CH628527A5 - Method for moving molecules or ions in a semiconducting transfer medium - Google Patents

Description

The present invention relates to a method for moving molecules or ions, such as organic molecules, molecular aggregates in the form of colloids or crystalloids, or else inorganic ions, in a semiconducting transport medium. The mobility of the molecules or ions is induced in the semiconducting transport medium with the aid of intensive electrical fields at or near the minimum and optimal current strengths. Orientation, storage or transport can be achieved by this movement of the molecules or ions.

In the semiconducting transport media used in the method according to the invention, there is an extremely rapid movement or a transport of the molecules or ions, which is referred to as electromolecular movement, abbreviated as EMB, and in the English-language literature as "electromolecular propulsion", abbreviated as EMP.

The electromolecular movement is explained in the publication in "Chemical and Engineering News" volume 49, October 1971, pages 23 and 24, and it is already emphasized that non-polar materials can also be moved by this electromolecular movement, and that Methodology can be used instead of chromatography and electrophoresis.

The electromolecular movement not only results in a rapid movement of the molecules or ions, but also a great differentiation and resolution of the types of molecules or ions. Such a resolution makes it possible to achieve very sophisticated analytical separations.

In comparison to conventional techniques, previously unattainable or unique mobility and versatility of the system can be achieved. The invention provides a method for inducing mobility in molecules that were previously considered immobile due to their non-polar nature. In the case of polar molecules or ions, e.g. certain metal derivatives, a higher resolution is obtained than with conventional conductive or aqueous electrolytes.

The present invention relates to a method for moving molecules or ions in a transport medium, which is characterized in that a voltage of 0.05 to 30,000 V / cm which is sufficiently high around a current density is applied to a semiconducting transport medium to produce in the range of 0.001 to 400 [iA / cm2 and which is equal to or above the threshold current value for the molecules or ions in the medium below which the molecules or ions become practically stationary, and the voltage applied to the Molecules or ions a high speed of movement is induced.

When carrying out the method according to the invention, it is possible to use a semiconducting transport medium which allows working at high voltage and low current densities. In this case, a voltage of 50 to 25,000 V / cm is applied to the semiconducting transport medium, which is sufficiently high to achieve a current density in the range of 0.2 to 400 [iA / cm2, the voltage being equal to or above is the threshold current value for the molecules or ions in the medium below which the molecules or ions remain practically stationary and the molecules or ions are induced to move at high speeds by the voltage applied.

When carrying out the method according to the invention, a voltage in the range from 0.05 to 50 V / cm, which is sufficiently high around a current density, can be applied to a semiconductor fluid transport medium which contains a component of the group of the mobilizing agents and the initiators in the range of 0.01 to 0.2 (iA / cm2, and which is equal to or above the threshold current value for the molecules or ions in the medium below which the molecules or ions remain practically stationary, and wherein this induces a high speed of movement for the molecules or ions.

In connection with the examples, constituents are then mentioned which can be used as movers or initiators in this last-mentioned embodiment of the invention. Preferred compounds of this type are organic compounds with clearly polar properties, such as, for example, nitro compounds, aldehydes, ketones, nitrols, alcohols, phenols, amides, esters, ethers, organic acids and their salts and also also inorganic acids and salts.

According to a preferred embodiment of the invention, the composition of the semiconducting transport medium is selected so that it can be conducted with an applied voltage of 0.05 to 30,000 V / cm.

Preferred molecules or ions which are moved in the semiconducting transport medium when carrying out the method according to the invention are organic molecules, molecular assemblies assembled to form colloids or crystalloids and inorganic ions.

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In connection with the development of the method according to the invention, suitable media and systems have been produced within which the semiconducting molecular transport can be reliably achieved.

The method according to the invention is explained in more detail with reference to FIGS. 1 and 2.

When carrying out the method according to the invention, the conductivity of the entire system is shifted to the semiconducting area by adjusting the level of the conductivity of the media representing the mobile phase. Very high voltages can be maintained at low currents, so that thermoelectric heat generation (I2RT) allows the use of readily available materials and techniques for work systems. In contrast to conventional electrochemical transport methods, according to the invention very low current intensities are actually required, which correspond to the semiconducting nature of the process. This often precludes the need to use external heat convection devices and allows for small work arrangements and small power supply dimension requirements. Another advantage of the method is that the diffusion influence is minimized with the low heat values. The very low current values, which are sufficient in the method according to the invention, are almost optimal for the molecular movement, as induced by the attractive-repulsive interaction within the electric field, and under such conditions a very intense migration effect can be induced, which is proportional to the applied voltage potential is. This migration effect is characteristic of the molecular nature of the material and can be sharply differentiated from such similar or related, if not identical, molecules. The characteristic mobility or mobility of a substance in cm / sec can be used to classify or identify substances. The high degree of molecular resolution or differentiation can be achieved over a distance of a few centimeters in seconds or minutes, with comparatively less time being required over short distances - or by using higher voltages. It has been found that certain low amperage values are almost optimal for the EMB process, and they are defined here as a threshold function depending on the molecular type of the materials involved. The threshold value relates to the excitation states in a solvation-adsorption system. The usual observed ranges are 2 X KP to 1.6 X 10 ~ 5 A / cm2 for a cellulose substrate. Such thresholds relate to minimum power requirements to start the EMB process and are usually close to the optimal power requirements for a given system. The semiconducting area refers to methods of achieving suitable high voltage conductivity at the threshold area.

The method according to the invention can be carried out as a semiconductor transport in the liquid state or gas state.

Because of the ability to perform molecular shifts and the use of a mobile phase, it is a semiconductor fluid process. This distinguishes it from the stationary solid and amorphous semiconductor systems. Because of its influence on the electromolecular nature of the materials through induction and reaction with suitable electric fields, this method is applied to the main classes of known molecular substances, including inorganic ions, organic molecules, colloids and crystalloids. Therefore this is

Process applicable to inorganic materials, such as those derived from iron, copper, nickel, cobalt, rare earths, heavy metals, zirconium, and to the separation of ionic solvates from metal derivatives. It is also applicable to other materials such as e.g. Proteins, antibiotics, vitamins, antihistamines, amino acids, dyes and blood components.

In preparative chemistry, chemical reactions carried out under suitable EMB conditions can be used to shift reaction equilibria in favor of certain yields. There is an opportunity for selective consumption of the equilibrium product or of impurities or by-products in the reaction zone. When it comes to extraction, the EMB process acts as a minimal time-consuming process.

In applied chemistry it is applicable where very rapid and / or selective penetration-requiring processing or processing is desired, e.g. when dyeing or decoloring fabrics. The dyes or other detectable molecules in a mixture can be individually separated in a preselected or ordered pattern by controlling their EMB behavior.

Another advantage of the invention is that it allows the separation, identification or investigation of types of molecules based on the different threshold values. It enables control at different values under different conditions of pH, temperature, different media or other internal or external factors. An application for this would be a method that can first be controlled by operating the system with a lower threshold value for the first separation and then by switching to subsequent values to complete the resolution.

Main features for operation in practicing the invention are:

1. Set the work or operating phase to the semiconducting range to allow operation at or near the molecular thresholds and maximum or reasonable voltage levels that the system can maintain.

2. Establishing the optimal current value at or near the molecular threshold at the given voltage for effective molecular resolution.

3. Use of those components within the system and setting the system characteristics so that overall stability, reproducibility and security are achieved.

A useful analogy of this phenomenon and its relationship to electrochemistry is the comparison of solid state semiconductor physics with previous thermionic electrical engineering. Some similarities can be seen in the following properties of the EMB process:

1. The requirements for consumption (and dimensions) of the power supply are reduced to a minimum.

2. Minimum electrothermal losses allow small working dimensions and increased field intensities; this contributes to rapid resolution times with low distortion values.

3. The deteriorating influence on the system as a result of the need for high currents and the associated heat effects is eliminated. For example, at higher current densities than those used according to the invention, the mobility and the resolution of the type of molecule can be changed.

4. The scope and manner of electrical use is not limited to the more conventional types of conductivity, e.g. Ion transport in the liquid phase in aqueous electrolyte. Therefore, many different

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whose types of materials are influenced, examined or used in the EMB process. These include materials and systems, the electrical or ionic contribution of which would initially be regarded as poor in terms of their molecular structures. In addition, this can include a large number of non-aqueous, hydrophobic and otherwise non-polar substances as well as ionic, polar, covalent, aprotic or other conductive substances.

5. Operation at or near the lower thresholds can be achieved with high overall electrical motion. These threshold values are characteristic of a material and are generally present at very low current values.

The method can work at current values that are just sufficient to cause the movement of the molecular species, the electrothermal losses reaching negligible values.

Counteracting factors include evaporative cooling, the heat capacity of the container, thermal convection and the electroendosmotic flow. Controlled operation with increasing threshold values in turn stimulates the different types of molecules to move at the appropriate and characteristic values. This leads to an additional high resolution technique that is capable of differential molecular discrimination. This method of differentiation is further improved by the speed of movement, which is also characteristic of the type of molecule involved. This speed can be varied considerably by modifying the media.

