CN108103583A - Low defect albumen monocrystal culture systems based on single drop microenvironment precision control - Google Patents
Low defect albumen monocrystal culture systems based on single drop microenvironment precision control Download PDFInfo
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- CN108103583A CN108103583A CN201711475183.2A CN201711475183A CN108103583A CN 108103583 A CN108103583 A CN 108103583A CN 201711475183 A CN201711475183 A CN 201711475183A CN 108103583 A CN108103583 A CN 108103583A
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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
- C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
- C30B29/54—Organic compounds
- C30B29/58—Macromolecular compounds
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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
- C30B7/08—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by cooling of the solution
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Abstract
The invention discloses a kind of low defect albumen monocrystal culture systems based on single drop microenvironment precision control, including load sample pond, sampling system, temperature control system, externally-applied magnetic field component, optical element group a, optical element group b and transmission and electric power system, the load sample pond is embedded by load sample pond outer wall and optical glass to be formed, the outside that the optical glass embeds is provided with load sample pond outer wall, and load sample pond outer wall is embedded with optical glass and is an integral structure, the top of load sample pond outer wall is fixedly installed load sample pond upper cover by hinge, the center position of load sample pond upper cover is provided with sample holes, the load sample pond is internally provided with load sample passage；The sampling system is made of fixing bracket, converter and six identical sample arms, one end of the firm banking is provided with cable buncher b, the present invention is scientific and reasonable for structure, safe to use convenient, realizes the full-automatic process control of the two-step crystallization method carried out along secondary nucleation path.
Description
Technical field
The invention belongs to structure biology, crystallography and X-ray crystal diffraction technical fields, and in particular to one kind is based on
The low defect albumen monocrystal culture systems of single drop microenvironment precision control.
Background technology
Structure biology is to illustrate vital movement rule based on the Accuracy Space structure of living matter and its movement
With the subject of biological phenomena essence, core content is research protein and its compound, assembly and the cell being consequently formed
Three-dimensional structure, movement and the interaction of kinds of ingredients and they between natural biological function and abnormal pathologic phenomenon
Relation.This Discipline determines that structure biology will be in strategic key position in the genome times afterwards comprehensively, is life
One of most challenging Disciplinary Frontiers in science.Protein molecular is the most important research object of structure biology, parses egg
White structure has a multiple technologies means at present, and wherein precision and reliability highest, most widely used still spread out for X-ray crystal
Penetrate method.The crystallization process of protein molecule is generally divided into three phases：Nucleation process, crystal growth and growth stop；It uses at present
Mainly there is following four in the method for albumin crystal culture：Evaporation and diffusion crystallisation, stand still for crystals in batches method, equilibrium dialysis and
Crystal seed is inoculated with or repeated inoculation method.
However, above method can not realize the real-time perception to protein crystal process and state, can not to nucleation rate,
Crystal growth rate is accurately controlled, that is, is merely given as primary condition and result is waited to generate and cannot have to process naturally
The real-time intervention of effect, therefore crystalline quality can not be efficiently controlled, the crystal quality of gained has very big randomness, is as a result difficult to
It is accurate to repeat, it is also difficult to obtain the big granularity suitable for X-ray crystal diffraction, the albumen monocrystal of low-defect-density, be unfavorable for
The development of related discipline research.
The content of the invention
It is an object of the invention to provide a kind of low defect albumen monocrystal trainings based on single drop microenvironment precision control
The system of supporting, can not to solve the real-time perception mentioned above in the background art that can not be realized to protein crystal process and state
Nucleation rate, crystal growth rate are accurately controlled, crystalline quality can not be efficiently controlled, obtained crystal quality has
As a result very big randomness is difficult to accurately repeat, it is difficult to obtain the big granularity suitable for X-ray crystal diffraction, low-defect-density
Albumen monocrystal and be unfavorable for related discipline research development the problem of.
To achieve the above object, the present invention provides following technical solution：It is low scarce based on single drop microenvironment precision control
Albumen monocrystal culture systems are fallen into, including load sample pond, sampling system, temperature control system, externally-applied magnetic field component, optical element group
A, optical element group b and transmission and electric power system, the load sample pond is embedded by load sample pond outer wall and optical glass to be formed, the light
It learns the outside that glass embeds and is provided with load sample pond outer wall, and load sample pond outer wall is embedded with optical glass and is an integral structure, it is described
The top of load sample pond outer wall is fixedly installed load sample pond upper cover by hinge, and the center position of load sample pond upper cover is provided with
Sample holes, the load sample pond are internally provided with load sample passage, and the sampling system is identical by fixing bracket, converter and six
Sample arm composition, one end of the firm banking is provided with cable buncher b, and the upper surface of the firm banking is fixed by nut
Fixing bracket is provided with, described support bracket fastened one end is provided with converter, and there are six the vertical connections in lower section of the converter
Sample arm, and the sample arm is symmetrical in regular hexagon, the sample arm is by glass syringe needle microsyringe, micro-injection
Pump, guide rail slide block lifter are formed, and the position residing for a sample arm farthest apart from fixing bracket in six sample arms
Referred to as working position is put, on the sample arm in working position on the glass syringe needle face load sample pond of glass syringe needle microsyringe
The sample holes at lid center；The temperature control system is by Pt-100 micron order standard platinum resistances temperature sensor, aluminium foil-carborundum
It is Ceramic Composite thin layer magnetic screen shell, heat-insulated inorganic insulation shell, pressure sensitive low noise pre-amplification circuit, digital control
Device, silicon controlled toggle, silicon-controlled actuator, infrared lamp common-base, infrared lamp and protection shell e compositions, the aluminium foil-carbon
Heat-insulated inorganic insulation shell is provided on the outside of SiClx Ceramic Composite thin layer magnetic screen shell, the heat-insulated inorganic insulation shell
Lower section is provided with pressure sensitive low noise pre-amplification circuit, and the lower section of the pressure sensitive low noise pre-amplification circuit is set
