CA1308690C - Techniques for enhancing the permeability of ions through membranes - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
A method and apparatus are provided for enhancing the transport of a selected ion having a predetermined charge-to-mass ratio through a biomolecular membrane located in a space subjected to a local magnetic field. The apparatus includes field creating means response to signals for creating a magnetic field which, when combined with a local magnetic field, produces a magnetic field having a flux density with at least one component representable by a component vector having a direction extending along a path through the membrane and having a magnitude that fluctuates at a predetermined rate to create a non-zero average value. The ratio of the predetermined rate to the non-zero average value has a predetermined relationship with respect to the charge-to-mass ratio of the predetermined ion which is a function of the cyclotron resonance frequency of the ion.

Description

I 30~690 BACKGROUND AND SU. 1 ~ARY O~ THE INVENTION
ield of the l~vention This invention relates to the tr~nsfer of ions through membranes, ~nd more specifically relates to the electromagnetic alter~tion of biochemical activity in living cells.
DescriPtion of Related Art and Summary of the Invention ~ _ _ _ _ The biochemical and medical fields have long sought an inexpensive ~nd accurate method of enhancing the movement of selected ions involved in life processes across living cell membranes. Until the discovery described in this specification, no investigator had found a s~tisfactory technique for achieving such results. The control of such ions has been achieved up to now solely by theadrninistration of pharmaceutical agents which often entail invasive hazard ~nd which at best are less than effic~cious in their results. The applicants have succeeded where others failed because they have discoYered the cause ~nd effect relationship between certain types of extremely low frequency (ELP) magnetic fields Rnd the movement of selected iorls across the membranes of living cells.
The closest known related work is described by Blflckman et ~. in "A Role For The Magnetic Field In The Radiation-lnduced Efflux Of Calcium lons From Brain Tissue In Yitro," 6 Bioelectrornsgnetics 327-337 (1985). Blackman et ~.
noted changes in the efflux of c~lcium ion from brain tissue in r esponse to various magnetic fields. Since Blackmr n et al. used tissue specimens rather than single cells, it is impossible to tell whether the efflux of cfllcium ions noted by them w~s due to a cell membrane res~onse as opposed to movement of ions in bulk interstitiRI fluids or in damaged cells.
Blackman et al. used both a constant unipolar magnetic field and a fluctuating bipolar magnetic field arranged perpendicular to each other. The fluctu~ting biopolar field was generated by n transmission line. According to conventional field theory, the transmission line produced magnetic flux lines ~rrsnged in concentric ring~ around the ~xis of the line. Blackm~n et al. note~
modest ~ium efflu~ (e.e., 20 to 30% increase i when compared to conts ol3J
when the ~on~tant nnd iluctu~ting fields were perpendicular, but f~iled to note ~ny e~flu~ for any other orientation of the nuctLIating ~ield and ~onstnnt ~ield (p.
334). ~thermoret according to the B~MS Seventh Annu~l Meetin~ Ab~trQCt~

~ ~, 1 30g6qo (1985), Blackman et 81. ruled out a simple cyclotron resonance model as the onderlying csusative mechQni~m for their observations.
Contrary to the observations of Blackman et al., the appli~ants h~ve discovered that they can substantially incr~se the permeability Or a ~elected ion 5 through 8 membrane subjected to either the eflrth's geomagnetic field or to anarbitr~rily chosen static magnetic field by superimposing a fluctuating m~gneticfield with a nux density having a nonzero net averege value that is properly proportioned with respect to the frequency of the fluctuations. The ~pplicants have succeeded by creating a magnetic field which, when combined ~ith either 10 the earth's geomagnetic field or an arbitrarily chosen static magnetic field,results in a magnetic field having at least one rectangular component extending along an axis projecting through the cell and hflving a ma~nit!lde that fluctuQtes at a prescribed predetermined rate to create a nonzero average value. The field is generated so that the ratio of this predetermined rate to the nonzero ~verage15 value is limited by me~ns of a predetermined relationship with respect to the charge to m~ss r~tio of the predetermined ion.