Regarding the mechanism of the movement threshold value, it is found that this behavior determines the point at which the total energy supplied counteracts the molecular attraction or adhesion to the substrate (surface). It consists of the electrical energy supplied from outside plus what is otherwise based on distribution based on additional distribution functions. The molecules can then move freely or be moved by electrical attraction or other convective factors. The electrical characteristic of the system shows a non-linearity as the current gradually increases after the initial application of a given voltage. The preferred systems stabilize rapidly and remain electrically balanced during the separation process, although the process can be carried out when there are gradual changes in electrical properties. In cases where lack of stability leads to difficulties but the medium is otherwise considered useful, the rate of change in the resistance of the system can be slowed down by adding a sufficiently large external resistance, e.g. is about the same or greater than the internal resistance of the system. Alternatively, an active electrical element can be used that can sense the current-voltage or temperature values within a system and serves to regulate these factors or changes with the aid of a control of the current source. This procedure is also of value as a security measure.

Studies of components for the composition of the media have shown that certain combinations of connections are unsuitable for use in EMB when stable current values are desired. If a constant voltage is applied, these combinations always have a different resistance than if a capacitor were charged.

This effect is illustrated in Fig. 1 of the drawing. The current is plotted on the ordinate and time is plotted on the abscissa, working at constant voltage. The points t1 and t represent different

Represent times that are on the order of several minutes or seconds.

The behavior of three material types (A), (B) and (C) is illustrated. In the case of a material or a mixture of type (A), the current increases steadily over time and arcing may occur.

Type (C) illustrates a material or mixture in which there is a rise in current for a certain time and then the current drops again. This can be caused by the material evaporating or burning, charring or drying out when heated.

Type (B) illustrates a material or mixture that is a preferred medium from the point of view of electrical control because it enables reproducibility in operation and the readjustment of electrical properties is not a problem. Materials with an electrical behavior of type A can be freely chosen as components for the medium in order to balance properties of a medium which otherwise shows the behavior of type C, and vice versa. The electrical properties of a given connection can also change depending on the other substances with which it is mixed. Examples of compounds that illustrate the behavior of type A in mixtures and type B in other mixtures are given below. In general, one will choose a component for a medium that shows Type B behavior in conjunction with the other components in the system.

links

Behavior type

N, N-dimethylacetamide in water

A

N, N-dimethylacetamide in formamide

A

N, N-dimethylformamide in water

B

cycl. 1,2-propanediol carbonate in water

A

Ethylene carbonate in water

B

3-methylsulfolane in water

A

2-pyrrolidinone in water

A

N-methylformamide in water

A

N-methylacetamide in water

B

Tetrahydrofurfuryl alcohol in water

B

Tetrahydrothiophene dioxide in formamide

A

Diacetone alcohol in formamide

A

Diacetone alcohol in thiodiethylene glycol

B

Cellosolve in formamide

A

Cellosolve in thiodiethylene glycol

B

The EMB process differs from the known processes of electrophoresis and board electrophoresis in various respects.

The EMB response does not appear to be adversely affected by viscosity; it is improved by increasing the dielectric constant in the solution, while the electrophoresis mobility is inversely proportional to the dielectric constant, so the EMB can be performed at dielectric values that go far beyond the values that are practical in electrophoresis. The EMB has been carried out in media with a dielectric constant up to 190, e.g. in N-methylacetamide.

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The migration speed in cm / sec of molecules transported by EMB is significantly higher than the speeds achieved with dielectrophoresis and electrophoresis. This difference is illustrated by Fig. 2 of the drawing.

FIG. 2 shows a diagram in which the logarithm of the speed of migration is plotted on the ordinate. In Fig. 2 this is called log WG. There are three areas marked with the numbers (1), (2) and (3). Dielectrophoresis occurs in area (1). Area (2) is the area of the EMB where the conductivity is in the semiconducting area. Conduction of the electrolyte occurs in area (3).

The EMB process is presumably based on proton-donor-acceptor interactions and the formation of electron-batch transfer (charge transfer) complexes for transport. In this context, reference is made to the publication by R. Foster in Organic Charge-Transfer Complexes (1969).

In practical terms, a major aspect of this method involves the use of a relatively non-conductive medium. Numerous different media and techniques can be used to meet the needs of the semiconducting areas used. The piping can be carried out in solids, in semi-solid substances, e.g. Gels, as well as in the gas phase, in aerosols, foams and liquids. Combinations of these are also practical, such as melting, high-temperature melting, pseudo-crystals (paracrystals and meso-morphic substances), ice, mud, lubrication or suspensions, glasses, plastics, fibers, threads, porous materials and powders. Ion exchange materials, selectively permeable and membrane-like barriers, dialysis membranes, molecular sieves and special ion source materials are suitable as carriers or barrier substances. The process can be carried out continuously or in batches.

Many substances are relatively dielectric; among these, the non-polar organic substances represent a large group. Some of these show intermediate areas of conductivity or are accessible for a suitable adjustment of their conductive nature by adding relatively small amounts of additives. This may be similar to the method of doping or introducing or inoculating as used in solid phase devices. A relatively polar material can be used as a medium, e.g. aqueous solutions by limiting the system's ion content to achieve the desired conductivity value. Suppressive substances can also be added to the conductive system, among which desirable materials are those which have a suppressive effect beyond the pure dilution effect which their presence contributes to the system. Furthermore, the suppressive effect of non-polar materials used in a mixture with otherwise conductive systems offers a very general and useful solution for controlling conductivity. It is important to note that, with respect to all of these techniques, other factors may favor certain additional properties and characteristics of the materials used for the nature of the application, such as Miscibility, compatibility, toxicity, boiling point, melting point, reactivity, cost, removability, dialyzability and osmolality. Often a high dielectric constant material is preferred because of its ability to hold the charges formed in the system (involving solvation or interaction) or otherwise acquired or chemical particle induced or induced charges.

Mixtures of solvents can be used with the intermediary of a coupling agent, usually of a semi-polar cosolvent nature. The term semipolar is used for a material that exhibits a certain conductivity, which increases after dilution with water (or another, similarly polar material) and which increases after the addition of a soluble ionic salt. Thus, in the context of the invention, the solvation of a strongly ionic material in a non-polar material by means of a semipolar material generally only leads to a slight increase in conductivity, while the solution of the ionic material in the semipolar solvent alone can be moderately conductive. In fact, the non-polar material can be viewed as suppressing the bulk conduction capabilities to form a three component system. The three-component system therefore comprises an inert base, a conductivity agent and a semi-polar material, e.g. Xylene, ammonium bromide or dimethylformamide. Furthermore, a significant increase in the amount of the semipolar solvent can only minimally improve the conductivity. The addition of a relatively small volume of a second type of semi-polar solvent (a four-component system) can then cause a significant increase in the conductivity of the entire system. No cosolvent alone with the non-polar material, without or with the solvated ionic material, will achieve the conductivity value achieved in this way. This technique for increasing the conductivity of essentially non-polar materials forms a convenient working basis for the use of substances such as e.g. Xylene, p-cymene, mineral oil and chlorinated solvents. A four component system is illustrative e.g. the system xylene, ammonium bromide, dimethylacetamide and dimethylformamide.

The above effects can also be applied to systems that are not easily ionizable, and the components can be determined by factors such as the dielectric constant and proton donor ability of the solvating molecules. While medium donor capacity can generate solvated molecules, a high donor capacity in a highly dielectric system can easily maintain the ionic charges generated in this way. Of particular utility are media with a dielectric constant greater than 10 that tend to hold charges generated by proton-donor-acceptor exchange.

The media used according to the invention are distinguished by the fact that they are liquid at or near room temperature and have a boiling point which is sufficiently high to withstand the process heat. The boiling points are generally above 140 ° C, preferably above 165 ° C. The media do not have to be able to dissolve the chemical that is to be given mobility, but solubility is preferable for separating different types of molecules.

The invention is further illustrated by the following examples, which are directed to the separation of chemical substances in the specified media. The device consisted of a separation cell made of high density polyethylene divided into two 15 ml chambers.

The cell was built to withstand and withstand high voltage fields, as well as against a conductive leak or leakage of media under such fields and the leakage of the many strong and corrosive solvents used here. A platinum electrode in each chamber was connected to a DC power source, which generally operated at 1.25 mA. The current source could be in certain working areas with different voltage values in the ranges from 0 to 100 [iA, 0 to 1 m A and 0 to 10 m A

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for threshold value investigations and the implementation of the procedures described here. A filter paper wick in each chamber was connected to the opposite ends of the filter paper substrate protruding from the top of the cell. The filter paper was 5 cm wide and 10 cm long and was Whatman # 3 unless otherwise noted. Typically, the voltage drop in this system occurs substantially across the impregnated support, e.g. from 70 to 90% or more. The cell was enclosed by a transparent cover.

A suitable solvent can be selected from the class of low molecular weight glycols with a small amount of an additive which increases the conductivity. The following solvent systems are useful for relatively non-polar dyes as well as other soluble organic materials. The solvents listed were used to separate chemical mixtures, e.g. of dyes, mercurochrome and sodium riboflavin phosphate used at the specified values of voltage and current. The term "stabilized" is used to indicate that the electrical parameters reached the specified values and remained constant for the few minutes (generally 2 to 10 minutes) during which the separation process was completed.

example

Solvent electrical compositions

Parameter

(stabilized)

1

0.3 ml water, 0.2 ml Sörensen buffer (pH 7.0), 24.5 ml propylene glycol. The amount of water in this type of system should preferably not exceed about 2%.