There is digitial controller, silicon controlled toggle is provided with below the digitial controller, the one side of the silicon controlled toggle is set
It is equipped with silicon-controlled actuator, the bottom of the silicon-controlled actuator is provided with infrared lamp common-base, and described four identical red
Outer lamp is divided into two groups, is wired to infrared lamp common-base, every group of two infrared lamps are staggered relatively and lamp cap in
Axle position is on same level straight line, and the lamp cap axis of two groups of infrared lamps is orthogonal in same level, each infrared lamp lamp cap
Towards the intersection point of two axis and equal with the distance of the intersection point of two axis, after the infrared lamp lamp cap axis spider rotates 45 °
It is overlapped with the axis spider of optical element group a and optical element group b, i.e., two axis spiders stagger 45 °, the circuit a
High-precision adjustable power source is connected to by cable concentrator with circuit b, passes to steady current, the circuit c is connected to by cable concentrator
Computer；The optical element group a is a set of laser particle size analyzer component, by laser, microcobjective, pinhole blind, standard
Straight mirror, electronic slide block guide rail, fourier transform lens, ccd image sensor a, A/D converter a, protection shell a, protection shell b and
Data cable connector forms, and the inside of the protection shell a is provided with electronic slide block guide rail by being fixed, the electronic sliding block
Collimating mirror is provided with by engaging on the inside of guide rail, the one side of the collimating mirror is provided with microcobjective, the microcobjective and standard
Pinhole blind is provided between straight mirror, the microcobjective, pinhole blind, collimating mirror can be under the drivings of electronic slide block guide rail
Level is slided, and the one side of the microcobjective is provided with laser, and one end of the laser is provided with data cable connector, described
One end for being internally provided with A/D converter a, the A/D converter a of protection shell b is provided with data cable connector, the protection
The other end of shell b is provided with fourier transform lens, and the one side of the fourier transform lens is provided with ccd image sensor a；The light
It is a set of improved self-action abbe's refractometer component to learn element group b, and by white light source, light source runner, (center has slotted barrier
One runs through upper and lower vertical slots), rotation index glass, half paraboloid mirror, series connection narrow band fiber bragg grating dispersion compensator, lifting half
Lens, control circuit, ccd image sensor b, A/D converter b, protection shell c, protection shell d, data cable connector composition, institute
That states protection shell c is internally provided with light source runner, and one end of the light source runner is provided with white light source, the protection shell
D's is internally provided with control circuit, and rotation index glass is provided with above the control circuit, and the top of the rotation index glass is set
There is half paraboloid mirror, the one side of the half paraboloid mirror is provided with series connection narrow band fiber bragg grating dispersion compensator, and the series connection is narrow
One side with fibre-optical grating compensator with dispersion is provided with lifting pellicle mirror, and the one side of the lifting pellicle mirror is provided with ccd image
Sensor b, the one side of the ccd image sensor b are provided with A/D converter b；The transmission and electric power system are by each connecting line
Road, firm banking, cable concentrator, high-precision adjustable power source composition, and each connection circuit, firm banking, cable concentrator and high-precision
It spends between regulated power supply through conducting wire and data cable connection.
Preferably, load sample pond outer wall be opaque non-magnetic metal (not iron content, cobalt, nickel) material cylindrical structure, side
The protection shell a of face and optical element group a and optical element group b, protection shell b, protection shell c, protection shell d joints are
The lamp cap joint of four infrared lamps of round hole at 4, side and temperature control system is square perforate at 4, infrared lamp
Lamp cap axis spider overlaps after rotating 45 ° with the axis spider of optical element group a and optical element group b, i.e. two axis
Spider staggers 45 °, and the optical glass is embedded as optical glass material known to high transparency and refractive index, and surface is by transparent
Based superhydrophobic thin films coat；Its structure may be regarded as a diameter it is equal with load sample pond outer wall internal diameter, it is high with load sample pond outer wall in high phase
Deng cylinder cut out a diameter 2mm from axis, it is high with high equal cylinder in the outer wall of load sample pond, then from upper and lower two bottom surface difference
The geometry that the radius hemisphere equal with load sample pond outer wall inside radius obtains is cut out, optical glass embeds can be just
Pars intramuralis outside embedded load sample pond.
Preferably, the protection shell e be thickness 2mm by Dehydrogenation Annealing Process processing Mumetal (addition copper,
Nickeliferous 76% dilval of chromium) material, there is high permeability, can effectively shield externally-applied magnetic field, eliminate externally-applied magnetic field pair
Interference caused by its internal components works.
Preferably, the coated crust of all transmission lines is " insulating layer-aluminium foil-insulating layer " three layers of composite junction
Structure, wherein aluminum foil thickness is in more than 0.12mm.
Preferably, the half paraboloid mirror is the paraboloidal mirror of only half of the part of axis place above the horizontal plane,
Vertex is located at the center of circle of the left bottom surface of the cylindrical space inside protection shell d, axis and the cylinder inside protection shell d
The middle overlapping of axles in shape space；The only horizontal plane where axis that the lifting pellicle mirror is fixed on for one piece on miniature crane with
On half of part convex lens, the one side focus of lens falls just in CCD when lens component is risen to top by miniature crane
The sensing surface center of imaging sensor b.
Compared with prior art, the beneficial effects of the invention are as follows：The present invention is scientific and reasonable for structure, and high degree of automation makes
Use safe and convenient；The full-automatic process control of the two-step crystallization method carried out along secondary nucleation path is realized, first in unstable state
Nucleation, then make crystal further growth in metastable state by the real-time monitoring to system status and adds crystallization in whole process
The Real-time Feedback of the factors such as agent concentration, temperature, applied field strengths is added to regulate and control to realize to crystalline rate and crystallize the essence of process
Quasi- control, so as to obtain the high-quality protein monocrystal that granularity is big, defect concentrations in crystals is small in optimal conditions；It solves
Real-time sense to protein crystal process and state can not be realized by stating the existing albumin crystal cultural method proposed in background technology
Know, nucleation rate, crystal growth rate can not accurately be controlled, crystalline quality can not be efficiently controlled, obtained crystal
Quality has very big randomness, is as a result difficult to accurately repeat, it is difficult to obtain the big granularity, low suitable for X-ray crystal diffraction
The albumen monocrystal of defect concentration and be unfavorable for related discipline research development the problem of.
