JP2007152306A - Process and apparatus for suppressing convection - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a process and an apparatus for suppressing convection produced when crystals deposit from a solution. <P>SOLUTION: The process and the apparatus for suppressing the convection is characterized in that when the crystal deposits from the solution, a gradient magnetic field with the magnetic flux density reduced or increased perpendicularly upward to the solution and the crystal, thereby the convection produced around the crystal is suppressed. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for suppressing convection generated when a crystal is precipitated from a solution, a method for crystal precipitation and growth using the method for suppressing convection, and an apparatus therefor. Specifically, the present invention relates to a convection suppression method for controlling convection by applying a gradient magnetic field to a crystal and a solution, a crystal precipitation growth method using this convection suppression method, and an apparatus therefor. More specifically, the present invention relates to a convection suppression method, a crystal precipitation growth method using the convection suppression method, and an apparatus thereof, in which a gradient magnetic field is controlled by decreasing or increasing a magnetic flux density along a vertically upward direction.

  When a crystal is produced in a microgravity space environment, a high quality crystal is often obtained because convection generated with crystal growth is suppressed. However, using the actual space environment is expensive and the opportunities for experimentation are limited. On the other hand, as a means for suppressing convection on the ground, a method using a Lorentz force generated by applying a magnetic field is widely used in melts of metals and semiconductors with extremely high electrical conductivity (Non-patent Documents). 1).

  However, this method cannot be applied to a solution such as water or an organic solvent whose electrical conductivity is 10 to 5 digits lower than that of a metal or semiconductor melt. For example, convection when crystals are precipitated from an aqueous solution will be described with reference to FIG. FIG. 1 shows how crystals 11 are precipitated from an aqueous solution. Since the solute is taken into the crystal at the periphery 12 of the crystal, the concentration of the solution is lower than that of the solution 13 far from the crystal. Convection generated by this solute concentration difference is called solute convection.

In this solute convection, for example, when a protein crystal used for X-ray structure analysis is precipitated from an aqueous solution having a depth of 1 cm, the Rayleigh number Ra, which is a parameter indicating the strength of the solute convection, is Ra = 1.4 × 10 ^9. It is very large and convection is very strong.
By the way, the Rayleigh number of thermal convection that occurs when the temperature difference between the top and bottom is 1 ° C. in water of 1 cm depth is 1.7 × 10 ⁴ .

Until recently, there was little means to suppress the strong convection that occurs when crystals precipitate from solution on the ground. However, in 1996, an apparatus for controlling gravity using magnetic force was invented (see Patent Document 1). All material is attracted to or repels the magnet, just as iron is attracted to the magnet. The magnetic force acting on a unit volume of material is expressed by the following (Equation 1) under a one-dimensional gradient magnetic field.

In the equation, M ₀ is the magnetic permeability of vacuum (= 4π × 10 ⁻⁷ Hm ⁻¹ ), K is the volume magnetic susceptibility which is the magnetic susceptibility per unit volume, y is the position coordinate, B is the magnetic flux density, D is the density, K _g is a mass magnetic susceptibility that is a magnetic susceptibility per unit mass. K = D × K _g .

Table 1 shows the mass magnetic susceptibility and K _g of various substances at room temperature. As is apparent from this table, most substances such as water and organic compounds have diamagnetism repelling the magnet and K _g has a negative value.

  The zero-gravity environment is typically realized inside the International Space Station, which orbits the earth, but the inside of this space station is zero-gravity and the centrifugal force generated by orbiting the Earth. Is just to balance. Both gravity and centrifugal force are proportional to density. As apparent from the equation (1), the magnetic force is also proportional to the density. Therefore, as shown in FIG. 2, if the upward magnetic force 23 equal to the gravity 22 is applied to the liquid 21, the liquid 21 is suspended on the ground or the liquid It is possible to generate a zero-gravity environment in which the apparent gravity acting on 21 is zero (see FIG. 2).