11 kV / mA

2nd

2.0 ml dimethylacetamide, 1.0 ml phenol, 25.0 ml propylene glycol.

8 kV / mA

3rd

2.5 ml formamide, 22.5 ml propylene glycol.

5.5 kV / mA

In Examples 1 to 3, a potential difference of 11 kV and a current of 1 mA were used.

In the longitudinal direction, the filter paper used measured about 10 cm, and a field strength in the size

11 KV

Order of = 1100 volts / cm applied.

10 centimeters

The filter paper used was 10 cm X 10 cm, and accordingly had a cross-sectional area of 100 cm 2. The current density is determined by dividing the current (in the present case = 1 mA) by the cross-sectional area (in the present case = 100 cm2). Accordingly

1

in the present case the current density = 0.01 mA /

100

cm2 = 10 [iA / cm2.

It should be noted that the thickness of the filter paper used is not included in the formula for calculating the current density.

The system used in Example 3 is excellently suited for dye dissolution of the following mixture: saframine O, toluene red (neutral red) and sodium ribofla-

vin phosphate. This medium is also useful for the separation of members of the rhodamine dye family.

Unlike conventional ion transport processes, the mobilization of metal derivatives is not easy to achieve, even if the metal derivatives are soluble in the medium. By setting the medium and the electrical parameters, however, a very fine resolution in a system such as the following can be achieved according to the method according to the invention, which illustrates a new mode of operation, as described here. Examples of suitable metal ions are Co ++, Cu ++, Ni ++ from salts, such as the chlorides and nitrates.

The same potential difference, field strength and filter paper as used in Examples 1 to 3 were also used in the following examples.

example

Composition of the solvent electrical

Parameter

(stabilized)

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10 ml dimethylformamide, 15 ml pro

8 kV / mA

pylene glycol and (if applicable)

1 ml triethanolamine.

A non-aqueous system based on ester is illustrated below and also leads to satisfactory results. Instead of the cellosolve in the medium, other related compounds can be used, e.g.

30 hexyl cellosolve, methyl carbitol, cellosolve acetate and carbitol acetate.

example

Composition of the solvent electrical parameter (stabilized)

5

4 ml formamide, 14 ml cellosolve, 34 ml dimethyl phthalate.

15 kV / mA

The following solvent systems are useful for the separation of metal ions and complexes; of these metal complexes, dithizone, nitroso-B-naphthol, pyro-catechol-violet, rhodamine B, 8-hydroxyquinoline and di-benzoylmethane derivatives were used.

example

Composition of the solvent electrical parameter (stabilized)

6

30 ml methoxy-athoxy-ethanol + 30 ml cyclic 1,2-propanediolcarbonate + 3 drops of nitric acid (1:30 in H20).

6.4 kV / 1.25 mA

The medium of Example 6 gave multi-zone dissolution (5 min) with 8-hydroxyquinolinates rare earths, 60 such as e.g. Sc and Eu, as well as other metals, such as: Ni. The heavy metal derivatives of dibenzoylmethane and rhodamine showed good to excellent movement, while the movement with heavy metal nitrates was very sparse and did not occur with hafnium (as chloride) at all. Adequate mobility was also obtained for Co + 2, Cu + 2 and Ni + 2 (as chlorides).

In the previous example, the nickel chloride resulted in 3 zones, with spots of blue and violet. Such reproducible

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Effects show the very large resolution of the technology. This also indicates the formation of a number of metal complexes, such as through proton-donor-acceptor exchange, and on the ability of technology to differentiate and resolve them. This unusual ability comes to light in another situation where not only do several zones appear, but they also appear as (+) - as well as (-) - mobile units. Mobility of +2 cm / min was achieved with the following system:

Example composition of the solvent electrical parameter (stabilized)

15 ml methoxyethoxy - ethanol + 15 ml cycl. 1,2-propanediol carbonate + 13 ml ethylene carbonate + 3 drops of nitric acid (1:30).

6 kV / mA Co * 2 (chloride) 2-3 zones (+ and Nr2 (chloride) 2-3 zones (+ and Cu-2 (chloride) 4-5 zones (+ and 6 min running time

Dye saframine 0 at 500 V and 100 [xA rapidly, and an orange contaminant remained immobile. This is an example of separation of components by reaching the threshold for a compound in the mixture.

Acidification with an inorganic acid is not essential, as the following example shows:

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The medium of Example 7 also provided excellent mobility for salts of europium, lutetium, thallium and ytterbium. The location, mobility and character of the zones obtained are characteristic of the material within the system under given conditions. In the following system, nickel and cobalt (as chlorides) gave 1 or 2 zones, while the mixture gave 3 zones corresponding to the individual metal components. In addition, the zones had three colors with clearly different pink and blue.

example

Composition of the solvent electrical parameter (stabilized)

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12 ml 1,2-propylene glycol + 3 ml

14 kV / 1.5 mA

Dichloroacetic acid + 16 ml ether

oxy-ethoxy-ethanol.

Bases, such as Media containing triethanolamine or y-picoline instead of acid have the ability to separate metals.

The applicability of the invention to organic compounds is further illustrated by the following systems for the separation of sulfa drugs, sulfamerizine, sulfaquanidine and sulfamethazine.

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The composition of the solvent is electrical

Parameter

(stabilized)

30 11 20 ml methoxy-ethoxy-ethanol + 5.8-5.0 kV / 12 ml l-methyl-2-pyrrolidinone + 1.25 mA 0.8 ml dichloroacetic acid. 4 min run time

Example composition of the solvent electrical parameter (stabilized)

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21 ml cycl. 1,2-propanediol-carbonate + 9 ml methoxy-ethoxy-ethanol + 8 ml Y-butylrolac-clay + 3 drops of nitric acid (1:30).

7.8-7.6 kV / 1.25 m A 6 min running time

The groups of rare earths as well as hafnium and zircon represent the most difficult elements to dissolve. Furthermore, just like hafnium and zircon form a particularly close pair, 3 major sub-groups are known within the rare earths. The following systems are for the transition heavy metals, rare earth salts and zircon / hafnium elements, e.g. those with an atomic number of 21 and above, included, can be used.

The composition of the solvent is electrical

Parameter

(stabilized)

15 ml cycl. 1,2-propanediol carbonate + 15 ml methoxy - ethoxy ethanol + 13 ml ethylene carbonate + 3 drops of nitric acid (1:30).

9.6-7.2 kV / 1.25 mA 3 min running time

40

45

The latter system, although found slow, could provide different zones with the rhodamine 5G, 6G and B dye family and a mixture.

The following media gave high resolution of the above dyes in 20 to 25 seconds and mobilities above 12 cm / min.

Compositions of the solvent electrical parameter (stabilized)

12 24 ml cycl. 1,2-propanediol carbonate + 12 ml ethylene diacetate + 6 ml salicylaldehyde + 3 drops nitric acid (1:30).

13 24 ml cycl. 1,2-propanediol carbonate + 12 ml ethylene diacetate + 6 ml salicylaldehyde + 2 ml ammonium bromide (saturated solution methoxy-ethoxy-ethanol) + 2 ml tributyl phosphate + 4 drops tetramethylam monium hydroxide (about 25%

60 in methyl alcohol).

50

55

13.2 kV / 0.8 mA

13-12.6 kV / mA

In a system with cyclic propanediol carbonate, nitric acid, methoxy-methoxy-ethanol and tetrahydrofuran furyl alcohol in proportions similar to the above, the moved

It should be noted that urea or propylene glycol in such systems in concentrations of up to several moles do not change the conductivity, although the mobility of protein molecules is also promoted. These substances act as diluting or suppressing agents and are in aqueous solutions for biochemical separations from

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Substances such as Proteins and enzymes, useful. The mobility of albumin in such systems can exceed that of glycol-soluble dyes, as shown by the following information about the migration from the starting point:

example

Solvent electrical compositions

Parameter

(stabilized)

14

16 ml tris chloride (0.03 m) +

6 kV / 2 mA

40 ml propylene glycol + 50 ml

Whatman No. 1

Glycerin.

Albumin 1

i-h "

soluble dye

6 min run time

As discussed below, the above systems can be improved in speed and level of resolution using starters, suppressants, and / or stabilizers.

The method according to the invention was also carried out in such a way that a sample was added to a bed made of a gel made from agar, silicon dioxide and gelatin. This procedure was used to separate dyes, proteins and other types of organic compounds. The media and electrical parameters. were similar to those described in the previous examples. Bulk separations were also carried out in a column with powdered minerals or cellulose carriers.

A very useful system for non-polar substances that resolved isomers of methylnaphthalene and provided good dissolution for rhodamine B and 6G and food colors is:

21 ml cycl. Propylene carbonate 9 ml methoxy-ethoxy-ethanol 12 ml tetrahydrofurfuryl alcohol 3 drops nitric acid (1:30).

In the above formulation, various types of compounds have been used to perform various important functions. For purposes of illustration, a number of them have been selected to be grouped into different categories according to some of their common functions in recipes. However, these categories are not rigidly defined restrictions on the use of the connections, and some fall into several categories across their boundaries at the same time. Thus, dimethyl phthalate is an example of a good suppressive agent, although it also acts as an inert base when used as a base medium. It can also make it insoluble or restrict mobility or influence other factors in order to increase resolution. Water can be used as a fairly active solvent with a massive proton donor capacity and high dielectric constant. However, water is generally less useful as a major component at higher voltage levels in non-cooling systems because of its low boiling point.