According to a preferred prsctice of the invention, the predetermined rate (in Hz) times 2 7r is substantiallv equ~l to the charge-to-mass ratio (in Coulombs per kilogram) of the predetermined ion times the nonzero average value of 20 magnetic flux density (in Tesla~. This is a relationship of the type .ejected by Blackman et al. and hereufter c~lled the "C~clotron Resonance Relationshipn:
fc (~ B
By properly orienting ~nd controlling the resul~nt magneti~ field, the 25 applic~nts have discovered that the cyclotron resonance can be used to enhance the transfer of ~ selected ion scross the membrane of a living cell. This technique enables the ~pplicsnts to alter the tr~nsfer of s~me ions by a substantial f~ctor up to ten or more times greater than would occur normal1y, orby ~ny other technique. By using this technique, the infl~uY or efn L~ of selected 30 ions from living cells can be regul~ted economic~lly wi~h Q degree of precision and ~peed previously unknown.

-` 1 30~690 DESCRIPTION O~ THE DRAWINGS
These ~nd other advantages and fe~tures of the Invention will here~ter sppear for purposes of illustration, but not of limit~tion, in connection with the accompanying drawings, wherein like num~er3 refer to like parts throughout, and wherein:
FIG. 1 is a schematic, perspective view of an~ exemptary living cell located in a bounded active volume in 6 space defining a rectangular coordinate axis system and subjected, within this active volume, to a magnetic nuX density created by an electric~l coil, or an equivalent perm~nent magnetic array or ~ny other equivalent source of magnetic flux density, such QS the earth's geomsg-netic field;
FIG. 2 is a schemstic electrica~ diagram of 8 preferred form of generating apparatus usPd to drive the coil shown in EilG. 1 und the signal shapes employed;
FIGS. 2A-2D are diagrams of signal waveshflpes generated by the app~ratus shown in FIG. 2;
FIGS. 3A and 3B are schematic diagr~ms of an active volume containing an exemplary living cell located in a space defining a rectangular coordinate a~rissystem, showing the combination of magnetic flux densities created by a pair of electric~l coils and by the local mQgnetic field;
FIG. 4 is ~ schematic, perspective view OI another exemplary living cell located in a space defining a rectangular coordinate axis system and subjected, within a bounded uctive volume, to a mQgnetic flux density created by a p~ir of electrical coils, or by an equivalent combination of sources of magnetic fields,such as ~ permanent magnetic and/or the earth's gevmagnetic field;
FIG. 5 is an electrical, schematic diagram of B preferred form of signal gener~ting apparatus used to drive the coils shown in FIG. 4;
FIG. 6 is ~ schematic, perspective view of the active volume surrounding ~n exemplary living cell located in a sp~ce defining a rectangular coordinate ~ris system and subjected, within this active active volume, to a magnetic flux density created by three pflirs of electrical coils, or an equivalent combination o~
sources of magnetic fields, such ~ permanent msgnets and/or the e~rth's m~gnetic field;

1 3n~6qo ~ 5 --FIC~. 6A is a schematic, perspective view of a preferred form o~ coil pairs used to subje~t the ~ctive volume shown in FIG. 6 to magnetic waves;
~IGS. 6B and 6C are vector diagrams illustrating a preferred form o~
magnetic flux density located within the active volume shown in FIG. 6;
FIG. 7 is a schematic electrical diagram o~ a typical signal gener~ting apparatus u.sed to drive the coils in PIG. 6; and FIGS. 7A-7C are diRgrams of signal waveshapes generated by the apparatus shown in FIG. 7.

1 30~6~0 DESCRIPTION OF THI~ PREFERRED EM~ODIMENTS
When used in the present epplication ~nd cl~irns:
r'B" represents Magnetic ~lux Density measured in TeslQ (1 Tesla = I x 104 gauss). B is also often referred to as Magnetic Induction or Magnetic Field (seeP.A. Tipler, Physics, 2nd ed., p. 723, Worth Pub~ishe~s, Inc., 1982, New York).
~m" represents ionic mass, measured in l~lograms.
"q" represents ionic charge, measured in Coulombs.
"f" represents frequency, measured in Hertz.
"fc" represents cyclotron resonance frequency, measured in Hertz.
"Helmholtz coils" refers to a coaxial configuration of a p~ir of equal electrical coils, each having the same number of total turns of wire, with the mid-planes of the two coils separated by a distance equal to the radius of either coil, with the two coils wound and electrically connected such that the magneticflux density from each coil at the point on the axis halfw~y between the coils points in the same direction.
