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WO2001086037A1 - Appareil de cristallogenese et procede de cristallogenese - Google Patents

Appareil de cristallogenese et procede de cristallogenese Download PDF

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Publication number
WO2001086037A1
WO2001086037A1 PCT/JP2001/003782 JP0103782W WO0186037A1 WO 2001086037 A1 WO2001086037 A1 WO 2001086037A1 JP 0103782 W JP0103782 W JP 0103782W WO 0186037 A1 WO0186037 A1 WO 0186037A1
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WO
WIPO (PCT)
Prior art keywords
region
solution
dielectric
solid member
crystal
Prior art date
Application number
PCT/JP2001/003782
Other languages
English (en)
Japanese (ja)
Inventor
Shigeru Inoue
Akira Sanjoh
Koji Akioka
Original Assignee
Sumitomo Metal Industries, Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sumitomo Metal Industries, Ltd. filed Critical Sumitomo Metal Industries, Ltd.
Publication of WO2001086037A1 publication Critical patent/WO2001086037A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C30—CRYSTAL GROWTH
    • C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
    • C30B7/12—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by electrolysis
    • C—CHEMISTRY; METALLURGY
    • C30—CRYSTAL GROWTH
    • C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
    • C30B29/10—Inorganic compounds or compositions
    • C30B29/12—Halides
    • C—CHEMISTRY; METALLURGY
    • C30—CRYSTAL GROWTH
    • C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
    • C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions

Definitions

  • the present invention relates to an apparatus for growing crystals of a necessary substance, and more particularly to an apparatus applied to crystallization of various biopolymers such as proteins and enzymes.
  • Crystallization of biological macromolecules such as proteins is carried out in the same manner as in the case of low molecular weight compounds such as ordinary inorganic salts, by removing the solvent from water or a non-aqueous solution containing the macromolecules so that they become supersaturated and crystallized. It is fundamental to grow.
  • Typical methods for this include a batch method, a dialysis method, and a gas-liquid phase diffusion method, which are properly used depending on the type, amount, and properties of the sample.
  • FIG. 1A and 1B schematically show the hanging drop method and the sitting drop method included in the gas-liquid phase diffusion method.
  • a mother liquor 221 containing a biomolecule to be crystallized is dripped in a closed container 220 containing a precipitant 222.
  • a mother liquor 221 containing a biopolymer to be crystallized is placed on a plate 233 in a closed container 230.
  • the precipitant 222 is contained in another container 231 in the closed container 230. In these methods, equilibrium is slowly established by evaporation of the precipitant and volatile components in the mother liquor.
  • An object of the present invention is to provide an apparatus capable of promoting crystallization of a biopolymer. Specifically, an object of the present invention is to reduce the influence of convection in a solution due to the effect of gravity on the crystallization of various biopolymers and biological tissues mainly composed of biopolymers. And a device capable of controlling nucleation.
  • a further object of the present invention is to provide an apparatus capable of suppressing or controlling the mass production of microcrystals and obtaining a large crystal capable of X-ray structure analysis. It is a further object of the present invention to provide an apparatus for enabling crystallization with a small amount of a biopolymer solution.
  • an apparatus for growing crystals of a biopolymer contained in a solution comprises: a solid member having a surface for growing crystals in contact with a solution; a solution and a solid member in contact with the solution; and a direction from the solution to the solid member or from the solid member. Means for applying an electric field in a direction to the solution.
  • at least a portion of the solid member that contacts the solution is formed of a dielectric.
  • the solid member has at least a first region and a second region that are in contact with the solution via the dielectric and are adjacent to each other, and when a predetermined electric field is applied through a means for applying an electric field.
  • the capacitance per unit area of the first region is different from the capacitance per unit area of the second region, so that either the surface of the first region or the surface of the second region is different. It promotes crystal growth more than the other.
  • the solid member can be composed of a plurality of types of dielectrics, and the dielectric in the first region and the dielectric in the second region can have different dielectric constants from each other.
  • the solid member may be a combination of a semiconductor and one or more dielectrics, and the dielectric may be laminated on the semiconductor.
  • the dielectric in the first region and the dielectric in the second region have different relative dielectric constants from each other. Can be.
