at two-end-point place of liquid bridge, (R (z) z) is the pattern of the irregular microgel of simulation to the numerical solution of trying to achieve.
Relative to prior art, the present invention has following beneficial effect:
Irregular microgel preparation method based on liquid bridge phenomenon provided by the invention, hydrogel precursor drop is made to form liquid bridge between first surface material and second surface material, namely irregular microgel is obtained after crosslinking curing, by adjusting with the volume size of the shape of first, second surfacing of hydrogel precursor drop contact, parent/hydrophobicity, hydrogel precursor drop and regulating the height stretching or compress liquid bridge, the shape control to irregular microgel can be realized.Due to the shape of liquid bridge and the hydrophilic and hydrophobic of first, second surfacing, the spacing of first, second surfacing in the present invention, the shape of first, second surfacing, the parameters such as hydrogel precursor droplet size are closely related, therefore by changing the hydrophilic and hydrophobic of first, second surfacing, or just can be easy to by the height changing liquid bridge the object that realization changes liquid bridge shape.The present invention is based on liquid bridge phenomenon and prepare irregular microgel, have that cost is low, preparation method is simple, easy and simple to handle, by material restriction, obtained irregular microgel structure and size is controlled, pattern is adjustable, easily realize the advantage such as inner gradient and high flux, and for dissimilar hydrogel precursor solution, diverse ways is taked to make its crosslinking curing, easily after crosslinked being separated with first, second surfacing, is a kind of preparation method of very potential irregular microgel.And obtained irregular microgel can be used in cell-cell interaction in organizational project and regenerative medicine, cell and matrix interact, and the application studies such as microgel assembling, biologic applications has good prospects.
Accompanying drawing explanation
Fig. 1 is the microgel preparation flow schematic diagram based on liquid bridge.
1 be first surface material, 2 be wherein second surface material, 3 for hydrogel precursor drop.
Fig. 2 is the polyethylene glycol microgel schematic diagram and numerical simulation result figure that embodiment 1 upper and lower surface is prepared by glass surface, and wherein the black line of liquid bridge both sides is the microgel pattern that analog result obtains.
Fig. 3 is polyacrylamide microgel schematic diagram and the numerical simulation result figure that embodiment 2 upper and lower surface is the preparation of PMMA plate surface, and wherein the black line of liquid bridge both sides is the microgel pattern that analog result obtains.
Fig. 4 is the gelatin microgel schematic diagram prepared of glass surface that embodiment 3 upper and lower surface is super-hydrophobic process and numerical simulation result figure, and wherein the black line of liquid bridge both sides is the gel pattern that analog result obtains.
Fig. 5 is the microgel schematic diagram that embodiment 4 upper and lower surface is respectively the preparation of different hydrophobe surface, wherein the first surface material of (a) is the slide of super-hydrophobic process, second surface material is simple glass slide, and the first surface material of (b) is the slide of super-hydrophobic process, second surface material is PMMA plate.
Fig. 6 is the microgel figure of PEG parcel cell prepared by embodiment 5 upper surface alteration of form, and wherein (a) is the overall diagram of the microgel of preparation, and (b) is the partial enlarged drawing of (a).
Fig. 7 is high flux microgel matrix diagram prepared by embodiment 6.
Fig. 8 is the schematic diagram with the irregular microgel of chemical gradient and the experimental result picture of embodiment 7 preparation, and wherein (a) is schematic diagram, and (b) is experimental result picture.
Fig. 9 is upper and lower surface prepared by embodiment 8 microgel figure when becoming 20 ° of angles.
Detailed description of the invention
Below in conjunction with drawings and Examples, the invention will be further described.
Irregular microgel preparation method based on liquid bridge phenomenon provided by the invention, as shown in Figure 1, comprises first, second surfacing 1,2 contacted with hydrogel precursor drop 3, and can form the hydrogel precursor drop 3 of liquid bridge.Can by controlling the hydrophilic and hydrophobic of first, second surfacing, the volume size of hydrogel precursor drop with hydrogel precursor drop contact, the height of adjustment stretching or compression liquid bridge and the shape of first, second surfacing realize the regulation and control to the irregular microgel of difformity.Concrete steps are:
Step 1: adopt an elevation and subsidence mechanical platform that can control the stretching of liquid bridge or compression height, first surface material 1 is fixed on the liftable end of elevation and subsidence mechanical platform, second surface material 2 is fixed on the stiff end of elevation and subsidence mechanical platform, ensures that first, second surfacing and elevation and subsidence mechanical platform fixedly secure.