  The solution in which crystals are precipitated is a mixture of a solute and a solvent. If the mass magnetic susceptibility of the solvent and the solute has almost the same value, it is possible to control the gravity by the magnetic force. It is possible to realize a zero-gravity environment by applying a gravity control method when depositing. As shown in Table 1 above, most materials are diamagnetic and many have similar mass susceptibility.

  However, for example, when diamagnetic KCl crystals are precipitated from an aqueous solution, when the mass magnetic susceptibility of the solute and the solvent is greatly different, such as when paramagnetic cobalt sulfate crystals are precipitated from an aqueous solution, However, even if the apparent magnetic force acting on the liquid becomes zero, the solute convection based on the concentration gradient generated with crystal growth cannot be suppressed.

R. W. Series and D.C. T. T. et al. Hurle, J.M. Cryst. Growth 113, 305 (1991). Nobuko Wakayama “Gravity Control Device”, Japanese Patent No. 3278865

  An object of this invention is to provide the method and apparatus which suppress the solute convection which generate | occur | produces when a crystal precipitates from a solution.

As a result of intensive research in view of the above problems, the present inventor has found that convection is generated by buoyancy, so if the buoyancy due to gravity is canceled out by buoyancy due to magnetic force, the convection caused by crystal growth can be significantly suppressed. Based on knowledge, it came to make this invention.
That is, the present invention
(1) In a method for suppressing convection generated around a crystal when the crystal is precipitated from a solution, by applying a gradient magnetic field to the solution and the crystal, the buoyancy generated by gravity is canceled by the buoyancy caused by the magnetic force, and the convection A method for suppressing convection generated around a crystal when the crystal is precipitated from a solution.
(2) The gradient magnetic field described in the above (1) decreases or increases the magnetic flux density along the vertical upward direction, and the product of the magnetic flux density and the differential value by the vertical position coordinate has a specific value that suppresses gravity convection. The method for suppressing convection according to (1), wherein the convection is controlled so as to be taken.
(3) Precipitation and growth of crystals from solution In the crystal precipitation and growth method, by applying a gradient magnetic field to the crystal and the solution, the buoyancy generated by gravity is offset by the buoyancy due to the magnetic force, and the convection around the crystal A method for depositing and growing crystals from a solution, characterized in that crystals are precipitated and grown while suppressing the above.
(4) The gradient magnetic field described in the above (3) decreases or increases the magnetic flux density along the vertical upward direction, and the product of the magnetic flux density and the differential value by the vertical position coordinate has a specific value that suppresses gravity convection. The method for crystal precipitation and growth from a solution according to (3), wherein the method is controlled so as to take.
(5) In a crystal growth apparatus for precipitating and growing crystals from a solution, a gradient magnetic field generating means capable of applying a gradient magnetic field to the crystal and the solution is provided, and the convection around the crystal is controlled by controlling the gradient magnetic field. An apparatus for depositing and growing crystals from a solution, wherein
(6) The gradient magnetic field is controlled so that the product of the magnetic flux density and the differential value based on the vertical position coordinate takes a specific value that suppresses gravity convection by decreasing or increasing the magnetic flux density along the vertical upward direction. An apparatus for depositing and growing crystals from a solution according to (5), characterized in that:

  The present invention suppresses convection around a crystal by applying a gradient magnetic field to the crystal and the solution in a crystal precipitation and growth method for depositing and growing a crystal from a solution. As a result, the buoyancy generated by gravity is offset by the buoyancy due to the magnetic force, and convection based on the concentration difference around the crystal is suppressed, so that a high-quality crystal can be obtained. That is, according to the present invention, it becomes possible to create a non-convection space on the ground, which is dependent on costly experiments in outer space, and to precipitate and grow crystals from solution. It is expected that gravitational convection due to concentration difference can be suppressed, and high quality crystals, especially high quality protein crystals and organic semiconductor crystals can be produced.

  The present invention relates to a method and apparatus for suppressing solute convection generated when a crystal grows from a solution by applying a gradient magnetic field. Hereinafter, the present invention will be described in detail.

