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BACKGROUND OF THE INVENTION
The present invention is based on the phenomenon of dielectrophoresis--the
translational motion of neutral matter caused by polarization effects in a
non-uniform electric field. The dielectrophoresis phenomenon was first
recorded over 2500 years ago when it was discovered that rubbed amber
attracts bits of fluff and other matter. Over 300 years ago, it was
observed that water droplets change shape as they approach a charged piece
of amber. The basic concept of dielectrophoresis is examined in detail in
a text entitled Dielectrophoresis by Herbert H. Pohl, published in 1978 by
the Cambridge University Press. Further discussion of this phenomenon also
can be found in an article by W. F. Pickard entitled "Electrical Force
Effects in Dielectric Liquids", Progress in Dielectrics 6 (1965)--J. B.
Birks and J. Hart, Editors.
All known practical applications of the dielectrophoresis phenomenon have
been directed to either particle separators or clutches. For example, U.S.
Pat. No. 1,533,711 discloses a dielectrophoretic device that removes water
from oil; U.S. Pat. No. 2,086,666 discloses a dielectrophoretic device
which removes wax from oil; U.S. Pat. No. 2,665,246 discloses a
dielectrophoretic separator used in a sludge treatment process, U.S. Pat.
No. 2,914,453 provides for separation of solid polymeric material from
fluid solvents; U.S. Pat. No. 3,162,592 provides for separation of
biological cells; U.S. Pat. No. 3,197,393 discloses a separator using
centripetal acceleration and the dielectrophoretic phenomenon; U.S. Pat.
No. 3,304,251 discloses dielectrophoretic separation of wax from oil; U.S.
Pat. No. 3,431,441 provides a dielectrophoretic separator which removes
polarizable molecules from plasma; U.S. Pat. No. 3,980,541 discloses
separation of water from fluid; and U.S. Pat. No. 4,164,460 provides for
removal of particles from a liquid. U.S. Pat. Nos. 3,687,834; 3,795,605;
3,966,575; and 4,057,482 disclose other dielectrophoretic separators for
removing particulates and water from a fluid. Other separators, not
necessarily dielectrophoretic separators, are disclosed in U.S. Pat. Nos.
465,822; 895,729; 3,247,091 and 4,001,102.
U.S. Pat. No. 2,417,850 discloses a clutch mechanism using the
dielectrophoretic phenomenon.
The object of the present invention is to provide a reaction chamber or
housing in which one or more chemicals can be selectively manipulated to
different locations within the chamber using the dielectrophoresis
phenomenon. A variety of apparatus for performing chemical manipulations
are known to the art. Such apparatus provide mechanical manipulation (such
as by pressurized fluid transfer), inertial or gravimetric manipulation
(such as by centrifigation), or phase separation (such as by
distillation). Automated chemical analysis can be accomplished, for
example, by automatic titrators, which substitute electrically operated
components, such as solenoid driven stopcocks, for operations normally
performed manually. Automated chemical synthesizers as, for example,
protein sequencers are also known.
The present invention provides a technique for electronic manipulation of
chemicals using the phenomenon of dielectrophoresis. Dielectrophoretic
forces are used to selectively position, mix, separate and transport one
or more chemical species within a housing. For example, chemical species
may be transported to a typical reaction site, such as heated catalytic
surfaces to induce a chemical reaction. Likewise, chemicals may be
transported to analytical devices, such as absorption spectrometers.
Dielectrophoretic manipulation of one or more chemicals is well suited for
automatic control such as, for example, direct computer control.