Description of the drawings
Fig. 1 is the structural diagram of the present invention；
Fig. 2 is that Fig. 1 shown devices of the present invention cross cuing open for load sample pond axis and the perpendicular where optical element group b axis
Face structure diagram；
Fig. 3 is that Fig. 1 shown devices of the present invention cross cuing open for load sample pond axis and the perpendicular where optical element group a axis
Face structure diagram；
Fig. 4 is the partial enlargement structural representation of optical module in Fig. 2 of the present invention；
In figure：1- firm bankings, 2- fixing brackets, 3- converters, 4- sample arms, 5- glass syringe needles microsyringe, 6-
Micro-injection pump, 7- guide rail slide blocks lifter, 8- positioning baffles, 9- embed guide rail slide block lifter, 10- guiding bars, 11- load samples
Pond outer wall, 12- optical glass embed, 13- load samples pond upper cover, 14- sample holes, 15- fixing buckles, 16- load samples passage, 17- albumen
Drop, 18- white light sources, 19- light sources runner, 20- protection shell c, 21- protection shell d, 22- data cable connector, 23- rotations
Index glass, 24- half paraboloids mirror, 25- control circuits, 26- series connection narrow band fiber bragg grating dispersion compensator, 27- liftings pellicle mirror,
28-CCD imaging sensor b, 29-A/D converter b, 30-Pt-100 micron order standard platinum resistances temperature sensor, 31- aluminium foils-
The preposition amplification electricity of the compound thin layer magnetic screen shell of silicon carbide ceramics, the heat-insulated inorganic insulation shells of 32-, 33- pressure sensitive low noises
Road, 34- digitial controllers, 35- silicon controlled toggles, the silicon-controlled actuators of 36-, 37- infrared lamps common-base, 38- cable bunchers
A, 39- protects shell e, 40- circuit a, 41- circuit b, 42- circuit c, 43- protection shell a, 44- protection shell b, 45- laser
The electronic slide block guide rail of device, 46-, 47- microcobjectives, 48- pinhole blinds, 49- collimating mirrors, 50- fourier transform lens, 51-CCD images
Sensor a, 52-A/D converter a, 53- infrared lamp, 54-Helmholtz coil a, 55-Helmholtz coils b, 56- high-precision
Regulated power supply, 57- cable concentrators, 58- cable buncher b, 59- slotted barriers.
Specific embodiment
Below in conjunction with the attached drawing in the embodiment of the present invention, the technical solution in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, those of ordinary skill in the art are obtained every other without making creative work
Embodiment belongs to the scope of protection of the invention.
It please refers to Fig.1, Fig. 2, Fig. 3 and Fig. 4, the present invention provides a kind of low defect based on single drop microenvironment precision control
Albumen monocrystal culture systems technical solution：Low defect albumen monocrystal training system based on single drop microenvironment precision control
System, including load sample pond, sampling system, temperature control system, externally-applied magnetic field component, optical element group a, optical element group b and biography
Defeated and electric power system, load sample pond are embedded by load sample pond outer wall and optical glass and formed, and the outside that optical glass embeds is provided with load
Sample pond outer wall, and load sample pond outer wall is embedded with optical glass and is an integral structure, the top of load sample pond outer wall is fixed by hinge
Load sample pond upper cover is provided with, the center position of load sample pond upper cover is provided with sample holes, and the load sample that is internally provided in load sample pond is led to
Road, sampling system are made of fixing bracket, converter and six identical sample arms, and one end of firm banking is provided with cable buncher
B, the upper surface of firm banking are fixedly installed fixing bracket by nut, and support bracket fastened one end is provided with converter, conversion
The lower section of device is connected vertically there are six sample arm, and sample arm is symmetrical in regular hexagon, and sample arm is micro by glass syringe needle
Injector, micro-injection pump, guide rail slide block lifter are formed, and a sample-adding farthest apart from fixing bracket in six sample arms
The location of arm is known as working position, and the glass syringe needle face of glass syringe needle microsyringe carries on the sample arm in working position
The sample holes at sample pond upper cover center；Temperature control system is by Pt-100 micron order standard platinum resistances temperature sensor, aluminium foil-carbonization
It is silicon Ceramic Composite thin layer magnetic screen shell, heat-insulated inorganic insulation shell, pressure sensitive low noise pre-amplification circuit, digital control
Device, silicon controlled toggle, silicon-controlled actuator, infrared lamp common-base, infrared lamp and protection shell e compositions, aluminium foil-carborundum
Heat-insulated inorganic insulation shell is provided on the outside of Ceramic Composite thin layer magnetic screen shell, the lower section of heat-insulated inorganic insulation shell is set
There is pressure sensitive low noise pre-amplification circuit, be provided with below pressure sensitive low noise pre-amplification circuit digital control
Device is provided with silicon controlled toggle below digitial controller, and the one side of silicon controlled toggle is provided with silicon-controlled actuator, can
The bottom of control silicon actuator is provided with infrared lamp common-base, and four identical infrared lamps are divided into two groups, are connected by conducting wire
To infrared lamp common-base, every group of two infrared lamps are staggered relatively and lamp cap axis is located on same level straight line, and two groups red
The lamp cap axis of outer lamp is orthogonal in same level, each infrared lamp lamp cap towards two axis intersection point and with the intersection point of two axis
Distance it is equal, infrared lamp lamp cap axis spider rotate 45 ° after with optical element group a and the middle axial cross of optical element group b
Fork overlaps, i.e., two axis spiders stagger 45 °, and circuit a and circuit b are connected to high-precision adjustable power source by cable concentrator, leads to
With steady current, circuit c is connected to computer by cable concentrator；Optical element group a is a set of laser particle size analyzer component, by
Laser, microcobjective, pinhole blind, collimating mirror, electronic slide block guide rail, fourier transform lens, ccd image sensor a, A/D turn
Parallel operation a, protection shell a, protection shell b and data cable connector composition, the inside of protection shell a are provided with electricity by being fixed
Movable slider guide rail, electronic slide block guide rail inside are provided with collimating mirror by engaging, and the one side of collimating mirror is provided with microcobjective, shows
Pinhole blind is provided between speck mirror and collimating mirror, microcobjective, pinhole blind, collimating mirror can be in electronic slide block guide rails
The lower horizontal slip of driving, the one side of microcobjective are provided with laser, and one end of laser is provided with data cable connector, and protection is outer
Shell b's is internally provided with A/D converter a, and one end of A/D converter a is provided with data cable connector, the other end of protection shell b
Fourier transform lens are provided with, the one side of fourier transform lens is provided with ccd image sensor a；Optical element group b is a set of improved
Self-action abbe's refractometer component, by white light source, light source runner, slotted barrier, (center has one through up and down vertical narrow
Seam), rotation index glass, half paraboloid mirror, series connection narrow band fiber bragg grating dispersion compensator, lifting pellicle mirror, control circuit, CCD figures
As sensor b, A/D converter b, protection shell c, protection shell d, data cable connector composition, protection shell c's is internally provided with
Light source runner, one end of light source runner are provided with white light source, and protection shell d's is internally provided with control circuit, control circuit
Top be provided with rotation index glass, rotate and half paraboloid mirror be provided with above index glass, the one side of half paraboloid mirror is provided with string
Join narrow band fiber bragg grating dispersion compensator, the one side of series connection narrow band fiber bragg grating dispersion compensator is provided with lifting pellicle mirror, rises
The one side of drop pellicle mirror is provided with ccd image sensor b, and the one side of ccd image sensor b is provided with A/D converter b；Transmission
And electric power system is made of each connection circuit, firm banking, cable concentrator, high-precision adjustable power source, and respectively connect circuit, fixed bottom
It is connected between seat, cable concentrator and high-precision adjustable power source by conducting wire and data cable.