First, the method and apparatus for suppressing convection of the present invention will be described in detail with reference to the drawings.
When the crystal grows at the bottom of the container as shown in the left of FIG. 3, since the solute is taken into the crystal around the crystal, the concentration of the solute is lower than the concentration of the solution far from the crystal, and as a result, the periphery of the crystal Since the density of the solution becomes low, solute convection 30 is generated.
The present invention is characterized in that a solute convection is suppressed by applying a gradient magnetic field as shown in the right of FIG. 3 to cancel buoyancy due to gravity with buoyancy due to magnetic force. The gradient magnetic field causes the magnetic flux density B to decrease (solid line 31) or increase (broken line 32) in the vertical upward direction so that the product of the magnetic flux density and its differential value by the y coordinate takes a specific value that suppresses gravity convection. . A gradient magnetic field is applied to the container 35 containing the crystals 33 and the solution 34. The gradient magnetic field generating means used at that time is not particularly limited, and a superconducting magnet, an electromagnet, a permanent magnet, or the like can be used. What is necessary is just to be able to supply a gradient magnetic field of a necessary magnitude to a container containing a solution and crystals. The container 35 may be made of a nonmagnetic material, and the shape thereof is not limited. The method of crystallization is not limited. For example, in the case of protein crystal production, not only the batch method as shown in the left of FIG. 3, but also the vapor diffusion method such as the hanging drop method and the sitting drop method, when crystals are precipitated from the solution. Are all included.

FIG. 4 shows that a solution I (41) having a concentration c _I and a density D _I is a solution II (42) having a concentration c _II and a density D _II.
(C _I <c _II , D _I <D _II ). The magnetic susceptibility per unit volume of the solutions I and II is defined as K _I and K _II .
When the equation (1) indicating the magnetic force is used, the sum of gravity and magnetic force acting on the solution I is expressed as D _I g + (1 / M ₀ ) K _I B (dB / dy) per unit volume. Further, the sum of gravity and magnetic force acting on the solution II is expressed as D _II g + (1 / M ₀ ) K _II B (dB / dy) per unit volume.

When the sum of gravity and magnetic force acting on the solutions I and II becomes equal and the following (Equation 2) holds, no convection occurs. In this case, the force acting upward is positive (g = −9.8 m / s ² ). The direction toward the y coordinate is also positive.

Here, when the solute concentration c changes continuously, c _I becomes as close as possible to c _II , and when D _I → D _II and K _I → K _II , rewriting (Equation 2) (Equation 3) Can be guided.

  That is, (Equation 3) is an expression representing that the buoyancy due to gravity is canceled by the buoyancy due to magnetic force.

From this equation, the magnetic field gradient necessary to suppress solute convection is expressed by the following equation (Equation 4).

Incidentally, when the gravity acting on the solution in the container becomes equal to the upward magnetic force as shown in FIG. 3, and as a result, the solution floats as shown in FIG. 2 (see FIG. 2), the following formula (
Equation 5) holds.

From this equation, the magnetic field gradient necessary to suspend the solution is expressed by the following equation (Equation 6).

Next, the present invention will be described in more detail based on examples.
Consider the case where a protein crystal called lysozyme is precipitated from an aqueous solution.

The mass magnetic susceptibility K _gLysozyme of lysozyme is K _gLysozyme = −8.95 × 10 ⁻⁹ m ³ Kg ⁻¹ ,
The mass magnetic susceptibility K _gH2O of water is substantially equal to K _gH2O = −9.00 × 10 ⁻⁹ m ³ Kg ⁻¹ (see Non-Patent Document 2). The aqueous solution for precipitating protein crystals usually contains a crystallizing agent, but the concentration hardly changes during crystal precipitation. When the NaCl concentration of the crystallization agent is 0.15 M / liter, the density D of the lysozyme aqueous solution is expressed by (Expression 7) (see Non-Patent Document 3).

The volume magnetic susceptibility of the lysozyme aqueous solution is expressed by (Equation 8).