SUMMARY OF THE INVENTION
The present invention provides method and apparatus for manipulating one or
more chemical species within a housing. The housing contains at least two
materials having different dielectric constants, one of the two materials
corresponding to the chemical species to be manipulated. Means for
applying a non-uniform electrical field to the materials within the
housing are provided. The dielectrophoretic forces resulting from the
applied non-uniform field vary the relative positions of the materials
within the housing. Accordingly, the non-uniform field is used to
manipulate the location of the chemical species within the housing. The
species may be transported to different regions in which, for example, it
may be analyzed or induced to react with other chemicals. Additionally,
two or more chemicals can be manipulated within the housing for mixing or
other reactions.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 of the drawings diagrammatically illustrates charged parallel
capacitor plates causing movement of a slab of material as a result of
dielectrophoretic forces;
FIG. 2 diagrammatically illustrates a dielectric material disposed between
a plurality of different pairs of capacitor plates;
FIG. 2A diagrammatically illustrates sequential movement of the dielectric
material of FIG. 2 by varying the charges on the pairs of capacitor
plates;
FIG. 3 is a top plan view of a gate electrode in accordance with the
present invention;
FIG. 3A is a side elevational view, in section, of the gate electrode of
FIG. 3;
FIG. 3B is a top plan view of a gate electrode similar to that shown in
FIG. 3 with the charges on the capacitor plates modified from that shown
in FIG. 3;
FIG. 3C is a side elevational view, in section, of the gate electrode of
FIG. 3B;
FIG. 4 is a sectional view of a structure for dielectrophoretically
ejecting material from a housing in accordance with the present invention;
FIG. 5 is a top plan view of a second structure for dielectrophoretically
inputting material into a housing;
FIG. 5A is a side elevational view, in section, of the structure of FIG. 5;
FIG. 6 illustrates a dielectrophoretic titrator in accordance with the
present invention; and
FIG. 6A is a flow diagram illustrating the operation of the
dielectrophoretic titrator shown in FIG. 6.
DISCUSSION OF THE PREFERRED EMBODIMENTS
This present invention utilizes the phenomenon known as dielectrophoresis,
or the motion of electrically neutral matter in non-uniform electric
fields caused by polarization effects in the neutral matter. Matter is
polarizable to the extent that electric charges are mobile inside the
material, specifically to the extent that the electric charge can respond
to external electric fields. The polarizability of material, at low
frequencies, is measured by the dielectric constant. For example, the
dielectric constant of a vacuum, which has no mobile charges, is one, and
the dielectric constant of a metal, which contains charges that are so
mobile that the material is termed a conductor, is infinite. Any gas,
liquid, or solid is therefore a dielectric material. It is known that a
material with a higher dielectric constant will experience a force tending
to move it into a stronger electric field and, in the process, it will
displace a material with a lower dielectric constant.
Such a process is shown in FIG. 1; a parallel plate capacitor 2, with some
potential difference between its two plates, will contain an electric
field between the two plates. A slab of material 4 having a higher
dielectric constant than the surrounding medium 5 will be attracted into
the region between the capacitor plates. The slab will move into the
region between the plates at a rate determined by a variety of factors:
its dielectric constant; the dielectric constant of the surrounding
material; the voltage and geometry of the capacitor; the viscosity of the
surrounding material; and any other forces which may be acting on the
slab, such as gravity and surface interactions.
The dielectric constant of a conductor is not a directly measurable
quantity. For the purposes of this discussion, conducting materials will
be considered as being subject to dielectrophoretic forces. Justification
for this assumption is that the induced polarization on, for example, a
non-conducting dielectric sphere in a uniform field can be calculated
analytically. The dielectric constant in this expression can then be
allowed to approach infinity in absolute value. In other words, the
dielectric sphere becomes a conductor and the expression for the induced
polarization remains well defined. Since it is the induced polarization
which in turn interacts with the external field to create
dielectrophoretic motion, a conductor can be considered subject to a
dielectrophoretic interaction.
In the following discussion, the material being manipulated will be
interchangeably referred to as a dielectric slab, a dielectric bubble, or
a dielectric particle. Each refers to an isolated region in space
containing a material of substantially different dielectric constant than
its surroundings. The manipulated material can be a solid, a liquid, or a
gas.
Alternative electrode configurations create bubble movement perpendicular
to the plane of the electrode array rather than parallel to it. Since the
slab is attracted to regions of higher electric field density, a field
between two electrodes of dissimilar geometry will cause the slab to move
towards the smaller electrode.