"Local magnetic flux density" refers to the arnbient magnetic field that is substantially constAnt in time and omnipresent in all environments. This will include the earth's geomagnetic field as it occurs n~turally or altered levels of the earth's field that result from the presence of local magnetic materials or the energization of electrical coils for the purpose of augmenting or decreasing thee~th's geomagnetic field.
"Active volume" is the working volume within the region defined by ~ set of Helmholtz coils, or a solenoid, or ~ny other arrangement of electric~l coils or permanent magnets, used in conjunction with the loc~l magrletic field, to createa net magnetic flux density. The magnetic flux density everywhere within the active volume is predictable, measurable Qnd uniform, (i.e., substantially equaleverywhere within this volume). The active volume, in the present c~se, encompA~ses the total volume of cell or tissue that ~re exposed to the magnetic n-.Y density required in the preferred prnctice Or this invention. The m~gnetic n~ density over the total volume of e~ d celL~ or tissue will thereby be ~ub~t~nti~lly the s~me.
~eferring to the drawings, the transfer o~ a predetermlned ion through ~
membrane can be dramgtically enhanced by 8 variety of magnetic nux densitie~.

I ;~0~690 Three pre~erred ~rrangements ror achieving such nux densities are shown schematica11y in PIGS. 1, 4 and 6.
Referring to FIG. 1, coils 10A ~nd 10B of a eonventional Helmholtz coil pair having N turns of wire making a loop with diameter 2R, have a longitudina~
axis identified by the letter Z (PIG. 1). The mid-plQnes of esch coil, located at XlYl and at X2Y2 are separated by a distance R. (The sc~le in the direction of the :Z-axis has been expanded to more clearly show volume 14.) One such coil pair has 500 turns of No. 24 wire on each loop, with a 23 centimeter diameter for each loop; the two loops are sep~rated by 11~5 centimeters. Helmholtz coils are described in Scott, The Physics of Electricity and Magnetism (John Wiley ~ Sons,Inc. 1962) at p. 315. The number of turns N, the diameter of the coils 2R, the separation of the coils R, and the wire gauge are only critical insofar as conventional practice requires constr~ints on these and other design parameters to allow optimal performance characteristics in achieving predetermined flux densities as required in the preferred practice OI the present invention. These predetermined nux densities may also be achieved by conventiona~ devices other than Hetmholtz coils, such as solenoids, electromagnets, and permanent magnets.
Whatever the means of generating this flux density, the essential aspect relevant to this invention is that a predictable, measurable ~nd uniform magnetic flux density having the value Bo be established everywhere within Qctive volume 14, and that this active volume will encompass the total volume of ceUs and/or tissue that are exposed to this n-,x density Bo. A unipol~r vector representing magnetic flux density Bo is pictured in FIG. 1 with arrows Al and A2 separated by a ~I ~ that represents the average nonzero value of the vector. The opposed ~rrows represent the fact that the magnitude of Bo changes ~t a predetermined rate. For purposes o illustration, a single exemplary living cell 12 is pictured in FIG. 1 within uctive volume 14.
Referring to PIG. 2, coils 10A and 10B receive electrical signals from a conventional AC ~ine wave generator 20 connected by means of a switch 26 eiU~er to ~ DC offset network 24 or to a full wave rectifier 22. The inst~ntaneous current I supplied to coils 10A and 10B a~ a function of time t i~shown or both switch positions 26a and 26b in ~IGS. 2A and 2B, respectively.
Simil~rly, the instantaneou~ m~ etic n~ de~sity Bo produced within ~ctive volume 14 i~ depicted as a ~unction ot time for both switch p~sitions 26A and 1 30~6qo 26B in FIGS. 2C and 2~, respective~y. The frequency and amplitude of the signals generated by circuits 20, 22 and 24 are explained later in detail.
Cell 12 contains a specific complement of intrinsic ionic species and is surrounded by a liquid or tissue medium containing ionic species required for cell and tissue function.
TABLE 1 lists a typical, but incomplete, group of such ionic species suitable for use with the invention and shows the charge-to-mass ra-tio ~q/m) of each species, in units of Coulombs per kilogram, as well as a preferred repetition rate or frequency ~fc), in Hz, for each species, for the specific case in which the magnetic flux density is 5 x 10 Tesla. For any other ionic species not indicated in TABLE 1, or for any magnetic flux density other density other than 5 x 10 5 Tesla, the preferred frequency is found using the Cyclotron Resonance ~elationship.
