CA1065274A - Electromolecular propulsion in diverse semiconductive media - Google Patents

Abstract

ABSTRACT
This application is directed to an electromotive pro-cess for exciting a chemical species which includes orientating, re-positioning and transporting and for the separation of chemical species on a support. Unlike conventional semiconductive tech-nology in the solid state and amorphous state, the present pro-cess is directed to electrically induced molecular transport in semiconductive media, as distinct from charge transport alone.
The semiconductive medium is generally of the liquid, gas or gel form.
The process of this invention is characterized by a high mobility rate in the separation process which is achieved by tailoring a semiconductive medium for operation over a wide range of voltages at low current density. The voltage applied is preferably in the range of about 0.05 to about 25,000 volts/cm.
The semiconductive media used in this invention generally comprise several components which are chosen to give a current density in the range of about 0.001 to 400 micro amp/cm2 on filter paper as a substrate. The media should also have a high boiling point. A further aspect of the process is that an external cooling means is not ordinarily required.

Description

1065;~74 This invention pertains to a method of exciting a chemical species to achieve mobility for orientating, reposi-tioning and transporting the species and for separation among species achieved by operation at the appropriate conductivity range of the media-and especially within the semiconductive range when induced by means of intense electrical fields at or near minimum and optimum current levels. Such systems are - characterized by extremely fast molecular motion, or transport, hereinafter called electromolecular propulsion (E~), as well as by great differentiation or resolution of molecular species.
Such resolution is capable of accomplishing very refined analytical separations.
- The present invention, in one broad aspect, resides in a process which comprises imparting mobility to a chemical species by providing a semiconductive transport medium and impressing a voltage of about 0.05 to 25,000 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.001 to 400 microamps/cm2 and equal to or exceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high mobility rate for the species.
In another broad aspect, this invention resides in a process which comprises imparting mobility to a biochemical species by providing a fluid semi-conductive medium comprising water, a conductivity suppressant, a high dielectric constant component, and a component selected from the group consisting of mobilizers and initiators, and applying a voltage within the range of about 0~05 to 25,000 volts/cm across the medium sufficiently h gh to produce a current density of at least

2 microamps/cm and equal to or exceeding the threshold current ., .

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~` 1065Z74 value for the biochemical species in the medium, below which value the biochemical speciss remains substantial'y stationary.
Also provided by this invention is a process for effecting conduction in a gas which comprises providing a multi-component gaseous semi-conductive medium containing components with proton donor/acceptor interaction capability, ,...
, high dielectric constant and high conductivity and applying i a voltage of about .05 to 30,000 volts/cm to achie~e continuous conduction.
A yet further aspect of the present in~ention is the method of separating a mixture of substantially non-polar dyes which comprises mixing said dyes with a semi-conductive medium on a substrate and applying a voltage in the range of from 200 to 25,000 volts/om at a current density in the range of about 0.001 to 400 microamp/cm across said substrate, said current density being equal to or exceeding the threshold current level for one dye but below the threshold for at least one other dye in said mlxture.
By comparison with conventional techniques, hereto-fore unobtainable or unique mobilities as well as system versa-tility can ke achieved. This invention provides a method for inducing mobility of molecules previously considered non-mObile due to their non-polar nature. In the case of polar molecules, such as certain metal derivatives, a greater resolution is obtained than that achieved with conventional conductive or aqueous eiectrolytes. These, plus additional useful factors favoring this technique, permit exceedingly high resolution separation or purification of different types of molecular species to be efficiently and very rapidly achieved. Suitable detection and/or separation means gives this process an import-ant utility for analytical, purification, and production :. .
proce2ures. It also serves as a research tool for the study, characterization and elucidation of structural and physical-chemical attributes of chemical systems, materials .. ..

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and their interactions.
An aspect of this invention pertains to the prepara-tion of suitable media and systems, within which the semicon-ductive molecular transport can be reliably accomplished. This S can be performed in various media; i~ being generally convenient to utilize liquids for the mobile phase. The conductivity of the entire system or process is brought within the semiconductive range by adjusting the conductivity level of the media constitut-ing the mobile phase. Very high voltages may be sustained at low current levels such that the thermoelectric heat buildup (I2RT) nevertheless permits usage of readily available materials and techniques for working systems. In contrast to conventional electrochemical transpoxt methods, in this invention very minute current levels are actually required which correspond to the semiconductive nature of the process. This often precludes the need for employing external heat convective means and permits small working configurations and small power supply size require-ments. Another advantage of the process is that at the low heat levels of this invention thermal interference is minimized. The very low current levels which suffice in this invention are near optimum for molecular movement as induced by the attractive-repulsive interaction within the electricfield, and, under such condition~, a very intense migratory effect can be induced which is proportional to the voltage potential applied. This migratory effect is characteristic for the molecular nature of the material and may be sharply differentiated from even similarly or related, though unidentically structured, molecules. The characteristic mobility of a substance in cm/sec may be used to classify or identify substances. The great degree of molecular resolution or differentiation may be accomplished over the distance of a 11)~;5Z74 few inches in a matter of seconds or minutes wherein proportion-ately less time i~ required over small distances or by the use - of higher voltages. I have discovered that certain low current levels are near optimum for the EMP process and are defined herein as threshold level function dependent upon the molecular nature of the materials involved. The threshold refers to excitation level states in a solvation-adsorption system. The usual observed ranges are 2xlO 7 to 1.6x10-5 amp/cm2 for a cellulose substrate. Such threshold levels refer to minimal current requirements for initiating the EMP process and are usually close to the optimum current requirements for a given system. The semiconductive range refers to method~ to achieve suitable conductivity at high voltage at the threshold range.
The media used are capable of sustaining high voltage electrical fields and are tailored to have a chemically adjusted and/or controlled level of aonductivity internal to the mobile phase and in combination with the substrate, by technique~ consistent with the various electrical, chemical and operative requirements of the working system.
Under such conditions an intense compulsive regponse with very fast mobility or orientation and high resolution separation of molecular types are readily achieved. Such systems are very convenient and advantageous to operate. Their effi-ciency is high; heat loss is a minimum, and they are applicable within aqueous, hydrophobic and otherwise non-aqueous media.
This process may be accomplished as a liquid-state semiconductive transport or gaseous state semiconductive trans-port. Due to it~ ability to effect molecular transpositions and its use of a mobile phase, it i8 a ~emiconductive fluidic process~ This distinguishes it from the sessile solid state 4.

and amorphous semiconductive system~. By vi~tue of it~ effect upon the electromolecular nature of materialR through induction by and reaction to suitably intense electrical fields this process has applications to major classes of known molecular materials including inorganic ions, organic molecules, colloids, and crystalloids. Thu6, this process i9 applicable to inorganlc materials such as derived from iron, copper, nickel, cobalt, rare earths, heavy metals, zirconium, and the separation of ionic-solvate specie~ of metal derivatives. It is alao appl~cable to other materials such a~ proteins, antiblo~ics, vitamins, anti-histamine~, amino acido, dye~tuffs and blood eon~tituents.
By virtue of the ex~remely great resolution whieh can be obtained by application of EMP and the very greAt speed with ; j~ which such s~parations can be achieved, and the various typeR of oy~tems in which the process can be applied, it offero advantages and applicatlon~ to various fields and operative procedures, including: analytlcal chemistry, quallty control, ellnlcal ehemistry~ renearch; preparative chemlstry~ physleal chemistry;
purifieationt extractionJ proce~ eontrolJ applled ehemi~try;
and semleonductlve technology.
By way of lllu~tratlon, ln preparatlvo choml_try, chemi-cal reaction~ conducted under ~ultable EMP aondltlono oan be uoed to dlaplaee roaetlon o~ulllbrla to ~avor ~rtaln ylelds.
It o~fer~ a meano for ooleetlve aeplotlon of e~ulll~rlum produet from the ~phere of the roaetlon zone, or of eontaminants, or byprodueto. In oxtraetlon, EMP aet~ ao a mlnlmal tlme eon~umlng proee~o eopsolally ~rom thln-walled matorlals, partleulate~, or ; porou~ ~ubotanees. In applled ehomiatry, it lo u~ful whore very rapid ana/or ~eloetlve ponetratlvo proee~ing ia d~lrad, e.g., ln dyoing or de~talnlng fabrle~. The dyoa or oth~r d~toetable ~065~74 - molecules in a mixture may be individually deposited in a pre-selected or ordered pattern by control of their EMP response.
Another advantage of the invention is that it permits the separation, characterization, or study of molecular types ` S by virtue of the differential threshold levels. It permits ~ control at different levels under various conditions of pH, - temperatures, different media, or other internal or external factors. An application of this would be a process which is con-; trollable by first operating the system at the lower threshold `
level to effect the first separation; then going on to subsequent ~`- levels in order to complete the resolution.
Major operative features for the practice of the invention are:
1. Adjusting the operative phase to the s~miconductive range to provide operation at or near molecular threshold levels and maximum or convenient voltage levels capable of being ` sustained by the system.
2. Establishing the optimum current level at or near the molecular threshold level at the given voltage for effective molecular resolution.

3. Utilizing those components within the system and arranging the systèm characteristics such that overall stability, reproducibility, and safety, are attained.
A useful analogy of this phenomenon and its relationship to electrochemistry is the comparison of solid state semiconduc-tive physics with its earlier thermionic electrical technology.
Some similarities may be noted from the following characteristics of the EMP process.
1. Power supply wattage (and size) requirements are minimized.

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1~)6S274 2. Minimal electrothermal losses permit small working dimensions and increased field intensities; this contributes to fast re~o~ution times at low distortion levels.
3. The deteriorating influence upon the system as a result of brute force power requirements, and its attendant heat effects, is eliminated. For example, at higher current densities than those used in this invention the mobility and resolution character of molecular species may be altered.

.!.,' 4. The degree and manner of the electrical utilization is not restricted to the more conventional conductivity modes, such as aqueous electrolyte ion transport in liquid phase.
Therefore, vast numbers of different types of materials may be acted upon, studied, or utilized in the EMP process. This includes materials and systems whose electrical or ionic contri-bution would be t~ou~htmeager from anticipation of theix molecularstructures. Additionally, a broad range of nonaqueous, hydrophobic, and otherwise nonpolar substances as well as ionic, polar, covalent, aprotic, or other types of conductive substances may be included. This semiconductive fluidic process thereby serves as a new and convenient tool to explore various aspects within these fields, some of which are relatively unknown; as well as to elucidate molecular structure, excitation states, electro-molecular interaction and nature of materials.
5. Operation at or near the low threshold levels can be achieved with an overall high electrical propulsive efficiency. These thre9holds are characteristic for a material and generally exist at very low power levels. This then defines an operational propulsive efficiency whereby this process is capable of use at power levels just sufficient to effect the molecular specieg' propulsion, and wherein the electrothermal 7.

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- 1C)65Z~
losses approach negligible values. Actually, thermal increments become negligible at very low power levels, especially in a low `, efficiency electrothermal system. Counteracting factors include evaporative cooling, reservoir heat capacity, thermal convection, ' 5 and in certain situations dissipation by convective factors such as electroendosmotic streaming. By the controlled operation at increasing threshold levels the molecular species in turn will be induced into propulsion at their appropriate and characteristic level irrespective of other materials which may be present. This provides an additional high resolution technique which is capable of differential molecular discrimination. This discriminatory process is further enhanced by virtue of the propulsion rate also being characteristic for the molecular species involved.
This migratory or propulsive rate can be caused to vary substan-tially by modification of the media.
Appropriate to the mechanism of propulsion threshold , ~ it is noted that this behavior determines that point where the molecular attraction or adhesion to the substrate (surface) is counteracted by the total energy input. ~his is comprised of the external electrical energy input plus what other distribu-tion is due to additional partition functions present. The ~, molecules are then free to migrate or be swept by electrical : attraction or othqr convective factors. The electrical charac-teristics of the systems show a nonlinearity a~ the current will !:, 25 gradually rise after the initial application of a given voltage.
The preferred systems rapidly stabilize and remain in electrical equilibrium during the separatory process, although the process r,' may be carried out as gradual changes occur in the electrical characteristics. In cases where a lack of stability causes i; 30 difficulty but the medium is otherwise considered useful, the : .

8.

rate of change in resistance of the system may be reduced by the addition of an external resistance of sufficient magnitude, for example, about equal to or greater than the magnitude of the internal resistance of the system. Alternatively, an active electrical element may be utilized which is capable of sensing the current-voltage or temperature levels within a system and serve to regulate these faGtors or changes therein by means of control of the power source. This procedure is also of value as a .
safety feature. --,: ...
Investigation of components for media formulation has shown that certain compound combinations are not feasible for use in EMP if stable current levels are desired. When a constant ~-voltage is applied, these combinations continually exhibit a different resistance as if a capacitor were being charged. This effect may be illustrated in the form of a plot of current against time at constant voltage, where tl and t2 are on the order of several seconds or minutes:
GRAPH II

A

~ B
Current ~
.. ~ C
tl t -- - Time A material or mixture with electrical characteristics 20 of type A (continually increasing current) may eventually suffer arcing over. A material or mixture of type C (increasing cur-- rent, and then decreasing current after a point) is subject to evaporative heating and so eventually burns, chars or dries out.
A material or mixture of type B is a preferable medium from the point of view of electrical control because it allows reproduci-bility of runs and readjustment of the electrical characteris--- g _ .
:
. . :, , - , . . -, , ~. : .
, ' ' : . : ~ - ' - ~ - :' - ~

` 10~527~
tics is not a concern. Materials exhibiting electical behavior of type A may be deliberately chosen as media components to off-set the properties of a medium which otherwise exhibits type C
behavior, and vice versa. Also, the electrical characteristics of a given compound may change depending on the other substances with which it is mixed. Examples of compounds illustrating type A behavior in some mixtures and type B behavior in others is given below. Generally one would choose a media component which exhibits type B behavior in conjunction with the other components in the system.
COMPOUNDS TYPE BEHAVIOR
:
N,N-dimethylacetamide in water A
N,N-dimethylacetamide in formamide A
N,N-dimethylformamide in water B

~' 1,2-propanediolcyclic carbonate in water A
ethylene carbonate in water B
3-methyl sulfolane 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 EMP process differs from the prior art processes of electrophoresis and dielectrophoresis in a number of respects, EMP exhibits non-linear electrical characteristics departing from the Kohlrausch requirement for electrolytes and from Ohm's Law.
- *Trademark for ethylene glycol monoethyl ether ''' `'' - 10 - ;
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. . - . : .

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` 106~74 ., Specifically, the following characteristics are observed with EMP:
(1) non-doubling of current with doubling of voltage (2) non-constant resistance with time , ; 5 (3) non-constant resistance with voltage or current Furthermore, the EMæ response does not seem to be very affected by viscosity; and the EMP response iR enhanced by increasing the dielectric constant of the solution while the electrophoretic mobility is inversely proportional to dielectric constant so EMP may be practiced at dielectric levels far exceeding those practicable with electrophoresis. Thus EMP
in media with a dielectric constant up to 190 has been practical, e.g., in N-methylacetamide.
The migration rate in cm/sec of chemical species transported by EMP is markedly superior to the rates achieved with dielectrophoresis and electrophoresis. This difference is illustrated by the following graph:
- GRAPH I
'. ` \
~og of Migration Rate ;~ Electrophor sis ielectrophoresis s~emiconductive e~ectrolyte conduction range Conductivity It is thought that the EMP process relies on proton donor/acceptor interactions and electron charge transfer com-;
plexes for transport. See R. Foster, Organ ~ ransfer 11 .
.

Complexes (1969).
In practical terms, a key consideration in this processpertains to the use of a relatively nonconductive medium. Various different media and techniques may be used to achieve the require-ment~ of the semiconductive ranges employed. Conduction can becarried out in solids, semisolids, such as gels, as well as in the gaseous phase, aerosols, foams and liquids. Also combina-tions of these are practical as are melts, high temperature melts, pseudo crystals (para crystals and mesomorphic materials), ices, slushes, glasses, plastics, fibers, filaments, porous - materials and powders. Ion exchange media, permaselective and membrane barriers, dialytic membranes, molecular sieves and specific ion source materials are suitable as supports or barriers. The process may be carried out continuously or by the batch technique.
Many substances are relatively dielectric; of these - the nonpolar organics constitute a vast grouping. Some of these exhibit intermediate ranges of conductivity or are susceptible to appropriate adjustment of their conductive nature by addition of relatively small amounts of adjuncts. This may be likened to the process of doping or implantation used with solid-state devices. Other means may include irradiation, polarization interaction, injection or radioactive or charged particulates, photo activation, superposition of AC fields, magnetic fields or other energizing means. These energizing fields may be oriented at different angles with respect to the DC field. For example, an AC field superimposed upon the DC field used in this invention may be used to impart additional mobility to chemical species within a medium. Pulsed DC or the superimposition of pulsed DC may also be u~ed. A relatively polar material can be 12.

~ 065~27~
used as the medium, such as aqueous solutions, by limiting the ionic content of the system to achieve the desired conducti~ity level. Also, suppressive substances can be add~d to a conductive system, desirable materials being those which exert a suppressive effect beyond the mere dilution effect which their presence contributes to the system. ~urther, the suppressive effect of nonpolar materials used in comixture with otherwise conducting systems offers a ~ery general and useful approach to the control of conductivity. It is important to note that in regard to all of these techniques other factors may favor certain additional properties and characteristics of the materials employed appro-; priate for the nature of the application, such as miscibility, compatibility, toxicity, boiling point, melting point, reactivity, cost, removability, dialyzability and osmolality. A high dielectric constant material is often preferred due to itsability to maintain the charges formed in the system (involving solvation or interaction) or charges otherwise acquired or - induced upon chemical species. The attainment of a controlled level of conductivity may be further controlled or adjusted by the simultaneous consideration of other system parameters, such as pH, physical state and temperature.
Mixed solvents may be used with the intermediation of a coupling agent, usually of a semipolar cosolvent nature. The term semipolar is used for amaterial which shows some conduc-tivity, which will increase upon dilution with water (or othersimilarly polar material), and which will increase upon addition of a soluble ionic salt. Thus, in the present invention the solvation of a strongly ionic material into a nonpolar one by means of a semipolar material will generally produce only a minor conductivity increase; whereas the solution of the ionic ~ .

