Metal clad lipid microstructures

Tubular, spheroidal, and helical lipid microstructures are individually clad with a metal coat deposited on the microstructures by an electroless plating bath. In metal cladding the microstructures, the surfaces of the lipid microstructures are sensitized by adsorption thereon of a catalytic precursor which enables metal from the electroless plating bath to deposit upon and adhere to the sensitized surface. The metal plate is electrically conductive and may also be magnetic. A composite material is produced by embedding the metal clad microstructures in a matrix of a polymer such as an epoxy or a polyurethane.

FIELD OF THE INVENTION 
This invention relates in general to the production of individual lipid 
microstructures each of which is covered by its own adherent metal coat. 
More particularly, the invention pertains to the production of metal 
coated lipid microstructures which are in the form of a hollow cylinder or 
in the form of a helix or in the form of a sphere. 
BACKGROUND OF THE INVENTION 
It is known that phospholipids which possess a diacetylenic functional 
group in each of two fatty acid chains, e.g. 1, 2-bis 
(10,12-ticosadiynoyl)-sn-glycero-3-phosphocholine (DC.sub.23 PC), 
self-assemble to form a variety of microstructures under certain well 
defined conditions in agueous solutions. 
Vesicles are spheroidal structures in which one or more lipid bilayers are 
wrapped in a lamellar fashion to enclose a volume of solution. Vesicles 
range in size from approximately 50 nanometers (a nanometer is a billionth 
of a meter) to 25 microns (a micron is a millionth of a meter). These 
structures are also formed by non-diacetylenic lipids. The vesicles used 
in this invention were prepared in the manner described in a monograph by 
Paul Yager and Paul E. Schoen in the "Journal of Molecular Crystals And 
Liguid Crystals", vol. 106, pp 371-381 (1984). 
Tubules are hollow, cylindrical structures composed of up to approximately 
ten bilayers; characteristic diameters are 0.2 to 3.0 microns, wall 
thicknesses are approximately 5 to 50 nanometers. Tubule length is a 
controllable parameter, based on fabrication procedure. The aspect ratio 
(ratio of length to radius) is therefore also controllable. 
Preparation of tubules for this invention was accomplished by two methods. 
The first method involved raising the temperature of an aqueous vesicular 
dispersion above the chain melting temperature, T.sub.m, of the 
diactylenic lipid (43.degree. C. for DC.sub.23 PC) followed by slow 
cooling to just below T.sub.m as described in "Polymer Preprints", by A. 
Sinqh and J. Schnur, vol. 26, pp 184-185, (1986), in the above cited 
"Journal of Molecular Crystals and Liquid Crystals" monograph, and in U.S. 
Pat. Application No. 852,596, which was filed on April 16, 1986 now 
abandoned on an invention by Paul Schoen, Paul Yager, and Joel Schnur in 
Lipid Tubules. The structures thus formed are referred to as 
"thermally-grown tubules". In the second procedure, a non-solvent such as 
water is added to a solution of the diacetylenic lipid in an organic 
solvents such as an alcohol, until the solubility of the material in the 
mixed medium is exceeded and precipitation occurs. Such structures are 
referred to as "solvent grown tubules". 
Helices are spiral-shaped structures that are also produced by the tubule 
formation methods described above. The helical structures have a pitch of 
about one micron and are typically one or two bilayers thick. The 
diameters of the helices are comparable to those of the tubules. 
The diacetylenic lipid microstructures are known to undergo free-radical 
topotactic polymerization upon exposure to photons or electrons of 
sufficient energy, such as can be produced by ultraviolet (UV) radiation, 
by X-rays, by gamma rays, and by an electron beam. The integrity of the 
resultant polymeric microstructures is improved over their monomeric 
analogues in regard to thermal, chemical, and mechanical stability. In one 
utilization of this invention, diacetylenic microstructures were 
polymerized as a dispersion in aqueous alcohol (ethanol/water=20/80 v/v) 
at 0.degree. C. by exposure to 1.33 Mev .sup.60 Co gamma radiation at 
dosages of 6 to 9 Mrad. 
The lipid microstructures referred to above are electrical insulators and 
those microstructures have weak diamagnetic susceptibility--that is, the 
lipid microstructures can be aligned only by a strong (2.times.10.sup.4 
gauss) magnetic field and have poor electrical conductivity. 
PRINCI OBJECT OF THE INVENTION 
The principal object of the invention is the production of lightweight, 
rugged, electrically conductive individual microstructures (which can also 
be magnetic) by the adhesion of a thin metal coat to those individual 
microstructures.