TABLE I

Basis for the inert medium property:

Solvent of minimal conductivity, inert carrier,

solution-limiting p-Cymol

Mineral oil n-decanoi

1-octanethiol xylene

5 inhibitors (suppressive agents)

Property:

negative influence on the conductivity tributyl phosphate dimethyl phthalate io triacetin

2-ethyl-hexyl chloride

Basis for the neutral medium property:

15 low or sparse conductivity with a tendency to actively change conductivity with dilution with solvent, highly effective agent for promoting solubility, coupler.

-Butyrolactone 20 cycl. 1,2-propanediol carbonate propylene glycol 2-phenoxy-ethanoi 2-ethyl-l, 3-hexanediol tetrahydrothiophene-1,1-dioxide 23 methoxy-ethoxy-ethanol

Conductivity means perchloric acid dichloroacetic acid 30 formamide

Ammonium bromide pyridazine iodide nitric acid mercaptoacetic acid

35

Basis for the active medium property:

low conductivity with a tendency to increase the conductivity of the base for the neutral medium.

40 Strong solubilizer, solvent 2-chloroacetamide dimethylformamide N, N-dimethylacetamide l-methyl-2-pyrrolidone 45 dimethyl sulfoxide cyclic ethylene carbonate 2,5-hexanedione

Mobilizers such as isophorone nitrobenzene salicylaldehyde

4-hydroxy-4-methyl-2-pentanone ethylene diacetate 55 Y-picoline o-dichlorobenzene

Initiators property:

60 strong influence on conductivity, proton donor solvent action and acidity-alkalinity diethyl-ethyl-phosphonate N-cyclohexyl-2-pyrrolidone bis- (2-methoxyethyl) -ether 65 hexamethylene-phosphoric acid triamide aminoethyl-piperazine imino-bis-propylamine 2,2'- Imino-diethanol

2-aminoethanol triethylenetetramine triethanolamine mercaptopropionic acid mercaptoacetic acid

A starting point for the development and selection of a solvent medium for special chemical substances is the determination of those media which stabilize or are compatible with the substances and which have a good to excellent distribution coefficient with a standard chromatographic technique for the substance at different pH values have using substrate. Then the conductivity value for use in this method is adjusted by adding the solvent as a main ingredient to a compatible basic system of the medium having an appropriately adjusted conductivity,

or the conductivity of the solvent can be dimensioned such that a base system for the medium is formed by using the types of agents described in Table I. Mobility is typically achieved at around 1.25 mA, a value that generally exceeds most threshold current values. Further adjustment may be necessary to start or refine the mobility or mobility of the chemical particles by adjusting the composition of the system as indicated above. For example, adjustment can be made using complexing agents, modifying agents, similar solvents as determined by chromatographic separation, pH adjustment, and less active substrates (such as poly-tetrafluoroethylene).

The following list of substances can be seen in three main categories, as indicated below. Other factors to be considered are a larger range of the liquid and the dielectric constant, low viscosity, compatibility and miscibility with water and strong donor-acceptor influence or neutrality:

1. The main group has boiling points at or above 160 ° C and is liquid at or near room temperature. In general, it has good solvent activity.

2. A number of useful compounds have boiling points below 160 ° C or melting points slightly above room temperature. They are often used in lower percentages in modified systems. Often they can also be liquefied with a smaller amount of cosolve or used in melting systems.

3. The other compounds are modifying agents whose melting points can be considerably higher and which are used in solution with other media or in melting systems.

On the basis of physical characteristics, chromatographic and solvent separation experiments and the techniques for adjusting the media described here, a long series of suitable compounds can be developed from known commercially available materials or those which are available through synthesis by the person skilled in the art. For this reason, only a brief exemplary compilation of those compounds which are suitable as initiators is given below by way of illustration.

Aldehydes, ketones, nitriles cinnamaldehyde 1,2-cyclohexanedione 4-anisaldehyde p-chlorophthetol

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Butyrophenone

4-chloro-3-hydroxybutyronitrile ethyl cyanoacetate glutarnitrile hexachloroacetone iminodiacetonitrile 2,4-imidoxolidinedione 2-hydroxy-acetophenone p-methoxyphenyl acetonitrile O-methyl-anisole

2-methylpiperazine-N, N'-dicarboxaldehyde

N-morpholino-carboxaldehyde

Nicotinitrile

5-nitrosalicylaldehyde nicotinaldehyde picolinitrile 2-piperidone pimelonitrile piperonal

1.4-piperazine-dicarboxyaldehyde pyrrole-2-carbaldehyde pyridine-3-carbaldehyde tetrahy droionone veratraldehyde

Alcohols, glycols, phenols, polyglycols

2-amino-2-methyl-1-propanol cedrol

3-chloro-1,2-propanediol cyanoethyl-sucrose dehydroisophytol dehydrolinalool dichlorotriethylene glycol 2,6-dinitrothymol furfuryl alcohol

3-hydroxycampher hydroxyethylpiperazine 5-hydroxy-2- (hydroxymethyl) -4H-pyran-4-one 5-indanol dl-menthol 2-mercaptoethanol N-methylol-2-pyrrolidone 2,2 ', 2 "-nitrilo-triethanol 2- Nitro-1-propanol

Polyethoxyated lanolin (5+) alcohols

4-pyridine propanol

2,5-tetrahydrofuran-dimethanol l, l, l-trichloro-2-methyl-2-propanol (and hydrates) thiodiethanol

Amides and related compounds urea

N-ethyl-p-toluenesulfonamide

N-2-hydroxyethyl acetamide

Methane sulfonamide

N-ethylformamide

Picramid

Thioacetamide

2-furamide

Formamidine acetate

4-acetamido-butyric acid

2-acetoacetamido-4-methylthiazole

Anthranilamide

Chloral formamide

Diacetamide

N, N'-diallyl-tartaric acid diamide n-butyramide

Cinnamic acid

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N-methyl nicotinamide

N-isopropyl salicylamide

5-hydroxy valeramide

N-methyl propionamide

Iso-nipecotamide

2-hydroxy-ethoxy-acetamide

N-hydroxyacetamide

3,5-dinitrobenzamide

N, N-dimethylacetoacetamide

N, N-diethyl-1-piperazine carboxamide

N-ethyl acetamide

Hexamethyl phosphoric acid triamide

Hexamethyl phosphoric acid triamide

N-formyl hexamethyleneimine

2,2,2-trichloroacetamide p-nitrobenzamide

Sulfamide

N-Fulf onyl stearami d

Thionicotinamide

Pyrazinamide

2-hydroxyethyl carbonate 1-N aphthaline acetamide tert-butyl carbazate lactamide

N-methyldiacetamide p-acetamidobenzaldehyde

Esters

Butyl chloroacetate

Bis (2-chloroethyl) carbonate

Butyl stearate

2-chloroethyl chloroacetate

Ethyl methyl carbamate

Giykol dimercaptoacetate

Hydroxyethyl acetate

Isopentyl nitrite

Phenyl carbonate

Methyl oleate

Polyethylene glycol (200) dibenzoate

Tetrahydrofurfuryl oleate

Tributyl borate

Tributyl citrate

2,2,4-trimethyl-l, 3-pentanediol diisobutyrate ether

Dibenzyl ether

Dimethoxy-tetraethylene glycol

Dimethyl polysiloxanes

Diethoxy ethyl phthalate

N-butylphenyl ether

Crown ethers

o-ethoxyphenol

1-ethoxy-naphthalene

Glycerol dimethyl ether p-hexyloxyphenol

Methoxyethyl ricinoleate

2-vinyl oxyethyl ether

Different connections

Lewis acids, bases and salts

Tetranitromethane

N-acetyl morpholine

Acriflavin

amino acids

Benzothiazole o-aminophthalic acid hydrazide butyl sulfone

Bis (2-ethylhexyl) hydrogen phosphate acidic dimethyl pyrophosphate

Guar gum

1-nitrosopiperidine

Indole

Pyridazine

T rimethy lsulf oxonium iodide

Inorganic salts, acids Cedren

Trimethylene sulfide

Chloropicrin

Lithium stearate inorganic salts

Calcium borgluconate

Aminophosphoric acids

Diphenyl selenide

Bismuth ethyl campherate

Sulfur iodide

Trimethyl sulfoxonium iodide

Trichloromethylphosphonic acid

Picramic acid

Aminoethane thiosulfonic acid.

As part of the method that can be used to classify the materials listed here, they can be titrated with distilled water and their conductivities preserved. The dilution / conductivity curve thus obtained indicates the rate of change of conductivity with the dilution, as well as the point of decrease or plateau values of conductivity as achieved in reasonable diluents, which helps to characterize the materials in terms of the various categories discussed here, such as such as very effective solvents, effective solvents, etc. The following information illustrates the use of this technique (the resistances are given in MQ). The very low resistance plateau at the specified dilution values shows that dichloroacetic acid and mercaptoesacetic acid belong to the category of very effective media. The somewhat higher plateau of ethylene carbonate and 2,5-hexanedione places them in the active media category.