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material in the ~emipolar solvent alone may be moderately con-ducting. In effect, the nonpolar material may b~ viewed as - suppressing the capabilities for moderate conduction to form a three-way system. The three-way system therefore comprises ; 5 an inert base, a conductivity agent and a semipolar material, such as, respectively, xylene, ammonium bromide and dimethyl formamide. Further, a considerable increase in the amount of the semipolar solvent may only minimally improve the conductivity.
The addition of a relatively small volume of a second type of semipolar solvent (a four-way system) can then effect a very substantial conductivity increase of the entire system. Neither . .
cosolvent alone with the nonpolar material, without or including the solvated ionic material will approach the conductivity level so achieved. This technique for augmenting the conductivity of essentially nonpolar materials forms a convenient working basis for the use of substances such as xylene, p-cymene, mineral oil and chlorinated solvents. An illustration of a four-way system is xylene, ammonium bromide, dimethyl acetamide and dimethyl ` formamide.
The above effects also may be applied to systems which are not readily io~izable and the components determined by such factors a~ dielectric constant and proton donor capability of the sol~ating molecules. Whereas medium donor capability may give rise to solvated molecules, a high donor capability in a high dielectric system readily tends to preserve the ionic . .
charges so created. Of particular use are media having dielectric constants above 10, which tend to maintain charges formed by proton donor acceptor exchange.
The media used in this invention are characterized by ` 30 liquidity at or near room temperature, and sufficiently high - ' 14.
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106527~ :
boiling points to withstand the process heat. The boiling points are generally above 140C, and preferably above 165C.
The media need not be capable of dissolving the chemical to which mobility is to be imparted, but solubility is preferable for separation of different molecular species.
This invention is further illustrated by the following examples directed to the separation of chemical species in the indicated media. The apparatus consisted of a high density polyethylene separation cell divided into two 15cc compartments.
These are separated by a space containing a support bridge for a spanning support substrate.
The cell was constructed to withstand and provide security from the high voltage fields and conductive leakage of media under such fields and the wide range of strong and cor-rosive solvent materials used herein. A platinum electrode in each compartment was connected to a DC power source generally - operated at 1.25 ma. The power source was capable of metered operation at variable voltage levels in the ranges of 0-lOOJ~a, .j~
0-1 ma, and 0-10 ma, for threshold studies and operation of the processes described herein. A filter paper wick in each compart-ment was connected to opposite ends of the filter paper substrate which extended across the top of the cell. The filter paper was five cm wide by ten cm long and except where stat~d otherwise it was "Whatman"* #3. Normally, the voltage drop in this system occurs substantially across the impregnated support, for example 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 minor amount of an additive to increase conductivity. The following solvent systems are useful for relatively nonpolar dyestuffs as well as other *Trademark - 15 -soluble organic materials. The solvents listed were used for the separation of mixed chemical species, such as dyes, "Mercurochrome"*, and sodium riboflavin phosphate, at the voltage and current shown. The term "stabilized" is used to indicate that the electrical characteristics reached the indicated values and remained constant for the few minutes (generally two to ten minutes) during which the separation process was completed.
ELECTRICAL
CHARACT~RISTIC
EXAMPLE SOhVENT FORMULAE (Stabilized) LD 1 0.3 ml. water, 0.2 ml. Sorensen Buffer (pH 7.0), 24.5 ml. propyl-ene glycol. The amount of water in this type of sy~tem should preferably - not exceed about 2~ ll KV/ma 2 2.0 ml. dimethyl acetamide, 1.0 ml.
phenol, 25.0 ml. propylene glycol. 8 KV~ma ` 3 2.5 ml. formamide, 22.5 ml. propylene L5 glycol. 5.5 KV/ma Example 3 is excellent for dye resolution of the following mixture: safranine O, tol~ylene red (neutral red) and sodium riboflavin phosphate. This medium is also useful for separation of members of the rhodamine dyestuff family.
!0 Unlike conventional ionic-transport processes the mobilization of metal derivatives is not readily achieved, even when the metal derivatives are soluble in the media. However, by adjustment of the media and electrical characteristics in accordance with this invention a very fine resolution is !5 obtained, which illustrates a new mode of operation as described herein. By suitable modification of the above solvent systems, metal ion movement may be made practical, as in the following systems. Examples of suitable metal ions are Co++, Cu++, Ni++ from ~alts, such as the chlorides and nitrates.

16.
* Trademark for the disodium salt of dibromohydroxymercury-fluoresceine; it is used as an antiseptic.

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. 1065274 ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)

4 lO ml. dimethyl formamide, 15 ml.
propylene ~lycol 10 KV/ma lO ml. dimethyl formamide, 15 ml.
propylene glycol, l ml. triethanola-: mine 8 KV/ma Another approach is to use dithizone derivatives of metals such as cobalt, copper and nickel in solvent systems such as (4) and (5) above.
An ester based nonaqueous system is also satisfactory as illustrated below. In place of the "Cellosolve"* in the medium, other related compounds can be used, such as hexyl "Cellosolve"l, " 2 3 4 methyl Carbitol" , "Cellosolve" acetate , and "Carbitol" acetate .
i,. ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized) 6 4 ml. formamide, 14 ml. "Cellosolve", 34 ml. dimethyl phthalate15 KV/ma The following examples show tailoring of the conductivity levels (doping) via nonaqueous salt methods and especially the additional influence of a second semipolar material wherein n-butanol S is a saturated solution of ammonium bromide in n-butanol. This medium is illustrative of a four-way system dis-cussed above, and is useful for the separation of dyes and other compounds soluble therein.

ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE(Stabilized) .
7 5 ml. n-butanol S, 30.5 ml. n-decanol, 2 ml. l-methyl-2-pyrrolidinone 14 KV/ma The following solvent ~ystems are useful for separation of metal ~ons and complexes; of the metal complexes, dithizones, 17.

* Trademark for a series of mono- and dialkyl ethers of ethylene glycol and their derivatives. The term "Cellosolve" used alone signifie~ ethylene glycol monoethyl ether.
1 Trademark for ethylene glycol monohexyl ether.
2 "Carbitol" is the trademark for a series of mono- and dialkyl ethers of diethylene glycol and their derivatives. Methyl "Carbitol" is diethylene glycol monomethyl ether.
3 Trademark for ethylene glycol monoethyl ether acetate.
4 Trademark for diethylene glycol monoethyl ether acetate.
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: ` ~065Z74 ,. :
' nitroso ~ -naphthol, pyrocatechol violet, rhodamine B, 8-hydroxy ~, quinoline, and dibenzoylmethane der'ivatives were used.
i ELECTRICAL
CHARACTERISTI~
EXAMPLE SOLVENT FORMULAE (Stabilized) 8 30 ml. methoxy ethoxy ethanol + 30 ml.
1, 2-propanediol cyclic carbonate +
3 drops nitric acid (1:30 in H20) 6.4 KV/1.25 ma ~ ' Thè medium of Example 8 gave multizone resolution ,~ (5 minutes) with rare earth 8-hydroxy quinolinates such as Sc ~'~
and Eu as well as other metals such as Ni. The heavy metal ,,~
~ 10 derivatives of dibenzoylmethane and rhodamine showed good to j', excellent movement whereas with heavy metal nitrates movement , .... .
, was very sparse and with hafnium (as chloride) not at all. ,~
.. . " .
, , Satisfactory mobility was also obtained for Co+2, Cu,+2, and ,,,, Ni+2 (as chlorides).
In the previous example the nickel chloride gave '~
three zones, with spot coloration of blue and violet. Such '' reproducible effects demonstrate the very great resolution of ' ,, the technique. This also points to the formation of a series ~ of metal complexes, such a~ by proton donor/acceptor exchange, ,,, 20 and the ability of the technique to differentiate and resolve ' them. This unusua,l capability is evidenced by another situation ,; where not only do multizones appear, but these appear as both ~+) or (-) moving entities. Mobility rates of +2 cm/min were ~'; achieved with the following systems.
ELECTRICAL
CHARACTERISTIC
. EXAMPLE SOLVENT FORMULAE (Stabilized?
,' 9 15 ml. methoxy ethoxy ethanol 6.8 XV/ma + 15 ml. 1,2-propanediol cyclic Cu+2 (chloride) carbonate +6 ml. isophorone 3 zones (+ and -) ;' +3 drops nitric acid (1:30) Fe+3 (chloride)

5-6 zones (+ and -) , Ni+2(chloride) , 3 zones (-) ,, , 6 min. run ~' ~
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~065274 15 ml. methoxy ethoxy ethanol 6 KV/ma +15 ml. 1,2-propanediol cyclic Co+2(chloride) carbonate + 13 ml. ethylene 2-3 zones (+ and -) carbonate +3 drops nitric acid Ni+2 (chloride) 30) 2-3 zones (+ and -) Cu+2(chloride) 4-5 zones (+ and -)

6 min. run The medium of Example 10 also provided excellent ; mobility for salts of europium, lutetium, thallium and ytterbium.
~- The positlon, mobility rate, and character of the zones o~tained are characteristic for the material within the system under given conditions. Thus, in the following system, nickel and cobalt ~as chlorides) gave 1 and 2 zones respectively, whereas the mixture gave 3 zones corresponding to that of the individual metal constituents. Further, the zones had 3 colors with sharply distinguished pink and blue.

ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized) 11 21 ml. 1,2-propanediol cyclic 7.8-7.6 KV/1.25 ma carbonate +9ml. methoxy 6 min. run ethoxy ethanol +8 ml. r-Butyro-lactone +3 drops Nitric acid (1:30) Another similar system resolves nickel and cobalt mixtures into pink and blue colored zones. This system is parti-cularly fast with certain nonpolar dyestuffs giving 5 cm/min mobility rates at 7.5 KV levels. Operation at higher voltage i level~ would increase further the mobility rates:

ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized) 12 21 ml. 1,2-propanediol cyclic 8.4-6.6 KV/1.25 ma ; carbonate +9 ml. methoxy ethoxy ethanol +12 ml. bis (2-methoxy ethyl) ether +3 drops nitric acid (1:30) The rare earth groupings as well as hafnium and zir-, . .
: 19.

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conium repre~ent the most difficult elements for resolution.
Further, just a hafnium and zirconium form a particularly close pair, within the rare earths 3 major paired groupings are known. The following systems are useful for the transition and heavy metal categories; including salts of the rare earths - and zirconium - hafnium elements, such as those having an atomic number of 21 and greater.
ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized?
LO 13 15 ml. 1,2-propanediol cy~lic 3.6-7.2 XV/1.25 ma carbonate +15 ml. methoxy3 min. run ethoxy ethanol +13 ml. ethylene carbonate +3 drops nitric acid ~
- (1: 30) ~ :
- Example 13 was successfully repeated with the medium substantially the same except that in each run the ethylene LS carbonate was replaced by one of the following: tetrahydrafur-furyl alcohol, isophorone, "Cellosolve"*, ~yclohexanone, and 2-ethylhexyl chloride.
In a system comprising propanediol cyclic carbonate, nitric acid, methoxy methoxy ethanol and tetrahydrofurfuryl alcohol in proportions similar to those above at 500V and 100~n, the dye safra~ne ~ moved readily, and an orange contaminant remained immoblle. This i9 an example of the separation of components by reaching the threshold level for one compound in a mixture.
Acidification with an inorganic acid is not essential as the following example illustrates.
; ELECTRICAL
C}IARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized) 14 12 ml. 1,2-propylene glycol14 XV/1.5 ma + 3 ml. dichloro acetic acid ~O +16 ml. ethoxy ethoxy ethanol ~ .
* Trademark ~-;

1()65~7~
Also, media containing bases such as triethanolamine or ~-picoline in place of an acid, have the capability for the separation of metals.
~; The application of this invention to organic compounds is further illustrated by the following systems used for the separation of sulfa drugs, sulfamerazine, sulfaguanidine and sulfamethazine.
~ ELECTRICAL
Y CHARACTERISTIC
' : EXAMPLE SOLVENT FORMULAE(Stabilized) 20 ml. methoxy ethoxy ethanol 5.8-5.0 KV/1.25 ma + 12 ml. l-methyl 2-pyrrolidinone 4 min. run + 0.8 ml. dichloroacetic acid The latter system, though found to be slow, was able to yield differential zones with the dyestuff family of rhodamine 5 G, 6 G, and B, as well a~ a mixture.
The following media gave high resolution of the above dyes in 20-25 seconds and mobility rates in excess of 12 cm/min.
ELECTRICAL
CHARACTERISTIC
~: EXAMPLE SOLVENT FORMULAE~Stabllized) :
16 24 ml. 1,2-propanediol cyclic13.2 KV/0.8 ma carbonate + 12 ml. ethylene diacetate + 6 ml. salicylaldehyde + 3 drops nitric acid (1:30) The following two very fast related formulae approach , 20 cm/min mobility rates with excellent resolution:
~: ELECTRICAL
::~ CHARACTERISTIC
` EXAMPLE SOLVENT FORMULAE~Stabilized) 17 24 ml. 1,2-propanediol cyclic 14.2 KV/ma carbonate + 12 ml. ethylene - diacetate + 6 ml. salicylaldehyde ~; + .4 ml. ammonium bromide (saturated in methoxy ethoxy ethanol~

,' . ~ .

` ~ 21.

1~65274 18 24 ml. 1,2-propanediol cyclic car- 13-12.6 KV/ma bonate + 12 ml. ethylene diacetate + 6 ml. salicylaldehyde + 2 ml.
ammonium bromide (saturated solution methoxy ethoxy ethanol) + 2 ml. tri-butyl phosphate + 4 drops tetramethyl ammonium hydroxide (about 25~ in methyl alcohol) 19 10 ml. tris-chloride ~0.14m) + 90 ml. 2 KV/ma water Isucrose to 67%) It is noted that urea or propylene glycol in such systems, in concentrations to several molar, doesn't alter the conductivity, although it may aid the mobility of protein molecules. These substances act as a diluent or suppressant and are useful in water solutions for biochemical separations of substances such as proteins and enzymes. Albumin mobility in such systems can exceed that of glycol soluble dyestuffs, as shown below by the data for migration from the origin.
ELECTRICAL
; CHARACTERISTIC
EXAMPLE ~OLvENr FORMULAE (Stabilized) 16 ml. tris-chloride (.03M) 6 KV/2 ma + 40 ml. propylene glycol '~a~n"* #1 ; + 50 ml. glycerin Albumin 1-1/4 -1-1/2"
Soluble dye 3/4"
- 6 min. run 21 10 ml. tris-chloride buffer 7.2 KV/2 ma (0.03M) Cellulose ace-+40 ml. propylene glycol tate +50 ml. methyi "Carbitol" Paper -As discussed further below, the foregoing systems can be improved in speed and degree of resolution using initiators, suppres~ant~ and/or stabilizers.
Operation of this process was also carried out by adding a sample to a bed of a gel made from agar, silica, and gelatin. This procedure has been used to separate dyes, proteins and other types of organic compounds. The media and electrical . ~ademar3c - ~ :

10`65Z74 characteristics were Rimilar to those described in the preceding examples. Bulk separations have also been carried out in a column with powdered minerals or cellulose supports.
A very useful system for non-polar substances, which has resolved isomers of methyl naphthalene and provided good resolution of Rhodamine B and 6G and food dyes is:

21 ml. propylene cyclic carbonate 9 ml. methoxy ethoxy ethanol 12 ml. tetrahydrofurfuryl alcohol 3 drops nitric acid (1:30) 10In the preceding formulae, use was made of various - types of compounds to perform or provide different important functions. For illustrative purposeC, a number of ~hese are selected for arrangement into several categories according to some of their common formulation functions. However, these categories are not rigidly defined limitations for the use of any compounds and some fall equally well across several category boundaries. Thus, dimethyl phthalate is an example of a good suppres~ant although it also functions as an inert base if used as the base media. Further, it may act to insolubilize or limit mobility or influence other factors, ther~by enhancing resolution. Water is useful for a fairly active solvent with moderate proton donor capabilitie3 and high dielectric constant.
This latter feature tends to maintain the chargeR once established.
However, water is generally less useful as a major constituent at the higher voltage levels in non-externally cooled systems due to its low boiling point.
TABLE I
Inert Media-base ~olvent, inert carrier, Characteristic: solution limiter.

minimal conductivity p-cymene 23.

' ~106S~
;' Inert Media-base, con't. formamide mineral oil ammonium bromide ` n-decanol pyridazine iodide l-octanethiol nitric acid xylene mercaptoacetic acid , Inhibitors (sup~ressant) Active Media Base Characteristic: Characteristic: -negative conductivity slight conductivity with influqnce. tendency to enhance con-> 10 tributyl phosphate ductivity of neutral dimethyl phthalate media base.
triacetin potent solubilizer, solvent s 2-ethyl hexyl chloride 2-chloroacetamide Neutral media-base dimethyl formamide Characteristic: N,N,-dimethylacetamide ,~ slight to poor conductivity l-methyl-2-pyrrolidone :", .
with tendency for active dimethyl sulfoxide change in conductivity with ethylene cyclic carbonate dilution ~olvent, potent 2,5-hexanedione solubilizer, coupling agent. Modifying agents ~-butyrolactone isophorone 1,2-propanediol cyclic carbonate nitrobenzene propylene glycol salicylaldehyde 2-phenoxy ethanol 4-hydroxy~4-methyl-2-pentanone 2-ethyl, 1,3-hexanedlol ethylene diacetate tetrahydrothiophene l,l-dioxide ~-picolLne methoxy ethoxy ethanol o-dichlorobenzene Conductivity Agents Very Active Media Perchloric acid Characteristic:
dichloracetic acid strong conductivity , ,"' 24.