The potentials of various electrodes have been denoted by the d.c. voltage
levels V+ and V- for the sake of clarity. The sign of the field, which is
determined by the relative potentials on both electrodes, is immaterial,
because for electrically neutral bubbles of dielectric material, the force
that they experience due to the voltages on the electrodes is attractive
and independent of sign. In practice, dielectric media have some
non-negligible electronic or ionic conductivity. Ions in the surrounding
medium will migrate under the influence of the electrode fields and
configure themselves so as to shield the dielectric bubble from these
external fields. This is usually an undesirable effect, so that the actual
voltages applied to the electrodes is held constant in absolute value but
also oscillates in time at a rate sufficient to decrease ionic shielding
to an acceptable level.
Although reference has been made to a higher dielectric bubble surrounded
by a lower dielectric medium, the opposite is also possible. If a bubble
of a lower dielectric medium is immersed in a higher dielectric
surrounding, it will tend to be repelled by dielectrophoretic forces.
Elaborating on the geometry of FIG. 1, instead of a single pair of
capacitor plates, a sequence of capacitive electrodes may be provided, as
shown in FIG. 2. Two insulating plates 6 in a surrounding medium 8 enclose
a bubble 10 of a higher dielectric material and carry on their non-opposed
surfaces electrodes 12, 14, 16 and 18. Those electrodes which carry the
same reference numeral are electrically connected. This may be referred to
as a ladder electrode geometry. With a voltage V+ applied to electrodes 12
and 16 and V- applied to electrodes 14 and 18, the bubble 10 of higher
dielectric material will have a stable position between electrodes 12 and
18. If V+ is applied to electrode 18 and V- to electrodes 12, 14 and 16,
the bubble 10 of high dielectric material (hereafter referred to as the
bubble) moves to the right, finding a stable position over electrode 18,
as shown in the second diagram from the top of FIG. 2A. This process can
be continued, as shown by the sequence of diagrams in FIG. 2A, by applying
the voltages given in Table 1 below, to the various electrodes, causing
the bubble to move reversibly to the right. The voltages on the electrodes
in the ninth step are the same as in the first step, indicating that the
system has returned to its initial condition with the exception that the
bubble has been moved to the right.
TABLE 1
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Elec- Step
trode 1 2 3 4 5 6 7 8 9
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12 V+ V- V+ V- V+ V- V+ V+ V+
14 V- V- V- V+ V- V- V- V- V-
16 V+ V- V- V- V+ V+ V- V- V+
18 V- V+ V+ V- V- V- V+ V- V-
______________________________________
Reference is also made to co-pending application Ser. No. 265,637 filed May
20, 1981, entitled "Method and Apparatus for Providing a Dielectrophoretic
Display of Visual Information", the disclosure of which is incorporated
herein by reference, for an example of a half-ladder electrode array.
Note that FIGS. 2 and 2A include insulators placed between the electrodes
and the mobile dielectric materials. These are not necessary if the
conductivity of the dielectric media is low enough, and if there are no
detrimental interactions between the electrode material and the dielectric
media.
The electrode arrays pictured in FIGS. 1-2 allow for manipulation of the
bubble position in only one dimension. However, it is clear that such
techniques can be extended to give manipulation capacity in two or three
dimensions as well. The two pairs of electrodes in FIG. 2 can be extended
to an arbitrary number of electrode pairs in two dimensions. In addition,
multiple arrays of electrodes can allow for the vertical movement
previously described.