  • the solid member is composed of a semiconductor having a different conductivity type and a 1 '
  • it can be a combination with two or more kinds of dielectrics, and the dielectrics can be laminated on a semiconductor.
  • the semiconductor forming the first region and the semiconductor forming the cable 2 region can be of different conductivity types.
  • the device according to the invention further comprises an electrically insulating enclosure formed on the solid member for retaining the solution on the first and second regions.
  • the device according to the present invention can have a structure in which one of the first region and the second region protrudes from the solution more than the other.
  • the means for applying an electric field consists of a pair of electrodes which respectively contact the solution and the solid member.
  • one of the surface of the first region and the surface of the second region can be smaller than the other. In that case, crystal growth can be promoted on the surface of the region having the smaller area.
  • the device according to the present invention is a device for growing a crystal of a biopolymer contained in a solution, comprising: a solid member having a surface on which a crystal is grown by contacting the solution; and a solid member.
  • An enclosure wall provided on the solid member to hold the solution on the surface of the solid member, and an electrode attached to the enclosure wall, at least a portion of the solid member surrounded by the enclosure wall is formed of a dielectric.
  • the dielectric has at least a first dielectric and a second dielectric, and the first dielectric and the second dielectric have different dielectric constants from each other.
  • a method for growing a crystal of a biopolymer contained in a solution using the above-described apparatus comprises the steps of: holding a solution containing a biopolymer on a solid member; and applying an electric field to the solution and the solid member in contact with the solution in a direction from the solution to the solid member or from the solid member to the solution.
  • the growth of biomolecular crystals is promoted more than either one of the surface of the first region and the surface of the second region.
  • the present invention also provides another method for growing crystals of a biopolymer contained in a solution using the above-described apparatus.
  • the method comprises the steps of: A step of holding a solution containing a biopolymer on a member, a step of applying a voltage to the electrodes of the device to generate electric charges on the surfaces of the first dielectric and the second dielectric, Maintaining contact between the surface of the charged first dielectric and the surface of the second dielectric and the solution, wherein the surface of the first dielectric or the surface of the second dielectric is provided. In either case, the growth of the crystal of the biopolymer is promoted more than the other.
  • FIG. 1A and 1B are schematic diagrams showing a conventional crystal growth apparatus.
  • FIG. 2 is a schematic sectional view showing a specific example of the device according to the present invention.
  • FIG. 3 is a schematic diagram showing a state in which biopolymers to be crystallized gather in the first region in the apparatus shown in FIG.
  • FIG. 4 is a schematic sectional view showing another embodiment of the device according to the present invention.
  • FIG. 5 is a diagram showing the relationship between capacitance and voltage for the device shown in FIG.
  • FIG. 6 is a schematic sectional view showing a solid member of the device according to the present invention.
  • FIG. 7 is a schematic sectional view showing another solid member of the device according to the present invention.
  • FIG. 8 is a schematic sectional view showing a further solid component of the device according to the invention.
  • FIG. 9 is a schematic sectional view showing another solid member of the device according to the present invention.
  • FIG. 10 is a schematic diagram showing a state in which the biopolymer to be crystallized in the device according to the present invention gathers in the protruding first region.
  • FIG. 11 is a schematic diagram showing how a biopolymer to be crystallized is attracted to an electrode in the device according to the present invention.
  • FIG. 12A is a schematic sectional view showing another specific example of the device according to the present invention
  • FIGS. 12B and 12C are schematic sectional views of electrodes of the device.
  • FIG. 13 is a schematic view showing a state in which a crystal grows in the narrowed first region in the device according to the present invention.
  • FIG. 14 is a schematic diagram showing patterns of the first and second regions used in the device according to the present invention.
  • FIG. 15 is a schematic diagram showing another pattern of the first and second regions used in the device according to the present invention.
  • FIG. 16 shows another pattern of the first and second regions used in the device according to the invention. It is a schematic diagram which shows a turn.
  • FIG. 17 is a schematic plan view showing a further specific example of the device according to the present invention.
  • FIG. 2 shows an example of the device according to the present invention.
  • the crystal growth apparatus 10 has a pair of opposing electrodes 11a and 11b, and a solid member 12 provided on the electrode 11a.