In the present embodiment, it is preferred that load sample pond outer wall is opaque non-magnetic metal (not iron content, cobalt, nickel) material cylinder
Structure, side and protection shell a, protection shell b, protection shell c, the protection shell d of optical element group a and optical element group b
Joint is round hole at 4, and the lamp cap joints of four infrared lamps of side and temperature control system is opened for square at 4
Hole, infrared lamp lamp cap axis spider overlap after rotating 45 ° with the axis spider of optical element group a and optical element group b, i.e.,
Two axis spiders stagger 45 °, and optical glass is embedded as optical glass material known to high transparency and refractive index, surface by
Transparent hydrophobic film coated；Its structure may be regarded as a diameter it is equal with load sample pond outer wall internal diameter, it is high with load sample pond outer wall in
High equal cylinder cuts out a diameter 2mm, the high cylinder equal with height in the outer wall of load sample pond from axis, then from upper and lower two bottom surface
The geometry that the radius hemisphere equal with load sample pond outer wall inside radius obtains is cut out respectively, and optical glass embeds can
It is embedded just below pars intramuralis outside load sample pond.
In the present embodiment, it is preferred that the Mumetal processed by Dehydrogenation Annealing Process that protection shell e is thickness 2mm
(addition copper, nickeliferous 76% dilval of chromium) material, has high permeability, can effectively shield externally-applied magnetic field, eliminate outer
Magnetic field is added to be disturbed caused by working its internal components.
In the present embodiment, it is preferred that all coated crusts of transmission line are three layers of " insulating layer-aluminium foil-insulating layer "
Composite construction, wherein aluminum foil thickness is in more than 0.12mm.
In the present embodiment, it is preferred that half paraboloid mirror is the parabolic of only half of the part of axis place above the horizontal plane
Face mirror, vertex are located at the center of circle of the left bottom surface of the cylindrical space inside protection shell d, and axis is with protecting in shell d
The middle overlapping of axles of the cylindrical space in portion；It is horizontal where the only axis that lifting pellicle mirror is fixed on for one piece on miniature crane
The convex lens of half more than face of part, the one side focus of lens falls just when lens component is risen to top by miniature crane
The sensing surface center of ccd image sensor b.
Laser particle size analyzer in the present invention measures granular size according to the scattering principle of light, the dynamic model with measurement
The advantages that big, measuring speed is fast is enclosed, can be used in measuring the size distribution of various solid powders, emulsion particle, droplet.Light is expert at
When molecule is run into, it may occur that scattering, the angle of scattering of bulky grain is smaller, and short grained angle of scattering is larger.
It obtains the light intensity through sample in real time using ccd image sensor simultaneously, vacuum state is in reference to load sample passage
When the reference light intensity that measures the real-time transmittance data of albumen drop is calculated.(when using light source irradiation crystallization solution, by
In the interference of crystal grain, the intensity of light will be weakened, i.e. the light intensity of transmitted light is less than the light intensity of incident light, two light intensity it
It is known as light transmittance than custom, is represented using r.According to Beer-Lambert laws, light transmittance is depended mainly on the size of in system
Have the granularity and number of crystal grain, value corresponds to the surface area summation that characterize crystal grain, i.e.,
In formula：I1And I2The respectively light intensity of incident light and transmitted light, w be light transmission sensing chamber width, kaFor the surface of crystal
Product form factor, L and L0The respectively granularity of crystal and new core, f (L, t) are Lens capsule function.)
Protect Mumetal (addition copper, the chromium by Dehydrogenation Annealing Process processing that shell a, protection shell b are thickness 2mm
Nickeliferous 76% dilval) material, there is high permeability, can effectively shield externally-applied magnetic field, eliminate externally-applied magnetic field to it
Interference caused by internal components work.
All coated crusts of transmission line are " insulating layer-aluminium foil-insulating layer " three-layer composite structure, and wherein aluminium foil is thick
It spends in more than 0.12mm, good magnetic screening action can be played.
Modified self-action abbe's refractometer component, that is, optical element group b is every one under the control of computer control system
A shorter time interval carries out one-shot measurement, and in single measurement, when beginning, which lifts pellicle mirror and is in, falls state (lens section
Divide and drop to bottom, be fully located at access the latter half；Here the cylindrical space inside shell d will be protected to cross its central axes
Horizontal plane is divided into upper and lower two parts for boundary, is referred to as " access top half " and " access the latter half "), white light source hair
The light gone out passes through slotted barrier, and front and rear two pieces are embedded by the optical glass for being respectively equivalent to entering light prism, refracting prisms
It is projected after protein solution layer refraction in glass part and load sample passage therebetween, through the reflection for rotating index glass and half paraboloid mirror
It is shot to the right from access top half, ccd image sensor b is incident upon after narrow band fiber bragg grating dispersion compensator of connecting
On, image is finally generated in computer control system；It is straight that computer control system adjusts the incident light direction of light source runner change
Occurring apparent light and shade boundary into the image for capturing ccd image sensor b, (it is more than setting threshold to occur luminance difference in image
Two parts of value), then adjust series connection narrow band fiber bragg grating dispersion compensator and eliminate dispersion, it then lifts pellicle mirror and becomes rising shape
State (lens component is raised to top, is fully located at access top half), computer control system control rotation index glass is around its shaft
The dihedral angle size where changing its minute surface between plane and horizontal plane is rotated until the projection pattern of ccd image sensor b captures
Becoming a bright spot for being located at image center, (light after rotation index glass reflection is just past half paraboloid mirror under this state
Focus becomes the directional light that a branch of level is shot to the right after the reflection of half paraboloid mirror, is converged at after lifting pellicle mirror refraction
Lift the right focus of pellicle mirror, i.e. the sensing surface center of ccd image sensor b；In the angle-determining that light source runner turns over
In the case of can realize that the rotation angle of rotation index glass of this state is unique), fall lifting pellicle mirror, record projection again at this time
The position of pattern on the image, the angle and finally project pattern on the image that computer control system is turned over according to rotation index glass
Position calculate through being respectively equivalent to the optical glass of entering light prism, refracting prisms embed front and rear two pieces of glass parts and
The emergent ray after the refraction of protein solution layer in load sample passage therebetween and the angle between horizontal direction, in conjunction with light source runner
The refractive index of albumen drop is calculated in the refractive index that the angle and optical glass turned over embeds, so as to be reflected according to protein solution
Relation between rate and concentration obtains the concentration of protein solution, and then light source runner and rotation index glass reset, and so far one-shot measurement is complete
Into.