THE INVENTION 
Essential to the production of the metal coated lipid microstructures is 
the adaptation of the electroless metal plating procedures that were 
developed for metalization of electrical insulators of the kind used as 
substrates in printed circuitry. For review of electroless metal plating 
procedures, see the article by C. R. Shipley, Jr., in "Plating And Surface 
Finishing", Vol. 71, pp 92-99, (1984). In the performance of an 
electroless metal plating procedure, the insulative surface of the 
substrate must be sensitized to enable plating to occur. A number of 
different procedures are known for sensitizing the surface of insulative 
substrates. Some of those procedures involve conditioning the surface by 
mechanical abrasion or by etching the surface with strong acids or bases. 
Most of the sensitizing procedures cannot be employed to sensitize lipids 
without damaging the lipid microstructures. 
In the practice of this invention, the lipid microstructures are sensitized 
by the attachment of a catalyst precursor to the surfaces of the lipid 
microstructures. That catalyst precursor preferably is palladium but can 
be of other materials, such as platinum or gold. More specifically, it is 
preferred to sensitize the lipid microstructure by attachment of a 
palladium/tin (Pd/Sn) colloidal catalyst precursor to the surface of the 
lipid microstructure. Once the catalytic precursor is attached to the 
lipid microstructure, the remainder of the electroless metal plating 
procedure is straightforward. 
The metal coatings produced by the procedures disclosed herein can consist, 
but are not limited to, electroless nickel and electroless copper. The 
nickel coat produced by an electroless Ni plating bath is actually an 
alloy of nickel and phosphorus of varying composition. An alkaline nickel 
plating bath produces a nickel alloy having approximately 3% phosphorus. 
That alloy has a dc electrical conductivity of between 1.0.times.10.sup.4 
and 1.7.times.10.sup.4 mho/cm and magnetic susceptibility of 30 oersteds. 
An acid electroless nickel plating bath produces a nickel alloy having 
approximately 12% phosphorus. The dc electrical conductivity of the high 
phosphorus content alloy is similar to that of the alloy of low phosphorus 
content, but the high phosphorus alloy is essentially non-magnetic as 
discussed in the above cited monograph of C. R. Shipley, Jr. 
The metal deposit produced by electroless copper plating bath is 
essentially entirely of elemental copper. The dc electrical conductivity 
of the copper metal deposit is 6.0.times.10.sup.5 mho/cm and is 
non-magnetic. 
The metal coatings produced on the lipid microstructures are reasonably 
uniform and continuous. The metal layers are of controllable thickness, 
typical ranging between about 20 nm to 100 nm. After the initial metal 
coat has been formed on the lipid microstructure, the coat can be covered 
with other materials (such as different metals) to increase its thickness 
or to alter its surface characteristics. The metalization procedures 
disclosed herein are substantially compatible with the chemical and 
mechanical constraints of the lipid microstructures so that the morphology 
of the microstructure is preserved. 
Advantages of the procedures disclosed herein are that they mainly involve 
inexpensive reagents and do not require complicated or expensive 
processing equipment. Further, the procedures present only minimum safety 
hazards inasmuch as they are principally concerned with agueous solutions 
and do not produce environmentally unacceptable residues or wastes. 
UTILITY OF METAL CLAD LIPID MICROSTRUCTURES 
Among the many ways of utilizing the metal clad microstructures, one of the 
most important is the use of the microstructures as electrical components 
in microcircuits that otherwise could not be built. The helical 
microstructures provide electrical inductors. The tubules can be used as 
capacitors by coating the inside and outside surfaces with metal. The 
tubules may serve as resistors or as low loss electrical connectors, 
depending upon the properties of the metal coated on the tubules. The 
microstructures can be utilized as adjuncts to semiconductor microcircuits 
in locations where it is difficult to provide inductance or capacitance. 
Nickel clad ferromagnetic tubules and tubules clad with other magnetic 
metals may be used in display devices by suspending the tubules n a medium 
that permits the tubules to turn under the control of a magnetic field. 
Copper clad tubules and tubules clad with other non-magnetic metals may be 
used in display devices by controlling the orientation of those tubules 
through fluid flow. The optically opaque tubules, for example, can be 
brought into alignment by a flowing fluid. 
The metal clad microstructures, particularly the tubules and helices, are 
useful in polymeric and other structural materials as replacements for or 
in addition to the glass fibers and graphite fibers now used as 
reinforcing materials. In such applications, the lightweight 
microstructures, especially the helices, can be effective in improving the 
mechanical properties of the composite material and the metal clad 
microstructures can provide electrical conductivity in the composite that 
is similar to the graphite's conductivity. 