The preferred ratio of the predetermined rate of the average non-zero magnitude of flux density is substantially between 152.5 x 105 and 2.50 x 105, where the predetermined rate is measured in Hertz and the flux density is measured in Tesla.

TAsLE 1 Ionic Species (q), ~oulombs per Kilogram (f~), * Hz . _ _ _ _ .. _ . _ . ... _ . _ Hydrogen, H95.6 x 106 761 Lithium, Li13.9 x 106 111 Magnesium, Mg~7.93 x 106 63.1 Calcium, Ca+*4.~1 x 106 38.3 Sodium, Na~.19 x 106 33.3 Chlorine, Cl2.72 x 106 21.6 Po-tassium, K2.46 x 106 19.6 Bicarbonate, HCO 3 1.57 x 106 12.5 " .
, .

9 ~

Resonance frequency at 5 x 10 Tesla.
When coils lOA and lOB are energized by the apparatus shown in FIG. 2, the coils generate a magnetic Elux density within active volume 14 that varies with time as shown in FIGS.
2C and 2D. A non-zero average magnetic flux density Bo, uniform throughout the active volume, results either from an offset sinusoidal signal or from a full-wave rectified signal applied to coils lOA and lOB.
Referring to FIG. 3A, the local constant magnetic flux density BL will in general be superposed on the applied magnetic flux density Bo generated by coils lOA and lOB in active volume 14. The local flux density BL will have three 1 30~qn rectan~ular components, one of which is a eomponent along the direction of the Z-Axis. The effect of the Z-component of the lloe~l fllL~ density will be to change the nonzero ~verage magnetic nux density Bo created by coils lOA and 10B within active volume 14 to Q different net average velue Bl.
S For purposes of illustr~tion, in order to transfer c~lcium ions across the membrane of cell 12, sine wave gener~tor 20 and ~ither offset circuit 24 or fullwAve rectifier 22 are regulated such thAt the charg~to-mass ratio for the Ca ion equals the ratio of the supplied frequency fc to the resultant averflge magnetic flux density Bl times 2 ~r . Referring to FIG. 2, the freguency supplied to coils lOA and lOB will change depending on switch 26. Assuming sine w~ve generator 20 has an amplitude th~t cre~tes an average flux density in active volume 14 which, when combined with the Z-components of the local magnetic flux density, produces a net average value of Bl equal to 5 x 10 5 Tesl~, the frequency of the sine wave generator should be set, for switch position 26~, to 38.3 Hz. If one chooses switch position 26b, the frequency of the sine wave gener~tor should be se~ to ~38.3/2) Hz, because rectifier 22 doubles the frequency output of the sine wave generator.
The resultan~ nonzero aYerRge magnetic flux density Bl can be adjusted for maximum ion trensîer in two ways; first, without adjusting the loc~l magnetic 2n field Bz, and second, by separately reducing Bz to zero. The first case hQsalre~dy been described, wherein sine wave generator 20 is regulated to create, via coils lOA and lOB, magnetic flux density B~, which when added to Bz, resultsin Bl. In the second c~se, Bz can be separ~tely reduced to zero with a simple set of coils or ~ permanent magnet array, and sine wave generator 20 regulated to create, vi~ coils 10A and 10B~ a magnetic flux density Bo already e~u~l to the desired nwY density Bl.
Referring to FIG. 4, one example of the manner in ~ which `the local magnetic field Bz can be reduced to zero is illustrated. This is achieved by means of additional Helmholtz coils 8A nnd 8B having N2 turns of wire in eaeh loop, with the loop diameter 2R2 and the separation ~f the midpl~nes of each loop equal to R~ Coils ~A and 8~ have their axis colinear with that of c0il3 lOA~nd lOE3, and coincident with the Z-axi~.

1 30~3~)90 ~o --Referring to PIG. 5, coils 8A and 8B nre energized by a D~ power supply 28. When ~oils 8A Qnd 8B are energized in the manner described, they create in active volume 14 ~ unipolnr constant magnetic n~ density directed along the Z-~is such that the local m~gnetic tield in the Z-direction ~Bz) clm be enhanced or decreased, and in particulQr, can be reduced to zero.