Such a method can be used to set up an appropriate evaluation scale for evaluating the various media. This technique helps to bring media to a desired conductivity value by determining resistance values at various dilution values.

sample

Initial resistance 0.3 ml

Resistance with 0.05 ml water addition

Resistance with 1 ml of water

Dichloroacetic acid

100

0.042

0.001

Mercaptoacetic acid

1

0.050

0.004

Ethylene carbonate

0.2

0.20

0.065

2,5-hexanedione

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2.2

0.060

Often, even miscibility with water is sufficient to specify the expected activity range or properties. These investigations are further expanded by titration against substances other than water. For example, Dichloroacetic acid, formamide and thiodiethylene glycol are used. These then embody a different solvent miscibility and

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-profile. Among these agents, the formamide has a very high dielectric constant and a higher conductivity than water, while the conductivity of the thiodiethylene glycol was in the range of the water used and also reached the conductivity value of the water when a drop of water was added; i.e. so, after only a slight dilution with water. The conductivity changes caused by dilution with non-aqueous substances were further characterized by observing changes in the plateau values caused by the addition of a very small amount of secondary solvents, which may be water. This helps to establish a relationship between the influence of secondary solvents, e.g. of the active or very active type (or the inert type for suppressive activity) and the conductivity profile. Such effects are variable or characteristic of the diluents to which the secondary diluent is added. Furthermore, the conductivity titration curves can be examined with a special diluent of value for conductivity, which can be an already ionized system or a system with higher conductivity. E.g. can be called the dilution of hydroxy compounds and ethers with moderately conductive aqueous ammonium nitrate solution and acetic acid. The comparison was made where the latter two systems had equivalent conductivities. The dilution of the aforementioned aqueous conductive solutions by the compounds 1,3-butanediol, 2,2-methoxy-ethoxy-ethanol, 2-oxydiethanol, bis- (2-methoxyethyl) ether, sorbitol (40 vol .-% solution) and sorbitol (57 vol .-% aqueous solution)

generally shows a similar decrease in conductivity over the titration range, although certain clearly defined waveforms have been derived. The relative activity and the suppressive profile of the various diluents became apparent. With this technique, the essential difference with bis (2-methoxyethyl) ether can be easily recognized. Differences were also noted in the effects of aqueous sorbitol at various concentrations compared to non-aqueous materials on the ionized ammonium nitrate solution, which were otherwise less pronounced than on dilute acetic acid solution. Furthermore, the different systems can be examined under the aspect of how they influence the data for equilibrium characteristics, ionization and / or formation for the substances of interest and at different pH values. A large anthology or a library of data can be created for these different possibilities in order to achieve a reduced empirical basis for the conditions of the system selection for use. As a result of the invention, an already developed extensive table for basic solvent systems is available, from which future classification for the development of media for use with particular species or substances can be made.

As illustrated by the above examples and the list of chemical substances, the method according to the invention partly includes the separation or mobilization of chemical particles or substances, conveniently on a carrier, such as e.g. a filter paper, in a medium of low conductivity, to which a high voltage is applied. The base of the medium comprises one or more connections, e.g. inorganic or organic compounds, e.g. Glycols, ethers, esters, diones, lactones, amides, nitriles, alcohols and water. A medium can be added to the medium to adjust its conductivity, which can be selected from the group consisting of water, acids, bases and salts. The voltage used in the process is in the range of about 50 to 25,000 V / cm. Cooling may be required at very high voltages, and particularly with volatile or gaseous substances. The preferred range is about 200 to 3000 V / cm, and in this range the process can be carried out without external cooling. The conductivity of the medium is preferably set in such a way that a current density in the range from approximately 0.2 to 100 (iA / cm 2, based on the area of the substrate, such as filter paper, for example. The preferred range is 1.4 to 54 (iA / For work in bulk or substance and with external cooling, current densities above 100 (iA / cm2 can be used. After the conductivity has been suitably adjusted, the transport medium is subjected to a sufficiently high voltage at a low current value (for example at the threshold value) in order to separate the chemical Inducing substances or particles therein at a rate of about 1 cm / sec to about 0.25 cm / min In the above examples, no external cooling was required under the conditions given.

Refinement of media assembly techniques can lead to improved resolution in the separation of given components by EMB. E.g. the medium of 5 ml of cyclic propanediol carbonate, 5 ml of propylene glycol, 2 ml of N-methylacetamide and 0.4 ml of tetrahydrofurfuryl alcohol enables the dissolution of rhodamine B and 6G from example 12 in considerably less than the 3.6 cm required in example 12. The use of improved resolution to shorten the separation distances makes it possible to minimize the diffusion effects.

It is possible to generally improve the resolution according to the following procedure. A suitable solvent is found for the chemical to be transported. The nature of the chemical to be transported is then analyzed in terms of its proton donor acceptor properties. The donor-acceptor properties of a number of chemical substances are listed in the literature in the catalog. See e.g. V. Gutmann, Coordination Chemistry in Non-Aqueous Solutions (1968). Then a component should be added to the medium that participates in a proton-donor-acceptor interaction with the chemical. In many cases, the proton donor acceptor properties of the chemical have not yet been cataloged or are complex. In such cases, the nature of the components of the medium that improve the resolving power can be determined by testing the system, simply by adding a very strong proton donor to one sample and then a very strong proton acceptor to another. If the strong donor increases the mobility (rate of movement) of the connection, donors of different strengths are then tested to determine which of them provides the greatest improvement in mobility and resolution. The procedure is analogous if the strong proton acceptor increases the mobility of the chemical. The addition of a component that can relate to the chemical or particle being transported through proton-donor-acceptor interaction appears to facilitate the initial mobility of the chemical species. The dielectric constant of the medium is then set to a moderately high value if necessary. It may also be necessary to correct the electrical instability of the medium by adding a compensating component as detailed above.

As a further aspect of the invention, it was found that an improved composition of the semiconducting media also enables certain chemical species to develop an EMB response that is visible to the naked eye at relatively low voltages and low current values compared to the high 5 described above

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voltage processes, can be observed. Voltages below 50 V / cm and even below 20 V / cm have been used on conventional carrier media. You can e.g. Achieve EMB transport with current values down to approximately 3 X 10 ~ 6W to 1.7 X 10 "5W with voltages of 2 to 4 V at 1.5 to 4.2 jiA over several centimeters of Whatman No. 1 filter paper This means EMB operation at potentials of several mV / cm at tenths of fxW / cm2. The limit at low voltage EMB is the value at which electrical diffusivity comes into play. It has also been found that certain means meet the threshold current value of a chemical species (chemical substance or chemical particles) Low voltages of 0.05 to 50 V / cm applied to the medium to produce a current density of 0.001 to 0.2 or up to 4 jxA / cm2 can be used .

A media system is modified so that it can respond to low voltage EMB and lower the threshold current value in the same way as it is modified to improve resolution. In particular, starters (initiators) and mobilizing agents are added. Starters are compounds that act to lower the threshold current of a given chemical species, and mobilizers are compounds that increase the mobility (rate of transport) of a given chemical species. There is some overlap between the classes of compounds that can be used as starters or initiators or as mobilizers, i.e. some compounds act both as starters and as mobilizers.

In general, materials that act on a proton donor acceptor value with the chemical species to be transported and materials with high dielectric constants are useful as initiators and mobilizers. Examples of compounds that are often useful as both starters and mobilizers are N-methylacetamide and salicylaldehyde.

With the use of starters, threshold currents can be set down to 0.2 to 0.002 or 0.001 [xA / cm2, and the EMB can operate with these currents at lower but still effective moving speeds with voltages down to 0.05 to 10 V / cm can be performed. The voltage value of 0.05 V / cm was a practical minimum in the practical implementation, since voltage effects of this magnitude, which are inherent in the system, occurred. Overall, considering both the high voltage and the low voltage EMB, the EMB voltage range can be 0.05 to 25,000 V / cm, with the power values down to 1.2 X 10-9 to 5 X 10-5 W / cm2.

The following examples illustrate how the media used for EMB transport according to the criteria of semiconductor capability and compatibility with chemical species, as described in connection with high voltage EMB, are modified with starters to reduce the threshold current.

Example compositions of the solvent

16 7 ml propylene glycol, 3 ml diacetone alcohol (mobilizing agent, also increases the resolution), 2.2 ml N-methylacetamide (high dielectric constant, acts as a starter and mobilizing agent), 1.3 ml formamide (also).

17 21 ml cycl. Propanediol carbonate, 9 ml methoxy-ethyl-ethanol, 12 ml tetrahydrofurfuryl alcohol, 3 drops ENT diluted 1: 3 with water.

The medium of Example 16 was used to separate rhodamine dyes and also to separate vitamin B12 and sodium riboflavin phosphate mixtures.

The medium of Example 17 was used to separate Rhodamine B and 6G over less than 0.5 cm. The tetrahydrofurfuryl alcohol increased the mobility of the compounds and thus increased the molecular differences. Without this component, the two fabrics showed almost equivalent movement over several centimeters.