Computer control system is made of the connection circuit between PC (personal computer) and PC and other each hardware.
Computer control system is responsible for entire crystal culture systems operation by control program and each correlation function software
The operation of the processing feedback and each equipment of process control, especially real time data controls, to realize that entire crystal culture systems are transported
Capable automation and the optimization of crystallization path and condition.
Six sample arms are connected on converter vertically, symmetrical in regular hexagon, farthest apart from fixing bracket
The location of one sample arm is known as working position, the glass needle of the glass syringe needle microsyringe of the sample arm in working position
The sample holes in the upper cover center in head face load sample pond；Converter can in units of 60 ° around its central axis with will be required
Sample arm is moved to working position；A kind of crystallization additive is contained in the glass syringe needle microsyringe of each sample arm, works as needs
When such crystallization additive is quantitatively added in albumen drop, computer control system driving converter moves corresponding sample arm
Working position is moved, then driving guide rail slide block lifter that its sliding block is made to drop to designated position causes sample arm elongation downwards extremely
The glass syringe needle of its glass syringe needle microsyringe passes through the sample holes of load sample pond upper cover and stretches into the protein liquid in load sample passage
Drop center (the glass of the lower end of sample arm, that is, glass syringe needle microsyringe when the sliding block of guide rail slide block lifter is located at initial position
Glass syringe needle, will not be with other device contacts higher than the upper end of other devices such as load sample pond, externally-applied magnetic field component), computer control
The sliding block of the embedded guide rail slide block lifter of system drive micro-injection pump accurately declines respective distance so as to promote glass syringe needle
The piston of microsyringe declines same distance by the additive liquid of respective volume accurately from glass syringe needle microsyringe
Middle extrusion and be discharged into albumen drop that (syringe of glass syringe needle microsyringe is the cylinder that internal diameter determines, therefore discharges liquid
Volume can directly be scaled the distance of piston decline), after liquid is discharged, the embedded guide rail slide block lifter of micro-injection pump
It remains stationary as and the sliding block of guide rail slide block lifter rises back original position so as to by the glass syringe needle of glass syringe needle microsyringe
(super-hydrophobic processing is passed through in the outer surface of the glass syringe needle of glass syringe needle microsyringe, can effectively prevent for extraction from load sample pond
Glass syringe needle takes the liquid in albumen drop out of when extracting out), so far, a sample-adding process is completed.
The operation principle and process for using of the present invention：After the present invention installs, first check for the present invention installation fixation with
And security protection, then it can be used；In use, a complete working period of the system is divided into " study stage " and " formally
Two stages of operation phase "：
【1】" study stage "
Due to the thermodynamics that is influenced in current protein crystal field on all kinds of environmental factors on protein crystal process and
Kinetics mechanism research also rests on phenomenon description mostly and hypothesis proposes the stage, rarely has specific formula as conditional parameter meter
Foundation is calculated, therefore to each factor is analyzed and prejudged to the impact effect of crystallization process to find out optimal conditions, it is necessary to base
In actual experimental result, optimal conditions is drawn by substantial amounts of experimental data statistical analysis.However, due to influencing protein crystal
The environmental factor of process is numerous, even if only considering to influence more significant factor, it is also desirable to while consider Multiple factors (such as a variety of knots
Concentration, temperature, applied field strengths of brilliant additive etc.), since the effect of each factor is not necessarily mutually independence, it is possible to
It interacting between existing factor, the method for independent analysis single factors searching optimal value is simultaneously unreliable, therefore in order to find totally most
Excellent condition, it is necessary to while consider the effect of all factors.However, considering the effect of each factor simultaneously necessarily causes huge experiment
Amount, not only workload is huge is difficult to complete, it is also difficult to obtain enough sample sizes to support the development of experiment.It is asked to solve this
Topic, we use orthogonal experiment method, and institute is farthest reduced in the case where ensureing that conclusion accuracy does not generate significantly loss
Need experiment number.
Orthogonal experiment method is a kind of multifactor multilevel experimental design method of research, it is tested according to orthogonality from comprehensive
In pick out the representational point in part and tested, these representational points possess it is homodisperse, neat than the characteristics of.
Orthogonal experiment method is a kind of experimental design method efficiently, economic, it is set using a set of normalized form (i.e. orthogonal arrage)
Experimental program and analysis experimental result are counted, a few representative strong experiment item can be selected in substantial amounts of experiment condition
Part, and pass through this data tested several times, finds preferable condition, i.e., optimal or preferably scheme.
(1) design of orthogonal arrage
Orthogonal arrage is a whole set of regular design table (schedule), very widely used today Ln[tc] type Construction of Orthogonal Arrays thought
Comparative maturity, it is using L as the code name of orthogonal arrage, and n is the number of experiment, and t is number of levels, and c is columns, that is, may be arranged most
More factor numbers.
With L9[34] type Quadrature table construction process exemplified by：
1) row and column of orthogonal arrage is determined
Altogether there are four factor, each because being known as 3 levels, 9 experiments need to be arranged altogether.Therefore, which is one 4
Row, the table of 9 rows.The gauge outfit for generating orthogonal arrage is as shown in the table.
The level of each factor is numbered, is respectively 1,2,3, and experiment is grouped according to number of levels 3, i.e., it is every
Three experiments are one group.
For first row：In first group of experiment, the 1st level of whole service factors 1；In second group of experiment, all make
With the 2nd level of factor 1；In 3rd group of experiment, the 3rd level of whole service factors 1；
For secondary series：In each group of experiment, all three levels 1,2,3 of service factor 2 respectively；
For the 3rd row：In each single item experiment, each level number is determined；
For the 4th row：In each single item experiment, each level number is determined.
3) orthogonal arrage is generated
The horizontal number of each factor, which is inserted, can obtain orthogonal arrage in table.