SZ7~
Very Active Media, con't.
influence, proton donor solvent action and acidity-alkalinity diethyl ethyl phosphonate - 5 N-cyclo-hexyl-2-pyrrolidone bis (2-methoxy ethyl) ether ~exa methylene phosphoric triamide amino ethyl piperaz~ne imino bis propylamine 2,2'-imino diethanol 2-amino ethanol triethylene tetramine triethanolamine mercaptopropionic acid mercaptoacetic acid A starting point for developing and choosing a solvent media for particular chemical species is to determine those . media which stabilize or are compatible with the species andwhich exert a good to excellent partition coefficient in a standard chromatographic technique for the species on the sub-strate to be used at various pH. The conductivity level is then adjusted for use in this process by adding the solvent as a major constituent to a compatible media base system which has : a properly adjusted conductivity or, the conductivity of the solvent can be tailored to form a media base system by the use of the types of agents described in Table I. Mobility is normally achieved at about 1.25 ma, which generally exceeds most threshold current levels. Further adjustment may be necessary to initiate or refine the mobility of the species by the adjust-ment of the composition of the system as indicated above.

~ 1065Z74 For example, adjustment may be made by the use of complexing agents, modifying agents, similar solvents as determined by chromatographic screening, by pH adjustment and less active substrates (such as "Teflon"*).
The compo~nds listed herein are representative of a s : . .:
much vaster possible grouping of like or related materials useful as solvents, cosolvents, coupling agents with moderate, ~;~ strong or nil effects on conductivity; many form complexes and , . . .
; metal adducts substantially modifying the effective properties . 10 of the compounds or materials involved.
These materials are often used in comixtures to achie~e their desired combined properties. Such formulations, aside from their electrical properties, achieve a very broad scope of applicability for diferent classes of molecular species.
The following list of substances may be considered Ln three main categories, given below. Other factors to be considered are a larger liquidity range, and dielectric constant, low viscosity, water compatibility and miscibility and strong donor/acceptor influence or neutrality:
1. The major grouping has boiling points at or above -160~C which are liquid at or near room temperature. Generally they have good solvent action.
.. . .
; 2. A number of the compounds listed having boiling ~ . .
` points in the 130-160C range, or melting slightly above room temperature. These are often used in lesser percentages to modify systems. Also, they often can be liquified with a minor amount of cosolvent.
3. The remainder are modifying agents, ~hose melting !~ ~ points may be substantially higher and which are used in solution with other media.
26.
* Trademark of the DuPont Company for poly(tetrafluoroet:hylene) resin (PTFE). Its properties and characteristics are as described in m e Merck Index, 8th Ed. (1968) p. 849.

. .
. - .

.,; , . . .

` ` ` ~065274 . . Based upon physical characteristics, chro~atographic : screening tests, and the media.adjustment techniques described herein, the following compounds are representative of the type ; i~ of media component useful in this process:
TABLE II
Alcohols 2-(hydroxymethyl)-2-nitro-1, - 3-propanediol 2-aminoethanol . 2-ethylaminoethanol phenol 2,3-epoxy-1-propanol aziridine ethanol ethylene dinitrile tetraethanol hydroxy ethyl piperazine 2,2-iminodiethanol piperazine ethanol dl-menthol 5-hydroxy-2-(hydroxymethyl)-: - 4H-pyran-40ne 2 mercaptoethanol furfuryl alcohol 2-(2-ethoxy ethoxy) ethanol tetrahydro furfuryl alcohol 2-[2-(ethoxy ethoxy) ethoxy]
.: ethanol :. 2,2'-oxydiethanol 2,2'2"-nitrilotriethanol 2-(2-butoxy ethoxy)ethanol 1,1'1"-nitrilotri-2-propanol 1-[[ [2-(2-methoxy-1-methyl-ethoxy)]-l-methyl ethoxy]]-.. l-phenylethanethiol 2-propanol 2,2'-(phenylimino)diethanol n-butanol 1,3-propane dithiol 1,3 butanediol : thiodiethanol 1,4-butanediol 4-pyridine propanol 2-~2-butoxy ethoxy) ethanol 2-nitro l-propanol 2-butoxyethanol . .
2-nitro-1-butanol 2-(2-methoxy ethoxy) ethanol 2-amino-2-~hydroxymethyl)-1, 2-methoxy ethanol 3-propanediol 3-methoxy-1-butanol ~ geraniol 2-butoxy-ethanol : . 2-methylamino ethanol 2-ethyl hexane-1,3-diol 2-methyl-2-nitro-1, . t-butanol 3-propane diol .

27.

.. . ~ . . . . .

.. : . . .. :

1(~65Z74 Alcohols (cont'd) iso-amylalcohol dimethyl phthalate caprylic alcohol diethyl phthalate decanol ethyl lactate dehydroisophytol ethyl malonate ~- glycerin di iso octylazelate ; dehydrolinalool di-2-ethyl hexylazelate thioglycerol methyloleate 3-chloro-1, 2-propanediol tri (n-octyl) mellitate 2-amino-1-butanol tri (n-decyl) mellitate 2-amino-2-ethyl-1,3, propanediol acetyl tributyl citrate 2-amino-2-methyl-1-propanol tributyl citrate 2-Dimethyl amino-2-methyl-1- ethylene diacetate :.
: propanol tributyl phosphate :
sorbitol triethyl phosphate glucose tricresyl phosph~te sucrose triphenyl phosphate. .
. ethylene glycol tri(2-ethyl hexyl) phosphate . propylene glycol tributoxy ethyl phosphate 20 dipropylene glycol o,o,o-triethyl phosphorothioate ~ polyethylene glycol diethyl ethylphosphonate thiodiethylene glycol dibutoxy ethyl sebacate l-octanethiol 2-ethyl hexylchloride 4-hydroxy-4-methyl-2-pentanone bis [2-(2-methoxy ethoxy) ethoxy] ether linalool linalool oxide bis (2-methoxy ethyl) ether Ethers, esters 2~methoxy ethyl acetate dibutyl phthalate ethoxy ethyl acetate :
phenyl acetate 2-(2-butoxy ethoxy) ethylacetate dibutyl fumarate diethylene glycol monomethylether ' - ' ~
.
- ,.
. ~ 28.

~- ~06S27~
., ~ Ethers, esters (cont'd) di propylene glycol dibenzoate ".
diethylene glycol monoethyl polyethylene glycol (200) ether dibenzoate ' ethylene glycol monoethyl tri ethylene glycol diacetate-ether acetate ~:: bis (diethylene glycol mono .. ~ ethyl ether) phthalate-n~ ethylene glycol mono ethyl . ether acetate ~, bis (2-ethyl hexyl) adipate ethylene glycol monohexyl ether 1,2-bis (2-chloroethoxy) ethane .: diethylene glycol monoethyl bis (2-chloroethyl) carbona~e : 10 ether acetate bis (2-methoxy ethyl) phthalate s diethylene glycol monomethyl di mercaptodiethyl ether ether . - glycol di mercaptoacetate . ethyl cyanoacetate di methyl thiodipropionate `. 3-acetyl-3-chloropropyl acetate tri methylol ethane tri (3-~,: mercaptopropionate) `, butyl chloroacetate ,, ~ butyl lactate pentaerythritol tetra (3-,~. mercaptopropionate) . . butyl stearate dl tetra hydro furfuryl adlpate bis (2-chloro-isopropyl) ether ,. . .
tetra hydro furfuryl oleate glycerol triacetate ~.
'. 20 tris (chloro ethyl) phosphate glycerol tripropionate ,, 2,2,4-trimethyl-1,3-pentanediol 1,2/1,3-glycerol diacetate . diisobutyrate hexyl acetate ~, . di ethoxy ethyl phthalate ethylmethyl carbamate ,, . methoxy ethyl ricinoleate hydroxy ethyl acetate ,;
,` glycerol monoacetate phenyltrimethoxy silane ~:
~j , .
di n-hexyl adipaté trimethoxy trimethyl mercapto ~, silane ; glycerol tributyrate :~
butane diol dicaprylate dimethyl polysiloxanes , ethylene glycol dibenzoate 1,2-bis (2-methoxy ethoxy)ethane ' 30 di ethylene glycol dibenzoate 2-(ethoxy ethoxy) ethylacetate , - 29 -.

6S~74 ~ . .
Ethers, esters (cont'd) 2,5-hexanedione ~ -` di~enzyl ether 6-hexanolactone : Amides l,2-propanediol cyclic carbonate formamide oxohexamethylenimine S N,N-dimethyl acetamide 2,3-butanedione 2-chloroacetamide . ethylene trithiocarbonate urea propiolactone :~.
l,1,3,3,-tetra methyl urea 2-piperidone acrylamide ~ n-butyl carbonate lO cyanamide 4,4,4,-trifluoro-1,2 ~ thienyl-1,3-butanedione .. . N,N-bis (2-cyanoethyl) formamide :~ -. 2-cyanoacetamide 2,4-pentanedione 2-furamLde dipropyl carbonate N-2 hydroxy ethylformamide 2,4-pentanedione . 15 N-ethyl p-toluene sulfonamide Nitriles_ N-ethyl-o-toluene sulfonamide ethylene dinitrile tetrace-.-: tonitrile N-2-hydroxy ethylacetamide methane sulfonamide pimelonitrile N-(2-methoxy ethyl) acetamide 3,3-thiodipropionitrile N,N'-methylene ~is acrylamide 3,3-oxydipropionitrile - N-ethyl formamide phenylacetonitrile . N-methyl formamide hydracrylonitrile : thioacetamide imino diacetonitrile picramide p-methoxyphenyl acetonitrile hexamethyl phosphoric triamide glutaronitrile formamidine acetate succinonitrile . ~, . . Lactones, lactams, dioneQ, picolino nitrile : and carbonates ' nicotinonitrile ~ ethylene cyclic carbonate benzonitrile :- 30 -butyrolactone ethylcyanoacetate . . . , ' ':

,'~. ~ .
. ' .
~ ~ 30.
,.. :,....
- , - Nitriles (cont'd) mineral oil 4-chloro 2-hydroxybutyronitrile dichlorophenyl trichlorosilane 3,3'-12,2-Bis(2-cyano ethoxy octadecyltrichlorosilane methyl)- trime~lene dioxyl dipro2yl~nitrile diphenyl dichloro silane S Aldehydes, ketones, thiones, epibromohydrin miscellaneous compounds 1,1,2,2-tetrabromoethane r 2'-hydroxyacetophenone 1,2,3,4- tetrahy~naphthalene f~alicylaldehyde tetrachloroethane fenchone 1,2,4,-trichloro~enzene 4-anif~aldehyde indene o-chlorobenzaldehyde pyrrolidinone if~ophorone l-butyl-2-pyrrolidinone . cyclohexanone l-cyclohexyl-2-pyrrolidinone 2-piperidone Bafsic Compounds - and amines, hydroxides, oxides, sulfides, . lS 2-furaldehyde hydrates, alcoholates, hetero-l-methyl-2-pyrrolidinone cYclics 2,6-dimethyl-4-heptanone iodine chloride-iodine systems p-cymene sulfur chloride-iodine systems o-dichlorobenzene benzyltrimethylammonium hydroxide o-nitrotoluene betalne hydrate ;- nitrobenzene chollne i~osafrole n-ethyl morpholine o-methoxy benzaldehyde 2,6-dimethyl morpholine tetrahydroionone hexamethylene tetra-amine pyridazine lodide 2-picoline-1-oxide decahydronapthalene tetramethylammonium hydroxide diphenyl methane tetrabutylammonlum hydroxide-durene tetramothyl guanidine d-limonene 3-ethyl-4-methylpyridine . 30 turpentine 5-ethyl-2-methylpyridine : .

~ 31.
f ' .:
.
- . ' - ~065;~7~

hexamethylene imine 3,5 lutidine tetrahydrothiophene l,l-dioxide Acidic Media dimethyl sulfoxide methane sulfonic acid imino-bis-propylamine dichloroacetic acid triethylene tetramine mercaptoacetic acid butyraldoxime 3-mercaptopropionic acid 2-amino-4-methyl thiazole propionic anhydride n-propyl sulfoxide lactic acid n-butyl sulfoxide 2-chloropropionic acid . .
alpha picoline propionic acid : beta picoline sulfoacetic acid quinoline trichloroacetic acid 1,2-diazine (ethylene dinitrilo) tétra-acetic acid aminoethyl piperazine 2-methyl-5-ethyl pyridine trimethylacetic acid N-hydroxy ethyl piperidine picric acid 3-ethyl-4-methyl pyridine camphoric acid 4-ethyl pyridine hexanoic acid ,,~ 2,4 lutidine picramic acid 2,6-dimethyl pyridine-N-oxide cyanuric acid Lewis bases picrolinic acid : 3-methyl piperazine Lewis acids 4-methyl piperidine p-toluenesulfonic acid 4-methyl thiazole trifluoroacetic acid 2-methyl thiazole amino imino methane sulfonic acid 2-methyl tetrahydro furan tetrahydrothiazole amino ethane thio sulfuric acid 1,4 oxathiane r' 1,2,3-azimidobenzene 2-amino ethyl hydrogen sulfate 2-amino-1,3-bis (2-ethyl hexyl)- perchloric acid 5-methyl hydropyrimidine sulfamic acid . Acidic Media (con't) ammonium bromide : phosphoric acid lithium bromide sulfuric acid lithium iodide nitric acid morpholine oleate Salts lithium nitrate : betaine hydrochloride lithium hydroxide choline chloride cesium acetate . hydroxylammonium acetate cesium chloride - hexadecyltrimethyl ammonium cesium carbonate : bromide cesium salicylate i guanidine nitrate potassium iodide tetrabutyl ammonium iodide poly vinyl benzyl trimethyl ammonium chloride tetra ethylammonium bromide tetra methyl ammonium bromide hydroxylammonium acid sulfate . 15 1,1,1, trimethyl hydrazonium Lewis salts iodide acetylcholine bromide : acetylcholine iodide aminoguanidine nitrate ~: 20 6-amino-3-indazolinone dihydrochloride cyanuric chlorlde guanidine acetate .' guanidine hydrochloride amino guanidine bicarbonate 2,2'2" nitrilo triethanol hydrochloride semicarbazide hydrochloride ammonium formate ammonium thiocyanate ammonium nitrate ~ 33.

,, .

.

F~rmulation of the EM2 media is fundamental. It has been found that compounds or mixtures with a large liquidity range are particularly suited for use in EMP, especially those liquids with a glassy or vitreous structure. These compounds - 5 or mixtures apparently have an inherent structure which facili-tates regulation of proton donor/acceptor properties and electron charge transfer, as well as providing the advantage of low evaporation. It is sometimes practical to use high boiling point li~uids because the practice of EMæ at or above higher bhre~hald currents does generate some heat. Media with higher or lower melting and boiling components may be used for special applications.
Components used in EMP media formulation should have , a number of characteristics if they are to be maximally useful.
Water and solvent miscibility are often desired, as is general solvent action, availability, and thermal, shelf, chemical and electrical stability. Superior solvent activity is not always desired. It is feasible to limit or cause differential movement when two or more transportable chemical species are present in the media by using media components which are poor solvents for one or more species. Below is a list of additional compounds useful for their solvent action or their ability to mediate such properties in other materials. Also included are tracer agents which will be discussed more fully hereinafter.

34.
. ~ ~

:~ , - T~E ~
HYDROXY, ETHER COMPOUNDS
1,2,4-Butanetriol Dodecyl alcohol poly-,,!` ~ o-Tert-butyl phenol oxyethylene ether 2,2-Bis (hydroxy methyl) 2-(Ethyl thio) ethanol propionic acid Ethynyl cyclohexanol 2,3-Butanediol Ethynyl cycloheptanol -- -1,4-Butanediol diglycidyl Ethynyl cyclooctanol -~
ether Glycidol 2-Butene-1,4-diol Guaiacol ., .
2-(n-Butylamino)-ethanol 1,2,6-Hexanetriol . Butylhydroxytoluene Hydroxy acetone . 2-Butyne-1,4-diol 3-Hydroxy camphor Cetyl Alcohol 2-Hydroxy cyclodecanone . Chloral 2-Hydroxy ethyl ether Cyanoethyl sucrose 2-Hydroxy ethyl hydrazine . ~ Dichlorotriethylene glycol N-Hydroxy ethyl morpholine ,. ~ Hydroxy acetone 2-(Hydroxy methyl)-2-ethyl-l, i; 2,2-Diethyl-1,3-propanediol 3-propanediol 2,5-Dihydroxy methyl pyrrole l-(Hydroxy methyl)-5, : 1,3-Dimercapto-2-propanol 5-dimethyl hydantoin 2,3-Dimercapto-l-propanol 2-Hydroxy ethyl methacrylate Dimethoxy tetra ethylene l-(~-Hydroxy ethyl)2-methyl-glycol 2-imidazoline 2,3-Dimethyl-2, 3- 4-Hydroxy-3-methyl-2-butanone : butanediol 2-Hydroxy-3-methyl cyclopenten-, Dimethylol propionic l-one hydrate acid 3-Hydroxy-2-methyl-4-pyrone : 2,2'-Dithiodiethanol 5-Hydroxy oxindole o-Ethyl phenol 3-Hydroxy piperidone , .
.