  • the device 10 has a structure 15 for securely damping the flow of the solution 14 containing the biopolymer to be crystallized on the solid member 12, and the structure 15 is an electric device.
  • the structure 15 is typically an electrically insulating enclosure formed on the solid member 12.
  • the electrode 11 b contacts the solution 14 held on the solid member 12.
  • An electric field is generated by applying a voltage between the electrodes 11a and 11b.
  • the direction of the electric field is the direction from the solution 14 to the solid member 12 or the opposite direction.
  • the solid member 12 has a first region 12a and a second region 12b adjacent thereto.
  • the first region 12a has a surface area in contact with the solution 14 smaller than that of the second region 12b, and is arranged so as to be surrounded by the second region 12b.
  • the first region 12a is made of a first dielectric
  • the second region 12b is made of a second dielectric having a dielectric constant different from that of the first dielectric. Therefore, the capacitance per unit area in the first region 12a is different from the capacitance per unit area in the second region 12b.
  • the surface of the first region 12a agglutinates biomolecules such as proteins on the surface of the solid member 12 in contact with the solution 14 by stronger electric action, and more strongly adsorbs them. It is an area to be made.
  • the surface of the second region 12b is a region that does not adsorb much biomolecules such as proteins. This is achieved by making the capacitance per unit area of the first region larger than the capacitance per unit area of the second region, as described below. This is realized by making the relative permittivity of the second dielectric material larger than that of the second dielectric.
  • the capacitance per unit area of the first dielectric is C 1 and its relative permittivity is ⁇ 1
  • the capacitance per unit area of the second dielectric is C 2 and its relative permittivity is ⁇ 2
  • C2 ( £ 1 / / £ 2)
  • the applied charge voltage will cause a different charge density in each region.
  • C 1 is sufficiently larger than C 2 growing. Therefore, when a predetermined voltage Vg is applied between the electrode 11a and lib in the device 10 shown in FIG. 2, for example, as schematically shown in FIG. A high density of charges can be generated on the surface of the first region 12a.
  • Vg a predetermined voltage
  • the electrode 11 a is positive and the electrode 11 b is negative.
  • a high-density positive charge can be generated on the surface of the first region 12a, and the molecule 16 can be selectively adsorbed thereon. By this selective adsorption, crystal nuclei can be formed on the first region 12a, and crystal growth can be advanced. If the biopolymer to be crystallized is positively charged, a high-density negative charge may be generated in the first region 12a by applying a reverse electric field. As described above, in the device according to the present invention, by applying a voltage, the charge density generated in the first region and the charge density generated in the second region are positively differentiated, and the charged biopolymer is converted into a specific region. Can be absorbed and assembled.
  • the first region and the second region may each be formed from a plurality of materials. Also in this case, by making the electric capacity per unit area of the first region different from the electric capacity per unit area of the second region, the charge density generated in each region can be made different.
  • the capacitance C 1 of the first region is the capacitance C d 1 of the dielectric and the capacitance of the semiconductor near the dielectric (capacity of the depletion layer) C s 1 Can be obtained as a combined capacitance connected in series.
  • the capacitance C 2 of the second region can be obtained as a combined capacitance of the capacitance C d 2 of the dielectric and the capacitance C s 2 of the semiconductor.
  • FIG. 4 shows a specific example of the device according to the present invention using a semiconductor.
  • the crystal growth apparatus 40 includes a semiconductor substrate 42 such as a silicon substrate, a first dielectric layer 43 a and a second dielectric layer 43 b formed thereon, and both dielectric layers 43. It has an electrode 41 that contacts the solution 44 held on a and 43b. Adjacent first dielectric layers 43a 'and second dielectric layers 43b are provided on the same substrate 42 at substantially the same height. If necessary, the device 40 may be used to reliably block the flow of the solution 44 containing the biopolymer to be crystallized on the first dielectric layer 43a and the second dielectric layer 43b. It has a structure 45, and the structure 45 is made of an electrically insulating material.
  • Structure 45 is typically an electrically insulating enclosure.
  • the semiconductor substrate 42 also has a function as an electrode, and an electric field is generated by applying a voltage between the semiconductor 42 and the electrode 41.