During in face of a kind of new protein sample, computer control system automatically generates orthogonal experiment scheme, micro- by carrying out
Ary Quadrature is tested, and in the case where minimal sample is lost, is obtained under each rough situation scope when each factor changes jointly
Crystal growth rate, first nucleation rate, the value of secondary nucleation rate, find the small range closest to optimal objective value, at this
A a small range carries out the orthogonal experiment to become more meticulous again, so as to find the corresponding optimal overall conditions of corresponding target, surveys simultaneously
Obtain the saturated concentration c of corresponding protein solutionsat。
【2】" commencement of commercial operation stage "
Within " commencement of commercial operation stage ", system work is divided into as " nucleation stage " (first stage) and " crystal growth phase "
(second stage) two sub-stages.In each sub-stage, system is according to crystallization phasor and the optimal crystal theoretically obtained
It is corresponding to be incorporated in the corresponding optimal value that " learning the stage " obtains for growth rate, first nucleation rate, the value of secondary nucleation rate
Global optimum condition to adjust the value of each environmental factor, makes system time keep optimum state.
And another task of control system, it is the turning point correctly found between two sub-stages, is arrived in turning point
Timely conversion system state when coming, control system is according to the judgement variable K of arteface*Growth trend carry out turning point and sentence
It is fixed.
Below to the decision content of separation between the computational methods of kinetic parameters and nucleation stage and crystal growth phase
Construction is illustrated：
[1] calculating of kinetic parameters
Nucleation rate B0It is calculated using A Leiniwusi expression formulas association system degree of supersaturation, i.e.,：
In formula：B0For nucleation rate；kb、b、EbIt is nucleation kinetics parameter；R is ideal gas constant；T is temperature；S
For degree of supersaturation.
The quality of crystal is grown for volume change and grain density caused by grain growth in crystallizing system in the unit time
Product, be represented by：
In formula：ΔMGIt makes a living the quality of long crystal；mLFor solvent quality；c0For initial concentration solution；kVFor the volume of crystal
Form factor；ρvFor crystalline density；For the natural logrithm of light transmittance；kaFor crystal surface area form factor；W examines for light transmission
Survey the width of room；ρ0For solution density；kg, g be crystal growth kinetics parameter, S is solution degree of supersaturation.
Therefore the model expression for representing crystallization process can be established：
In formula：C is solution concentration (Solute mass dissolved in unit mass solvent)；T is crystallization time；c0For solution
Initial concentration；ρ0For solution density；kb、b、EbIt is nucleation kinetics parameter；R is ideal gas constant；T is temperature；S was
Saturation degree；mLFor solvent quality；kVFor the volume shape factor of crystal；ρcFor crystalline density；For the naturally right of light transmittance
Number；kaFor crystal surface area form factor；W is the width of light transmission sensing chamber；kg, g be crystal growth kinetics parameter.
From above formula, as long as measuring the real-time light transmittance and real-time concentration of solution in crystallization process, utilize non-linear time
Return method that can ask for the kinetic parameter k of nucleus formation and crystal growthb、Eb、b、kgAnd g.
Obtain kb, b, kg, can be according to crystallization kinetics empirical equation after g values：
G=kgSg (6)
Crystal growth rate G, first nucleation rate is calculatedWith secondary nucleation rate(according to different nucleation
Mechanism, nucleation rate B0First nucleation rate can be divided intoWith secondary nucleation rateCorrespond to respectively be not added with crystal seed from
It sends out nucleation and crystallization process and has secondary nucleation crystallization process existing for crystal seed.)
In formula：S is opposite degree of supersaturation；C is solution concentration；csatIt is dissolved for the saturated concentration of solution under corresponding temperature
Degree；G is crystal growth rate；kgIt is crystal growth kinetics parameter with g；For first nucleation rate；For secondary nucleation speed
Rate；kbIt is crystal nucleation kinetic parameter with b；μ3For the 3 rank square amounts of CSD (Lens capsule function, i.e. f (L, t)).
μ3Solution：
Define μiFor the i rank square amounts of Lens capsule function CSD, formula (9) to formula (11) gives each rank square amounts of CSD
Definition and its mutual replacement relation, i.e.,
In formula：F (L, t) is CSD (Lens capsule function)；μiFor the i rank square amounts of CSD；L is crystal size；T is knot
The brilliant time；G is crystal growth rate；μ0For the 0 rank square amount of CSD, value characterizes the total grain number of crystal in system；B0For crystal
Nucleation rate.
It is previously noted that according to Beer-Lambert laws, depending mainly on the size of for light transmittance has crystal in system
The granularity and number of grain, value correspond to the surface area summation that characterize crystal grain, i.e.,
By μ2Definition, that is, formula (9) understand, formula (1) can be rewritten as
In formula：
The light transmittance of r-- crystallizing systems, zero dimension；
ka-- crystal surface area form factor, zero dimension；
The width of w-- light transmissions sensing chamber, cm；
L0-- the granularity of new core, cm；
μ2-- the second moment amount of Lens capsule function, cm2·cm-3；
F (L, t) -- CSD (Lens capsule function).
μ can be asked by non-linear regression method2, μ is solved further according to (10) formula3。
[2] between nucleation stage and crystal growth phase separation identification model
1) Theoretical Basis and modeling derive
In crystallography research, since the second order of CSD, third moment amount characterize the total surface area and body of crystal in system respectively
Product, therefore when the number of crystal or granularity increase, the second order of CSD can show the growth of different amplitudes from third moment magnitude, and
The two again can be associated with the light transmittance of system and concentration respectively.Therefore analysis system light transmittance and concentration variation can be nucleation with
The dynamics research of two process of crystal growth provides important information.
Dynamic Modeling derives：
From Beer-Lambert laws, system light transmittance r's can be with the second moment amount μ of CSD to numerical value2It is associated,
I.e.
In formula：
The light transmittance of r-- crystallizing systems, zero dimension；
ka-- crystal surface area form factor, zero dimension；
The width of w-- light transmissions sensing chamber, cm；
The granularity of the new cores of L0--, cm；
μ2-- the second moment amount of Lens capsule function, cm2·cm-3；
F (L, t) -- CSD (Lens capsule function).
If in the dt times, crystal number increases to N+dN by N in unit volume magma, granularity increases to L+dl by L, then by
This causes the natural logrithm lnr rates of changing with time of solution concentration c and light transmittance to be respectively
In formula：
C-- solution concentrations (Solute mass dissolved in unit mass solvent), gg-1；
T-- crystallization times, min；
ρc-- crystalline density, gcm-3；
kV-- crystal volume form factor, zero dimension；
V-- magma volumes, cm-3；
mL-- solvent quality, g；
Crystal number in N-- unit volume magmas, zero dimension；
The granularity incrementss of dl-- crystal, cm；
The width of w-- light transmissions sensing chamber, cm.