Metals such as palladium, platinum, and nickel are well-known for their 
capacity to store molecular hydrogen in the form of metal hydrides. The 
high surface area to weight ratio of hollow nickel, platinum, and 
palladium clad tubules makes those tubules useful for the storage and safe 
transportation of hydrogen. 
Another way of usefully employing microstructures clad for example, with 
magnetic metals such as nickel or cobalt, is to implant those metal clad 
microstructures in tumors by injection through a needle or catheter or by 
drawing the microstructures to the desired site with a magnet that is 
outside the body. The minute size of the microstructures allows better 
control of the distribution of the magnetic material within the tumor than 
is feasible with the coarser magnetic particles now available. 
Hyperthermia can be induced in the tumor by employing an alternating 
magnetic field to produce eddy currents in the magnetic metal coated on 
the microstructures. Those eddy currents heat the metal and thereby enable 
localized heating of the tumor to therapeutic temperatures to occur. 
The foregoing only touches the myriad ways in which metal clad lipid 
microstructures can be usefully employed. 
The metal clad lipid microstructures can be produced by the procedures set 
forth in the following examples. 
EXAMPLE 1 
A dispersion of diacetylenic lipid vesicles in an agueous solution was 
prepared. Unpolymerized tubules at a concentration of 4 mg lipid/mL were 
thermally grown by raising the vesicular dispersion above the chain 
melting temperature of the diacetylenic lipids followed by slow cooling to 
just below that melting temperature. The average length of the tubules so 
produced was approximately thirty microns. XD2408 palladium chloride/tin 
chloride (Pd/Sn) colloidal activator (MacDermid Co., Waterbury, Conn.) was 
used as received. MaCuplex 9340 hypophosphite-reduced electroless nickel 
plating bath was made up from J-60 and J-61 concentrates as prescribed by 
the MacDermid Co. All solutions in this and other examples were prepared 
with distilled, deionized water. 
In a polypropylene centrifuge vial, approximately 1 mL of the agueous 
tubule dispersion was combined with an equal volume of the Pd/Sn colloid 
and gently mixed for two minutes. After centrifugation at 13,000 rpm for 
three minutes at room temperature, the supernatant liguid was drawn off 
and the compressed pellet of tubules was resuspended in clean water. At 
this point, the tubules were distinctly brown (the color of the colloid). 
No leaching of the brown color into the solution was observed, indicating 
strong binding of the colloid to the tubules. Thereafter, the colloid 
treated tubule suspension was mixed with a large excess of the previously 
prepared electroless nickel plating bath. After two minutes, rapid gas 
evolution was observed accompanied by a rapid change in the color of the 
dispersion from brown to black. It is known that hydrogen (H.sub.2) gas is 
produced when plating occurs in a nickel or copper plating electroless 
bath. The bubbles therefore indicated that nickel plating had occurred. 
The reaction was then quenched by repeated centrifugation and resuspension 
in clean water. 
The tubules were examined under a optical microscope with brightfield 
illumination. A dense, opaque, uniform black coating was observed on the 
surface of the tubules, indicative of an electroless nickel deposit. In 
contrast, the initial white lipid dispersion (i.e., the lipid dispersion 
before being mixed with the electroless plating solutions) is essentially 
invisible under brightfield illumination. The average length of the black 
coated tubules was approximately ten microns, considerably shorter than 
the typical distribution of lengths observed prior to metalization. The 
shorter length of the metal-coated tubules is attributed to the mechanical 
stress on the tubules from the centrifugation and resuspension procedures. 
The identity of the deposit as nickel was confirmed using a standard 
qualitative procedure. In that procedure, the metal coating was first 
leached from the tubules using concentrated nitric acid. The leach 
solution was then neutralized with sodium hydroxide to pH 7. Solid sodium 
dimethylglyoximate (dmg) was added to the neutralized solution until the 
solution became pink due to formation of nickel dimethylglyoximate, 
Ni(dmg).sub.2. 
The tubules were examined in a transmission electron microscope (TEM) both 
before and after the tubules were subjected to the electroless nickel 
plating bath. Before the tubules were plated with nickel, the TEM showed a 
relatively uniform attachment to the tubules of small, electron opaque 
particles. From the size of those particles (approximately 5nm to 25nm), 
it was concluded that the particles were colloidal Pd/Sn sensitizer 
particles that were bound to the lipid microstructure. After being 
subjected to the electroless plating bath, the nickel-plated tubules were 
observed to have an even, thin, fine grained metallic coating. 
The placement of a small (less than 10.sup.3 gauss) magnet in the vicinity 
of the nickel-coated tubules attracted the tubules to the magnet. The 
tubules quickly followed the movement of the magnet without a discernible 
time lag, thereby indicating that the metallic deposit on the tubules was 
ferromagnetic. 