  • the direction of the electric field is the direction from the solution 44 to the semiconductor substrate 42 or the opposite direction.
  • the first region 46a is formed by the first dielectric layer 43a and the portion of the semiconductor substrate 42 thereunder, and the second dielectric layer 43b and the lower half thereof are formed.
  • the second region 46 b is formed by the portion of the conductive substrate 42.
  • the first region 46a is arranged such that the area of the surface in contact with the solution 44 is smaller than that of the second region 46b, and is surrounded by the second region 46b. Since the first dielectric layer 43a and the second dielectric layer 43b have different relative dielectric constants, when a predetermined voltage is applied, as described later, a unit of the first region is used.
  • the capacitance C 1 per area is different from the capacitance C 2 per unit area of the second region, and the values of C 1 and C 2 change depending on the applied voltage.
  • the surface of the first region 46a is a region in which biopolymers such as proteins are aggregated by stronger electric action and are more strongly adsorbed.
  • the surface of the second region 46b is a region that does not adsorb much biomolecules such as proteins. this is, This is realized by making the relative permittivity of the first dielectric layer 43a larger than the relative permittivity of the second dielectric layer 43b.
  • a protein solution electrolytic solution
  • Vg voltage
  • the capacitance per unit area of the first dielectric layer is C d 1
  • its relative permittivity is ⁇ 1
  • the capacitance per unit area of the second dielectric layer is C d 2
  • the rate is ⁇ 2
  • C d 2 ( ⁇ 2 / ⁇ 1)
  • C d 1 the semiconductor substrate is an n-type silicon substrate
  • the C 1 -V characteristics of the first region and the C 2 -V characteristics of the second region are as shown in FIG. 5, for example.
  • C 1 is the combined capacitance of the capacitance C d 1 of the dielectric layer in the first region and the capacitance C s 1 of the semiconductor present in the first region
  • C 2 is the capacitance of the dielectric layer in the second region.
  • the capacitance of a semiconductor changes according to the applied voltage because the state of the depletion layer (width of the depletion layer) generated near the dielectric of the semiconductor changes according to the value of the applied voltage. Therefore, as shown in FIG. 5, the combined capacitance of the first region and the combined capacitance of the second region are not constant but change with various voltages. In this way, by combining the dielectric and the semiconductor, a region where the capacitance can be changed according to the value of the voltage can be formed.
  • the combined capacitance C1 of the first region is approximately equal to the dielectric layer capacitance Cd1 of the first region.
  • the combined capacitance C2 in the second region is approximately equal to the dielectric layer capacitance Cd2 in the second region. Therefore, in the case of Vg * VO or V3 * Vg, the capacitance difference between both regions is equal to the capacitance difference between the dielectric layers.
  • the capacitance difference between the two regions can be adjusted according to the value of Vg.
  • the charge density generated on the surface of each region can be made different, and the charge density between the first region and the second region can be adjusted by adjusting the applied voltage within an appropriate range.
  • the difference can be adjusted.
  • the capacitance can be changed by changing the voltage, and the difference in charge density between the two regions can be changed. This means that the same equipment can be used to change the crystallization conditions and select more appropriate crystallization conditions.
  • different dielectric layers 61 and 62 may be formed at the same height on a substrate 60 such as a semiconductor substrate as shown in FIG. 6, or as shown in FIG.
  • the dielectric layer 72 forming one region may be formed so as to protrude from the dielectric layer 71 forming the second region.
  • the capacitance is proportional to the relative permittivity of the dielectric and is inversely proportional to the thickness of the dielectric, the capacitance per unit area of the first region is sufficiently larger than that of the second region. In order to achieve this, not only the permittivity but also the thickness must be appropriately selected.
  • the conductivity type of the semiconductor in the first region may be different from the conductivity type of the semiconductor in the second region.
  • a region 83 made of p-type silicon is formed on a part of the n-type silicon substrate 81, and a dielectric layer 82 is formed thereon.
  • the first region 86a includes a p-type Si, a portion of the dielectric layer 82 thereon, and a portion of the n-type Si below the p-type Si
  • the second region 86b includes The remaining n-type Si portion and the portion of the dielectric layer 82 thereon are formed. The same dielectric is used for the first and second regions.