Special consideration must be placed on the effects of surface wetting or
adhesion, surface tension, and viscosity in a dielectrophoretic
manipulator. To first order, all electrically neutral materials attract
each other, to a greater or lesser degree, by the Van der Waals
interaction, which is the microscopic counterpart of the dielectrophoretic
interaction. Because of this attraction, any material which is to be
manipulated will tend to be attracted to the containing surfaces of the
device. That attraction can cause adhesion to, or in the case of fluids,
wetting of the containing surfaces by the material to be manipulated,
which degrades the performance of the device. To overcome this effect, a
secondary material may be placed between the material being manipulated
and the containing surfaces, with the characteristic that this secondary
material is more attractive to the material being manipulated than the
containing surfaces are. This secondary material can take the form of a
lubricant that coats the containing surfaces, or of a low viscosity liquid
(or gas) that fills the volume between the containing surfaces. For
example, if water, with a dielectric constant of 76, is the material to be
manipulated, and glass insulators form the containing surfaces, a
surrounding fluid that is effective at preventing the water from wetting
the glass is heptane, with a dielectric constant of 1.9, containing five
percent octyl alcohol. It is important to keep the viscosity of the
surrounding material as low as possible to afford the least resistance to
the movement of the material being manipulated. Finally, if the material
being manipulated is fluid, there may be a requirement to generate small
bubbles from larger ones. This can be accomplished by at least four
techniques. Moving a fluid bubble rapidly in a viscous medium causes the
larger bubble to break down into smaller ones due to viscous drag. The
velocity required to perform this fissioning process depends upon the
surface energy between the bubble and the surrounding medium. For example,
in the case of water in heptane, the addition of two percent of the
detergent Triton-x 100 to the water lowers the surface energy between the
water and the heptane from more than thirty to less than ten dynes per
centimeter. Another technique for fissioning bubbles is to use neighboring
inhomogeneous field regions. Roughly speaking, bubbles will split in two
if it is energetically favorable to occupy separate regions of higher
field. If a bubble is charged, it can break up into smaller bubbles due to
mutual repulsion of the like charges on the original bubble. Alternative
techniques for creating small bubbles include forcing the fluid through a
small orifice.
Modifications and elaborations of the linear electrode ladder array, shown
in FIGS. 2 and 2A will allow chemical species to be transported,
positioned, combined, mixed, separated, partitioned into smaller volumes,
and used in conjunction with standard chemical synthesis and analysis
techniques. The general process will be referred to as dielectrophoretic
chemistry. A number of devices for manipulating chemicals will be
described and them combined into a dielectrophoretic titrator, as an
example of an application of this general technique to a specific reaction
cell design.
If one electrode in the linear array of FIG. 2 is inoperative, the flow of
material will stop at that electrode. A gate electrode may be provided in
this manner between two separated ladder electrode arrays to control the
flow of material through the ladder arrays by synchronously operating the
ladder and the gate.
Such a gate electrode arrangement is illustrated in FIGS. 3 and 3A in which
a first ladder electrode array is separated from a second ladder electrode
array by a gate electrode 28. The first ladder array includes a plurality
of pairs of opposed diamond-shaped capacitive electrodes 20 while the
second ladder array includes a plurality of pairs of opposed generally
square-shaped electrodes 22. A pair of insulating plates 24 are disposed
between the upper and lower levels of electrodes of both the first and
second ladder arrays, and a quantity of higher dielectric material 26 is
located between the insulating plates and disposed between the electrodes
20 of the first ladder array. (The insulating plates are assumed to be
transparent for ease of explanation).
As already described with respect to FIG. 2A, varying the charges on the
electrodes 20 of FIG. 3 can result in movement of the higher dielectric
material through the first ladder electrode array. Varying the charge on
the gate electrode 28 can be used to control or assist the movement of the
material 26. For example, by setting the charges on electrodes 20 and 22
and the gate electrode 28 as shown in FIG. 3A, an electric field exists
between the rightmost electrode 20 of FIG. 3 and the gate electrode 28.
The dielectrophoretic forces resulting from this electric field cause the
end of the dielectric material 26 closest to the gate electrode 28 to
extend into the region beneath the gate electrode, as shown in FIGS. 3 and
3A.
In addition to providing flow control of the dielectric material 26 as
discussed above, the gate electrode 28 may also be used to separate a
small portion or bubble from the larger mass of material 26, as
illustrated by FIGS. 3B and 3C. These figures illustrate the gate
electrode--ladder array arrangement of FIGS. 3 and 3A except that the
polarity on the gate electrode 28 has been reversed. With the polarities
on the electrodes 20 and 22 and the gate electrode 28 as illustrated in
FIG. 3C, an electric field exists between the gate electrode 28 and the
leftmost electrode 22 of the second ladder array. No electric field exists
between the gate electrode 28 and the rightmost electrode 20 of the first
ladder array. The dielectrophoretic forces resulting from the field
between the gate electrode and the second ladder array cause a small
portion 30 of the material 26 to separate from the large mass of material
and move towards the right, as viewed in FIGS. 3B and 3C. The absence of
an electric field between the gate electrode and electrodes 20 of the
first ladder array, combined with the surface tension effects in the
larger mass of material 26, causes the larger mass of material to recede
to the left. The net result of the overall process illustrated in FIGS. 3B
and 3C is that a bubble 30 of higher dielectric material has been
separated from the bulk of material 26 between the first ladder array and
that bubble has moved towards the second ladder electrode array.