For further examples, the medium of Example 17 can be changed to increase its conductivity by dropwise addition of conductivity starter or mobilizing agents (A) to obtain the electrical values (B) and the performance values (C) of the table below .

electrical

Total EMB values

Medium EMB run (on performance value

4x1 cm filter- in [xW paper)

(A) (B) (C)

Nitric acid (1:30 in water)

4 V, 4.2 jxA

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Ammonium bromide (saturated in glycol)

10 V, 1.1 [xA

11

Formamide

10 V, 1.2 [XA

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N-methyl acetamide

20 V, 2 | xA

40

N-methylformamide

10 V, 4.1 [xA

40

Hexamethyl-phosphorus

10 V, 3.5 [XA

35

acid triamide

EMB can be used to mobilize high threshold current biochemicals such as proteins, polypeptides, nucleic acids, steroids, lipids, lipoproteins and fatty acids. Proteins and other biochemical compounds are easily subject to thermal and chemical changes and are usually handled in aqueous solution, often in ice-cooled, buffered electrolyte solution. Water as the main component in EMB media has the disadvantage of forming and rather evaporating electrolyte solutions. Special attention was paid to adapting systems with a high water content to EMB use, as well as the application of EMB to proteins and related substances in non-aqueous systems. Since the activity of biochemical compounds is tied to their structural integrity and sensitivity, another goal was to put together a diverse set of media that sustain this activity.

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The general technique for formulating an aqueous EMB medium for protein transport includes reducing the conductivity of water by adding a suppressive agent, adjusting the dielectric constant by adding a high dielectric material, if necessary, and adding strong and / or mobilizing agents to promote the movement of the proteins.

As indicated above, it has been found that a number of compounds suppress the conductivity of water to varying degrees, thereby alleviating the problem of high conductivity in aqueous media. These compounds also act as miscible protein solvents. The results of the conductivity suppression are given in the form of the example below.

Example 18

Numerous protein-compatible solvents have been combined with water (volume ratio 16/9). Pure solvents have been used, if possible, since the trace contaminants in commercially available materials can impair conductivity suppression (this is illustrated by the values given for compounds (7) and (18), which are the same substance but of two different ones Sources come from). Relative values of conductivity suppression compared to water conductivity were:

(1) Thiodethylene glycol 2.2

(2) 2,6-dimethylmorpholine 2,6

(3) methoxy-ethoxy-ethanol 2.6

(4) 2-pyrrolidone 2.7

The more strongly suppressive compounds are:

(5) Y-butyrolactone 3.3

(6) Sorbitol 3.8

(7) 1,3-butanediol 3.6

(8) Propylene glycol 3.6

(9) Dimethylformamide 3.6

A group of higher strength suppressants are:

(10) Dimethylacetamide 4.8

(11) tetrahydrofurfuryl alcohol 4.6

(12) Butoxy-ethoxy-propanol 5.0

(13) 6-hexanolactone 5.0

(14) Oxydiethanol 5.4

(15) Diacetin 5.6

The really powerful class of water suppressants can be represented by:

(16) 2- [2- (ethoxy-ethoxy) ethoxy] ethanol 8.3

(17) l - {[2- (2-methoxy-l-methylethoxy) J-10 -l-methylethoxy} -2-propanol 10

(18) 1,3-butylene glycol 12

1 Choosing a suitable suppressant solvent should take into account the effect of the suppressant on protein migration. Thus, the above compounds (10), (11), and (13) may promote protein motility, while (3), (4), (9), (14) and (18) may be less potent in this regard .

Other solvents for biochemical compounds include alcohols such as e.g. Methyl carbitol, phosphonates such as e.g. Diethyl ethyl phosphonate, lactones, e.g. 6-hexanolactone, and sugar.

The compatibility of the solvent with the substrate is another aspect. If the solvent is selected improperly, it can attack the substrate, which leads to a change in porosity, structural breakdown or similar effects. Appropriate choice of solvent in media formulations enables application e.g. the ion exchange of «thin-film» plates and films 5 of cellulose derivatives, e.g. nitrate or acetate, or agarose, acrylamide or silica gel, which are impregnated with EMB media.

The use of strong excess suppressants can result in a system with such high internal resistance that there is significant resistance heating, particularly where operation at high threshold current is indicated. The choice of a less powerful suppressant is often satisfactory. The Tc requirements of proteins and related substances are often in the range of 4.6 mA / 50 cm2 or above on a cellulose substrate, compared to 1.2 mA / 50 cm2 or less for most other compounds.

Lowering the water content of EMB media as described above can change the dielectric constant of the medium. This change can generally be compensated for by adding components with very high dielectric constants, as a result of which the high dielectric constant desirable for the EMB is restored. Examples of suitable materials for adjusting these dielectric constants are, for example, hydroxyethyl-form-amide, N-methyl-formamide, formamide, N-methyl-acetamide and related compounds. In general, N-alkyl and N-aryl amides are useful. Often, these compounds, especially if they are only commercially available, tend to increase the conductivity of the medium, which counteracts the suppressive mechanism. Such a contribution to conductivity can be used to compensate for an excessively high internal resistance caused by a strong suppressant.

35 High threshold values of biochemical species or substances can advantageously be reduced by using starters and mobilizing agents and mobility in EMB can be increased. Many proteins proved to be particularly susceptible to the influence of proton acceptor sub-40s in increasing mobility, but were relatively indifferent to mobilization by proton donor molecules. Starter or initiator substances, even when present in relatively low concentrations, contribute significantly to lowering the threshold current, and if they also act as mobilizing agents, then also to increase the mobility of the species. For proteins, initiators can be used to change the threshold values from 4.6 mA / 50 cm2 to 3.4 to 1.0 mA / 50 cm2 (20 [iA / cm2) at voltages in the range of 50 to 25 000 V / cm. Typical initiator substances, mobilizing agents and usable solvents are nitrobutanol, 3-acetyl-3-chloropropyl acetate, salicylaldehyde, N-methyl-acetamide, boric acid, phenols, guaia-kol, fumaric and barbituric acid, piperazine, furfural, tribut-55 oxyethyl phosphate, ß , ß, ß-trichloro-t-butyl alcohol, dimethyl - l, 3-dioxolane-4-methanol, 2-ethyl-sulfonyl-ethanol, tetrahydrofurfuryl alcohol, N-substituted pyrrolidones, dimethyl sulfoxide, 2,2-oxydiethanol, cyclic Ethylene carbonate, tetramethyl urea, thiodiethylene glycol, 1-ethynylcyclo-60 hexanol, tetrahydro-3-furanol, 2,6-dimethyl-m-dioxan-4-ol acetate and 2,5-bis (hydroxymethyl) tetrahydrofuran, other amides, in particular N-alkyl and dialkyl and hydroxy amides, other proton acceptors and buffer systems. Substances with a high dielectric constant very often act as mobilizing agents or initiators.

Proteins are often electrophoresed in a high pH (alkali) buffer due to the dependence on isoelectric points in electrophoresis. The EMB

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Protein transport, on the other hand, can be carried out in acidic media. Buffers can be made from the list of biologically compatible agents as given below, or they can be of the commonly used types such as Tris, Veronal or Sörensen. In addition, more common organic acids and bases can be used. Examples of acidic buffers that are useful for EMB transport of proteins and related substances are as follows:

Tetramethyl-ammonium hydroxide / acetic acid, triethylene tetramine / 2,2-oxydiacetic acid, dimethylamine / picric acid, diethanolamine / dichloroacetic acid, triethanolamine / dichloroacetic acid, piperazine / dichloroacetic acid.

A compilation of agents for using buffer formulations with minimal impairment of sensitive biological systems is given, as well as a brief list of other representative agents that are satisfactorily accepted to be generally useful for biological work. Additional criteria for this latter group are low melting point, a good range of liquid state, water solubility, other solubility, solvent activity, inert behavior or functionality, etc.

TABLE IV

Biologically compatible buffering agents and zwitterionic buffers

Cyclohexylaminoethane sulfonic acid,

N'-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid

Tris (hydroxymethyl) methylaminopropane sulfonic acid

TABLE V

Other representative materials suitable for use in EMB media in biological systems

Acetamidocaproic acid

L-x-acetamido-ß-mercaptopropionic acid

Acetamidophenol

Acetanilide

Allantoin

Alantolactone

1-allyl-2,5-dimetholy-3,4-methylene-dioxybenzene n-amyl-butyrate

Anhydromethylene citric acid

B-L arabinose

Arabitol

Arachidonic acid

Benzyl acetate

1,3-bis (hydroxymethyl) urea

Bis (2-ethylhexyl) -2-ethylhexylphosphonate

Ethoxy (10-20) glucose

Ethyl linoleate

Ethyl laevulinate

3-ethyl-1-hexanol

2-ethyl-2-methyl-succinimide 2-ethyl-sulfonylethanol ethylene glycol diacetate

1-ethynyl-cyclohexanol

Eugenol

Farnesol

Fructose

D-gluconic acid 5-lactone glutathione

Glycerophosphoric acid

14

2,6,10,15,19,23-Hexamethyltetracosan 3 -Hydroxy-2-butanone

2-hydroxybenzylphosphinic acid N- (2-hydroxyethyl) palmitamide

5-hydroxy-2-hexenecarboxylic acid lactone 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexene 15-hydroxy-pentadecanecarboxylic acid-s-lactone 5-hydroxy-2 ( hydroxymethyl) -4-pyrone

3-hydroxy-3,7, ll-trimethyldodecanecarboxylic acid, io ichthymal

Isoascorbic acid isoeugenol

Inositol hexaphosphoric acid isopropyl myristate

15 isovaleric acid isovaleramide kojic acid lactobionic acid linoleic acid

20 lipoic acid

Methylal-acetamide methyl nicotinate y-methyl-a, ß-crotonolactone N-methyl-pyrrolidinone 25 l-methoxy-4-propenyl-benzene p-methoxy-benzaldehyde p-methoxy-benzyl alcohol myristyl alcohol