  • the first region 96a has a protruding shape.
  • the n-type silicon substrate 91 projections 93 made of p-type silicon are formed, which are covered with a dielectric layer 92.
  • the first region 96 a is composed of a p-type Si and a portion of the dielectric layer 92 thereon and an n-type Si below the p-type Si, and the second region 96 b The remaining n-type Si portion and the portion of the dielectric layer 92 thereon are formed.
  • the same dielectric is used for the first and second regions.
  • the first region has a structure protruding from the second region.
  • the CI-V characteristics in the first region are different from the C2-V characteristics in the second region. This is because the conductivity type of the semiconductor is different between the two regions. Therefore, when a voltage is applied between the solution and the back surface of the substrate, as in the case where the material of the dielectric is changed as described above, the value of the voltage per unit area of the first region can be selected by appropriately selecting the value of the voltage.
  • the capacitance and the capacitance per unit area of the second region can be made different, so that the charge density generated on the surface of the first region and the capacitance of the second region The charge density generated on the surface can be different.
  • the voltage applied to the device according to the present invention is preferably a DC voltage such that the polarity of the electrode in contact with the solution is the same as the charge polarity of the biopolymer to be crystallized contained in the solution.
  • a negative voltage is applied to the electrode that contacts the solution.
  • the type, thickness, and applied voltage of the dielectric in each region are selected such that the capacitance per unit area of the first region is larger than the capacitance per unit area of the second region. With this selection, as schematically shown in FIG. 10, the charge density generated on the surface of the first region 102 becomes larger than the charge density generated on the surface of the second region 102.
  • the protein molecules 104 can be more strongly aggregated and adsorbed on the surface of the first region.
  • the magnitude of the voltage is desirably selected, for example, in the range of V0 to V3 shown in FIG. For example, it can be selected in the range of 15V to 0V.
  • the protein molecule 104 is connected to the electrode 101 as schematically shown in FIG. It is thought that the protein molecule 104 cannot move to the first region and cannot aggregate into the first region 102.
  • the applied voltage may be an AC voltage obtained by biasing a positive or negative DC voltage.
  • the voltage can be applied at the appropriate intensity and for the required time.
  • the voltage may be applied until crystal nuclei are formed, and the voltage application may be stopped after the nuclei are formed.
  • a structure that blocks the flow of the solution is created as shown in Fig. 2 or Fig. 4, and the inside of the structure
  • the electrodes can be arranged to cover the structure. Instead, a hole may be provided in a part of the electrode, and after the electrode is placed on the structure, the biopolymer solution may be supplied from the hole until it comes into contact with the electrode.
  • the biopolymer solution may be held on the substrate by surface tension, and the electrode may be held in contact with the solution.
  • an electrically insulating enclosure wall 1 25 is provided so as to surround the surface of the first area 1 26a and the surface of the second area 1 26b, Fence
  • the electrode 125 is attached to the inner surface of the electrode 125 in contact with the solution 124.
  • a second dielectric film 123b is formed on a large part of the semiconductor substrate 122, and the first dielectric film 123a is formed only in a part thereof in a predetermined pattern. Have been.
  • the first dielectric film 123a is formed so as to protrude from the surface of the second dielectric film 123b (to have a convex part).
  • An enclosure wall 125 made of an electrically insulating material is formed on the second dielectric film 123 b, and an electrode 121 in contact with the solution 124 is provided on the enclosure wall 125. Further, an electrode 127 for connection to a power supply is arranged also on the back surface of the semiconductor substrate 122.
  • the electrode 121 can be formed by using a general semiconductor integrated circuit manufacturing technique such as a sputtering method.
  • the electrode 121 has, for example, a ⁇ r layer 121 a with a thickness of about 1 001 111 and a thickness of about 20011111 as shown in FIG. It can have a two-layer structure consisting of a t-layer 12 1 b force.
  • the electrode 127 has a layer 501 a having a thickness of about 501 111, a layer 127 b having a thickness of about 30011111, and a layer 127 b having a thickness of about 50! ! ! ! ! It can have a three-layer structure consisting of the layer ⁇ 27 c.