Step 2: use micropipettor to draw the hydrogel precursor solution of certain volume, slowly drop on second surface material 2, second surface material 2 is formed the hydrogel precursor drop 3 that can form liquid bridge.
Step 3: adjustment elevation and subsidence mechanical platform, makes first surface material 1 near second surface material 2, when near to time to a certain degree, form liquid bridge between first, second surfacing.Continue adjustment elevation and subsidence mechanical platform, until the shape of liquid bridge is required irregular microgel shape.
Step 4: utilize chemical reaction or physical means to make the hydrogel in liquid bridge crosslinked fixing (concrete grammar is different according to hydrogel precursor drop kind, as ultraviolet lighting, intensification or cooling etc.), obtain the irregular microgel of required form.
To be all hydrophilies be first, second described surfacing from super hydrophilic to any one surfacing super-hydrophobic, first, second surfacing can be the same or different, can be the parent/hydrophobic surface of unlike material, as glass (contact angle is about 40 °), PMMA plate (contact angle is about 70 °), the different surfaces material such as glass (contact angle is about 90 °) through super-hydrophobic agent treatment, but be not limited in above-mentioned glass, PMMA plate and the glass plate through super-hydrophobic agent treatment.
First, second described surfacing can have any shape, and namely can have any shape projection, also can have any shape depression.Its relative position, can be parallel, also can become the angle of 0 ° ~ 45 °.Its spacing is any distance that can form liquid bridge.
Described hydrogel precursor solution is the hydrogel precursor solution by various ways crosslinking curings such as heating and cooling, UV-irradiation, chemical catalysis reactions, such as utilize the gel (as polyethylene glycol etc.) of ultraviolet light cross-linking, by the crosslinked gel (as gelatin etc.) of temperature change, the gel (as polyacrylamide etc.) utilizing chemical catalysis cross-linking reaction.The volume of hydrogel precursor drop 3 is 0.05 μ l ~ 2 μ l.And this hydrogel precursor solution is the hypotoxic biomaterial and the porous support materials that are suitable for Growth of Cells, cell can be carried to improve its biocompatibility, or add nano material to change its performance, be not limited to the above-mentioned hydrogel kind mentioned.
When preparing irregular microgel array, cell printing machine can be used on second surface material to print hydrogel precursor droplet array, also other equipment can be used, as hydrogel precursor droplet array prepared fast by the volley of rifle fire etc., then elevation and subsidence mechanical platform is adjusted, first surface material is near second surface material and form liquid bridge, after crosslinking curing, obtains irregular microgel array.
When preparing inside and there is the irregular microgel of hardness gradient, cell gradient and chemical gradient, first surface material and second surface material drip hydrogel precursor drop respectively, and cell containing variable concentrations or heterogeneity in the hydrogel precursor drop on first surface material and the hydrogel precursor drop on second surface material and chemical substance; Then elevation and subsidence mechanical platform is adjusted, make first, second surfacing close to each other and form liquid bridge, certain cell gradient, chemical gradient is formed at drop internal, after crosslinking curing, directly can form the irregular microgel that cell gradient, chemical gradient even obtain different hardness gradient in microgel.
In addition, the present invention can also simulate by setting up the shape of mathematical model to the irregular microgel of preparation, realizes the prediction to microgel shape.Specific as follows, assuming that reach stable state when microgel (liquid bridge) is shaped, is then zero with external force suffered by the interface of microgel,
Wherein z is the vertical direction coordinate of the interface each point of liquid bridge, the axial coordinate that R (z) is z, R is writing a Chinese character in simplified form of R (z), Δ P be liquid bridge interface inside and outside pressure difference, γ is the surface tension coefficient of liquid bridge, ρ is the density of liquid bridge, g is gravity constant, above formula can think the balance of surface tension and gravity, by gal the Liao Dynasty's above-mentioned equilibrium equation of golden finite element method and the boundary condition of interface at two-end-point place of liquid bridge, (R (z) z) is the pattern of the irregular microgel of simulation to the numerical solution of trying to achieve.By the result of comparative experiments measurement and theoretical prediction, both discoveries can be good at coincideing.
Embodiment 1 upper and lower surface is polyethylene glycol microgel schematic diagram and numerical simulation result figure prepared by glass surface
Step 1: fix two glass slide respectively in the stiff end of elevation and subsidence mechanical platform and liftable end, ensures that slide and elevation and subsidence mechanical platform fixedly secure, and ensures all complete level of two slides.