-- ~065;;~74 ~
.: . .

HYDROXY, ETHER COMPOUNDS (cont'd) 2-Hydroxy pyridine 1,3-Dichloro-2-propanol 5-Hydroxy-4-octanone 2,3-Dichloro-l-propanol Iodopropylidene glycerol 2,4-Dichloro phenol N-Methylol-2-pyrrolidone 1,3-Dichloro-2-methyl-2-Anilino ethanol propanol Amyl ether Diethanol sulfide -Benzene thiol ~ ~C~-Dimethyl phenethyl alco-Benzyl alcohol hol ~: 10 Benzyl butyl ether 2,4-Dimethyl phenol n-Benzyl ethyl ether 2,6-Dimethyl phenol 2-Benzyl oxythanol 4,6-Dinitro-o-cresol :, 4-Bromodiphenyl ether 2,4-Dinitro phenol n-Butyl phenyl ether 2,6-Dinitro thymol : n-Butyl diethanolamine 2,3-p-Dioxanediol l-Chloroethyl "Cellosolve"* Diphenyl ether l-Chloro-3-pentanol 2,6-Di-tert-butyl-p-cresol 4-Chloro cyclohexanol 2,6-Di-tert-butyl phenol 6-Chlorol-l-hexanol 2,4-Di-tert-pentyl phenol o,m,p-Cresols 6,6-Dimethyl bicyclo 3,1,1 o,m,p-Chlorophenols hept-2-ene-2-ethanol 6-Chloro thymol Dodecyl alcohol 2-Cyano ethanol p-Dodecyl phenol Cinnamyl alcohol l-Dodecane thiol . Cedrol 1,2-Ethane dithiol Cyclohexanol Ethane thiol 1,4-Cyclohexan di- l-Ethoxy naphthalene methanol o-Ethoxy phenol Decanediol Glycerol di methyl ether 2,3-Dibromo-l-propanol 3-Hydroxy propionitrile *Trademark for the (l-chloroethyl) ether of ethylene glycol.

'. ~ : ' ':

~ 106SZ74 . ~ .

HYDROXY, ETHER COMPOUNDS (cont'd) ~; 3-Hydroxy propylene oxide Poly ethoxy ethylated (1-20) 1,6-Hexanediol oleyl alcohols Hexyl "Cellosolve" Polyethoxylated lanolin (5+) ~ .
, D-Methoxy phenol alcohols ~.,:,;
Dl-ct-Methyl benzyl alcohol Polyethoxylated (75) lanolin 5-Methyl-2-isopropyl phenol Polyethoxylated (9) acetyl ....
:~ 2-Methyl-1,2,3-propanetriol lanolin alcohol ~, . 2-Imidazoline-l-ethanol p-Butoxy phenol ~ 10 5-Indanol Polyglycols :~- 2-(Iso propyl thio) ethanol Polymethyl alkyl siloxanes , : Lanolin alcohols, acetylated Pyrrole-2-ethanol : 5-Methyl-1,3-dioxane-5- Pyrrole-2-methanol !
methanol Stearyl alcohol ::x :: 2-Nitro-2-ethyl-1, 2,5-Tetra hydrofurandimethanol 3-propanediol 1,2,3,4-Tetra hydro-2-naphthol 2-Nitro-2-methyl-1-propanol Tetra hydro pyran-2-methanol o-Nitro anisole Tetra hydro-2)2)5-trimethyl-5-.' o-Nitro phenol cinyl furfuryl alcohol : 20 2-Methyl-l-phenol-3-butyne-1, Tetrahydropyran-2-methanol .~ 2-diol 2,2,4,4-Tetramethyl-1,3-m-Nitrobenzyl alcohol cyclobutanediol ,~ 2-Nitroethanol Tetra ethylene glycol 1,5-Pentanediol 2-Thenyl alcohol Pentaerythritol Thiobenzyl alcohol . p-Pentoxyphenol 2,2'-Thiodiethane thiol .~ Phenethyl alcohol 2,2-Thiodiethane thiol Sec. Phenethyl alcohol Triethylene glycol dimethyl l-Phenyl-1,2-ethanediol ether -- 1,1,1-Trichloro-2-propanol h ~ 37 -:
, ' .
.

~ 1065274 - HYDROXY, ETHER COMPOUNDS (cont'd) l,l,l-Trichloro-2-methyl-2- Crown ethers propanol (& hydrate) Trimethylol amino ethane l,l,l-Trimethylol ethane l-(2-Hydroxyethyl) piperazine Trimethylolpropane p-Hexyl phenol Tris (hydroxy methyl) nitromethane p-Hexyl oxyphenol Toluene-3,4-dithiol o-Phenyl phenol Aldol 2,4,5-Tr.ichlorophenol -l-Amino-2-propanol 2,4,6-Trichlorophenol 3-Amino-2-propanol 2,2,2-Trichloro-l-ethoxy 3-Amino-2-butanol ethanol 2-amino thiophenol 2-Vinyl oxyethyl ether 2-Methyl-2,4-pentanediol 2,4,6-Trinitroresorcinol 2-Methyl cyclohexanol o,p-Toluenethiol 3-Methyl cyclohexanol 3-Cyclohexene-l-methanol 4-Methyl cyclohexanol 3-Cyclohexene-l-dimethanol 2-Methyl-l-phenyl propanol-l 3-Nitro-2-butanol ~ -2-Methyl-l-phenyl propanol-2 2-Nitroethanol p-(Methyl thio) phenol 2-Nitro-l-propanol ~: 20 2-Nitro diphenyl ether AMIDES, IMIDES
l-Octanol 4-Acetami.no-2,2,6,6-tetra 1,2,3-Propanetriol methyl piperidino-l-oxyl l-Phenyl-2-propanol 2-Acetamido-3-butanone 3-Phenyl-l-propanol 4-Acetamido butyric acid 2,2,4,4-Tetra methyl-l, 4-Acetamidothiophenol 3-cyclobutanediol 2-Acetamido thiazole p-(1,1,3,3)-Tetra methyl 2-Acetoacetamido-4-methyl butyl phenol thiazole Thiophenol Adipamide m-Thiocresol N-Allyl methacrylamide ' 1065~274 MIDES, IMIDES (cont'd) 6-Amino nicotinamide N-Ethyl acetamide Anthranilamide Ethyl acetamido acetate Azodiacarbonamide N-Ethyl acrylamide N-Bromoacetamide N-Ethyl maleamic acid 2-sromo-2-ethyl Iso valeramide 3-Ethyl-3-Methyl gIutaramide N,n-Butyl acry1amide N-Ethyl methacrylamide N-Butyramide N-Ethyl nicotinamide Iso-butyramide N-Ethyl propionamide Chloral formamide Ethyl oxamate Cinnamamide Fluoroacetamide Diacetamide Fumaramide N,N'-Diallyl tartardiamide l-Glutamide ,.. .
N,N-Dibutyl formamide Glutaramide 2,2-Dichloroacetamide Heptamide N,N'-Dicyclohexyl carbo N,N-Hexamethylene formamide diimide Hexa methyl phosphorous triamide Diethyl formamido malonate 2,2,2-Trichloroacetamide N,N-Diethyl Iso nico- N-Hydroxy acet~mide tinamide 2-Hydroxy ethoxy acetamide N,N-Diethyl nicotinamide N-(2-Hydroxy ethyl?-phthalimide N,N-Diethyl nipecotamide N-(Hydroxy methyl)-nicotinamide N,N-Diethyl-l-piperazine N-Hydroxy succinimide carboxamide 5-Hydroxy valeramide N,N-Dimethyl acetoacetamide Iodo acetamide N,N-Dimethyl nicotinamide Iso-nicotinamide 3,3-Dimethyl glutaramide Iso-nipecotamide 2,4-Dihydroxybenz~mide N-Iso propyl acrylamide 2,3-Epoxy-2-ethyl N-Iso propyl salicylamide hexanamide N-Lauryl methacrylamide N,N'-Dimethyl oxamide 3,5-Dinitrobenzamide ."
" ` ' .

~ 39.
... .

AMIDES, IMIDES (cont'd) Maleamic acld N,N,N',N'-Tetra ethyl Maleimide phthalamide Maleondiamide N,N,N',N'-Tetra ethyl N-Methyl acetamide fumaximide N-Methyl acrylamide N,N,N',N'-Tetra methyl N-Methyl maleimide carbamide 2-Methyl malonamide Thiobenzamide ~ :
~, . .
N-Methyl nicotinamide Thionicotinamide -N-Methyl propionamide o,p-Toluamide N-Methyl 2,2,2-Trifluoroacetamide 2,2,2-Trifluoroacetamide Methyl-2,2,2-Trichloroacetamide Trimethylacetamide P-Nitrobenzamide Valeramide :-Oxamic acid . l-Naphthaleneacetamide Oxamide 4-Acetamido-2,2,6,6-tetra : ~-Phenyl butyramide methyl piperidine Phenyl formamide N-Butylacetamide N-Phenyl succinim{de tert-Butyl carbazate Phthalamide Diacetone acrylamide 20 N-Polyoxy ethylene fatty N,N-Diallyl formamide acid amides Dibutyl cyanamide Propionamide N,N'Dibutylpropionamide . Pyrazinamide N,N-Diethyl acetamide Stearamide Diethyl acetamido malonate Succinimide N,N-Diethyl butyramide Succinic diamide N,N-Diethyl formamide Sulfabenzamide N,N-Diethyl ~ropionamide Sulfacetamide N,N-Diethylm-toluamide Sulfamide . N,N-Dimethyl dodecanamide N-Sulfanyl stearamide N,N-Dimethyl propionamide .

' ,., , :: ' , ' ' , , ' - -. .
- , .~ .

AMIDES, IMIDES (cont'd) N,N,-Dimethyl thioacetamide Phenyl carbonimide N,N-Dimethyl thioformamide Acetamidine acetate :~ N,N-Dimethyl valeramide p-Acetamido benzaldehyde 3,5-Dinltro-o-toluamide p-Acetamido benzoic acid N,N-Diphenyl acetamide N-[2-(Acetamido)-imino]
N,N-Dipropyl acetamide diacetic acid ~ .
N,N-Dipropyl decanamide ESTERS, CARBONA~ES
N,N-Dipropyl propionamide Allylidene Diacetate N-Ethyl maleimide Bi~ (2-Ethyl hexyl)sebacate Ethyl methyl carbamate Bis (2-Ethoxy ethyl) sebacate Hexanamlde Bis ~2-Ethyl hexyl) phthalate Hexaethyl phospho~ triamide n-Butyl oleate 2-Hydroxyethyl carbamate Butyl nitrite N-2-~Hydroxy ethyl) 2-Chloro ethyl trichloroacetate auccinimide 2-Chloroethyl chloroacetate 2-Furamlae 6,9-Diamino-2-othoxy Lactamide acridine lactate N-Methyl benzamide Di isopropyl adipate N-Methyl diacetamide Dlmethyl methyl phosphonate N-Methyl-N-l-naphthyl 2-Di isopropyl aminoethyl-p-; acetamide amino benzoate N-Methyl-2-phenyl acetamlde Di iso-butyl carbonate N,N,N',N'-Tetra methyl Dibutyl sulfite glyclnamide Dlbutyl ~+) - tartrate N,2,2-Trimethyl propionamide Dimethyl maleate 2,2,5,5-Tetra methyl-3- Dimethyl malonate pyrrolin-l-glyoxy-3- D~ethyl oxalate - car~oxamide Dlbutyl oxalate 30 l-Naphthaleneacetamide Dlethyl adipate ; 41.
.
- . . .

` `` 106S274 . ESTERS, CARBONATES (cont'd) .
Dipropyl adipate Methyl abietate Dibutyl adipate . Methyl acetoacetate Diethyl sebacate Methyl benzoate Di iso-butyl adipate Methyl trichloroacetate Di-n-butyl.sebacate n-Octyl nitrate Dimethyl phosphite Phenyl carbonate Ethyl trichlorcacetate Polyoxy ethylene stearate Ethylene (mono) thio carbonate Isopropyl salicylate : 10 Ethyl-2-pyridine carboxylate . n-Propyl nitrate ;:
: Ethyl anthranilate Phenyl acetate Ethyl acetoacetate Propyl benzoate .
Ethyl benzoate . Tetra hydrofurfuryl nicotinate 2-Ethyl hexyl acetate Tetrahydro furfuryl acetate Ethyl dichloroacetate Tetra nitro methane Glucose-1-phosphate 2,2,2-Trichloro ethyl carbamate Glycol diformate Trilauryl phosphite IRO butyl carbonate Trilauryl trithiophosphite Iso-pentyl nitrite Trimethyl-3,3',3"-Iso-propyl salicylate nitrilotripropionate . -. . Methyl cyanoacetate Trimethyl phosphate Methyl cinnamate Triethyl orthopropionate Methyl decanoate . Triethyl orthopropionate : Methyl myristate Triethyl phosphite . 25 Methyl octanoate Tri Isopropyl phosphite Methyl palmitate Tri butyl borate Methyl salicylate Tri (2-Tolyl) phosphite Methyl stearate Tetra hydrofurfuryl propionate Monostearin --Monolein --:- :
': ~ 42.
.
. . - :, ,. ,: : :
- ' ~ ,,: .. ' . ,: ~ : :
- . .
-" ~065Z'74 i .
KETONES, ALDEHYDES
2-Acetyl cyclohexanone N-Morpholino carboxaldehyde - Acetaldehyde Nicotinaldehyde Anisole 5-Nitro salicylaldehyde Butyraldehyde Nitroso salicylaldehyde : Butyrophenone 2-Octanone p-Chlorophenetole l-Phenyl-2-propanone Cinnamaldehyde Phenetole 1,2-Cyclohexanedione Picolinoaldehyde 1,2-Cyclodecanedione l-Piperazine carboxaldehyde 3-Cyclohexene-l-carboxaldehyde 1,4-Piperazine 1,3-Dichloro-2-propanone dicarboxaldehyde Decanone N-Piperidino carboxaldehyde 2,5-Dimethyl cyclohexanone Piperonal - 3,5-Dimethyl-5-ethyl-2,4-dione Propiophenone N-Formyl hexamethyleneimine 2-Pyridone Hexachloroacetone 4-Pyridone 2,4-Imidazolidine dione Pyridine-2-carbaldehyde 2-Imidazolidone Pyridine-3-carbaldehyde : 20 Indole-3-cyclohexanone Pyrrole-2-carbaldehyde L-Menthone Thiophene-2-carbaldehyde 4-Methoxyacetophenone Tribromoacetaldehyde Methyl benzophenone Veratraldehyde o-Methyl anisole o,p-Vanillin 4-Methyl acetophenone o-Phthaldialdehyde c~-Methyl cinnamaldehyde 1 Phenyl-3-pyrazolisinone 2-Methyl piperazine-N, 2-Heptanone ~: N'-dicarboxyaldehyde Pentaerythritol diformal N-Methyl pyrrole Methyl-2-thienyl ketone carboxaldehyde Cyclododecanone Azacyclotridecanone HETEROCYCLICS, ACIDS, AMINES
( & SALTS), MISOELLANEOUS SUBSTANCES

N-Acetyl morpholine Butyl disulfide 2-Acetyl pyrrole Tert-butyl disulfide s 2-Acetyl thiophene 9-Chloroacridine Acridan 4-Chloromethyl-l-aeridine Acridine 2-Chloropyridine 4-Chloropyridine Acrldine orange ~ Cyclopentamethylene 0 Acridine yellow tetrazole Acriflavine 3,6-Diamino acridine Allyl thiourea 1,8-Diamino-p-menmane l-Allyl pyrrole 1,2-Diazole 2-Allyl pyrrole Dihydroacridine .. .5 Amino acid~ 1,2-Dihydro-3,6-9-Amlno acridlne pyridazinedione 3-Amlno acridlne 2,3-dihydrofuran ~ o-Aminophthalhydrazide 3,4-Dihydro-1(2H)-- ~enzothiazole naphthalenone ~0 N,N'3is ~3-amino propyl)- Dimethyl acid pyrosphosphate . .
piperazine 2,5-Dihydroth~io~hene 1, 1-~ Bi~ (2-Ethyl hoxyl) dioxide orthophosphoric acid 2,3-Dihydro-4-pyxan 2,2-Bis ~-thyl sulfonyl 2,4-Dlmethyl-3-ethyl pyrrole !5 butane 2,3-Dimethyl-4-ethyl pyrrole . 1,8 Bi~ ~dimethylamlno)- 2,5-Dimethyl pyrrole naphthalene 3,4-Dlmethyl-5-sulfanilamido 3utyl ~ulfone iso oxazole, salt~
; ~is ~2-ethyl hoxyl) D1 ~henyl ~ulflde - 30 hydrogen phosphate Di i~opropanolamino .;

.
: 44.
. .
.
.
.. ..