  • the first region preferably has a convex portion as shown in FIG. 7, FIG. 9 or FIG. If crystals are grown on the projections, the crystals can be easily separated and collected from the upper surface of the projections having a relatively small area.
  • the projection has a width such that the biopolymer crystal protrudes and grows. That is, it is desirable that the width of the projection is smaller than the diameter of the crystal to be obtained.
  • the surface 132a on which the biopolymer is to be strongly electrostatically adsorbed is provided on the protruding portion.
  • the protrusions are provided so as to protrude from the surface 132 b where the biopolymer is not easily adsorbed.
  • the surface on which the organic molecules are to be adsorbed is provided on the projection. Usually, this surface is provided on top of the protrusion.
  • 132a has a width d such that the biopolymer crystal 134 can grow out of the surface 132a. That is, the width is smaller than the size (diameter) of the crystal to be formed.
  • the width of the projection surface By setting the width of the projection surface in this way, the contact area between the grown crystal and the projection surface is limited.
  • the convex part table The surface has limited adsorption power to crystals, making it easier to take out grown crystals.
  • the width is set in an appropriate range according to the molecular species to be crystallized.
  • crystals having a diameter of about 0.2 to about 0.5 mm are generally suitable for X-ray crystal structure analysis, so a width smaller than that diameter, for example, a width of 10 to 200 in Preferably, 10 to:
  • the width of L 0 ⁇ is more preferable.
  • the arrangement pattern of the region where crystallization is to be suppressed (second region) and the region where crystallization is to be promoted (first region) is arbitrary.
  • second region an arrangement in which the first region 141 is surrounded by the second region 142 is preferably used.
  • first region 151 having a predetermined width may be arranged at predetermined intervals with respect to the second region 152, as shown in FIG.
  • the first region 161 having a predetermined shape and area may be arranged in a matrix at a predetermined distance from the second region 162.
  • the surface of the second regions 142, 152, 162 is significantly wider than the surface of the first regions 141, 151, 161.
  • These structures can be formed using general semiconductor integrated circuit manufacturing techniques such as a film forming technique, a photolithography technique, and an etching technique.
  • the dielectric used in the present invention include, for example, aluminum oxide (specific one ⁇ 1 2 0 3, yA 1 2 0 3), titanium oxide, metal acid I arsenide materials such as copper oxide, aluminum nitride, nitride titanium , Tungsten nitride, tantalum nitride, metal nitrides such as TaSiN and WSin, and semiconductor compounds (oxides and nitrides) such as silicon oxide and silicon nitride.
  • Preferred semiconductors for use in the present invention include silicon, gallium, arsenic (GaAs), gallium phosphorus (GaP), and the like.
  • the second dielectric film which covers the majority of the substrate surface can be used S i 0 2, S i 3 in the first dielectric film to form a protrusion N 4 and A 1 2 ⁇ 3 can be used.
  • the dielectric constant of the S i 0 2 is the relative dielectric constant of about 3.
  • S i 3 N 4 is a dielectric constant of about 7.
  • a 1 2 0 3 is about 9.5.
  • a solution in which the target protein is dissolved is placed at a predetermined position (dam or enclosure wall) of the apparatus.
  • an appropriate voltage is applied between the electrodes of the device for the required time. For example, a voltage is applied until crystal nuclei are formed.
  • the state of crystal growth can be observed on a closed glass container or with a microscope.
  • the precipitant may be placed in a separate container and sealed with the apparatus of the present invention, or a storage section 172 for storing the precipitant in the semiconductor substrate 17 1 as shown in FIG. 17 may be formed.
  • the precipitant 173 may be stored therein and the entire surface may be covered with a glass lid 174.
  • Such a reservoir can be easily prepared by anisotropically wet-etching the silicon substrate with a K ⁇ H etching solution or the like.
  • a biopolymer is selectively adsorbed to the surface of a specific area of a solid member by electric action, thereby reducing the influence of convection on the biopolymer. Nucleation can be stabilized. Further, according to the present invention, the crystallization conditions can be easily changed by changing the applied voltage.
  • the present invention can be used for purifying or crystallizing various biopolymers, particularly biopolymer electrolytes, in the pharmaceutical industry, the food industry, and the like.