It is important that bubbles can be generated with well governed volume,
since these bubbles form the unit of measure in a volumetric analysis. The
factors tending to cause variation in the bubble sizes are changes in the
surface curvature of the reservoir from which the bubbles are fissioned,
and variations in the interfacial surface tension and bulk viscosity of
the same material. The factors which regulate the bubble size by their
inherent design are the thickness of the fluid region, the size of the
electrodes, and any orifice which might be installed between the ladder
and gate electrodes. In actual operation, it is possible to regulate the
bubble size electronically. It has been experimentally observed that,
within certain operating limits, larger voltages produce larger bubbles.
If the size of the bubbles produced is monitored, for example, optically
or capacitively, this information can be fed back to the gate electrode
driver to regulate the bubble size produced.
It is noted that standard photolithographic techniques are able to produce
electrode arrays capable of manipulating very small quantities of
material. For example, a characteristic dimension of 5 mils for the fluid
gap and electrode spacing gives bubble sizes on the order of a millionth
of a cubic centimeter.
It is necessary to input and output material from the dielectrophoretic
manipulator of the present invention. A simple method for ejecting
material is to utilize the density difference between the material and the
surrounding fluid, as shown in FIG. 4. A ladder electrode array 32 moves
material to be ejected between the electrodes to a port 34, where the
material drops downwardly through a surrounding fluid 36 until it enters
an output reservoir 38. A similar geometry exists for materials which are
less dense than the surrounding fluid. In that case the ejected material
floats up to an output reservoir.
FIGS. 5 and 5A illustrate a second type of input/output device. An entrance
port 40 communicates with the center of an electrode array 42. A material
44, in this case material of a higher dielectric constant than the
surrounding fluid, is moved until it drops through the top of the port 40
and into the tube 46. The material 44 will be confined to the region of
high electric field between electrodes 42, forming a reservoir from which,
for example, bubbles can be fissioned and used in chemical reactions. The
reservoir area of the reaction cell may have a larger thickness than most
of the reaction cell to increase its storage capacity. In FIG. 5, it is
assumed that the port 40 is defined by transparent material 46 for visual
clarity of the drawings.
Although reference has been made to bubbles or slabs of material in a
surrounding fluid as the typical mode of operation of the
dielectrophoretic manipulator described herein, the regions of differing
dielectric constant can be as small as a single molecule. Such
manipulation requires high electric field strengths and relatively low
ambient temperatures to be effective. For example, such conditions allow
manipulation of regions of octyl alcohol in a surrounding fluid of
n-octane or the separation of chemical species without requiring a phase
separation.
The preferred configuration of the present invention allows manipulation of
aqueous solutions in inert hydrocarbon surrounding liquids. An example is
the manipulation of an acetic acid solution in n-heptane. At higher
pressures or lower temperatures, the manipulator operates efficiently with
liquid ammonia as the high dielectric solvent.
One of the most useful characteristics of dielectrophoretic manipulation is
the ability to transport material to reaction sites or analysis sites by
only electronic means. For example, ohmic heaters or thermoelectric
coolers can be mounted directly on the containing surfaces of a reaction
cell incorporating the present dielectrophoretic manipulator so as to
alter the local temperature of that region of the reaction cell. A bubble
transported into that region of a reaction cell will undergo a
corresponding temperature change. Similarly, the inner surface of the
reaction cell might be plated with catalytic material or some region may
be packed with a porous plug of catalytic material, which could be
selectively utilized by transporting a bubble to that region. A window
could be provided through which U.V., visible, or infra-red irradiation of
a single bubble can be performed. Such window also would allow
spectroscopic measurements of a sample of product material. Ion sensitive
electrodes may be mounted in the supporting structure of a reaction cell,
thereby providing a direct electrical indication of the pH or
concentration of other ions. A gel for electrophoretic separation might be
included in a region of the fluid layer.