EXAMPLE 2 
A dispersion of tubules, was prepared at a concentration of 0.7 mg/mL by 
the solvent growth method cited above. The procedure for coating the 
tubules with nickel was identical to that employed in Example 1 with the 
exception that solvent-grown, rather than thermally-grown, tubules were 
employed. As in Example 1, the electroless plating procedure produced a 
black dispersion. Optical and electron microscopy showed the presence of a 
thin, metallic coating on the surface of the tubules. 
EXAMPLE 3 
Some of the unused white, solvent grown umpolymerized tubules obtained at 
tee beginning of the Example 2 procedure were exposed to 
7.0.times.10.sup.6 rad of gamma radiation. That radiation initiated 
polymerization of the irradiated tubules and caused the dispersed tubules 
to turn red. The polymerized tubules were then subjected to the 
electroless nickel plating procedure of Example 1 (i.e. Pd/Sn colloid 
treatment followed by immersion in the electroless nickel plating bath). 
The red tubules turned brown after treatment with the Pd/Sn colloid and 
then turned black after being metal coated in the nickel plating bath. 
Examination of the black lipid microstructures by brightfield optical 
microscopy confirmed the presence of a black metallic coating over the 
lipid surfaces. By employing a small magnet as in Example 1, it was 
established that the metal coat was magnetic. 
EXAMPLE 4 
A sac of Spectrapor 12,000-14,000 molecular weight cut-off dialysis tubing 
(Spectrm Medical Industries, Los Angeles, Calif.) containing 1 mL of a 
solution of unpolymerized solvent-grown tubules (average length 40 to 200 
microns depending on batch) and 5 mL of XD 2408 Pd/Sn colloidal activator 
(MacDermid)was immersed in one liter of 0.1 M HCl and continuously stirred 
for four hours. The contents of the sac were then reduced to about 
one-fourth of its original volume by filtration through a 0.22 micron 
Millipore filter. The colloid treated tubules were then subjected to a 
Stabuff 500 (Stapleton Co., Long Beach, Calif.) electroless nickel plating 
bath which had been prepared as directed by the manufacturer. The plating 
reaction was quenched by pouring the tubule-nickel plating bath mixture 
into a large volume of water. The metal plated tubules wee then 
concentrated by filtration as above. 
Examination of the metal plated lipid tubules with an optical microscope 
showed the length distribution of those tubules to be centered about 30 to 
70 microns, depending on the starting batch. In contrast to the average 10 
micron length of the tubules obtained when centrifugation was used, the 
longer length of these tubules is attributed to the lower mechanical 
stress exerted on the tubules in the dialysis and filtration procedure. 
The dialysis and filtration procedure appears to be more effective than 
the centrifugation procedure in preserving the initial aspect ratio 
(length to radius) of the lipid microstructures. 
The nickel coated tubules were examined by X-ray fluorescence line scan in 
a scanning electron microscope (SEM) equipped with an energy dispersive 
X-ray spectrometer. The absence of electrical charging of the tubules in 
the electron beam indicated that the tubules were coated with an 
electrically conductive substance. The response of the X-ray emission line 
scan indicated that nickel was detected only when the electron beam moved 
across the metalized tubules. A back-scattered electron image of the 
nickel coated tubules indicated the presence on the microstructures of a 
uniform metal coat which was notable for its evenness. 
EXAMPLE 5 
A dispersion of unpolymerized tubules and helices was solvent grown in the 
manner previously described herein. Metex 9027 electroless copper plating 
bath wa prepared in accordance with the directions of the manufacturer 
(MacDermid Co.). 
Metalization of tubules and helices was accomplished using the Example 4 
procedure with substitution of the Metex 9027 copper plating bath for the 
nickel plating bath. After subjecting the colloid treated tubules and 
helices to the electroless copper plating bath for three minutes, gas 
bubbling became evident. The reaction was thereupon quenched as in the 
Example 4 procedure. 
The initially white dispersion of lipids had become copper-brown in color. 
Inspection by brightfield optical microscopy revealed the presence of a 
uniform, opaque coat on the surfaces of the tubular and helical 
microstructures. The thermal stability of the coated microstructures was 
investigated using an optical microscope with a hot stage attachment. The 
copper coated lipid microstructure remained intact when subjected for 20 
minutes or more to temperatures slightly above 40.degree. C. (The chain 
melting temperature for the DC.sub.23 PC lipid is 43.degree. C.) Even when 
subjected to a temperature of 210.degree. C. for two minutes, the copper 
coated lipid microstructures remained intact. 