~ - ` 106S~74 HETEROCYCLI CS, ACI DS, AMINES ( & SALTS ) MISOELLANEOUS SU~STANCES (cont'd) Dichloro propionic acid 2-Nitrofuran, 3-Nitrofuran N-Nitroso diethylamine l-Nitrosopiperidine l-Nitrosopiperidine Oxypolygelatin Dibutyl butylphosphonate Pantoic acid- ~ }actone o~-Glucose-l-phosphoric acid 1,5-Pentamethylene-tetrazole Gluconic acid o-Phenetidine . Guar Gum Phenyl hydrazine 0~ Indole Phenyl mercuric borate . Imidazole p-Phenetidine Iminodiacetic acid 4-~-3-Phenyl propyl)-Hexamethylene imine pyridine 3,5-Lutidine-N-oxide Phenyl phosphonous .5 2-Lactoyl oxypropanoic acid dichloridate Lithium acetate Phenyl phosphoro dichloridate .
, Lithium perchlorate Phenyl phosphone thioic .- l-Methyl imidazole dichloride 2-(Methyl thio) benzothiazole 0 2-Methyl glutaronitrile Methyl isobutyl ketoxime - Methyl phenyl sulfide Phenyl phosphoric dichloride . , l-Methyl-l-phenyl hydrazine Piperine ::
3-Methyl sulfolane Pyridine-l-oxide , '5 N-Methyl pyrrole Pyridazine '. Nepatolactone Pyrimidine !......... Nitrocyclohexane Pyrrole o-Nitrophenol Quinoxaline : :
i 2-Nitropyrrole Safrole 0 o-Nitroanisole Stearic acid ., ~ ' :
:

.. . . . ... ..

~065274 HETEROCYCLICS, ACIDS, AMINES ( & SALTS) MISCELLANEOUS SUBSTANCES (cont'd) -Trimethyl sulfoxonium iodide Caprylic acid 1,2,3-Trimethyl benzene l-Chloro octane 1,2-Epoxycyclododecane Chloropicrin N-(3-Amino propyl)-2- Caproic acid pyrrolidinone o-Chloroaniline N-(3-Amino propyl)-morpholine Cumene Acetonaphthane 2,4-Dichloropyrimidine 4-(2-Amino ethyl) morpholine 3,~6-Dichloropyridazine N-(3-Amino propyl)-morpholine 3,7-Dichloroquinoline n-Butylaniline 2,5-Dihydro-2,5-dimethoxy : Butyl sulfide furan Benzylamine N,N-Dimethyl cyclohexylamine Benzedrine 1,4-Dimethyl piperazine 2-Benzyl pyridine 1,4-Dinitroso piperazine l-Bromonaphthalene 2,3-Dichlorodioxane Butyl benzene 1,5-Dichloropentane l-Bromo-2-iodobenzene Dibenzylamine 1-Bromo-3-iodobenzene N,N-Dibutyl aniline Butyl nitrite Dipentylamine Cyclododecane 1,3-Dioxepane 1,5,9-Cyclododecatriene 1,3-Dioxolane Cyclododecene 2-(1,3-Dioxolane-2-yl) 1,2-Cyclohexane dicarboxylic pyridine anhydride 4,4'-Dithiomorpholine "Cedrene"* 3,4-Dimethyl furazan l-Chloronaphthalene Di iso amylamine 2-Chloroquinoline Di butyl amine 3-Cyclohexanepropionic acid o-Diethyl benzene * Trademark for terpenes obtained from cedarwood oil.

.
, , ~ ' ' ' , .

~065Z74 HETEROCYCLICS, ACIDS, AMINES (& SALTS), MISCELLANEOUS SUBSTANCES (cont'd) 3,4-Dimethylpyridine Methoxyacetic acid Dibutylamine 4-Methyl morpholine o-Diethylbenzene N-Methyl-p-nitroaniline l-Ethylnaphthalene N-Methyl-o-nitroaniline 2-Ethylnaphthalene 2-Methyl quinoline 3-Ethylrhodanine 2-Methyl pyridine l-Ethylpyrrole 3-Methylpyridine Ethyldiethanolamine 4-Methyldioxolane o-Ethyltoluene Methyl urethane Fluorosulfuric acid- ~ -Methyl styrene antimony pentafluoride l-Nitropropane Isopentyl nitrite 2-Nitropropane Heptanoic acid l-Nitrobutane :- Lactonitrile l-Nitrohexane . Lithium oleatè, palmitate, Nitro trichloro methane ` stearate n-Octyl nitrate J
o-Iodotoluene 4-Phenyl-1,3-dioxane p-Isopropyltoluene 3-Propyl rhodanine : l-Iodonaphthalene Propyl disulfide l-Iodo octane Propyl sulfide Iso pentyl nitrite Propyl sulfone 2-Methyl benzothiazole Piperidine 2-Methyl benzoxazole Valeric acid 1,2-methylenedioxybenzene Trimethylene sulfide l-Methyl naphthalene --: 2-Methyl naphthalene --2-Methyl-2 nitropropane --N-Methyl-N-nitrosoaniline --: - 47 -~ ' - - . . .
- ~ ... . : .
' ' ' , MlSCELLANEOUS SUBSTAN OE S
Acridine red Lutidines Acridine iso thiocyanate - 2-Methyl-2-thiazoline Acriflavine o-Methyl toluidine Aesculin Metrizamide Allantoin Nile Blue Aluminum lactate Neutral red Amino phosphonic acids Neutral violet ;: Bismuth ethyl camphorate Phenyl ethylene oxide Calciu~ carbamate l-Phenyl propane Calcium borogluconate Primuline Calcium palmitate 1,3-Propane sulfone Calcium stearate Isopropyl benzene :
: Calcium galactogluconate N-Propyl nitrate bromide 1,4-Pyrone Circumin Pyru~ic acid Cinnamonitrile Safranin ;: o-Diacetyl benzene Sulfonyldiacetic acid - Decahydroquinoline Sulfur iodide :~
: 20 1,4-Dichlor-2-nitro benzene Tetrabutyl ammonium perchlorate 1,2-Dichloro-4-nitro benzene Tetra~utyl ammonium fluoro-l,l-Diethyl urea borate Dimethyl phosphite Tetrabutyl ammonium bromide ~; Diphenyl selenide Tetraethyl ammonium perchlorate Diphenylimidazalone-sulfonated Tetraethyl thiuram sulfide Flu~resca~ine Tetraethyl ortho silicate N-Iodoacetyl-N'-~5-sulfo-1- Tetraethyl ortho titanate .
naphthyl)-ethylene diamine 1,1,3,3-Tetraethyl urea N-Iodoacetyl-N'-(8-sulfo-1- Tetra isopropyl ortho titanate ` 30 naphthyl)-ethylene diamine 1,1,3,3-Tetraethoxy propane .. _ . .. ... .

*A dyestuff which is a dieth~l dia~nino phenoxazonium salt.

NISCELLANEO~S SUBSTANOES (cont'd) Tetraethyl tin Trimethyl sulfonium iodide Tetrahydrofurfuryl oxy- Trimethyl sulfoxonium iodide betra~ydropyran Trimethyl amine N-oxide, hydrate 5 i,2,3,4-Tetrahydro 1,3,~_~dnltro ken~e isoquinoline 2,4,6-Trimethyl pyridine 2,3,4,5-Tetramethyl pyrrole Trichloromethyl phosphonic acid N,N,N',N'-Tetramethyl-l, Trioctylphosphine oxide 8-naphthalene diamine Trioctyl phosphine 10 2, 3, 5,6-Tetramethyl piperazine Tri-n-pentyl amine 2,2, 4,4-Tetramethyl-1,3-cyclo- Vasoflavin butadiamine Vinyl carbazoles ~:
1, 2, 3,4-Tetramethyl benzene Zinc oleate 3, 3 ', 5,5'-Tetramethyl benzidine Tetranitro methane Tetracyanoethylene Thiamorpholine Thiolactic acid _ . . . _ . .. . . .. . . . . .
3,3'-'~hiodipropi~nic acid ~ 20 Thiophthene : 1,4-Thioxane Thiofla~ine o,m,p-Toluidine Triazo benzene Tri-n-butyl amine Tri i~ butyl amine Tri-n-butyl phosphine oxide Trl butyl phosphine 3,5,5-Trimethyl-2,4-oxazolidine -30 dione ~ i~.4 . ~,,' .
.: 49.

As part of the methodology which may be used to categorize the materials such as those listed herein they may -- be titrated with distilled water and their conductivities ob-tained. The dilution/conductivity curve so obtained indicates the rate of change of conductivity with dilution as well as the diminishing point or plateau levels of conductivity achieved within reasonable dilution means which helps characterize the ~; materials as to the several categories discussed herein, such - as very active solvents, active solvents, etc. The following data illustrates the applicatlon of this technique (resistances are given in millions of ohms). The very low plateau of .. . .
resistance at the indicated dilution levels establishes that dichloroacetic acid and mercaptoacetic acid are in the category of very active media. The somewhat higher plateau of ethylene carbonate and 2,5-hexanedione place them in the category of active media. By such a method a convenient rating scale can be established for evaluation of different media. This technique assists in tailoring media to a desired conductivity value by observation of resistance values at different levels of dilution.

INITIAL RESIST~NCE RESISTAN OE
RESISTANCE WITH .05 ml. WITH 1 ml.
SAMPLE 0.3 ml. WATER ~DDED WATER ADDED
; , 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 7 2.2 0.060 Often even partial miscibility with water is sufficient to indicate the range of activity or character to be expected.
Further, these studies are extended by titration against materials other than water. Thus, for example dichloracetic acid, formamide and thiodiethylene glycol were used. These 50.
.
:

-- 1065Z'74 then represent a different solvent miscibility capability and profile. Of these agents, the formamide has a very high dielec-tric constant and greater conductivity than water, whereas the thiodiethylene glycol's conductivity was in the range of the water used and also achieved ~he level of conductivity of the water when a drop of water was added; that is, upon only slight dilution with the water. The conductivity changes so produced by dilution with nonaqueous materials were further characterized by observing changes in plateau levels so produced by addition of a minor quantity of secondary solvents which may be water.
This helps to relate the influence of secondary solvents such as the active or very active type (or inert type for suppressant activity) to the conductivity profile. Such effects are variable or characteristic for the diluted agents to which the secondary diluent is added. Further, the conductivity titration curves may be studied with a particular conductivity-valued diluent which may already be an ionized or higher conductivity system. For example, the dilution of hydroxy compounds and ethers with fairly conductive aqueous ammonium nitrate solution and acetic acid may be cited. The comparison was made where both latter systems had equivalent conductivities. Of the compounds 1,3-butane diol, 2,2-methoxy ethoxy ethanol, 2-oxydiethanol bis (2-methoxy ethyl) ether, sorbitol ~40% aqueous solution) and sorbitol (57~ squeou~ solution) by volume, the dilution of the aforementioned aqueous conductive solutians by the latter com-pounds generally shows a ~imilar decrease in conductivity over the titration range although certain definite curve shapes were derived. Thus, the relative activity and suppressant profile of the various diluants became evident. ~ith thi~ technique, the substantial difference with bis (2-methoxy ethyl) ether is 51.

. ~ . .

- ~ ~065Z74 readily evident. Also differences were noted in the effects of aqueous sorbitol at various concentrations, as compared to the nonaqueous materials, upon the lonized ammonium nitrate solution which effects were otherwi~e somewhat less pronounced than upon a dilute acPtic acid solution. Fur~her, the various systems may be studied as they affect equilibria characteristics, ionization and/or formation data for the materials of interest and at ; - various p~' Q . A large compendium or library of data may be prepared for these variou possibilities in order to achieve a lessened empirlcal ba~is for conditions of ~ystem selection - for use. As a re~ult of thi~ invention an already established broad table i~ given of basic ~olvent systems from which future ; screening can be made to develop media for use with particular ~pecies.
AB illustrated by the above examples and the lists of chemicals, the proce~s of thi~ invention comprise~ separating or mobilizing chemical specie~ which ~re conveniently on a support such as filter paper in a medium of low conductivity across which a high voltage i~ impressed. The media-baso comprises one or more compound~, for ex~mple, inorganic or orgnnlc compounds such as glycols, ether~, e~ter~, dlones, lactone~, amides, nitrile~, alcohol~ and water. An agent may be added to the medium to ad~u~t it~ conductlvity and ~uch agent may be sel3cted from the group con~i~ting of water, acld~, ba~es and salts.
The voltage used ln the procesB i8 withln the rango of about 50 to 25,000 volts/cm. At very high voltages, and particularly with volatile or gaseou~ ~ubstance~, cooling may be requir~d.
The preferred range i8 about 200 to 3,000 volts/cm, and in this range the proces~ can be c~rrledout wiff~textern~l cooling.
The conductivity of ~he medium i~ preferably ad~usted ~o provide 52.

; a current density in the range of about from 0.2 to 100 micro-; amps/sq. cm. based on the area of, for example, filter paper asa substrate. The preferred range is 1.4 to 54 microamps/sq. cm.
For bulk work and with external cooling, current densities above i 5 100 microamps/sq. cm. can be used. The transport medium, after appropriate adju~tment of its conductivity, is subjected to a sufficiently high voltage at a low current level (at about the threshold level) to induce separation of the chemical species therein at a rate of about 1 cm/sec. to about 0.25 cm/min.
In the above examples, at the conditions indicated, no external cooling was required.
Refinement of the media formulation techniques can lead to resolution improvement in the separation of given components by EMP. For example, the media of 5 ml. propanediol cyclic carbon-~ 15 ate, 5 ml. propylene glycol, 2 ml. N-methylacetamide and 0.4 ml.
- tetrahydrofurfuryl alcohol allows the resolution ~f rhodamine B
and 6G of examples 16 above in considerably less than the 3.6 cm.
required in example 16. The utilization of resolution improve-ment to ~horten separatlon distances makes it possible to mini-mize diffusional effects.
It is po~sible to improv2 resolution generally according to the followlng procedure. ~ suitable ~olvent is found for the chemical specie~ to be transported. The nature, of the chemical species to be transported is then analyzed in terms of its proton donor/acceptor properties. The donor/acceptor properties of a number of chemical species are catalogued in the literature. E.g., V. Gutmann, Coordination Chemistry in Non-Aqueous Solutions (1968). A component should then be added to the media which will interact in a proton donor/acceptor interaction with the chemical species. In many instances the .
.

:, . .~ .:

proton donor/acceptor properties of chemical species are not catalogued, or are complex. In such cases it is possible to determine the type of media components that will improve reso-lution by testing the system through the simple technique of addition of 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 compound, donors of varying strength are then tested to determine which provides the greatest improvement in mobility and resolution. An analo-gous procedure is followed if the strong proton acceptor increases the mobility rate of the chemical species. ThP addi-tion of a component which can interact with the chemical species -to be transported by proton donor/acceptor interaction seems to facilitate initial mobilization of the chemical species. The dielectric constant of the media is then adjusted if necessary to a moderately high level. It may also be necessary to correct `; for electrical instability of the media by addition of a com-pensating component as detailed above.
As an additional aspect of this invention it has been determined that improved tailoring of the semiconductive media also permits, for certain chemical species, exhibition of an EMP response observable with the unaided eye at relatively low voltages and reduced power levels, as compared to the high vol-tage, high power processes described above. Voltages below 50 v/cm and even less than 20 v/cm on conventional support media have been utilized. For example, one can achieve EMP transport at power levels as low as 3xlO 6W. to 1.7xlO 5W. with voltages of 2 to 4 volts at 1.5 to 4.2 ~A. over several centimeters of #l "Whatman"* filter paper. This represents EMP operation at potentials of several millivolts per centimeter at tenths of *Trademark ~` " 1065Z74 :~:
microwatts per square centimeter. The limit on low voltage EMP is the level at which electrical diffusivity comes into play. It has also been found that certain agents will act to reduce the threshold current of a chemical species.
A media system is modified to allow low voltage EMP
response and to reduce threshold current in much the same manner as it is modified for resolution improvement. Specifically, initiators and mobilizers are added. Initiators are compounds which act to reduce the threshold current of a given chemical species, and mobilizers are compounds which act to increase the mobility (transport rate) of a given chemical species. There is some overlap between the classes of compounds useful as ini-tiators and those useful as mobilizers, that is, some compounds will act both as initiators and as mobilizers. -In general, materials which will interact on a proton donor/acceptor level with the chemical species to be transported and high dielectric constant materials are useful as initiators and mobilizers. Examples of compounds which are often useful ;-both as initiators and mobilizers are N-methylacetamide and sali-cylaldehyde.
With the use of initiators, threshold currents may be adjusted to as low as 0.2 to 0.002 ~ /cm , and EMP may be carried out at these currents at slower but still effective mobility rates with voltages as low as 0.05 to lOv/cm. The . .
voltage level of 0.05 v/cm xepresented a practical minimum during experimentation because voltage effects on this order inherent to the system were encountered. Overall, considering both high voltage and low voltage EMP, the EMæ voltage range may be 0.05 to 25,000 v/cm, with power levels as low as _9 2 1.2xlO to 5xlO~5W/cm .

,', ~ ' ' . :
- :

' :
55.

- . .

~065Z74 .
The following examples illustrate the manner in which media, suitable for EMP transport according to the criteria of semiconductivity and compatability with chemical species des-cribed in connection with high voltage EMP above, are modified with initiators to reduce threshold current.

EXAMPLE SOLVENT FORMULAE

22 7 ml. propylene glycol, 3 ml.
diacetone alcohol (mobilizer, also enhances resolution), 2.2 ml. N-methylacetamide (high ~ ;
dielectric constant material~
acts as initiator and mobilizer), 1.3 ml. formamide (same).

23 21 ml. propanediolcyclic carbonate, 9 ml. methoxyethyl ethanol, 12 ml.
tetrahydrofurfuryl alcohol, 3 drops HNO3 diluted 1:3 with water.
, ,:
The media of example 22 above has been used to sepa-rate rhodamine dyes, and also to separate vitamin B12 and sodium riboflavin phosphate mixtures.
,. .~
j ~ The media of example 23 was used to separate rhodamine B and 6G in less than 0.5 cm. The tetrahydrofurfuryl alcohol acted to enhance the mobilization of the compounds magnifying molecular differences. Without this component the two species showed almost equivalent motion over several centimeters.
As further examples, the media of example 23 can be altered to increase its conductivity by the dropwise addition of conductivity, initiator or mobilizing agents (A.) to obtain the electrical values (B.) and power levels (C.) set forth in the table below.