The ~pparatus shown in FIG. 4 also can b~ used to generate Q nonzero unipolar resultant n,Lx density Bl if coils 8A and 8B are energized with a const~nt DC current that does not cancel the local magnetic field Bs~ and coils 10A and lOB are energized by an AC current, such as the current generated by AC sine wave generator 20, having the frequency described in connection with PIG. 2. The DC current creAtes a unipolar magnetic field represented by E~rows Bz in FIG. 3B h~ving a constant mflgnitude, and the AC current creates a biopolar magnetic field h~ving periodicslly opposed directions that reverse at the s~me rate as the AC current and having a magnitude that varies at the same rate as the AC signal.
~IG. 6 illustrates active volume 14 corresponding to a coil array in which 8 substanti~lly constnnt field magnitude having Q uniformly chsnging direction canbe used to enhance the transfer oî a selected ionic species across cell membranes. As shown in ~IG. 6A, coils 8A, 8B, lOA ~nd lOB are oriented in the sflme manner as shown in FIGS. 1 and 4. The local magnetic flux density in the direction of Z ~13z) is either reduced to zero by creating an opposite but equnlfield via coils 8A and 8B as shown in FIG. 4, or is added to, via coils 10A and 10B, to produce an overall net nonzero flux density Blin the Z~irection. Coils 4A, 4B, 6A ~nd 6B ~re arranged such that their axes are perpendicular to eflch other ~nd to Z. Coils 4A and 4B have their axis along the Y coordinate axis ~nd eoils 6A and 6B have their axis along the X coordinate direction. Coils 4A, 4B, 6A, 6B, 8A, 8B, lOA ~nd lOB are all deployed symmetrically about the XOYO
intersection on the Z-axis and each coil pair has the s~me physical properties described previously, th~t is, a su~ficient number of turns, ~ sufficient separ~tion between loop midplflnes, fl lOOp diameter equal to twice this separation~ ~nd a ~urfi~ient gauge of wireJ all properties chosen to (1) match the imped~nce ~nd current c~pacity of the power supply, (2) provide an adequflte~level of mAgnetic~ x der~ity, consi~tent with the requirements of this invention, and (3~ provide 1 30~69n the desired active volume to expose a predetermined quantity of cells ancl tissue to the combined m~gnetic flux densities created by these coils.
RefelTing to FIG. 6, one example of operfltion is to align the Z-~xis of the coil system with the direction of the local m~gnetic field and use power supply 28 snd coi~s 8A and 8B to reduce the 10CQ] magnetic n,.,c density ts zero. A
rotating magnetic field Bxy is crested by the join~ ~ction of coils 4A and ~B and 6A snd 6B and ~nother field B1 is created by coils 10A and 10B. As Bxy rotates in the XOYo plane, the net magnetic flux density resulting from the superposition of magnetic fields by coils 4A, 4~, 6A, 6B, 10A and lOB within active volume 14 is the resultant BR, the direction of which sweeps out Q cone, as indicated in FIG. 6B.
Referring to FIG. 7, coils ~A, 41B, 6A, 6B, 10A and 10B are driven by a function generator 30 that generates three synchronous outputs, a special voltage function g(t) 32 at frequency fl (FIG. 7A3 that is generated on a conductor 31A (FIG. 7), a sinusoidal signal 34 st frequence fc~ modulated by a ramp function lsflwtooth volt~ge) at frequence fl (FIG. 7B) that is generated on a conductor 31B (FIG. 7), and a cosine signal 36 at frequency fc, 90 out of phasewith sign~l 34~ and modulated by ~ ramp function at frequency f1 (FIG. 7C) that is generated on a conductor 31C (FIG. 7). These three synchronous outputs from generator 30, in turn, drive three progr~mm~ble power supplies 38, 40 and 42.
The frequence f1 is determined by the relation fc = cf1, where c is a large integer (i.e., an integer greater than or equal to 20). The frequence fc is the Cyclotron Resonance Relationship frequency fc for the magnetic flu~ density having the magnitude BR, when one wishes to transfer ions having charge-to-mass r~tio q/m across membranes located in active volume 14. Thus, to transfer cQlcium ions when BR = S x 10 lesla, fc will be set in generator 30 to the frequency 38.3 Hz and A typical value for fl will be 0.383 Hz (i.e., c = 100).