Step 2: take a certain amount of PEG1000 monomer, be dissolved in ultra-pure water, is mixed with the PEG solution that mass concentration is 10%.In the PEG solution prepared, add 2-hydroxyl-2 methyl phenyl ketone (quality is 0.5% of PEG solution) again, fully concussion makes it mix, and obtains the first mixed liquor (hydrogel precursor solution).Use micropipettor to draw first mixed liquor of 2 μ l, slowly drop to elevation and subsidence mechanical platform and be in the glass slide of below.
Step 3: adjustment elevation and subsidence mechanical platform, makes two slides close to each other, when near to time to a certain degree, will form liquid bridge between two slides.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: UV-crosslinked 15s makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 2.
Embodiment 2 upper and lower surface is polyacrylamide microgel schematic diagram and the numerical simulation result of the preparation of PMMA plate surface
Step 1: fix two panels PMMA plate respectively in the stiff end of elevation and subsidence mechanical platform and liftable end, ensures that PMMA plate and elevation and subsidence mechanical platform fixedly secure, and ensures all complete level of two PMMA plates.
Step 2: take acrylamide, methylene diacrylamide and ammonium persulfate and add in beaker, the mass ratio of methylene diacrylamide and acrylamide is 0.00375:1, and the mass ratio of ammonium persulfate and acrylamide is 0.0175:1, then adds ultra-pure water, the concentration of acrylamide is made to be 0.2g/ml, stirring makes dissolution of solid, finally adds N, N, N', N'-tetramethyl diethylamine, the mass ratio of itself and acrylamide is 0.0068:1, obtains the second mixed liquor after mixing.Use micropipettor to draw 1 μ l second mixed liquor (hydrogel precursor solution), slowly drop to mechanical platform and be on the PMMA plate of below.
Step 3: adjustment hoistable platform, makes two PMMA plates close to each other, when near to time to a certain degree, will form liquid bridge between two PMMA plates.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: the static hydrogel that makes solidifies, then obtain the microgel of given shape, as shown in Figure 3.
Gelatin microgel schematic diagram prepared by the glass surface that embodiment 3 upper and lower surface is super-hydrophobic process and numerical simulation result
Step 1: the slide fixing the super-hydrophobic process of two panels respectively, in the stiff end of elevation and subsidence mechanical platform and liftable end, ensures that slide and elevation and subsidence mechanical platform fixedly secure, and ensures all complete level of two slides.
Step 2: take a certain amount of gelatin powder, be dissolved in ultra-pure water, is mixed with the gelatin solution that mass concentration is 5%, raised temperature to 50 DEG C, and fully concussion makes it mix, and obtains the 3rd mixed liquor (hydrogel precursor solution).Use micropipettor to draw the 3rd mixed liquor of 0.5 μ l, slowly drop to mechanical platform and be in the glass slide of the super-hydrophobic process of below.
Step 3: adjustment hoistable platform, makes two slides close to each other, when near to time to a certain degree, will form liquid bridge between two slides.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: cooling makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 4.
Embodiment 4 upper and lower surface is respectively the microgel schematic diagram of different hydrophobe surface preparation
Step 1: fix the slide of super-hydrophobic process and simple glass slide respectively in the liftable end of elevation and subsidence mechanical platform and stiff end, or fix the slide of super-hydrophobic process and PMMA plate respectively in the liftable end of elevation and subsidence mechanical platform and stiff end, ensure that surfacing and elevation and subsidence mechanical platform fixedly secure, and ensure two surfaces level all completely.
Step 2: use micropipettor to draw the 3rd mixed liquor of 1 μ l, slowly drops in glass slide or PMMA plate that mechanical platform is in below.
Step 3: adjustment hoistable platform, makes two surfaces close to each other, when near to time to a certain degree, will form liquid bridge between two surfaces.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: cooling makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 5.
The microgel figure of polyethylene glycol parcel cell prepared by embodiment 5 upper surface alteration of form
Step 1: fixing PMMA sheet in the stiff end of elevation and subsidence mechanical platform, fix a termination be circular PMMA sheet in liftable end, ensure that PMMA sheet and elevation and subsidence mechanical platform fixedly secure.
Step 2: take a certain amount of PEG1000 monomer, be dissolved in the PBS containing C2C12 cell, is mixed with the PEG solution that mass concentration is 10%.In the PEG solution prepared, add 2-hydroxyl-2 methyl phenyl ketone (quality is 0.5% of PEG solution) again, fully concussion makes it mix, and obtains the 4th mixed liquor (hydrogel precursor solution).Use micropipettor to draw the 4th mixed liquor of 2 μ l, slowly drop to mechanical platform and be in the glass slide of below.