  • the present invention is particularly preferably applied to purify or crystallize proteins such as enzymes and membrane proteins, polypeptides, peptides, polysaccharides, nucleic acids, and complexes and derivatives thereof.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Materials Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne un appareil permettant la cristallisation d'un biopolymère. Un appareil (10) de cristallogenèse de l'invention comprend une substance solide (12) mise en contact avec une solution (14) contenant un biopolymère, et des électrodes (11a, 11b) servant à produire un champ électrique dirigé de la solution (14) à la substance solide (12) ou de la substance solide (12) à la solution (14). La substance solide (12) présente au moins des première et seconde zones (12a, 12b) mises en contact avec la solution (14) par l'intermédiaire d'un corps diélectrique. La densité de charge du corps diélectrique diffère de la première zone (12a) à la seconde zone (12b) lorsqu'un champ électrique prédéterminé est produit en passant par les électrodes (11a, 11b). De ce fait, si une charge supérieure est produite dans l'une des première ou seconde zones (12a, 12b) à l'application d'une tension, un biopolymère chargé se trouvant dans la solution (14) est absorbé de manière sélective jusqu'à la zone ayant la densité de charge la plus élevée, et est cristallisé.
PCT/JP2001/003782 2000-05-12 2001-05-01 Appareil de cristallogenese et procede de cristallogenese WO2001086037A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000-140192 2000-05-12
JP2000140192A JP2001322900A (ja) 2000-05-12 2000-05-12 結晶成長装置

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WO2001086037A1 true WO2001086037A1 (fr) 2001-11-15

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FR2837400A1 (fr) * 2002-03-25 2003-09-26 Centre Nat Rech Scient Dispositif de cristallisation d'une macromolecule chargee en solution
WO2004081264A1 (fr) * 2003-03-14 2004-09-23 Reijonen, Mika, Tapio Procede et dispositif destines a la cristallisation d'un ou plusieurs composes
WO2010100847A1 (fr) * 2009-03-03 2010-09-10 独立行政法人国立高等専門学校機構 Dispositif pour la cristallisation d'un biopolymère, cellule de solution pour la cristallisation d'un biopolymère, procédé pour le contrôle de l'alignement d'un biopolymère, procédé pour la cristallisation d'un biopolymère et cristal de biopolymère

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FI20050812A0 (fi) * 2005-08-10 2005-08-10 Mika Tapio Reijonen Menetelmä ja laite sähkökentän käyttämisestä aineen tai aineiden kiteytymisen hallitsemiseksi
CN108164059A (zh) * 2018-01-30 2018-06-15 浙江工业大学膜分离与水处理协同创新中心湖州研究院 一种膜法处理煮茧废水及回收丝胶蛋白的方法

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2837400A1 (fr) * 2002-03-25 2003-09-26 Centre Nat Rech Scient Dispositif de cristallisation d'une macromolecule chargee en solution
WO2003080210A1 (fr) * 2002-03-25 2003-10-02 Centre National De La Recherche Scientifique (Cnrs) Dispositif de cristallisation d'une macromolecule chargee en solution
WO2004081264A1 (fr) * 2003-03-14 2004-09-23 Reijonen, Mika, Tapio Procede et dispositif destines a la cristallisation d'un ou plusieurs composes
WO2010100847A1 (fr) * 2009-03-03 2010-09-10 独立行政法人国立高等専門学校機構 Dispositif pour la cristallisation d'un biopolymère, cellule de solution pour la cristallisation d'un biopolymère, procédé pour le contrôle de l'alignement d'un biopolymère, procédé pour la cristallisation d'un biopolymère et cristal de biopolymère
JP5626914B2 (ja) * 2009-03-03 2014-11-19 独立行政法人国立高等専門学校機構 生体高分子の結晶化装置、生体高分子の結晶化溶液セル、生体高分子の配向制御方法、生体高分子の結晶化方法、及び生体高分子の結晶
US8945303B2 (en) 2009-03-03 2015-02-03 Institute Of National Colleges Of Technology, Japan Device for crystallizing biopolymer, cell of solution for crystallizing biopolymer, method for controlling alignment of biopolymer, method for crystallizing biopolymer and biopolymer crystal

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