3,4- (methylenedioxy) benzaldehyde 30 nicotinamide ascorbate

Nicotinic acid monoethanolamine 2-nitro-2-propyl-l, 3-propanediol octane carbon (caprylic) acid oleic acid 35 oils, natural orotic acid

N- (pantothenyl) -ß-aminoethanthiol pantothenic acid cocoa butter 40 e-caprolactam choline salts

2- (chlorophenyl) -3-methyl-2,3-butanediol cineol (eucalyptol)

citric acid

45 oc, ß-cyclopentamethylene tetrazole diethyl ethyl phosphonate N, N-diethyl-isovaleramide N, N-diethyl-m-toluamide

2,2-dimethyl-1,3-dioxolan-4-methanol 50 2,6-dimethyl-m-dioxan-4-ol acetate

Dimethylpolysiloxane

2,3-Epoxy-2-ethyl-hexanamide eicosamethylnonasiloxane ethyl phenyl ether

55 O-ethoxybenzamide propoxy (10-20) glucose pentaerythritol chloral pentaerythritol tetraacetate

3-pentanone

60 3-phenoxyl-l, 2-propanediol phenoxyacetic acid

Polyethylene (20) sorbitan monooleate a-phenylbutyramide 2-phenyl-2-hydroxy-propionamide 65 2-phenyl-6-chlorophenol piperidinium salt

Poly (ethylene glycol) p-nonylphenyl ether polyoxyethylene stearate

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Polyvinyl alcohol

Polyvinyl pyrrolidone

N-polyoxyethylene fatty acid amides

6-propylpiperonyl-butyl-diethylene glycol ether

3-pyridineethanol

2-pyrrolidinone

Polyethylene glycol p-isooctylphenyl ether

Steroids, natural and derived, e.g., ex-lanolin

Salicylamide

Sorbic acid

Tannina cis-t erpin hydrate

T etrahydro-3-furanol

Tetrahydrofurfuryl alcohol poly ethylene glycol

3,7,11,15-tetramethyl-2-hexadien-l-ol

2,6,10,14-tetramethylpentadecane

Tetraethylene glycol dimethyl ether

Thiamine and derivatives

Theophylline and salts

O-thiocresol

Thuja acid

Tiglinamide

Tocopherols, tocols

2,2,2-trichloroethanol

Triethylene glycol

3,5,5-trimethyl-2,4-oxazolidinedione

Undecylenic acid

Veratrol

Viologens

Vital stains

Valerolactone

Vitamins K, A and derivatives wetting agents

Media prepared as above in combination with water, one or more suppressants, one or more dielectric constant increasing agents and one or more initiators (and / or mobilizing agents) enable the separation of proteins within about 1 min over a distance of a few centimeters a Whatman # 1 filter paper, while the same separation on the same substrate would take up to 16 hours over up to 15 cm of substrate using electrophoresis.

A number of proteins and related substances are insoluble in water. For example, some derived or conjugated proteins, as well as some polypeptides, keratins and prolamines, are water-insoluble. Although this problem can be overcome in some cases by using modified aqueous media, the use of non-aqueous media offers additional flexibility.

An alternative to aqueous EMB systems for proteins and other biochemical compounds is the use of other solvents, the water in the proton donor number (DZ = 18.0 for water) and in the dielectric constant (DK = 81.0 for Water) are analog. Cyclic ethylene carbonate (DZ = 16.4, DK = 89.1, boiling point 245 ° C) and propanediol-1,2-carbonate (DZ = 15.1, DK = 69.0, boiling point 240 ° C) are particularly useful ). These solvents give the composition of the medium superior thermal stability and enable work with larger resistance and higher voltage gradients without the need for external cooling.

Certain solvents show a more intense solvent effect than water for some proteins. For example, keratins that are water-insoluble can be used in other solvents, e.g. Dimethyl sulfoxide. Prolamines can be dissolved in glycols, glycol ethers and certain alcohols.

Solvents with moderate to strong proton acceptor properties are suitable for dissolving compounds and can even form the basis of the medium. Solvents of this type include iodine monochloride, sulfur dioxide and hydrogen fluoride. For example, anhydrous hydrogen fluoride is a good solvent for fibrous proteins that are normally insoluble in water. Collagen substances, as well as elastins and reticulins, especially resist being dissolved in aqueous media, while being soluble in non-aqueous media.

The media for protein EMB transport may include other protein solvents selected for certain properties, such as e.g. Glycols, amides, ethers, pyrrolidones, lactones, sulfoxides, phenols, alcohols and phosphonates.

Suitable aqueous systems for the transport of proteins are in accordance with the table of suppressants above using a solvent / water volume ratio of 16/9:

16 ml of thiodiethylene glycol 9 ml of water

2 drops of ethanol lamb

(Separation of protein mixtures including cytochrome C and myoglobin)

electrical characteristic 1.8 kV / 1.2 mA

16 ml 6-hexanolactone 9 ml water

3 drops of ethanolamine

(resulted in protein movement and dissolution)

electrical characteristic 1 kV / 1.2 mA

16 ml dimethylacetamide 9 ml H20

4 drops of ethanolamine (separation of protein)

electrical characteristic 1.6 kV / 1.2 m A

The following three examples illustrate non-aqueous media representative of those used for EMB transport of human and bovine albumin, hemoglobin, cytochrome C (an enzyme), myoglobin (muscle protein) and pancreatin. In addition, proteins have been separated from blood in experiments in which the cell fragments have been left in their initial state. In these last separations, phenol was a useful component of the medium.

Example 19 12 ml of cyclic ethylene carbonate 6 ml of ethoxyethoxyethanol 6 ml of thiodiethylene glycol

6 drops of tris-dichloroacetic acid buffer

Example 20

7 ml of cyclic ethylene carbonate 7 ml of ethoxy-ethoxy-ethanol

9 ml oxydiacetic acid 1.5 ml formamide

6 drops of tris-dichloroacetic acid buffer

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Example 21 10 ml cyclic ethylene carbonate 4 ml N-methyl-pyrrolidone

3 ml furfuryl alcohol 2.5 g boric acid

4 ml of 1,3-butylene glycol

16 drops of piperazine dichloroacetic acid buffer

(pH 3.7) acridine orange (fluorescence indicator)

The following example illustrates EMB media and electrical conditions used to separate albumins and especially globulins.

The composition of the solvent is electrical

Parameters

(stabilized)

22 10 ml cycl. Ethylene carbonate, 5.2 kV / 2.0-3.6 4 ml butylene glycol, 4 ml methyl mApyrrolidinone, 2 ml Form-Whatman No. 1 amide (initiator), 2.5 g boric acid, (10 cm) 3 ml Furfural (pH buffer and mobilizing agent),

] 6 drops of piperazine dichloroacetic acid buffer, pH 3.7 (pH buffer and mobilizing agent), acridine yellow (fluorescence indicator)

The same medium was used to separate cytochrome C, hemoglobin, myoglobin, albumin, yohimbine and atro-pin.

The use of dyes, which act as identifiers or tracers, can be desirable in some cases in order to visually monitor the separation of colorless biochemical substances, cf. Examples 21 and 22. However, the special dye must not interfere with the separation process itself. Bromophenol blue was commonly used with serum proteins. but can migrate separately from the protein in the EMB. Methylene blue is often suitable for redox-sensitive materials, and glutathione, either in oxidized or reduced form, can be used to buffer against redox reactions. Saframine-type dyes bind to proteolytic enzymes and change their solubility properties and can therefore be useful for separating them from other materials. A few milligrams of an easily coupled fluorescence tracer, e.g. Acridine orange enables visual observation of many substances, including proteins, under UV light without changing their migration properties. Other tracers such as Brighteners, fluorescent couplers, and even fluorescent antibody material can be useful for tracking protein transport. Other tracers for biochemical and other work are natural dyes, such as the flavine and primulin, Nile blue can be particularly useful alone or in combination with other dyes under UV and daylight. Neutral red with aesculin alone remains sensitive when diluted about 10,000 times with daylight. The UV dyes are also used to localize weak positive or negative Ladunde in biological structures. Antibodies or other coupling tracer substances as well as radioactive derivatives can also be useful, e.g. Rhodamine B-isothiocyanate, fluorescein isothiocyanate, p-isothiocyanato-acridine, 4-chloromethyl-l-acri-din, l-ethyl-2- [3- (l-ethylnaphthol-ri, 2b] -thiazolin-2-ylidine ) -2-methylpropenyl} naphth [1,2] thiazoium bromide. Other possible tracers are phenazine methosulfate, rema

zol-brilliant blue R, thiazolyt blue, protoporphyrin IX, citra-zinic acid, quinine, lisamin, rhedamine, Cleves acid and umbellifero) !.

Another aspect of the invention is the application of the EMF media formulation technique to produce gaseous semiconducting media, which allows controlled conduction without the need for evacuation, very high temperatures or very high voltages. The application of the formulation techniques for liquid EMB media to the formulation of gaseous media led to the achievement of high conductivity values without the need for high potential. The purpose of the construction of a gaseous EMB medium is to increase the conductivity value of the gas to the value of the semiconductor capability or another value that is suitable for the desired application.