Step 3: adjustment hoistable platform, makes two PMMA sheets close to each other, when near to time to a certain degree, will form liquid bridge between two PMMA sheets.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: UV-crosslinked 15s makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 6.
The high flux preparation of embodiment 6 microgel matrix
Step 1: use cell printing platform to print the microarray that volume is first mixed liquor of 2 μ l on PMMA plate.
Step 2: the PMMA plate fixedly with the first mixed liquor microarray, in the stiff end of elevation and subsidence mechanical platform, fixes another sheet PMMA plate at liftable end, ensures that PMMA plate and elevation and subsidence mechanical platform fixedly secure, and ensures two PMMA plates level all completely.
Step 3: adjustment hoistable platform, makes two PMMA plates close to each other, when near to time to a certain degree, will form multiple liquid bridge between two PMMA plates.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: UV-crosslinked 15s makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 7.
Schematic diagram prepared by the irregular microgel that embodiment 7 has chemical gradient and experimental result
Step 1: fix PMMA plate respectively in the liftable end of elevation and subsidence mechanical platform and stiff end, ensures that PMMA plate and elevation and subsidence mechanical platform fixedly secure, and ensures all complete level of two PMMA plates.
Step 2: add suitable blue ink and obtain the 5th mixed liquor in the 3rd mixed liquor, adds suitable red ink and obtains the 6th mixed liquor in the 3rd mixed liquor.Use micropipettor to draw the 5th mixed liquor of 0.5 μ l, slowly drop to mechanical platform and be on the PMMA plate of below.Re-use the 6th mixed liquor that micropipettor draws 0.5 μ l, slowly drop to mechanical platform and be on the PMMA plate of top.
Step 3: adjustment hoistable platform, makes two PMMA plates close to each other, when near to time to a certain degree, will form liquid bridge, and form certain chemical gradient at drop internal between two PMMA plates.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: cooling makes hydrogel solidify, then obtain the microgel of the given shape with chemical gradient, as shown in Figure 8.
Embodiment 8 upper and lower surface becomes the microgel figure prepared during 20 ° of angles
Step 1: respectively fixing metal sheet and PMMA plate are in the liftable end of elevation and subsidence mechanical platform and stiff end, and ensure that surfacing and elevation and subsidence mechanical platform fixedly secure, and ensure the complete level of lower surface, upper surface becomes 20 ° of angles with lower surface.
Step 2: use micropipettor to draw the 3rd mixed liquor of 1 μ l, slowly drops to mechanical platform and is in the glass slide of below.
Step 3: adjustment hoistable platform, makes two surfaces close to each other, when near to time to a certain degree, will form liquid bridge between two surfaces.Continue adjustment hoistable platform, until obtain the hydrogel shape needed.
Step 4: cooling makes hydrogel solidify, then obtain the microgel of given shape, as shown in Figure 9.
Operation principle of the present invention is: illustrate with the structure of embodiment 1, after glass surface drips the first mixed liquor, defines a drop, remain on the state of nature contact angle at glass surface.When using another block glass near this drop, between two glass, define liquid bridge.Because glass hydrophily is comparatively strong, the liquid bridge radian of formation is comparatively large, by controlling the distance between two glass plates, can obtain longer dumbbell shape drop until difformities such as disc-shaped drops.Use ultraviolet light to be cross-linked, then obtain the microgel identical with droplet profile.
Liquid bridge phenomenon is used for the preparation of microgel by the present invention first, and the development for the irregular microgel of controlled synthesis provides a kind of new thinking and strong instrument.In addition, the microgel described in the present invention refers to revolving body diameter or highly has one to reach micro-meter scale, namely assert that it is microgel.
The above embodiment only have expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.