When these (Equation 7) and (Equation 8) are introduced into (Equation 4), the equation (Equation 9) of the magnetic field gradient necessary for suppressing the solute convection generated by the concentration gradient of lysozyme is given.

When K _gLysozyme = −8.95 × 10 ⁻⁹ m ³ Kg ⁻¹ and K _gH2O = −9.00 × 10 ⁻⁹ m ³ Kg ⁻¹ are _added to this formula, B (dB / dy) is lysozyme. Regardless of the concentration, it is −1394T ² / m. This gradient magnetic field is a gradient magnetic field (corresponding to 31 on the right of FIG. 3) in which the magnetic flux density B decreases as it goes vertically upward, and B (dB / dy) takes a constant value.

FIG. 5 shows the relationship between the gradient magnetic field (marked with _■ ) and the protein concentration at which convection is suppressed. Regardless of the lysozyme concentration, a gradient magnetic field of −1394T ² / m is required for convection suppression.

(Equation 6) was used to calculate B (dB / dy) required to float the solution. Explanation Figure 5 shows the relationship between the gradient magnetic field (marked with _◇ ) required for suspending the solution and the lysozyme concentration. For the suspension, a gradient magnetic field of -1372 T ² / m ² is required regardless of the lysozyme concentration.
For example, when crystals are precipitated from a 7% solution, a gradient magnetic field of −1394T ² / m is required for convection suppression and −372T ² / m for suspending the solution. (Note that
In the published paper (Non-Patent Document 4) that presupposes the present invention, in Table II, the absolute value of the gradient magnetic field B (dB / dy) necessary to suspend the lysozyme solution by magnetic force increases the lysozyme concentration. Although it was supposed to be gradually reduced, it is a calculation error, and it is corrected here as described above. )

A protein crystal (lysozyme orthorhombic crystal) for X-ray structural analysis was prepared using a zero gravity environment obtained by a magnetic force generated by a superconducting magnet (manufactured by Japan Superconductor, LH15T40). At the same time, protein crystals were prepared in a gravity-free environment with a normal gravitational field and a superconducting magnet, and the quality of each crystal was compared. In order to compare the quality of crystals with different volumes, factor B, which is a value that does not depend on the volume of the crystal, is used as a parameter indicating the quality (usually called temperature factor, obtained from measurement data of X-ray scattering intensity of the crystal). It was. As shown in Table 2, the B-factor of the crystal created by zero gravity in all three experiments shows a smaller value than that of the normal gravity field outside the magnet, and the convection generated by crystal growth is small. It has been proved that high-quality crystals can be obtained in a restrained weightless environment.

The present invention is further described in detail below based on Example 3.
Unlike Example 1, when the mass magnetic susceptibility of the precipitated crystals and the magnetic susceptibility of the solvent differ greatly,
This is a case where diamagnetic potassium chloride is precipitated from a diamagnetic aqueous solution.
The mass magnetic susceptibility of KCl is K _gKCl = −6.28 × 10 ⁻⁹ m ³ Kg ⁻¹ (Non-patent Document 2), which corresponds to about 70% of the mass magnetic susceptibility of the solvent water. In general, the density D of the aqueous solution at 25 ° C. is given by (Equation 10).

In a KCl aqueous solution, a ₀ = 997.123, a ₁ = 629.819, a ₂ = 131.029, a ₃ = 300.027 (Non-patent Document 5), and c is a mass fraction. The volume magnetic susceptibility of the KCl aqueous solution is expressed by the following equation (Equation 11).

When (Equation 10) and (Equation 11) are introduced into (Equation 4), the magnetic field gradient necessary for suppressing the solute convection generated by the KCl concentration gradient is given by (Equation 12).

FIG. 6 shows the relationship between the gradient magnetic field (marked with _■ ) and the concentration of KCl necessary for suppressing solute convection. For example, when KCl crystals are precipitated from an aqueous solution having a mass fraction c = 0.26, the gradient magnetic field necessary to suppress convection is −3000 T ² / m. Incidentally, as shown in FIG. 2, the magnetic field gradient necessary for canceling the gravity acting on the KCl aqueous solution and generating the upward magnetic force to float the solution is from (Equation 6), (Equation 10), and (Equation 11). And is given by (Equation 13).