Referring to PIG. 7, the period ~or cycle time or modulation time) for each of the three outputs driving power supplies, 38, 40 and 42 will be ~1/fl) seconds.
In the exarnple given in which f1 = 0.383 Hz, the rtlodulation period for the signals supplied to ~oils 4A, 4~, 6A, 6B, lOA and lOB i~ 2.61 seconds.
Power supply 4D is îed by a signal which (cver one perind) v~ries in time ~s the runction fl sin (21r rct), where t lg the time~ given a~ zero seconds ~t thebeginning oî each period. Power ~upply 42 i9 fed by a ~ign~l which over one `1 3~)~36')0 period varies as the function fltcos t2 7r fct). Referring ts~ ~la. 7, i~ Al is the amplific~tion of power supplies 40 and 42, the signal s~rength driving the Y-~xis coils 4A and 4B over one period is Alfltsin (2 lr fct) snd the corresponding sign~l strength driving the x-~xis coils 6A and 6B is A1fl tcos (2rr fct). When energized in the manner indicflted, coils 4A, 4B, 6A and 6B ~ener~te a magnetic field thatrotates in time at the frequency fc within the plane defined by ~xes XO ~nd YO' as illustr~ted in FIG. 6B. Since the local magnetic flux density has been cancelled via coils 8A and 8B, the resultant m~gnetic field B~ equals the squareroot of the sum of the squares of the rnagnetic field created by coils 10 along the 2;-axis and the magnitude of the magnetic vector th~t rotates in time in the XOYo plane. The rotating vector is designated by Bxy~
To cover all possible ion chaMels located in the active volume 14, the value of Bxy increases line~rly in time, following the modulating function A1f1t, until the m~ximum signal occurs ~t t = l/f1 seconds, whereupon the entire process repeats. At any instant of time, the resultant magnetic field is BR = (Bl + B2XY)2 lnasmuch ~s it is desirable to maintain the Cyclotron Resonance Relationship ns given in TABLE 1 for the purposes of this invention, it is also desirable to maintain BR constant in magnitude over the course of this process. An ideal condition in this reg~rd is shown in FIG. 6C, in which BR describes a cone in space, the hslf-angle of which will increase over one period from 0~ to any ~ngle egual to or less than 180, during which time BR remains constant in magnitude.
Bec~use the value Bxy increRses in time, it is necess~ry to decre~se Bl synchronously in order to hold BR constant. The output of generator 30 to power supply 38 is designed to vary in time in such ~ manner as to reduce the field Blcreated by coils 10A and 10B by the proper factor required to maint~in BR
constHnt over the entire period. Referring to ~IG. 7, the input 32 to power supply 33 is g(t) Qnd the amplification of power supply 38 is AR, resulting In adri~ring signal to coils 10A and 10B equ~l to ARg~t). Over one period, starting at time t equ~l~ zero seconds, the function g~t) i~ given by g~t) = tl = r2t2) 2 1 3n~,6qo In the practice of this invention, the vQlues of amplification o~ power supplies38, 40 and 42, corresp~n~ing respectively to Al, Al and AR, are selected primarily with ~n eye towsrds convenience Ul producing a required B
If coils 8A and 8B do no~ cancel the local field ~3z, such thQt the rnQgnetic flu~ density ~long the Z-a2cis is not merely that prloduced by coils lOA ~nd IOB, but includes an extra 10CAI component Bz, the process pertinent to FIGS. 6 and 7remains unchanged, e~cept that the magnetic field 191 is in part produced by coils lOA and lOE~. Over the course of one modulation period, the Qngle between the Z-axis ~nd the resultant magnetic field BR increases so that the tip of the vector sweeps out an ever-incre~sing circle, but the magnitude of the resultant vector remains constant since B1 is being decreased ~t the same time. Thus, over one modul~tion period, the tip of the r~iultant magnetic field vector B~
traces out some portion of a hemisphere, depending on how large the angle between the Z-a2cis ~nd BR is allowed to become~ The locus of points traced out by BR can cover a cornplete sphere by reducing Bl below zero. By adjusting the value of large in~eger c, vector BR can be tuned to complete the generetion of ahemisphere or a sphere or any fraction thereof at a specified rate. In this way,all directions for variously oriented membrane surfaces will be covered by BR ina repetitiYe and efficacious manner, thereby allowing the Cyclotron Reson~nce 2~ Relationship for enh~nced permeability of ions to be met for elements of eQch membrane and ion channels th~t h~ve v~rious orientations. In this mode the frequency fc corresponds to lthe Cyclotron Resonance Relationship frequency fc~