Claims (10)
1., based on an irregular microgel preparation method for liquid bridge phenomenon, it is characterized in that, comprise the following steps:
Step 1: liftable end first surface material (1) being fixed on elevation and subsidence mechanical platform, is fixed on the stiff end of elevation and subsidence mechanical platform by second surface material (2);
Step 2: use micropipettor to draw the hydrogel precursor solution that can form liquid bridge, drop to and be fixed on the second surface material (2) of elevation and subsidence mechanical platform stiff end, the hydrogel precursor drop (3) of liquid bridge can be formed in the upper formation of second surface material (2);
Step 3: adjustment elevation and subsidence mechanical platform, make first surface material (1) near second surface material (2), until first surface material (1) contacts with hydrogel precursor drop (3), liquid bridge is formed between first, second surfacing (1,2), then adjustment elevation and subsidence mechanical platform is continued, make first surface material (1) away from or near second surface material (2), until the shape of liquid bridge is required irregular microgel shape;
Step 4: according to kind and the character of hydrogel precursor drop (3), adopts corresponding chemical reaction or physical means to make the hydrogel in liquid bridge crosslinked fixing, obtains the irregular microgel of required form.
2. the irregular microgel preparation method based on liquid bridge phenomenon according to claim 1, is characterized in that: described first surface material (1) and second surface material (2) close hydrophobicity scope be from super hydrophilic to super-hydrophobic.
3. the irregular microgel preparation method based on liquid bridge phenomenon according to claim 2, is characterized in that: described first surface material (1) and the material of second surface material (2) comprise glass, metal, PMMA plate and the glass through super-hydrophobic agent treatment.
4. the irregular microgel preparation method based on liquid bridge phenomenon according to claim 1, it is characterized in that: described first surface material (1) and second surface material (2) are arbitrary shape, first surface material (1) is parallel with the relative position of second surface material (2) or becomes the angle of 0 ° ~ 45 °, and the distance between first surface material (1) and second surface material (2) is any distance that can form liquid bridge.
5. the irregular microgel preparation method based on liquid bridge phenomenon according to claim 1, is characterized in that: the volume of described hydrogel precursor drop (3) is 0.05 μ l ~ 2 μ l.
6. according to the irregular microgel preparation method based on liquid bridge phenomenon in claim 1-5 described in any one, it is characterized in that: described hydrogel precursor solution is the hydrogel precursor solution that can be solidified by heating and cooling, UV-irradiation or chemical catalysis cross-linking reaction.
7. the irregular microgel preparation method based on liquid bridge phenomenon according to claim 6, it is characterized in that: described hydrogel precursor solution comprises the PEG solution containing 2-hydroxyl-2 methyl phenyl ketone, acrylamide, methylene diacrylamide, ammonium persulfate and N, N, N', the mixed solution of N'-tetramethyl diethylamine, gelatin solution, and the PEG solution containing cell.
8. according to the irregular microgel preparation method based on liquid bridge phenomenon in claim 1-5 described in any one, it is characterized in that: when preparing irregular microgel array, on second surface material (2), hydrogel precursor drop (3) array is printed with cell printing machine or the volley of rifle fire, then elevation and subsidence mechanical platform is adjusted, the close second surface material (2) of first surface material (1) also forms liquid bridge, after crosslinking curing, obtain irregular microgel array.
9. according to the irregular microgel preparation method based on liquid bridge phenomenon in claim 1-5 described in any one, it is characterized in that: when preparation has the irregular microgel of inner gradient, first surface material (1) and second surface material (2) drip hydrogel precursor drop (3) respectively, and cell containing variable concentrations or heterogeneity in the hydrogel precursor drop (3) on first surface material (1) and the hydrogel precursor drop (3) on second surface material (2) and/or chemical substance; Then adjust elevation and subsidence mechanical platform, make first, second surfacing (1,2) close to each other and form liquid bridge, after crosslinking curing, obtaining the irregular microgel that inside has cell gradient, chemical gradient and/or hardness gradient.
10. according to the irregular microgel preparation method based on liquid bridge phenomenon in claim 1-5 described in any one, it is characterized in that: simulate by setting up the shape of mathematical model to the irregular microgel of preparation,
Wherein z is the vertical direction coordinate of the interface each point of liquid bridge, the axial coordinate that R (z) is z, R is writing a Chinese character in simplified form of R (z), Δ P be liquid bridge interface inside and outside pressure difference, γ is the surface tension coefficient of liquid bridge, and ρ is the density of liquid bridge, g is gravity constant, by gal the Liao Dynasty's above-mentioned equation of golden finite element method and the boundary condition of interface at two-end-point place of liquid bridge, (R (z) z) is the pattern of the irregular microgel of simulation to the numerical solution of trying to achieve.
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| DK2625502T3 (en) * | 2010-10-06 | 2018-12-17 | Biocare Medical Llc | Method and system for efficient processing of biological samples |
| CN102344115B (en) * | 2011-09-28 | 2015-04-15 | 清华大学 | Micronscale/nanoscale connection method based on dip-pen principle |
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