FIG. 6 shows the relationship between the gradient magnetic field ( _◇ mark) required for suspending the solution and the concentration of KCl. For example, when KCl crystals are precipitated from an aqueous solution with c = 0.26, the gradient magnetic field required to suspend the solution is −1485 T ² / m, which is about half of the gradient magnetic field that suppresses convection. Thus, when the absolute value of the mass susceptibility of the solute is smaller than that of the solvent, a larger gradient magnetic field is required to suppress solute convection compared to the absolute value of the gradient magnetic field that suspends the solution.

In Examples 1, 2, and 3, both the solute and the solvent were diamagnetic, and their mass magnetic susceptibility was negative. When the solute is paramagnetic, the mass magnetic susceptibility has a positive value, and the solvent has a negative value, consider the case where cobalt sulfate crystals are precipitated from an aqueous solution as an example.
In a CoSO ₄ aqueous solution, a ₀ = 997.099, a ₁ = 1007.57, a ₂ = 356.4
96 (Non-Patent Document 5). K _gCoSO4 = 860.8 × 10 ^-9 m ³ Kg ^-1 (Non-patent Document 2)
_Is substituted into the equation (12) instead of the K _gKCl value, the relationship between B (dB / dy) necessary to suppress convection and the solute concentration c is obtained (FIG. 7). As a result, unlike Example 1-3, the value of B (dB / dy) is positive, and the gradient of increasing the magnetic flux density B along the vertically upward direction is represented by the broken line 32 in FIG. It is a magnetic field. As the concentration increases, B (dB / dy) gradually decreases. When the concentration of CoSO _{4 at which} crystals are precipitated is 0.09 in mass fraction, the gradient magnetic field necessary for convection suppression is as high as 12.9 T ² / m. Small.

FIG. 8 shows the result of calculating the gradient magnetic field necessary for _suspending the solution using K _gCoSO4 instead of the value of K _gKCl in ( _Equation 13). B (dB / dy) is larger than the gradient magnetic field necessary for convection suppression, and B (dB / dy) decreases as the concentration increases. When the concentration of CoSO _{4 at which} crystals are precipitated is 0.09 in terms of mass fraction, it is 178 T ² / m. In Example 4, it turns out that solute convection is suppressed by the gradient magnetic field whose absolute value is very small compared with Example 1-3. In the paper (Non-Patent Document 6) published in a magazine on November 21, 2005 after the publication of the published paper (Non-Patent Document 4) on which the present invention is based, paramagnetic nickel sulfate crystals were precipitated from an aqueous solution. The state of solute convection is observed by the Schlieren method, and it is observed that the convection is completely suppressed by a small gradient magnetic field (B (dB / dy) = 37.5 ± 0.5 T ² / m). It has been reported.

  As described above, the present invention has theoretically explained and demonstrated that convection can be controlled by a magnetic field based on a process in which some specific solutes are precipitated as crystals from a solution in which solutes are dissolved. However, it should be noted that the present invention has been described and disclosed for easy understanding of the present invention, and the present invention is not limited to these examples.

Chemical Chemistry Handbook II, pp. 507-510, Maruzen, 4th revised edition. W. L. Frederick, M.M. C. Hammonds, S.H. B. Howard and F.M. Rosenberger, J. et al. Cryst. Growth 141, 183 (1994). Nobuko I. Wakayama, “Damping of solid convection drastic crystal growth by applying magnetic field gradients”, Japan Journal of Applied Vs. 44, pp. L833-L835 (2005). Chemical Chemistry Handbook II, pp. 3-16, Maruzen, 4th revised edition. P. W. G. Pood, M.M. C. R. Heijna, K.H. Tsukamoto, W.H. J. et al. de Grip, P.M. C. M.M. Christianen, J.M. C. Maan, W.M. J. et al. P. van Enckevault, E.V. Vlieg, “Suppression of convection using gradient magnetic fields durning crystal growth of NiSO4 6H2O”, Applied Physics Letters Vol. 87, 214105 (2005).