Gases have been widely used in industry as insulators. The current practice of conducting gases is mostly aimed at the high dielectric properties of gases in general. The conduit usually takes place within a jacket or other controlled environment in a relative vacuum using an energy source (such as a thermoelectric filament) to control the conduit. In such devices, the presence of materials with lower dielectric properties is harmful or even destructive. The conductivity of gases is currently also important in the field of ionization or the plasma state. Attempts have been made to generate electricity by moving conductive gases relative to a magnetic field (magneto-30 gas dynamics), but it has been found necessary to use temperatures so high that corrosion of the containers occurred. Now it has become possible to obtain conductive gases at or near room temperature through the use of EMB, and this makes it possible to provide a practical means of generating electricity.

The formulation or combination of gaseous EMB media leads to a useful scientific technique for studying the molecular properties of. Fabrics. In addition, the invention can be used for the construction of devices for controlled lines in gases which are used for wireless transmission (e.g. in transformer cores, without winding), in the case of studies of light emission,

in charge transport and molecule transport in gases, electrically triggered gas diffusion and in devices with 4s low-voltage spark gap. EMB media formulation can be used to modify fuel combustion systems and the fuel itself in internal combustion engines in such a way that the ignition distance is increased (for example, to allow the ignition-50 candle electrodes to be moved further apart so that there is less danger of explosive propagation leave).

Principles similar to those that apply to the production of liquid semiconducting EMB media also apply to the production of gaseous semiconducting EMB media. Media containing a number of components, e.g. 3- or 4-component systems are necessary to effect a significant change in the conductivity of the gas to bring it into the semiconducting region. Agents whose interaction enables or facilitates a proton-donor-acceptor interaction, increased conductivity and a higher dielectric constant are specified.

For example, Water through hydrogen bonding in the vapor phase as both a donor and an acceptor molecule in interaction with proton donors, which range from strong acids to alkanols (e.g. l, l, l, 3,3,3-hexafluoropropane) 2-ol), and with acceptors, such as

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e.g. Amines (including pyridines), ethers, alcohols and ketones. In general, solvents have proven to be particularly suitable for conduction in gases, the more conductive or active they were as EMB solvents.

Mixing materials together also promotes improved conductivity.

For example, placing a few drops of tri-ethylenetetramine on the bottom of a test glass tube placed in a slightly heated sand bath increases the resistance between the electrodes with an electrode spacing of 0.5 cm and 2.5 cm above the bottom of the tube of more than IO9 Q in Air down to IO6 Q. The addition of a small iodine crystal reduced the resistance to less than 8 X IO5 Q. Addition of formamide instead of iodine resulted in 1.5 X IO6 Q, and both together reduced the resistance to less than 5 X IO5 Q. With some media, resistances of hundreds of Q were obtained at low voltages (5-10V) at around room temperature and atmospheric Get pressure.

medium

Cell resistance

Sequence of addition added - total quantity in the mixture

Tetramethyl urea oo (> 100 megQ)

5 parts

5 parts

+ N-methylacetamide

1.70 megQ

1.5 parts

6.5 parts

+ I2

75 KQ

Part 1

7.5 parts

+ Diethylamine

18 KQ

1.5 parts

9 parts

Agents useful for formulating or assembling gaseous EMB media include iodine, other halogens, amines, volatile salts, amides, nitroderivatives including nitrosyl chloride, acid chlorides, hydrazine, oxyhalides, sulfur dioxide, hydrogen fluoride, ammonia or other strong proton donor - or - acceptor molecules, their combinations and substances that they release. According to the principles of the formulation of liquid media, as modified above, semiconducting media composed of such components offer a controllably conductive gaseous environment even at atmospheric pressure in air. The use of high-boiling chemicals as classified for the use of liquid EMB media requires elevated temperature to produce the gas EMB effect. The use of low-boiling solvents is therefore preferable for the production of gaseous EMB media.

Voltages of, for example, 0.1 to 30,000 V / cm can be applied to gaseous EMB media, which leads to continuous conduction (instead of arcing). Modifying agents may be included in the media to induce arcing in the range of 110 to 30,000 V / cm to make them useful for fuel systems, so as to improve the propagation properties of the ignition sparks and / or the electrothermal evaporation before Modify or extend ignition.

Another aspect of the invention is the practical application of EMB in a gel. The gel consistency can be between liquid and solid. Gels are generally susceptible to resistance adjustment by adding a small amount of a conductivity agent with a high dielectric constant material, e.g. Formamide or another amide or alkylamide derivative and, if necessary, a coupler solvent to improve miscibility. The EMB medium can be flushed into the gel or the gel can be made with the medium. A difficulty associated with the use of gels as an EMB medium is that by-products still remaining from the gel manufacturing process have to be removed if they influence the setting of the EMB conductivity and the transport.

Agar gel, polyvinyl alcohol, silica gel, starch gel, carboxy-polymethylene (Carbopol) and "Crash Safe Aviation Jet Fuel" (with modified kerosene) are examples of gels that act as EMB media if they are used in accordance with the principles described above suitable, the conductivity 15 modifying agents are doped. Acrylamides could also be used. An example of a gel made with an EMB solvent is polyvinyl alcohol made into a gel with tetrahydrofurfuryl alcohol. Tetraethyl orthosilicate, which results in a clear, glass-like gel with numerous organic gels 20, enables compatibility with numerous organic EMB media. Gelatin also provides a clear gel base. Examples of chemical substances that can be transported in such gels are dye molecules, and even particulate substances can be transported at 25 high speeds in a "fluid" gel, such as e.g. the “crash safe aviation fuel”.

As with the EMB, voltage and current values are set on cellulose substrates. A somewhat higher current than 1.2 mA / 50 cm2 can also be used for thin gel plates [up to 3.175 mm 30 (1/8 ")]. Otherwise gels with a thickness of 9.53 to 12.7 mm (3/8 to 1/2 ") or more careful choice of current to avoid excessive heat generation.

With EMB separation processes, gels can lead to increased dissolution or separation due to their fine pore structure. EMB-induced movement of dye molecules in a gel can be used as an analytical technique to study the structure and properties of the gel itself.

40 The device used for gel EMB differed from that used for liquid EMB in that the filter paper substrate was replaced with the gel.

EMB in a gel is illustrated by the following examples.

45.

example

Composition of the solvent

23 glycol, ammonium bromide and formamide

50 24 5 w / v% ceresin or micro wax in 20% or 30% xylene plus EMB medium components that are suitable for use with xylene.

55

The components of the EMB medium mentioned in Example 24 can be the 4-component system described on page 5 or ammonium bromide in methoxy-ethoxy-ethanol, 2 (2-ethoxy-ethoxy) ethanol, dimethylformamide, 60 dimethylacetamide, Dimethyl sulfoxide, n-butanol or N-methyl-pyrrolidinone.

For various purposes, electromagnetic fields can be used in addition to the driving voltage in connection with the EMB. A second set of electrodes at an angle of 65 to the set that applies the driving voltage can be used to throw the transported chemical particles from a straight direction of travel. Similarly, one or more electrodes at an angle to the set,

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which applies the driving voltage can be used to compensate for any slight lateral deviation or spread of a species migrating on a substrate and to counteract the diffusion effect. In addition, a matched pair of electrodes can be placed perpendicular to the path of the chemical species being transported and used to detect the passage of different zones of chemical species based on the change in electrical forces between the second set of electrodes.

Pulsating direct current fields can be used instead of a constant direct current driving force to reduce the heating of the medium. As an additional modification, an alternating current field can be superimposed on the direct current driving force in order to mediate the dielectric and semiconducting properties of the medium and to take advantage of the Debye-Falkenhagen (solvent) effect.

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1 sheet of drawings

Claims (5)

628527 2nd PATENT CLAIMS 1. A method for moving molecules or ions in a transport medium, characterized in that a voltage of 0.05 to 30,000 V / cm is applied to a semiconducting transport medium, which voltage is sufficiently high to have a current density in the range from 0.001 to 400 [iA / cm2 to generate and which is equal to or above the threshold current value for the molecules or ions in the medium below which the molecules or ions become practically stationary, and wherein the applied voltage to the molecules or ions a high speed of movement is induced. 2. The method according to claim 1, characterized in that a voltage in the range of 50 to 25,000 V / cm is applied to a semiconducting transport medium, which allows working at high voltage and low current density, which is sufficiently high around a current density to deliver in the range of 0.2 to 400 [iA / cm2 and which is equal to or above the threshold current value for the molecules or ions in the medium under which the molecules or ions remain practically stationary, and whereby by the applied Voltage induces a high movement speed to the molecules or ions. 3. The method according to claim 1, characterized in that a voltage of 0.05 to 50 V / cm is applied to a semiconductor fluid transport medium containing a mobilizing agent and an initiator, which is sufficiently high to a current density in the range to produce from 0.001 to 0.2 [iA / cm2 and is equal to or above the Schwel-Ien current value for the molecules or ions in the medium below which the molecules or ions remain practically stationary, and thereby thereby the molecules or Ions a high movement speed is induced. 4. The method according to claim 1, characterized in that the semiconducting transport medium has a composition which allows conduction at an applied voltage of 0.05 to 30,000 V / cm. 5. The method according to claim 1, characterized in that the molecules or ions moving in the semiconducting transport medium are organic molecules, molecular assemblies assembled to form colloids or crystalloids or inorganic ions.