Coincidentslly, ~ second, altern~te mo~e of flpplication is possible, in thflt the arrQngement in PIGS. 6 ~nd 7 can ~Iso be used to simultaneously anh~nce the transfer of two distinctly different ionic species. In this mode, fc will correspond to the Cy~lotron ~e~onance Rel~tionship frequency for one species ~nd fl to the Cyclotron Resonance Rel~tionship frequen~y for another. Thus, cor~ider TABLE 1 In ~ ich the reson~nce frequency for hydrogen ions is ~61 Hz snd the reson~nce frequency for pot~ium ions Is 19.6 Hz for ~ magnetic flux density equ~l to 5 ~ 10 5 Tesl~. If coils 6A, 6B, 8A, 8B, lOA ~nd lOB ~re energized to cre~te d field BR equ~ll to 5 ~ 10 5 Tesla in the ~ctive volume 14,~nd if fl i9 ~djusted to 19.6 Hz, then ~hoo3ing fQ~tor ~ to be 39 result~ In frequency ~c substanti~lly the s~me as requlred to enll~nce hydrogen ion transfer. The result of thi~ procedure will be to slmult~neously enhsnce the I 30~690 ~- 14 --trQnsfer of both hydrogen and pota~sium lons acros~ membrQne sllrf~ces within actiYe volllme 14.
Those skilled In the ut wiLI recognize the embodiments descrlbed herein may be modified or a~tered without dep~rting from the true spirit and ~cope of S the invention ~s defined in the appended cl~ims~ Por e~ample, the llneer axes shown in the drawing may haYe more complicated paths~ or the ~xes may be oriented along planes other than the eonvention~l XYZ planes, or the size, 3hapeand physlcal properties OI the coils may be altered, or the coils mey tske formsother than Hemholtz coils, such as solenoids, wires and sheets, or the coils may10 be replaced by equiv~ent devices for producing the required nux densities. The ions may be put into cyclotron r0sonance in a wide variety of ways as long ~s the relationship between the charg~to-mass ratio and the frequency and magnetic n~ density is maintained. ~or some applications, ~ppropriate mechanical sign~ls may be substituted for the described electrical signals.

Claims

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

1. Apparatus for regulating the permeability of a predetermined ion having a predetermined charge-to-mass ratio through a biochemical membrane located in a space subjected to a local static magnetic field, the space defining at least one reference path passing through the biochemical membrane, the reference path extending in a first direction and also extending in a second direction opposite the first direction, said apparatus comprising:
field creating means responsive to signals for creating a magnetic field which, when combined with the local magnetic field, results in a resultant magnetic field having a flux density with at least one component representable by a component vector having a direction extending in the first direction along the path and having a magnitude that fluctuates at a predetermined rate to create a nonzero average value wherein the ratio of the predetermined rate to the nonzero average value is a function of the charge-to-mass ratio of the predetermined ion said predetermined relationship involving the cyclotron resonance frequency of said predetermined ion; and signal generating means adapted to generate said signals at the predetermined rate.
2. Apparatus, as claimed in claim 1, wherein the signals are electrical signals.
3. Apparatus, as claimed in claim 2, wherein:
(a) the resultant magnetic field comprises (1) a unipolar magnetic field having a flux density with at least one unipolar component representable by a unipolar vector having a direction extending in the first direction along the path and having a substantially constant magnitude: and (2) a bipolar magnetic field having a flux density with at least one bipolar component representable by a bipolar vector having periodically opposed directions that reverse at the predetermined rate and that extend along the path, said bipolar component having a magnitude that varies at the predetermined rate; and (b) the signal generating means comprises (1) means for generating a direct current signal for creating the unipolar magnetic field, and (2) means for generating an alternating current signal for generating the bipolar magnetic field.
4. Apparatus as claimed in claim 2, wherein the resultant magnetic field comprises a unipolar magnetic field having a flux density with at least one unipolar component represented by a unipolar vector having a direction extending in a first direction along the path and having a magnitude that varies at the predetermined rate.