- ..

(B.) Electrical Values (C.) Total EMP Power -- for EMP run (on Level In (A.) Agent 4 x 1 cm Filter Paper) Microwatts Nitric acid (1:30 in water) 4V, 4.2 ~a 17 Ammonium Bromide lOV, 1.2 ~a 11 (Sat'd. in glycol) formamide lOV, 1.2 ~a 12 N-Methyl Acetamide 20V, 2. ~a 40 N-Methyl formamide lOV, 4.1 ~a 40 Hexamethyl phosphoric triamide lOV, 3.5 ~a 35 , -~ The accomplishment of EMP at low voltages with accom-panying low power levels has important ramifications in that EMP
under such conditions would be compatible with living organisms.
Voltage, power and threshold current levels appropriate for low voltage EMP exist in living organisms and consequently are clearly ; tolerated by them. Thus the EMP techni~ue of formulation of semiconductive media may be effected within a living organism to control or study chemical substances in physiologically functional systems.
The voltage necessary to the EMP process may be supplied by potential differences existing naturally in an organism and merely applied to the appropriate site, or may be imposed from an ` outside source.
. .
` It is well known and recognized in the prior art that potential differences exist within living organisms naturally.
Also, in connection with the experimentation leading up to the present invention, it was found that a voltage reading on the order of tenths of volts or millivolts with a current of microamps ~ -or slightly less was generated across the phase boundary between two immiscible or partially immiscible liquids in certain instances.

.

: ^:

10652~
Not all phase boundaries produced this junction effect; for -liquids, partial solubility in each other seems to correlate with the effect to some extent. The junction effect may be modified by use of a permeable membrane between the phases.
Propanediolcyclic carbonate and water form different phases and exhibit this junction effect. It is believed that juxtaposition of liquids in the cells of living organisms could give rise to a liquid junction effect providing sufficient voltage for the effectuation of EMP. Such effects appear to be amenable to , 10 modification by EMP media formulation techniques.
The process of EMP media formulation may be carried ; out in conjunction with an externally applied voltage, as well as with one existing naturally within an organism or portion i~ thereof, to effect an EMP response. Some evidence already exists, for example, of improved bone and other tissue healing or growth in the presence of an applied voltage. See Lavine et al., Electric Enhancement of Bone Healing, 17 Science 1118 (March 1972). Such effects could be enhanced by application of the desired chemical species. For example, the initiators or dielectric constant modifiers for transport of biochemical species described herein could be applied to facilitate or en-hance an electrophysiological response such as transport or orientation of the appropriate materials across a bone break.
More generally, given voltages and current levels - within living organisms, the procedure of media formulation of the present invention could be used to construct or modify within the organism appropriate semiconductive media for en-` - hanced transport of physiologically significant chemical species.
For example, EMP media formulation techniques could be used to speed reparative or other chemical species to injured portions of the body. EMP media formulation might also be useful ~ .

` `
,` 1065Z7~
with respect to the application or retention of drugs. EMP
might be used to effect or control natural processes on a humo- -ral, intercellular, or even intracellular level.
-~; In the preparation of media within an organism, toxi-city of the media components and other aspects of compatability with the physiological system would be of key importance. Con-siderations of toxicity would include considerations of irrita-tional, inhibiting and denaturing characteristics. In selecting chemical materials useful for in vivo EMP work, the particular tissue or function to be modified must be taken into account.
Even nitriles can find utility in such work, e.g., 2-cyanoethanol is relatively non-toxic as well as non-irritating and non-absorbing dermally.
As an example, if it were desired to utilize an agent intravenously in mammals (including humans) which is well toler-~: .
ated in fair concentrations, and which should contribute amidebut not urea character, either lactamide or nicotinamide may be selected. For liquid or low melting N-alkylamides or N,N-dialkyl amides, often of high to very high dielectric constant, analogues - 20 such as N-ethyl nicotinamide or N,N-diethylnicotinamide may be considered. A number of related compounds, e.g., dibutyl forma-. ., mide, N-cyclohexyl-formamide, diethyl nipecotamide, or N-(2-hy-droxyethyl) lactamide, might be useful.
In addition to these examples, a listing of agents is given for use in formulating buffers with minimal impairment of sensitive biological systems. Also, a brief listing is given of .
other representative agents sufficiently tolerated to be generally useful for biological work. Additional criteria for this latter group include low melting point, good liquidity range, water solubility, other solubility, solvent activity, inertness or - functionality, etc.

; - 59 -.~' . .. . : - .: . ~, - , , ``' 106527~
TABLE IV
Biologically Compatible Buffer Agents and Zwitterionic Buffers cyclohexyl aminoethane sulfonic acid cyclohexyl aminopropane sulfonic acld N,N-bis (2-hydroxy ethyl glycine) N'-2-hydroxy ethyl piperazine-N'-2-ethane sulfonic acid N'-2-hydroxy ethyl piperazine-N'-2-propane sulfonic acid imidazole 2-N-(morpholino) ethane sulfonic acid morpholino propane sulfonic acid piperazine-N,N'-bis (2-ethane sulfonic acid N-tris (hydroxy methyl) methyl glycine N-tris (hydroxy methyl) methyl-2-aminoethane ~ulfonic acid tris (hydroxy methyl) methyl aminopropane sulfonic acid ; 25 ., .

.
- ' ~

`. 30 .

. .

:~ ~ 60.
. ~ , . . .
. , . -~ . ~ .
.

-`` 1065Z7~
TABLE V
Other Repre~entative Materials Suited for Use In EMP Media In Biolo~ical Systems ~-acetamidocaproic acid farnesol : 5 L- ~-acetamido-~-mercaptopro- fructose pionic acid D-gluconic acidGf-lactone acetamido phenol glutathione acetanilide glycerosphosphoric acid allantoin 2,6,10,15,19,23-hexamethyl 10 allantolactone tetracosane allyl-2,5-dlmethyl-3,4- ~-hydroxy-2-butanone . methylene dioxybenzene 2-hydroxybenzyi phosphinic n-amyl butyrate acid : anhydrom~thylene citric acid N-(2-hydroxyethyl)palmitamide D-L-arabinose 5-hydroxy-2-hexenoic acid arabitol lactone . _ : .arachidonic acid 2,6,10,15,19,23-hexamethyl-benzyl acetate 2,6,10,14,18,22-tetra-~: 1,3-bi~ ~hydroxy methyl) urea cosahexene . 0 bis (2-ethylhexyl) 2-ethyl- 15-hydroxy pentadecanoic acid : ~ hexylphosphonate E-lactone ethoxy (10-20) glucose 5-hydroxy-2 ~hydroxy methyl)-ethyl linoleate 4-pyrone ethyl le~ulinate 3-hydroxytrimethyl-3,7,11-dodecanoic i 3-ethyl-1-hexanol acid 2-ethyl-2-methyl succinimide "Ichthymall"*
2-ethyl ~ulfonyl ethanol i~oaAcorbic acid ethylene glycol diacetate iso-eugenol l-ethynyl cyclohexanol inositol hexaphosphoric acid ) eugenol isopropyl myristate ., :
61.
* Trademark for ichthanmol (ammonium ichthosulfonate).

-0:

- :
- :

`` 106SZ74 iso-valeric acid 2-(Chlorophenyl)-3-methyl-2, isovaleramide 3-butanediol kojic acid cineole lactobionic acid citric acid linoleic acid ~ cyclopentamethylene-lipoic acid tetrazole methylal acetamide Diethyl ethylphosphonate methylnicotinate N,N-diethyl iso valeramide ~-Methyl-~,~-crotonolactone N,N-diethyl-m-toluamide N-methyl pyrrolidinone 2,2-dimethyl-1,3-dioxolane-~.
l-methoxy-4-propenyl benzene 4-methanol p-methoxy benzaldehyde 2,6-dimethyl-m-dioxan-4-ol p-methoxy benzyl alcohol acetate myristyl alcohol dimethyl polysiloxane 3,4-(Methylene dioxy) benz- 2,3-epoxy-2-ethyl hexanamide aldehyde eicosamethylnonasiloxane nicotinamide ascorbate ethyl phenyl ether nicotinic acid monoethanol- o-ethoxybenzamide . amine propoxy (10-20) glucose `
- 20 2-nitro-2-propyl-1, 3-propanediol P~ntaerythritol chloral octanoic acid pentaerythritol tetraacetate oleic acid 3-pentanone .. oils, natural 3-phenoxyl-1,2-propanediol orotic acid phenoxyacetic acid ~;
: N-(pantothenyl)-~-amino- polyolyethylene (20) sorbitan ethanethiol monooleate Pantothenic acid phenylbutyramide,~-2-phenyl-2-cocoa butter hydroxy propionamide -caprolactam 2-phenyl-6-chlorophenol choline salts piperidinium salts ::

`` . 1065274 poly(ethylene glycol)-p- theophylline & salts nonyl phenyl ether o-thiocresol polyoxyethylene stearate thujic acid polyvinyl alcohol tiglic amide polyvinyl pyrrolidone tocopherols, tocols N-polyoxyathylene fatty acid 2,2,2-trichloroethanol amides triethylene glycol 6-propylpiperonyl butyl diethyl- 3,5,5-trimethyl-2,4-: ene glycol ether oxadolidinedione 3-pyridine ethanol undecylenic acid pyrrolidinone, 2- veratrole polyethylene glycol-p-iso viologens octyl phenyl ether . vital stains steroids, natural and derived, valerolactone lS e.g., ex-lanolin vitamins K, A, ~ derivatives salicylamide wetting agents sorbic acid -tannins . cis-terpinhydrate ; 20 tetrahydro-3-furanol : tetrahydrofurfuryl alcohol poly-~ ethylene glycol 3,7,11,15-tetramethyl-2-hexadien-l-ol ; 25 2,6,10,14-tetramethylpen- -~ tadecane `~ tetraethylene glycol dimethyl ether thiamine, salts & derivative~
: 30 ~ : 63.

:106527~

EMP media components may be applied to an organism through known techniques, including injection and local profusion.
EMP in living organisms or in tissues may be operated at threshold currents on the order of 0.002 ~A/cm or higher, - at voltages of 0.3 v/cm or higher. If slower EMP response is acceptable for a particular use, thresholds of 0.0005 ~A/cm may be utilized with voltages as low as 0.05 v/cm.
Related to the use of EMP in biological systems is the use of EMP to mobilize biochemical species including high thres-hold ones as proteins-globulins, enzymes, polypeptides, nucleic acids, steroids, lipids, lipoproteins and fatty acids. Proteins and other biochemical compounds are susceptible to thermal and ; chemical degradation, and are commonly handled in aqueous solu-tion, often in chilled buffered electrolyte solution. However, water as a major component in EMP media has the disadvantages of forming electrolytic solutions and of being rather evaporative.
Thus special attention has been given to the adaptation of high water content systems to EMP usage, and also to the application of EMP to proteins and related substances in nonaqueous systems.
Since the activity of biochemical compounds is linked to their . . .
structural integrity and sensitivity, an additional aim has been formulation of a versatile set of media which preserve this activity.
The general technique for formulation of an aqueous EMP media for protein transport involves reducing the conductivity of water by addition of a suppressant, adjusting the dielectric constant by addition of a high dielectric constant material if necessary, and adding initiators and/or mobilizers to beneficiate the movement of the proteins.
As disclosed above, it has been found that a number of compounds will suppress the conductivity of water to varying .

- 106S;Z74 extents, thereby alleviating the problem of high conductivity in aqueous media. These compounds also function as miscible protein solvents. The conductivity suppression results are set out in the form of an example below.

Various protein-compatible solvents were combined with water (volume ratio = 16/9). Pure solvents were used when possi-ble, as the trace contaminants in commercially available materials can affect conductivity suppression. (This is illustrated by the values given for compounds (7) and (18) below which are the same substance obtained from two different sources.) Relative values of conductivity suppression as compared to the conductivity of water were:
(1) thiodiethylene glycol 2.2 (2) 2,6-dimethyl morpholine 2.6 (3) methoxy ethoxy ethanol 2.6 (4) 2-pyrrolidone 2.7 More strongly conductivity suppressing compounds are:
! , :
(5) ~-butyrolactone 3.3 . .
'~ 20 (6) sorbitol 3.8 :

(7) 1,3-butanediol 3.6

(8) propylene glyco] 3.6 ; (9) dimethyl formamide 3.6 A ~roup of increased strength suppressants are:

(10) dimethyl acetamide 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 .' ' .

~ `
-` ` 1065Z74 The truly potent class of suppressantsfor water may be repre-sented by:
(16) 2-[2-~ethoxy ethoxy) ethoxy] ethanol 8.3 - (17) 1-[~2-(2-methoxy-1-methyl ethoxy)l -l-methyl ~thoxy]-2-propanol 10 (18) 1,3 butylene glycol 12 Selection of a suitable suppressant solvent should take into account the effect of the suppressant on protein migration.
Thus compounds (10), (11) and (13) above may beneficiate protein mobility, whereas (3), (4), (9), (14) and (18) may be less potent in this regard. -~ Additional solvents for biochemical compounds include ;; alcohols such as methyl "Carbitol", phosphonates such as diethyl ethyl phosphonate, lactones such as 6-hexanol~ctone and sugars.
Solvent compatability with the substrate is another consideration. With improper solvent selection, the solvent may attack the substrate resulting in altered porosity, structure ;~
collapse or similar effects. Proper solvent selection in media --formulation permits use, for example, of ion-exchange of "thin-layer" plates, as well as cellulose derivative films such as the ` nitrate or acetate, or agarose, acrylamide or silica gels impreg-nated with EMP media.
The excessive use of potent suppressants may result in a system with internal resistance so high that substantial resistive heating results, especially where high threshold current operation i8 indicated. Thus, selection of the less potent sup-pressants is often satisfactory. The Tc requirements of proteins and related ~ubstances are often in the range of 4.6 ma/50 cm2 or more on a cellulose substrate as opposed to 1.2 ma/50 cm2 or less for most other compounds.

:, :

~ -- 66.
- : . :

- : ., . :.: .. : . -` - ` 1065Z'74 - Reducing the water content of EMP media as described above may alter the dielectric constant of the media. This change may be offset, with resulting re-establishment of the high dielectric constant desirable for EMæ, by addition generally of very high dielectric constant components. Examples of suit-able materials for this dielectric constant adjustment include hydroxy ethyl formamide, N-methyl formamide, formamide, N-methyl acetamide and related compounds. Generally, N-alkyl and N-aryl ; amides are useful. Often these compounds, especially when of only commercial purity, will tend to increase the conductivity of the media, thereby opposing the suppressant mechanism. Such conductivity contribution may be used to compensate for an overly high internal resistance caused by a strong suppressant.
; High threshold values of biochemical species may be '' 15 advantageously reduced, and the mobility of the speciee in EMP
increased, by the use of initiators and mobilizers. Many proteins ` were found to be particularly susceptible to the influence of pro--~ ton acceptor substances in increasing mobility, but were relative-ly ind$fferent to mobilization by proton donor molecules. Initi-~20 ator substances, though in relatively low concentration, contri-bute substantially to the lowering of threshold current, and if `` they also act as mobilizer~, to the enhancement of species mobili-ty. For proteins, initiators may be used to bring threshold levels down from 4.6 ma/50 cm to 3.4 to 1.0 ma/50 cm2 ~20~A/cm ) with voltages in the 50 to 25,000 v/cm range. Typical initiator sub-stances, mobilizers, and worthwhile solvents are: nitrobutanol;
3-acetyl 3-chloropropyl acetate; salicylaldehyde; N-methyl-acetamide;
boric acid; phenols; guaiacol; fumaric and barbituric acids; piper-~; azine; furfural; tributoxy ethylphosphate; ~ trichloro-t-butyl alcohol; dimethyl-l, 3-dioxolane-4-methanol; 2-ethyl sulfonyl `:
,'~' , , . 67.

;~ . .

ethanol; tetrahydrofurfuryl alcohol; N-substituted pyrollidones;
dimethyl sulfoxide; 2,2-oxydiethanol; ethylene cyclic carbonate; `
tetramethyl urea; thiodiethylene glycol; l-ethynyl cyclohexanol;
tetrahydro-3 furano,2,6-dimethyl-m-dioxan-4-ol acetate; and 2,5-bis (hydroxy methyl) tetrahydro furan, other amides, parti-cularly N-alkyl and dialkyl and hydroxy amides, other proton acceptors and buffer systems. Very often high dielectric cons-tant substances will act as mobilizers or initiators.
. .
Electrophoresis of proteins is often done in high pH
(alkaline) buffer because of the dependence in electrophoresis on isoelectric points. In contrast, EMP transport of proteins -~
may be carried out in acid media. Buffers may be prepared from the list of biologically compatible agents given above, or may be of the more commonly used Tris, Veronal or Sorensen types.
In addition, more common organic acids and bases may be used.
Examples of acid buffers useful for EMP transport of proteins and related substances are:
; tetramethyl ammonium hydroxide/acetic acid triethylene tetramine/2,2-oxydiacetic acid dimethyl amine/picric acid diethanolamine/dichloracetic acid triethanolamine/dichloracetic acid piperazine/dichloracetic acid Media prepared as described above, with combination of water, one or more suppressants, one or more agents for increasing the dielectric constant, and one or more initiators (and/or mobi-iizers) may effect separation of proteins within a minute or so in a few centimeters of "Whatman"* #1 filter paper, while the same separation on the same substrate would take up to 16 hours over as much as 15 cm. of substrate with electrophoresis.
*Trademark - 68 -.