Formula (13) and formula (14) transposition are divided by, arrangement can obtain
In formula：μ1-- the first moment amount of Lens capsule function, cmcm-3。
In formula (15), becauseAnd μ1>0, thereforeSeparately due to(breakage of crystal or coalescence), therefore have
Except μ1Outside, remaining variables are the physical quantity that can be measured or convert in formula (16), μ2It can be according to formula (12) by light transmittance
Data take.μ1With number of crystals purpose ratio μ1/ N levies the particle mean size of crystal in system, for the crystallization generated with nucleation
Process constantly changes because crystal number N is in, therefore μ1Value is generally difficult to accurately obtain.
2) proposition of criterion variable
To be difficult to definite CSD first moment amounts μ in alternate form (16)1, a dimensionless variable K is now defined, is made
In formula：The variable that K-- is newly defined, zero dimension；
μ3-- the third moment amount of Lens capsule function, cm3·cm-3。
Formula (17) is substituted into formula (16), can be obtained
In formula (18), μ3It can also be expressed by the mass balance of solute, in order to abbreviation.For being not added with or adding
The crystallization process (i.e. first nucleation and secondary nucleation crystallization process) of crystal seed, accounting formula accordingly can be written as
mL(c0-c)+mS=ρckVVμ3 (19)
I.e.
In formula：
c0-- the initial concentration of solution, gg-1；
mS-- the crystal seed quality of addition is (for being not added with the crystallization process m of crystal seedS=0), g.
Simultaneous formula (12), formula (18) and formula (20), arrangement can obtain
For formula (21), and if only if in crystal invariable number in system, that is, formula (15)When, equation just strictly into
It is vertical.
For ease of expression, the right that can further make formula (21) is K*, i.e.,
In formula：K*-- with being also the variable newly defined, zero dimension as variable K.
K and K*Variation tendency has high similarity, and this similitude is due to the granularity L of newborn nucleus in crystallization process0
Crystal size after generally much less than growing, therefore causeItem will be much smaller thanWithTwo, i.e. formula (16) is represented by
So as to which formula (21) can be rewritten as
By formula (24) variables K and K*Numerically approximately equal, therefore the curve tendency of the two also necessarily coincide.
3) establishment of identification model criterion
It is found by simulating to calculate, variable K and K*Numerical value be respectively provided in nucleation stage monotone decreasing, crystal growth phase
The variation characteristic of monotonic increase.Based on K and K*This variation characteristic, can using the growth trend of its numerical value as nucleation stage with
The criterion of crystal growth phase quantitative identification.
Due to when calculating K values according to formula (17) oneself being needed to know the low-order moment amount μ of CSD1、μ2And μ3And corresponding kinetic parameter,
And on-line determination μ in crystallization operation1Value is more difficult, calculates μ values with kinetic parameter and relatively complicated, therefore the reality of K variables
Border application is subject to larger limitation.And if calculate K using formula (22)*Value, then need to only know that solution concentration and light transmittance etc. are several can
Crystalline information measured directly, and convenient for the Synchronization Analysis to process.Therefore, we are with parameter K*Growth trend as area
Divide the criterion of nucleation stage and crystal growth phase.
System operation control principle：
(1) by controlling the relation of temperature and protein concentration, system status is first made to be in unstable state (first stage), is formed
During the nucleus of suitable number, then changing makes system status be in metastable state (second stage), carries out crystal growth.
(2) control dynamics parameter k is passed throughb,b,kg, g controls nucleation rate and growth rate, in unstable state (the first rank
Section) promote nucleation, promote crystal growth in metastable state (second stage).
(3) K is passed through*The turning point for changing to judge first stage and second stage of the growth trend of value, so as in time
System status is moved to from the unstable state beneficial to nucleation to the metastable state beneficial to crystal growth.
(4) nucleation rate and growth rate and each impact factor (each crystallization additive learnt by orthogonal experiment
Concentration, temperature, applied field strengths etc.) correlativity between value regulates and controls the size of each impact factor, by anti-in real time
Feedback regulation and control are adjusted in real time, remain the optimum state at corresponding moment.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
Understanding without departing from the principles and spirit of the present invention can carry out these embodiments a variety of variations, modification, replace
And modification, the scope of the present invention is defined by the appended.
Claims (5)
1. the low defect albumen monocrystal culture systems based on single drop microenvironment precision control, including load sample pond, sampling system,
Temperature control system, externally-applied magnetic field component, optical element group a, optical element group b and transmission and electric power system, it is characterised in that：
The load sample pond is by load sample pond outer wall（11）It is embedded with optical glass（12）Composition, the optical glass embed（12）Outside set
It is equipped with load sample pond outer wall（11）, and load sample pond outer wall（11）It is embedded with optical glass（12）It is an integral structure, the load sample pond
Outer wall（11）Top load sample pond upper cover is fixedly installed by hinge（13）, load sample pond upper cover（13）Center position
It is provided with sample holes（14）, the load sample pond is internally provided with load sample passage（17）；The sampling system is by fixing bracket
（2）, converter（3）The sample arm identical with six（4）Composition, the firm banking（1）One end be provided with cable buncher b
（58）, the firm banking（1）Upper surface fixing bracket is fixedly installed by nut（2）, the fixing bracket（2）One
End is provided with converter（3）, the converter（3）Lower section vertically connection there are six sample arm（4）, and the sample arm（4）
It is symmetrical in regular hexagon, the sample arm（4）By glass syringe needle microsyringe（5）, micro-injection pump（6）, guide rail slide
Block lifter（7）It forms, and six sample arms（4）It is middle apart from fixing bracket（2）A farthest sample arm（4）Residing
Position is known as working position, the sample arm in working position（4）Upper glass syringe needle microsyringe（5）Glass syringe needle face
Load sample pond upper cover（13）The sample holes at center（14）；The temperature control system is passed by Pt-100 micron order standard platinum resistances temperature
Sensor（30）, the compound thin layer magnetic screen shell of aluminium foil-silicon carbide ceramics（31）, heat-insulated inorganic insulation shell（32）, pressure sensitive
Low noise pre-amplification circuit（33）, digitial controller（34）, silicon controlled toggle（35）, silicon-controlled actuator（36）, it is infrared
Lamp common-base（37）, infrared lamp（53）With protection shell e（39）Composition, the compound thin layer magnetic cup of aluminium foil-silicon carbide ceramics
Cover shell（31）Outside be provided with heat-insulated inorganic insulation shell（32）, the heat-insulated inorganic insulation shell（32）Lower section set