  When a crystal is produced in a microgravity space environment, a high quality crystal is often obtained because convection generated with crystal growth is suppressed. In order to elucidate biological phenomena, develop new drugs, and research new treatments for diseases, detailed molecular structures of proteins are necessary. The structure of many proteins is determined by X-ray structural analysis, and the production of high-quality crystals is indispensable for determining the detailed molecular structure. When a crystal is produced in a microgravity space environment, a high quality crystal is actively studied and studied. However, actually conducting experiments directly in outer space is very expensive, and there are difficult circumstances such as limited opportunities for experiments. Therefore, if the convection can be suppressed on the ground, it is expected to greatly contribute to the development of the industry, and the development of a method for suppressing the convection on the ground and a device for implementing this method has been desired. The present invention can sufficiently meet such expectations. In the future, according to the present invention, it is possible to control convection by gravity and solute convection even on the ground, which leads to the creation of various high-quality crystals, especially high-quality protein crystals and organic semiconductor crystals. It is expected to contribute greatly to the development of industries by being used greatly in the development of electronic devices.

The figure explaining the solute convection which arises when a crystal precipitates from a solution. The figure explaining in principle the method of obtaining a zero gravity environment using upward magnetic force on the ground. The figure explaining in principle the method of suppressing the convection which arises with crystal growth with a gradient magnetic field. The figure which shows the case where solutions I and II from which a density | concentration differs exist. Lysozyme Concentration (Kg / m ³⁾ and convective inhibition _(■ marks), shows the relationship between solution stray gradient field value required _(◇ mark) (T ² / m). KCl concentration c and convective inhibition _(■ marks), it shows the relationship between solution stray gradient field value required (◇ mark) (T ² / m). Diagram showing the relationship between the required B (dB / dy) to inhibit the concentration c and the solute convection CoSO _4. Diagram showing the relationship between the required B (dB / dy) for suspending an concentration c and a solution of CoSO _4.

Claims (6)

  In a method for suppressing convection generated around a crystal when the crystal is precipitated from a solution, by applying a gradient magnetic field to the solution and the crystal, the buoyancy generated by gravity is offset by the buoyancy generated by the magnetic force, thereby reducing convection. A method for suppressing convection generated around a crystal, characterized by suppressing the convection.   The gradient magnetic field according to claim 1 controls the magnetic flux density to decrease or increase in the vertical upward direction, and the product of the magnetic flux density and the differential value based on the vertical position coordinate takes a specific value that suppresses gravity convection. 2. The method for suppressing convection according to claim 1, wherein:   In crystal deposition and growth methods, crystals are deposited and grown from solution. By applying a gradient magnetic field to the crystal and the solution, buoyancy generated by gravity is offset by buoyancy generated by magnetic force, and convection around the crystal is suppressed. Then, the method for depositing and growing crystals from a solution is characterized in that crystals are precipitated and grown.   The gradient magnetic field according to claim 3 is controlled so that the magnetic flux density decreases or increases along the vertical upward direction, and the product of the magnetic flux density and the differential value by the vertical position coordinate takes a specific value for suppressing gravity convection. The method for growing a crystal from a solution according to claim 3, wherein:   In a crystal precipitation growth apparatus for depositing and growing crystals from a solution, a gradient magnetic field generating means that can apply a gradient magnetic field to the crystal and the solution is provided, and the convection around the crystal can be controlled by controlling the gradient magnetic field. An apparatus for depositing and growing crystals from a solution. The gradient magnetic field is controlled to decrease or increase the magnetic flux density along the vertical upward direction so that the product of the magnetic flux density and the differential value according to the vertical position coordinate takes a specific value that suppresses gravity convection. An apparatus for crystal growth from a solution according to claim 5, which is characterized.