`- 1065274 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. While this problem may be overcome in some s instances, as with zein (prolamine) by use of the modified aqueous media described above, the use of nona~ueous media pro-vides additional flexibility.
An alternative to aqueous EMP systems for proteins and other biochemical compounds is the use of other solvents analogous to water in proton donor number (DN=18.0 for water) and dielectric constant (DC=81.0 for water). Especially useful are ethylene cyclic carbonate (DN=16.4, DC=89.1, boiling point ~- (BP) =245C) and propanediol-l, 2-carbonate (DN=15.1, DC=~9.0,- - BP=240C). These solvents contribute superior heat stability to the media formulation, permitting operation with greater re-sistivity and hlgher ~ltage gradients without need for ex~x~l cooling.
- Certain solvents show amore intense solvent action than does water for some proteins. Thus, keratins which are water insoluble may be dissolved in other solvents such as dimethyl sulfoxide. Prolamines may be solubilized in glycols, ; glycol ethers, and certain alcohols.
Solvents of moderate to strong proton acdeptor proper-ties are suitable for protein solubilization, and may even form the basis of the media. Solvents of this type include iodine monochloride, sulfur dioxide and hydrogen fluoride. For example anhydrous hydrogen fluoride is a good solvent for fibrous proteins normally insoluble in water. The collagenous substances, as well as elastins and reticulins are particularly resistant to solu-bilization in aqueous media, whereas they are soluble in non-a~ueous media.
:

~ 69.

," .

`` 1065274 The media for EMP transport of proteins may include other protein solvents chosen to provide particular properties such as glycols, amides, ethers, pyrrolidones, lactones, sulf-oxides, phenols, alcohols and phosphonates.
Suitable aqueous systems for the transport of proteins in accordance with the foregoing ~able of suppressants using a solvent/water volume ratio of 16/9 are:
16 ml. thiodiethylene glycol

9 ml. water 2 drops ethanolamine (separation of protein mixtures including cytochrome C and myoglobin - electrical characteristic of 1.8 Kv/1.2 ma) 16 ml. 6-hexanolactone 9 ml. water 3 drops ethanolamine (gave protein movement and resolution -electrical characteristic of 1 Kv~1.2 ma) 16 ml. dimethyl acetamide 9 ml. H2O
4 drops ethanolamine (separation of proteins -electrical characteristic of 1.6 Kv/1.2 ma) The following thre~ examples illustrate nonaqueous media repre~entative of those which have been used for EMP trans-port of human and bovine albumin, hemoglobin, cytochrome C, (an enzyme), myoglobin (muscle protein) and pancreatin. In addi-tion, protein~ have been separated from whole blood in experi-70.

ments in which the cell debris remained at the origin. Phenol was a useful media component in these last separations.

12 ml. - ethylene cyclic carbonate 6 ml. - ethoxyethoxy ethanol 6 ml. - thiodiethylene glycol 6 drops tris-dichloracetic acid buffer 7 ml. - ethylene cyclic carbonate 7 ml. - ethoxy e~hoxy ethanol 9 ml. - oxydiacetic acid 1.5 ml. - formamide 6 drops triq-dichloracetic acid buffer `:

':

,~. .

~ 30 ~.065Z74

10 ml. - ethylene cyclic carbona~e 4 ml. - N-methyl pyrrolidone 3 ml. - furfuryl alcohol s 2.5 gm. - boric acid 4 ml. - 1,3-butylene glycol 16 drop~ piperazine-dichloracetic acid buffer (pH 3. 7) Acridine orange (fluorescent and indicator) The following example illustra~es EMP media and 0 electrical conditlons used for the ~eparation of albumins and e~pecially globulin~.
- ELECTRICAL
CHARACTERISTICS
EXAMPLE SOLVENT FORMULAE ~Stabilized?
28 10ml. ethylene cyclic carbonate 5.2 KV/2.0-3.6ma 4 ml. butylene glycol, 4 ml. "Whatman" ~1 methyl pyrrolidinone, 2 ml. ~10 cm.) formamide (in~tiator), 2.5g boric acid, 3 ml.
; furfural tpH buffer and mobilizer), 16 drops piperazine dichloracetic acid buffer pH 3.7 - (pH buffer and mobilizer), acridine yellow tfluorescent indicator) : .
C The ~ame media was used to separate cytochrome C, hemoglobin, myoglobin, al~umin, yohimbine, and atropine under the following condltions:
ELECTRICAL
CHARACTERISTICS
EXAMPLE SOLVENT FO~MULAE tStabilized) _ 29 10 ml. ethylene cyclic carbonate, 4.4 KV/3.6ma;
4 ml. butylene glycol, 4 ml. 2.2 KV/1.2ma methyl pyrrolidlnone, 2 ml. "Whatman" #3 formamlde tinltiator), 2.5 g ` boric acid, 3 ml. furfural tpH ~uffer and mobilizer), 16 drops piperazlne dichloracetic acid buffer pH 3.7 tpH buffer and mobllizer), acridine yellow tfluor-e~cent indic~tor) o -The use of dyes which act as tracers may be desirable in some cases to visually follow the separation of colorless biochemical species. See examples 27-29 above. It must be -established that the particular dye does not interfere with the -resolution process itself. Bromphenol blue has been commonly used with serum proteins, but may migrate separately from the protein in EMP. For redox sensitive materials, methylene blue is often suitable, and glutathione either in oxidi3ed or reduced form may be used to buffer against redox reactions. Safranine-type dyes bind to and alter the solubility characteristics of proteolytic enzymes and can therefore by useful in separating them from other materials. A few milligrams of an easily coupled fluorescent tracer such as acridine orange will allow visual observation of many substances including proteins under ultra-violet light without altering their migration characteristics.
Other tracers such as brightening agents, fluorescent coupling agents, and even fluorescent antibody material may be useful in following protein transport. Additional tracer agents for bio-chemical and other work are vital dyes such as the flavines and . ~. .
primulin. Nile blue may be especially useful alone or in combi-nation with other dyes under U.V. and daylight. Neutral red with aesculin remains sensitive at about 1000x dilution with daylight alone. The U.V. dyes are also convenient for locali-zing weak positive or negative charges in biological structures.
Antibodies or other coupling tracer materials as well as radio-active derivatives can also be useful, e.g., rhodamine B-isothio-cyanate; fluorescein isothiocyanate; p-isothiocyanato acridine;
4-chloro methyl-l-acridine; 1-ethyl-2-[-3-(1-ethyl naphthol [1, 25] - thiazolin-2-ylidine)-2-methyl propenyl]-naphth [1,2]
thiazolium bromide. Additional possible tracers are phenazine methosulfate, Remazol brilliant blue R, thiazolyte blue, protoporphyrin IX, citrazinic acid, quinine, lisamine, rhodamines, Cleve's acid and umbelliferone.
Another aspect of the present invention is the use of S the technique of EMP media formulation to fabricate gaseous semiconductive media which will allow controlled conduction without need ~or evacuation, very high temperatures, or very high voltages. The application of the techniques of formulation of liquid EMP media to gaseous media formulation led to the achievement of high levels of conductivity without the need for high potential. The aim in construction of a gaseous EMP
media is to increase the conductivity level of the gas to the level of semico~ductivity or other level convenient for the desired application.
Industry has made use of gases largely as insuiators.
Most gaseous conduction performed currently focuses on the high dielectric characteristics of gases generally. The conduction commonly takes place wlthin an envelope or other controlled environment in a relative vacuum with the use of an energy source (such as a thermoelectric filament) to control conduction. In such devices the presence of materials of lesser dielectric character iB deleterious. Gaseous conductivity i~ also of ;~ importance currently in the area of ionization or the plasma state. Attempts have been made to produce electricity through the motion of conductive gases relative to a magnetic field - (magnetogasdynamics) but it has been found necessary to employ temperatures 80 high that corrosion of the containers resulted.
It is now possible to achieve conductive gases at or near room temperature through the use of EMP, and thereby may be possible to provide a practical means for producing electricity.

; 74.
.' ' .,~ . .
-.
~a~

: ~ :

Formulation of gaseous EMP media provides a useful scientific technique for investigating the molecular characteris-tics of materials. In addition, it may be employed in the con-struction of controlled gaseous conduction devices used for wireless transmission te.g., in coilless transformer cores), in light emission studies, gaseous charge transport, gaseous molecular transport, electrically mediated ga~eous diffusion, and low potential spar~ gap devices. EMæ media formulation may be employed to modify fuel combustion systems and the fuel itself in c~mbustion engines so as to extend the spark propa-gation distance (e.g., allow separation of the spark plug electrodes by larger distances thus relying less on explosive propagation).
Similar principles to those applied in preparation of liquid semiconductive EMP media are applied in the preparation of gaseous semiconductive EMP media. Media containing a number of components, such as three- and four-way systems, are necessary to effect a substantial alteration in conductivity of the gas ; to bring it into the semiconductive range. Agent~ which acting together facilitate proton donor/acceptor interaction, increased conductivity and enhanced dielectric constant are indicated.
For example, water acts by hydrogen bonding in the vapor phase as both a donor and acceptor molecule, interacting with proton donors ranging from strong acids to alkanols ~e.g., 1,1,1,3,3,3,-hexafluoropropan-2-ol) and with acceptors such as amines (including pyridines), ethers, alcohols and ketones.
In general, the more conductive or active EMP solvents have been found particularly suited to gaseous conduction. (See the list of active agents above.) Also, comixing of materials helps to 75.

: , ........... . .
-. :. . . - . ~ .

10~SZ74 effect enhanced conductivity.
' For example, placing a few drops of triethylene tetra-' mine in the base of a glass test tube'seated in a mildly heated sand hath reduced the resistance between the electrodes located 0.5 cm apart and 2.5 cm. from the bottom of the tube to 106 ohms ' from more than 109 ohms in air. The addition of a small crystal of iodine reduced the resistance to less than 8 x 105 ohms.
Addition of formamide instead of iodine gave 1.5 x 106 ohms, and the two together reduced the resistance to less than 5 x 105 ohms. With some media, resistances in the hundreds'of ohms were obtained at low voltages (5-lOv) near room temperature and ; atmospheric pressure.
' As a further example, in ~uch a cell, at a five volt '" potential, a media was formulated from agents (A.) added stepwise ; 15 'by measuring the resistance (B.) obtained after each step in ' the sequence of addition (C.) (A.) Agent (B.) Resistance in Cell (C.) Seq~ence of Addition C~ative Amount AmDunt in ; Ad d Mixture ' 20 ~etra methyl urea o~ ~100 meg ohms) 5 pts 5 pts + N~metbyl acetamide 1.70 meg J~- 1.5 pts 6.5 pts + I2 75 K -~ 1 pts 7.5 pts '' + diethylamine 18 K _rL- 1.5 pts 9 pts Agents which are useful to formulate gaseous EMP Media ' 25 include iodine, other halogens, amines, volatile salts, amides, nitro derivatives including nitrosylchloride, acid chlorides, hydrazine, oxyhalides, sulfur dioxide, hydrogen fluoride, ammonia or other potent proton donor or acceptor moleculeq, combinations ' thereof, and substances liberating such. Semiconductive media ; '30 formulated from such components ~ccord~ng to the principles of 76.

,. .

' ~ ~
' . - ~ - - ~ -~` \

liquid media formulation as modified above provide a controllable conductive gaseous environment even at atmospheric pressure in air. The use of high boiling chemicals as classified for liquid EMP media use requires an elevated temperature to produce the gaseous EMP effect. Use of lower boiling solvents is therefore advantageous in the preparation of gaseous EMP media.
Gaseous EMP media may be subjected to voltages of, for example, 0.5 to 30,000 v/cm, with continuous conduction (rather than sparking) resulting. Modifying agents may be included in the media so as to make it susceptible to arc over in the range ;
of 50 to 30,000 v/cm and therefore useful in fuel systems so as -~
to modify or extend the spark propagation properties and/or electrothermal vaporization prior to ignition.
A further aspect of the present invention is the prac-tice of EMP within a gel. The gel consistency may range from fluid to rigid. Gels generally are susceptible to resistance ..:
j adjustment by addition of a small amount of conductivity agent with a material of high dielectric constant such as formamide or another amide or alkylamide derivative and a coupling solvent if necessary to improve miscibility. The EMP media may be washed into the gel or the gel fabricated with the media in it. One difficulty with the use of gels as EMP media is that by products left over from the gel formation process must be removed if they interfere with the EMP conductivity adjustment and transport.
,: .
Agar gel, polyvinyl alcohol (PVA), silica gel, starch gel, "Carbopol"* (carboxypolymethylene) and "Crash Safe Aviation Jet Fuel" (additive-modified kerosene) are examples of gels which function as EMP media when doped with the appropriate conductivity-modifying agents in accordance with the principles described above. Acrylamides could also be employed. An * Trademark for a vinyl polymer having active carboxyl groups, used as a thickening or dispersing agent.
77 ~ -.
' : : -- : , . .
, .- . - ~ - .

example of a gel fabricated with an EMP sol~ent within it is PVA gelled with tetrahydrofurfuryl alcohol. Tetraethyl ortho silicate which gives a clear glass-like gel with numerous organic gels permits compatability with various organic EMP media.
Gelatin also provides a clear gel ba e. Examples of chemical - species which may be transported in such gels include dye molecules, and even particulate matter may be moved ~t fast ~ates in a "fluid" gel such as crash Qafe aviation fuel.
Voltage and current levels are adju~ted just as in O cellulo~e supported EMP. A slightly higher current, than 1.2 ma/50 cm2 can also be used for thi~ slabs of gel (to 1/8").
Otherwise, gels 3/8" to 1/2" thick or greater require careful current consideration to avoid excessive heat buildup.
In EMP separ~tion processes, gel3 are capable of ~5 providing enhanced re olution because of their fine pore ~- structure. EMP induced mov~ment of dye molecules within a gel may be used as an analytical techni~ue to study the structure and properties of the gel ~t~elf.
~ he apparatus used for gel EMæ differed from that used for liquid EMP in that the filter paper ~ubstrate was replaced with the gel.
EMP within a gel i9 illustrated by the examples below.
EXAMPLE SOLVENT FORMULAE
. .
glycol, ammonium bromide ~to form a saturated ~olution in N-methyl pyrrolidone), and formamide O
31 5~ welght/volume ceresin or microwax in 20~
sr 30~ xylene plus EMP media components appro-prlate for use with xylenQ.
The EMP media components referred to in Example 31 may be the four-way system descrlbed at page 12 or ammonium bromide ) in methoxy ethoxy ethanol, 2(2-ethoxy ethoxy) ethanol, dimethyl :

r; 7 8 ~

~ .

10~i5274 formamide, dimethylacetamide, dimethyl sulfoxide, n-butanol, or N-methyl pyrrolidinone.
EMP is susceptible of application to a wide variety of uses, a number of which have been detailed above. The appli-cation of EMP to several specialized areas will be urther des- -cribed here.
EMP may be used in conjunction with media phase control to provide an information storage, processing and dis-play mechanism. For example, a medium may be used which is solid at ambient temperature, which melts or at least increases in fluidity when warmed. Dye molecules or other detectable or ;~
traceable materials in the media may be transported by applica-tion of a potential difference when the media is fluid, and stored with display capabilities when the media is rendered non- -fluid. The system is non-volatile; the resolidification curtails diffusionary information loss, and the positioning of the dye spots in the solidified media provides for information storage.
Gel or porous media might also be used for information storage and display. A permeable solid support substrate may be incor-porated in the system to minimize thermal diffusion. By use of a transparent substrate with refractive index approximating that of the liquid media, additional clarity can be achieved.
Parallel capillaries, e.g. of glass, may be used to limit dif-fusion and fix the geometry of the system. Transparent electrodes (e.g., NESA glass) may be used for display purposes.
EMP is particularly suited for this application in a number of respects. The high response speed o~ EMP systems would allow, for example, response times of less than a secondwith a 10 cm/min transport rate between parallel plate electrodes 1 mm apart. In addition, different threshold currents may be used to 79.
: . - .

:: : , : , .', . . .
~- . . . ~ . .......... - ~ . . .

selectively transport a sequence of chemical species for super-imposed displays within a single EMP unit or cell.
The components of EMP media which are suitable for use in an information storage and display system are generally -~
~ those with melting points in the neighborhood of room temperature.
- From any class compounds whose use in the media is indicated, one or more media components may be chosen for their melting point. For example, the class of phenols offers the following choices: -, lO Compound Melting Point ,.
~- 2,4-dichlorophenol 40-42 2,4-dimethylphenol 22-24 2,6-dimethylphenol 45-47 2,4-ditertiary-pentylphenol 24-26 2,6-ditertiary-butyl phenol 35-36 ;-~ 2,6-ditertiary-butyl-p-cresol 62-68 - o-ethoxyphenol 25-27 p-methoxyphenol 54-56 l-phenyl-2-propanol 36 20 thiophenol 70-75 :
Lower melting compounds, such as 3-phenyl-1-propanol (MP=-18C) ,, .
and m-thiocresol (MP=-20C) may be useful in combination with one or more of the compounds listed above.
, The use of EMP with melts is not restricted to room ; temperature melts. Additional media components which may be employed include resins, glasses, glazes and chalcogenides.
Glycol-boric acid glasses are low-melting glasses suitable for EMP media. Various mole ratios of boric acid or . .~ ., boric anhydride fused with most glycols yields a rigid trans-parent glass at room temperature, suitable for modification ~r ~065274 ~

for EMP use. Starches, sugars, amines, borax and many other compounds can also enter into the glass formation. Increasing the ratio of glycol or amine to the boric acid adjustably lowers -~
the melting point. Similarly, agents such as metallic stearates can act as crystallization retardants and can be used with, for example, sugars to produce glassy EMP media. Rosin and methacrylates are other organic glass forming media. Inorganic glasses can be derived from phosphates, tellurium, selenium and other materials. Iodine, as well as other compatible conducti-vity agents may be used for adjusting the glass to EMP media requirements.
EMP may be conducted in other solid media by applying heat energy to liquify the media during EMP and allowing the media subsequently to solidify. For example N-methylacetamide was heated above its melting point and placed on a paper strip ("Whatman"* #1). The paper strip was suspended between electro-des, rhodamine and ink dyes were then placed on the filter paper and a potential applied across the paper. After the rhodamine . .
dyes migrated, the molten n-methyl-acetamide was allowed to cool and solidify.