Many different types of chemical reactions can be performed in a reaction
cell embodying the manipulator of the present invention. Examples are
exchange, hetero- or homogeneous catalysis, precipitation, distillation,
redox, chelate formation, and polymerization. A simple example of a
dielectrophoretic reaction cell which will perform a complex titration for
Ca++ in an aqueous sample will be discussed with respect to FIGS. 6 and
6A.
In FIG. 6, the lower electrode array for a dielectrophoretic titrator is
illustrated. Contact pads 48 provide the connections with external control
circuits. Electrode array 50 is a reservoir ladder array, such as array 42
shown in FIG. 5. Electrode arrays 52 and 54 in FIG. 6 are reservoir ladder
arrays which contain and dispense buffer/indicator and titrant solutions,
respectively. Electrode array 56 is a mixing and analysis electrode. Port
58 is a waste exit port, corresponding to port 34 in FIG. 4. Gate
electrodes 60, 62, 64 and 66 are gates allowing bubble generation from the
buffer/indicator, sample, titrant, and mixing reservoirs, respectively.
Two gate electrodes 68 allow bubbles to be directed from the sample
reservoir to the buffer/indicator reservoir or to the mixing reservoir, or
from the buffer/indicator reservoir to the mixing reservoir. Ladder
electrode arrays 70, 72, 74, 76 and 78 are similar to the ladder electrode
array shown in FIGS. 2 and 2A. They provide for the movement of bubbles
between the various reservoirs.
FIG. 6A illustrates a template or spacer to be positioned between two
insulating layers, serving to confine the reservoirs and to define the
fluid layer thickness. The lower insulator includes the electrode pattern
as shown plated on it in the form of a transparent conductor using
standard photolithographic techniques. The upper insulator would have a
similar electrode array plated on it, (not shown).
The operation of the dielectrophoretic titrator is illustrated generally by
the flow diagram of FIG. 6A. A buffer/indicator reservoir 80 contains an
ammonia/ammonia chloride solution (buffer for pH=10) and 10.sup.-6 F
Eriochrome Black T indicator. A titrant reservoir 82 contains a
concentrated solution of EDTA (ethylenediaminetetraacetic acid). A sample
aqueous solution containing an unknown concentration of Ca++ ion is placed
in the sample reservoir 84 using, for example, the apparatus and method
discussed with respect to FIGS. 5 and 5A. A known number of bubbles of
known size are fissioned off of the sample and transported into the mix
and detection reservoir 86. A known number of bubbles of known size are
fissioned off of the buffer/indicator solution and are also transported to
the mix and detection reservoir. Single bubbles of the EDTA titrant are
then added to the mixture in the reservoir 86, and the solution in that
reservoir is dielectrophoretically driven from one side of the reservoir
to the other in order to mix the different solutions. Light of a
wavelength of 4800 Angstroms is transmitted through the mix and detection
reservoir and monitored. When the transmitted intensity drops down to a
characteristic plateau, the titration is complete. Knowledge of the
volumes of titrant, the buffer/indicator and the sample added together
allows computation of the initial Ca++ concentration in the sample.
Finally, the excess sample and material from the mix and detect reservoir
are then driven into a discharge chamber or waste reservoir 88 on the far
right of FIG. 6A.
A similar sort of device might utilize a calcium ion sensitive electrode
rather than an EDTA titration. In that case, the dielectrophoretic
manipulator is convenient for alternatively placing bubbles of buffer
solution and sample solution between the reference and indicator
electrodes for calibration and measurement, respectively.
Other modifications and applications of the above-described
dielectrophoretic manipulator will become apparent to those skilled in the
art. Accordingly, the above discussion is intended to be illustrative
only, and not restrictive of the scope of the invention, that scope being
defined by the following claims and all equivalents thereto.
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