There is pressure sensitive low noise pre-amplification circuit（33）, the pressure sensitive low noise pre-amplification circuit（33）Lower section set
There is digitial controller（34）, the digitial controller（34）Lower section be provided with silicon controlled toggle（35）, it is described silicon-controlled tactile
Send out device（35）One side be provided with silicon-controlled actuator（36）, the silicon-controlled actuator（36）Bottom be provided with infrared lamp and be total to
Use pedestal（37）, four identical infrared lamps（53）It is divided into two groups, is wired to infrared lamp common-base
（37）, every group of two infrared lamps（53）Staggered relatively and lamp cap axis is located on same level straight line, two groups of infrared lamps
（53）Lamp cap axis be orthogonal in same level, each infrared lamp（53）Lamp cap towards two axis intersection point and with two axis
The distance of intersection point is equal, the infrared lamp（53）Lamp cap axis spider rotate 45 ° after with optical element group a and optical element group
The axis spider of b overlaps, i.e., two axis spiders stagger 45 °, the circuit a（40）With circuit b（41）Pass through cable concentrator
（57）It is connected to high-precision adjustable power source（56）, pass to steady current, the circuit c（42）Pass through cable concentrator（57）It is connected to meter
Calculation machine；The optical element group a is a set of laser particle size analyzer component, by laser（45）, microcobjective（47）, pin hole gear
Plate（48）, collimating mirror（49）, electronic slide block guide rail（46）, fourier transform lens（50）, ccd image sensor a（51）, A/D conversion
Device a（52）, protection shell a（43）, protection shell b（44）And data cable connector（22）Composition, the protection shell a（43）It is interior
Portion is provided with electronic slide block guide rail by being fixed（46）, the electronic slide block guide rail（46）Inside is provided with standard by engaging
Straight mirror（49）, the collimating mirror（49）One side be provided with microcobjective（47）, the microcobjective（47）With collimating mirror（49）
Between be provided with pinhole blind（48）, the microcobjective（47）, pinhole blind（48）, collimating mirror（49）It can be in electronic sliding block
Guide rail（46）Driving under it is horizontal slide, the microcobjective（47）One side be provided with laser（45）, the laser
（45）One end be provided with data cable connector（22）, the protection shell b（44）Be internally provided with A/D converter a（52）, institute
State A/D converter a（52）One end be provided with data cable connector（22）, the protection shell b（44）The other end be provided with Fu
Vertical leaf lens（50）, the fourier transform lens（50）One side be provided with ccd image sensor a（51）；The optical element group b
For a set of improved self-action abbe's refractometer component, by white light source（18）, light source runner（19）, slotted barrier（59）（In
Centre has one through upper and lower vertical slots）, rotation index glass（23）, half paraboloid mirror（24）, series connection narrow band fiber bragg grating dispersion
Compensator（26）, lifting pellicle mirror（27）, control circuit（25）, ccd image sensor b（28）, A/D converter b（29）, protection
Shell c（20）, protection shell d（21）, data cable connector（22）Composition, the protection shell c（20）Be internally provided with light source
Runner（19）, the light source runner（19）One end be provided with white light source（18）, the protection shell d（21）Inside set
There is control circuit（25）, the control circuit（25）Top be provided with rotation index glass（23）, the rotation index glass（23）It is upper
Side is provided with half paraboloid mirror（24）, the half paraboloid mirror（24）One side be provided with series connection narrow band fiber bragg grating dispersion compensation
Device（26）, the series connection narrow band fiber bragg grating dispersion compensator（26）One side be provided with lifting pellicle mirror（27）, the lifting
Pellicle mirror（27）One side be provided with ccd image sensor b（28）, the ccd image sensor b（28）One side be provided with A/
D converters b（29）；The transmission and electric power system are by each connection circuit, firm banking（1）, cable concentrator（57）, high-precision it is adjustable
Power supply（56）Composition, and each connection circuit, firm banking（1）, cable concentrator（57）And high-precision adjustable power source（56）Between
It is connected by conducting wire and data cable.
2. the low defect albumen monocrystal culture systems according to claim 1 based on single drop microenvironment precision control,
It is characterized in that：Load sample pond outer wall（11）For opaque non-magnetic metal（Not iron content, cobalt, nickel）Material cylindrical structure, side
Face and the protection shell a of optical element group a and optical element group b（43）, protection shell b（44）, protection shell c（20）, protection
Shell d（21）Joint is four infrared lamps of round hole at 4, side and temperature control system（53）Lamp cap joint be
Square perforate at 4, infrared lamp（53）Lamp cap axis spider rotate 45 ° after in optical element group a and optical element group b
Axial cross fork overlaps, i.e., two axis spiders stagger 45 °, and the optical glass embeds（12）For high transparency and refractive index
The optical glass material known, surface is by transparent hydrophobic film coated；Its structure may be regarded as a diameter and load sample pond outer wall
（11）Internal diameter is equal, high and load sample pond outer wall（11）The equal cylinder of interior height cuts out a diameter 2mm, high and load sample pond from axis
Outer wall（11）The equal cylinder of interior height, then a radius and load sample pond outer wall are cut out respectively from upper and lower two bottom surface（11）Inside radius phase
Deng the obtained geometry of hemisphere, optical glass embeds（12）Load sample pond outer wall can be embedded just below（11）It is internal.
3. the low defect albumen monocrystal culture systems according to claim 1 based on single drop microenvironment precision control,
It is characterized in that：The protection shell e（39）For the Mumetal processed by Dehydrogenation Annealing Process of thickness 2mm（Addition copper,
Nickeliferous 76% dilval of chromium）Material has high permeability, can effectively shield externally-applied magnetic field, eliminates externally-applied magnetic field to it
Interference caused by internal components work.
4. the low defect albumen monocrystal culture systems according to claim 1 based on single drop microenvironment precision control,
It is characterized in that：The coated crust of all transmission lines is " insulating layer-aluminium foil-insulating layer " three-layer composite structure,
Middle aluminum foil thickness is in more than 0.12mm.
5. the low defect albumen monocrystal culture systems according to claim 1 based on single drop microenvironment precision control,
It is characterized in that：The half paraboloid mirror（24）There was only the paraboloidal mirror of half of the part of axis place above the horizontal plane,
Vertex is located at protection shell d（21）The center of circle of the left bottom surface of internal cylindrical space, axis and protection shell d（21）It is interior
The middle overlapping of axles of the cylindrical space in portion；The lifting pellicle mirror（27）The only axis being fixed on for one piece on miniature crane
The convex lens of half of the part of place above the horizontal plane, the one side focus of lens when lens component is risen to top by miniature crane
Just fall in ccd image sensor b（28）Sensing surface center.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113673154A (en) * | 2021-08-16 | 2021-11-19 | 深圳市八零联合装备有限公司 | Diameter searching method, device, equipment and storage medium in grain sorting process |
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