Photoconductive materials, such as polyvinyl carbazole, may be employed in conjunction with EMP effectuated information storage, processing and display. For example, in an information reproduction system, a conductive substrate may be coated with polyvinyl carbazole. Where li~ht passing oVer or through the document, film, object or other image to be reproduced strikes :, the polyvinyl carbazole, a short circuit will occur, and dye molecules contained in a juxtaposed EMP media will not be caused to move or will be under a reduced potential and therefore subject to reduced movement. Where light does not strike the :.
polyvinyl * Trademark for a brand of filter paper made in England . .

carbazole, dye molecules may be mobilized or deposited. Because of the fast molecular migration achieved with EMP, such a repro-duction process could be carried out a~ a much lawer voltage than used in conventional electrostatic techniques. For example, a .` 5 process of the type disclosed in U.S. Patent no. 3,384,566 to Clark could be modified with use of EMP for opera~ion at lower voltage and enhanced transport rates.
- EMP may be employed to obtain a number of electro-optic effect~. For instance, it may be used in a manner analogous to electrophoresis in fluid glass-sandwich display techniques.
See Fluid Glass-Sandwich Display Technique Permits Large, : Multicolored Characters, 22 Electronic Engineering Times (March 29, 1974). EMP would provide the-advantages of faster response, wider selection of materials and less heat generation compared to electrophoresis in such an application. EMP could also be used in place of electrophoresi~ in applications such as that described . .
in U.S. Pat. No. 3,511,651 to Rosenberg. EMP media may additionally be used in electrochromic devices to form the junction material between the electrochromic material of, e.g., molybdenum trioxide on NESA glass and t~e second electrode. (Sulfuric acid has been employed as the junction fluid in the past.) The technique ; of EMP media formulatlon may be used to modify or study liquid crystals.
; The technlque of EMP media formulation may also be use~ to modify the Kerr effect (alteration of a material's influence on polarized light by imposition o~ a high voltage electric field) in variouq 11quids.
Electromagnetic fields in addition to the driving voltage may be employed in connection with EMP for various purposes. A second electrode 4~tat angles to the set providing 82.

`

the driving voltage may be used to cause thechemicalspecies being transported to swerve from a straight line path. Similarly, one or more electrodes angulated to the set providing the driving voltage may be used to compensate for any slight lateral deviation or spreading of a species traveling on a substrate and to counteract the effects of diffusion. In addition, a balanced electrode pair may be placed perpendicular to the path of the ;-chemical species transported, and used to detect the passage of various zone~ of chemical species based on the change in electrical forces between the second set of electrodes.
; Pulsed DC fields may be used instead of a constant DC
driving force to reduce media heating. As an additional modifica-tion, an AC field may be superimposed on the DC driving force to mediate the dielectric and semiconductive properties of the .
media, as well as to take advantage of the Debye-Falkenhagen (solvent) effect.
Magnetic fields may also be employed to modify t~e ' EMP process. A magnetic field, preferably on the order of one kilogauss or greater, applied at right angles to the EMP voltage will, by virtue of the Faraday magneto-optic effect, cause the D
and L forms of stereoisomers transported under the influence of EMP to separate into distinct paths. This procedure must be carried out in an apparatus of special design. A suitable EMP
cell comprises two separable electrode compartments and sub-strate (e.g., filter paper) clamping means. These compartmentsare mechanically fixed in position so as to allow the pole faces of a puwerful electromagjnet to be brought within close proximity to the ~op and underside of the substrate surface. An insulating film such a~ ~Mylar~* can be used to retard arc-over to the pole face. --83. i-* Trademark for a polyester (polyethylene terephthalate) film, havinq very high tensile strength.
.'' ,~' . ' . .

.

- ~ \
:` 106SZ74 \

Magnetic fields may be used to stabilize the media so as to reduce long-term diffusion of a molecular species during a continuous EMP process in a manner analogous to that described for electrophoresis in Kolin, Continuous Electrophoretic Fractionation Stabilized by Electromagnetic Rotation, 46 Chemistry 509 (1960). Unlike the Kolin application, there is no significant stabilization prob~em in EMP due to thermal factors. Further, whereas it has been found that the magnetic response of the migrating specieq in the aqueous electrophoretic media was nil, the response of species in EMP media as well as the media itself, will differ from electrophoretic aqueous media, and can be further modified and controlled.
The invention herein includes the processes of impart-ing mobility to or separating chemical species by providing a semiconductive transport medium (which may be liquid, gaseous or solid) and impressing a voltage of about 0.05 to 25,000 volts/cm acroqs the medium sufficiently high to produce a current denrity in the range of about 0.001 to 400 microamp/cm2 or - .002 to 100 microamps/cm2 and equal to or exceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high '~ mobility rate for the species. In an aspect of this invention the fluid semiconductive transport medium contains a component selected from the group consisting of mobilizers and initiators and comprises impressing a voltage within the range of about 0.05 to 50 volts/cm acros~ the medium sufficiently high to produce a current density in the range of about .001 to 4 micro amp/cm2, or from about .002 to 0.2 microamps/cm2 and equal to or exceed the thre~hold current value for the species in the medium, below which value the ~pecie3 remains substantially .

84, 1()65279~
: stationary, to induce a high mobi~ity rate for the species.
Where the fluid semiconductive medium comprises water, a conductivity suppressant, a high dielectric constant component, and a component selected from the group consisting of mobilizers S and initiators, the process for imparting mobility to a biochemical species is carr~ied out by applying a voltage within the range . of about 0.05 to 25,000 volts/cm across ~he medium sufficiently high to produce a current density of at least 2 microamps/cm2 .
' or at least 20 microamps and equal to or exceeding the threshold .j: O current value for the biochemucal species in the medium, below which value the biochemical species remains substantially stationary.
; Where EMP i~ carried out on a support member, an : adsorbent may be used, such as cellulose, cellulose acetate, S cellulose nitrate, alumina, silica, glass, asbestos, wood, flour or resin as "Teflon", "Pevikon"*, or ion exchange resin as "Amberliten** or modified cellulose, or molecular ~ieve resin as "Sephadex"***, or mineral as diatomaceous earth or apatite.

* Trademark ** Trademark *** Trademark ,' :

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v -8s-.- :
.~ ~

Claims (40)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A process which comprises imparting mobility to a chemical species by providing a semiconductive transport medium and impressing a voltage of about 0.05 to 25,000 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.001 to 400 microamp/
cm and equal to or exceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high mobility rate for the species.

2. me process of claim 1 wherein the current density is in the range of about .002 to 100 microamp/cm2.

3. The process of claim 1 wherein the species is on a support member in the medium.

4. A process which comprises imparting mobility to a chemical species by providing a semiconductive transport medium which will allow operation at a high voltage and low current density and impressing a voltage within the range of about 50 to 25,000 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.2 to 400 microamp/cm2 and equal to or exceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high mobility rate for the species.

5. A process which comprises imparting mobility to a chemical species by providing a fluid semiconductive transport medium containing a component selected from the group consisting of mobilizers and initiators and impressing a voltage within the range of about 0.05 to 50 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.001 to 4 microamp/cm2 and equal to or exceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high mobility rate for the species.

6. The process of claim 5 wherein the current density is in the range of about .002 to 0.2 microamps/cm2.

7. A process for separating chemical species which comprises mixing said species with a fluid semiconductive medium containing a component selected from the group consist-ing of mobilizers and initiators and applying a voltage within the range of about 0.05 to 50 volts/cm across the medium to produce a current density in the range of about 0.001 to 0.2 microamp/cm2 and equal to or exceeding the threshold current value for at least one species in the medium below which value the species remains substantially stationary.

8. A process which comprises imparting mobility to a biochemical species by providing a fluid semiconductive medium comprising water, a conductivity suppressant, a high dielectric constant component, and a component selected from the group consisting of mobilizers and initiators, and applying a voltage within the range of about 0.05 to 25,000 volts/cm across the medium sufficiently high to produce a current density of at least 2 microamps/cm2 and equal to or exceeding the threshold current value for the biochemical species in the medium, below which the biochemical species remains substantially stationary.

9. A process which comprised imparting mobility to a biochemical species in a nonaqueous medium by providing a fluid semiconductive medium comprising a non-aqueous solvent with proton acceptor properties and applying a voltage within the range of about 0.05 to 25,000 volts/cm across the medium sufficiently high to produce a current density of at least 2 microamps/cm2 and equal to or exceeding the threshold current value for the biochemical species in the medium, below which value the biochemical species remains substantially stationary.

10. A process for effecting conduction in a gas which comprises providing a multi-component gaseous semiconductive medium containing components with proton donor/acceptor interaction capability, high dielectric constant and high conductivity and applying a voltage of about .05 to 30,000 v/cm to achieve continuous conduction.

11. A process which comprises imparting mobility to a chemical species by providing a semiconductive transport medium with a gel and impressing a voltage of 0.05 to 25,000 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.001 to 400 microamp/cm2 and equal to or esceeding the threshold current value for the species in the medium, below which value the species remains substantially stationary, to induce a high mobility rate for the species.

12. A process which comprises imparting mobility to a chemical species by providing a semiconductive transport medium which will allow operation at a high voltage and low current density and impressing a voltage with the range of about 50 to 25,000 volts/cm across the medium sufficiently high to produce a current density in the range of about 0.2 to 100 microamps/cm2 and equal to or exceeding the threshold current value for the species in the medium below which value said species remain substantially stationary to induce a high mo-bility rate for the species.

13. The process of claim 12, wherein the species is on a support member in the medium and the current density applied across the medium is from about 1.4 to 54 microamps/cm2.

14. The process of claim 12 wherein the medium comprises a neutral media-base, and at least a conductivity or modifying agent and the chemical species is one or more heavy metal compounds.

15. The process of claim 14 wherein said neutral media-base is selected from the group consisting of .gamma.-butyro-lactone, 1,2-propanediol cyclic carbonate, propylene glycol, 2-phenoxy ethanol, 2-ethyl 1,3-hexanediol, tetrahydrothio-phene 1,1-dioxide, and methoxy ethoxy ethanol the conductivity agent is selected from the group consisting of perchloric acid, dichloracetic acid, formamide, ammonium bromide, pyri-dazine iodide, nitric acid and mercaptoacetic acid the modify-ing agent is selected from the group consisting of isophorone, nitrobenzene, salicylaldehyde, 4-hydroxy-4-methyl-2-pentanone, ethylene diacetate, .gamma.-picoline and o-dichlorobenzene; and wherein the conductivity of the neutral media-base is adjusted by at least one of said agents to provide a current density in the range of about 1.4 to 54 microamps/cm2 at a voltage of about 200 to 3,000 volts/cm.

16. The process of claim 12 wherein the medium comprises a solvent for said species, and said solvent has a dielectric constant of at least 10.

17. The process of claim 12 wherein the threshold level is reached for one species and said current is maintained below the threshold for a second species, thereby separating said species.

18. The process of claim 12 wherein said species are selected from a group consisting of metal compounds and organic compounds, and said medium comprises aprotic substances or inorganic substances.

19. The process of claim 12 wherein the transport medium exhibits non-linear electrical characteristics upon application of said voltage.

20. The method of separating chemical species which comprises mixing said species with a semi-conductive medium and applying a high voltage and a low current density across said medium wherein said semi-conductive medium comprises a base solvent for said species and an additive to provide a current density of about 1.4 to 54 microamps/cm2 across the medium at an applied voltage of about 200 to 3,000 volts/cm.

21. The method of separating a mixture of substantially non-polar dyes which comprises mixing said dyes with a semi-conductive medium on a substrate and applying a voltage in the range of from 200 to 25,000 volts/cm at a low current density in the range of about 0.001 to 400 microamp/cm2 across said substrate, said current density being equal to or exceeding the threshold current level for one dye but below the threshold for at least one other dye in said mixture.

22. The method of claim 21 wherein said semi-conductive medium comprises a low molecular weight glycol and an additive to increase conductivity to provide a current density of about 1.4 to 54 microamps/cm2 across the substrate at an applied voltage of about 200 to 3,000 volts/cm, and said substrate is a cellulose strip.

23. The method of separating chemical species which comprises mixing said species with a semi-conductive medium and applying a high voltage and a low current density across said medium wherein said semi-conductive medium comprises as a major constituent a substantially non-conductive, non-polar solvent for said species and at least one additive to provide a current density of about 0.2 to 100 microamps/cm2 across the medium at an applied voltage of about 50 to 25,000 volts/cm, aid solvent is selected from those which are compatible with said species and which exhibit a suitable partition coefficient for the species in a standard chromatographic technique, and said medium has a high dielectric constant above 10 to maintain charges formed by proton donor/acceptor interactions between the medium and the species.

24. In the method of separating chemical species on a substrate in a fluid medium the improvement which comprises providing a solvent medium which is substantially non-conductive and non-polar;
adjusting the conductivity level of the solvent with an additive to form a semi-conductive medium to provide a current density of about 0.2 to 100 microamps/cm2 across the medium at an applied voltage of about 50 to 25,000 volts/cm and wherein the semi-conductive medium is characterized by a high dielectric constant above 10 to maintain charges formed by proton donor/acceptor interactions, and a boiling point above 140°C for the medium;
applying said chemical species on said substrate and dissolving said chemical species in said medium; and applying a voltage of 50 to 25,000 volts/cm across the medium at a low current density within said range of about 0.2 to 100 microamps/cm2 to overcome the residual binding energy for one of said species in the medium to induce a mobility for the chemical species between about 1 cm/sec.
and 0.25 cm/min. without the application of external cooling means.

25. A process which comprises imparting mobility to a non-polar chemical species by providing an electrically non-linear, semi-conductive transport medium a residual binding energy existing between said species and medium tending to maintain said species in generally fixed relationship to said medium, said medium being of dielectric constant greater than 10 and providing charged transfer interaction capability with-out chemical reaction being of the proton donor/acceptor type with charge deficient molecular species, and adapted to allow operation at a high voltage and low current density, and impres-sing a voltage within the range of about 50 to 25,000 volts/cm across the medium sufficiently high to produce a current den-sity in the range of about 0.2 to 100 microamps/cm2 and equal to or exceeding the threshold current value to overcome the residual binding energy for the species in the medium to induce a high mobility rate for the species.

26. The process of claim 25 wherein the species is on a support member in the medium.

27. The process of claim 26, wherein said support member is selected from the group consisting of a cellulose substrate, a gel, a membrane and porous materials.

28. The process of claim 26 wherein said voltage is from about 200 to 3,000 volts/cm across the medium.

29. The process of claim 28 in which no external cooling means is used.

30. The process of claim 25 wherein the voltage is raised to a sufficiently high value at a low current density consonant with the threshold level to induce a trans-port range of the chemical species between about 1 cm/sec.

and 0.25 cm/min.

31. The process of claim 25 wherein more than one species is added to the medium and said species are separated by applying said voltage across the medium.

32. The process of claim 25 wherein the medium is substantially nonaqueous.

33. The process of claim 25 wherein said medium comprises a member selected from the group consisting of a glycol, ether, ester, amide, aldehyde, ketone, dione, lactone and alcohol and a conductivity modifier.

34. The process of claim 33 wherein said modifier is present in a minor amount and is selected from the group consisting of iodine, water, acids, bases and salts.

35. The process of claim 25 wherein the medium comprises an inert media-base, at least one active media-base and a conductivity agent.

36. The process of claim 35 wherein said inert media-base is selected from the group consisting of p-cymene, mineral oil, n-decanol, 1-octanethiol and xylene, said active media-base is selected from the group consisting of 2-chloro-acetamide, dimethyl formamide N,N-dimethylacetamide, 1-methyl--2-pyrrolidone, dimethyl sulfoxide, ethylene cyclic carbonate and 2,5-hexanedione, and said conductivity agent is selected from the group consisting of perchloric acid, dichloracetic acid, formamide, ammonium bromide, pyridazine iodide, nitric acid and mercaptoacetic acid.

37. The process of claim 25 wherein the medium comprises an active base, at least one conductivity agent and a suppressant.

38. The process of claim 37 wherein said active base is selected from the group consisting of 2-chloroacetamide, dimethyl formamide, N,N-dimethylacetamide, 1-methyl-2-pyrroli-done, dimethyl sulfoxide, ethylene cyclic carbonate and 2,5--hexanedione; said conductivity agent is selected from the group consisting of perchloric acid, dichloroacetic acid, formamide, ammonium bromide, pyridazine iodide, nitric acid and mercaptoacetic acid; and said suppressant is selected from the group consisting of tributyl phosphate, dimethyl phthalate, triacetin and 2-ethyl hexyl chloride.

39. The process of claim 25 wherein said chemical species comprises a protein, and said medium comprises water and a conductivity suppressant.

40. The process of claim 25 wherein said medium has a boiling point about 140°C.