5. Apparatus, as claimed in claim 4 wherein the signal generating means comprises means for generating an alternating current signal offset by a predetermined DC level.
6. Apparatus, as claimed in claim 4, wherein the signal generating means comprises means for generating an alternating current signal and means for rectifying the alternating current signal.
7. Apparatus, as claimed in claim 2, wherein:
(a) the resultant magnetic field comprises a unipolar magnetic field having a flux density with at least one unipolar component representable by a unipolar vector having (1) a direction extending only in the first direction along the path, and (2) a magnitude fluctuating at the predetermined rate; and (b) the signal generating means comprises means for generating a direct current having a magnitude that fluctuates at the predetermined rate.
8. Apparatus, as claimed in claim 2, wherein:
(a) the resultant magnetic field comprises a magnetic field having a flux density with at least one component representable by a vector having (1) a direction that sweeps across the path at the predetermined rate, and (2) a substantially constant magnitude; and (b) the signal generating means comprises means for generating signals, whereby the resultant magnetic field rotates.
9. Apparatus, as claimed in claim 8, wherein:
said space defines first and second intersecting coordinate axes lying in a first plane and a third coordinate axis perpendicular to the first plane and passing through the point of intersection of the first and second axes;
the resultant magnetic field comprises a magnetic field having a flux density with at least one component representable by a vector having a direction that passes through said point of intersection and passes around said third coordinate axis to define a cone, the rate at which the angle between the vector and the first plane changes being proportional to the predetermined rate; and the signal generating means comprises:
(a) means for generating a first AC signal having a first predetermined phase angle, a second AC signal having a second predetermined phase angle substantially 90 degrees out of phase with the first phase angle in order to create a component of a magnetic field that rotates in the first plane, and a DC
signal; and (b) means for synchronously modulating the said first AC signal, the said second AC signal and the said DC
signal, each signal simultaneously fluctuating at the said predetermined rate.
10. Apparatus, as claimed in claim 2, wherein the signal generating means comprises means for tuning the electrical signals so that the charge-to-mass ratio of the predetermined ion is substantially equal to 2.pi.times the ratio of the predetermined rate to the nonzero average value.
11. Apparatus as claimed in claim 2, wherein the ratio of the predetermined rate to the average nonzero magnitude of flux density is substantially between 152.5 x 105 and 2.50 x 105, where the predetermined rate is measured in Hertz and the flux density is measured in Tesla.
12. Apparatus, as claimed in claim 3, wherein the signal generating means comprises means for tuning the electrical signals so that the charge-to-mass ratio of the predetermined ion is substantially equal to 2.pi.times the ratio of the predetermined rate to the flux density magnitude of the unipolar vector.
13. Apparatus, as claimed in claim 3, wherein the ratio of the predetermined rate to the flux density magnitude of the unipolar vector is substantially between 152.5 x 105 and 2.50 x 105, where the predetermined rate is measured in Hertz and the flux density is measured in Tesla.
14, Apparatus, as claimed in claim 4, wherein the signal generating means comprises means for tuning the electrical signals so that the charge-to-mass ratio of the predetermined ion is substantially equal to 2.pi.times the ratio of the predetermined rate to the average value of the flux density magnitude of the unipolar vector.
15. Apparatus, as claimed in claim 4, wherein the ratio of the predetermined rate to the average value of the flux density magnitude of the unipolar vector is substantially between 152.5 x 105 and 2.50 x 105, where the predetermined rate is measured in Hertz and the flux density is measured in Tesla.
16. Apparatus, as claimed in claim 8, wherein the signal generating means comprises means for tuning the electrical signals so that the charge-to-mass ratio of the predetermined ion is substantially equal to 2.pi.times the ratio of the predetermined rate to the average flux density magnitude of the unipolar vector in the first direction.
17. Apparatus, as claimed in claim 8, wherein the ratio of the predetermined rate to the average flux density magnitude of the unipolar vector in the first direction is substantially between 152.5 x 105 and 2.50 x 105, where the predetermined rate is measured in Hertz and the flux density is measured in Tesla.
18. Apparatus, as claimed in claim 2, wherein the predetermined ion is any ionic species having a predetermined charge-to-mass ratio.
19. Apparatus, as claimed in claim 2, wherein the predetermined ions are selected from a group consisting of H+, Li+, Mg2+, Ca2+, Na+, K+, Cl- and HCO3.