When the metal coated microstructures were examined in the SEM, the 
secondary election image clearly showed the presence of a uniform metallic 
coat on both tubules and helices. Examination by X-ray fluorescence line 
scanning confirmed the presence of elemental copper on the 
microstructures. Back-scattered electron and specimen current maps were 
also used to establish the presence of a metallic coat on the 
microstructures. 
EXAMPLE 6 
Some of the nickel coated tubules obtained at the end of the Example 2 
procedure were immersed in the Metex 9027 electroless copper plating bath 
prepared in Example 5. The evolution of gas (H.sub.2) bubbles indicated 
the onset of copper deposition. The reaction was quenched and the tubules 
were concentrated by centrifugation as described in Example 1. 
Examination of the tubules by optical microscopy revealed the presence of 
both black (nickel) and brown (copper) on the same microstructure. X-ray 
fluorescence mapping of the microstructure surfaces, using the SEM, 
confirmed the presence of both copper and nickel on the microstructures. 
This experiment demonstrated the feasibility of using the initially 
metalized microstructures as substrates for subsequent processing. 
EXAMPLE 7 
Cataposit 44 Pd/Sn colloidal activator was prepared from Cataposit 44 
concentrate and solid Cataprep 404 in accordance with the directions of 
the manufacturer (Shipley Co., Newton, Mass.). An electroless copper 
plating bath was prepared from 328 A and 328Q stock solutions as 
prescribed by the Shipley Company which had supplied those materials. 
Metalization of a portion of the unused solvent-grown dispersion of tubules 
and helices obtained at the start of the Example 5 procedure was 
accomplished using a simulation of the Example 5 procedure with the 
substitution of the Shipley colloid and the Shipley copper plating bath 
for the MacDermid analogues. A plating of copper on the microstructures, 
similar to that produced in Example 5 was obtained. The presence of a 
metallic deposit on the microstructures was confirmed by optical and 
electron microscopy. 
EXAMPLE 8 
The Example 7 procedure for lipid microstructure metalization was employed 
using the MacDermid Metex 9027 electroless copper plating bath in place of 
the Shipley copper plating bath. Results similar to those produced by the 
Example 7 procedure were obtained. 
EXAMPLE 9 
The Example 7 procedure for metalization of lipid microstructures was 
employed using tubules formed from the diacetylenic lipid 
1,2-bis(heptacosa-8,10-diynoyl)-sn-glycero-3-phosphocholine in place of 
those prepared with the DC.sub.23 PC lipid. Copper deposition on the lipid 
microstructures was confirmed by brightfield optical microscopy. 
EXAMPLE 10 
Multilamellar vesicles were prepared as an agueous dispersion from 
hydrogenated soy lecithin (American Lecithin Co., Atlanta, Ga.). That 
substance is a non-diacetylenic phosphocholine lipid. The procedure for 
the preparation of that agueous dispersion is described in the previously 
cited article by Paul Yager and Paul E. Schoen published in 1984 in the 
"Journal of Molecular Crystals And Liguid Crystals", vol 106, pp 371-381. 
Those non diacetylenic lipid vesicles were metalized by the Example 1 
procedure. A grey black coating of nickel was produced on those lipid 
microstructures. The presence of the nickel coating was confirmed by 
examination of the grey-black microstructures under brightfield 
illumination with an optical microscope. 
EXAMPLE 11 
Some of the unused copper-plated tubules from Example 7 were dehydrated by 
exchanging into acetone. The metalized microstructures were allowed to 
settle to the bottom of the container, the agueous solution was pipetted 
off and the tubules resuspended in acetone. EPON 828 epoxy was prepared 
using a 1,3-diaminobenzene crosslinker as directed by the manufacturer 
(Shell Chemical Co.). A concentrated dispersion of the copper-coated 
tubules was added, with gentle mixing, to the epoxy, the ratio of tubules 
to epoxy was about 1% by volume. The resulting dark brown epoxy/tubule 
composite mixture was poured into a rectangular mold and the tubules were 
flow-aligned along the long axis of the mold. The composite was cured for 
24 hours while in a vacuum. The composite was sliced perpendicular to the 
long axis and then placed in an RF (radio frequency) plasma etcher so that 
the aligned tubules were oriented vertically. The composite was etched in 
an oxygen plasma for six hours to remove the epoxy from around the 
tubules. Examination by SEM (scanning electron microscope) revealed 
copper-coated tubules protruding vertically from the epoxy substrate. 
EXAMPLE 12 
Nickel-plated tubules were prepared as described in Example 4 with the 
exception that the J60/J61 electroless nickel plating bath (MacDermid Co.) 
was substituted for the Stabuff 500 bath, and that the time of exposure of 
the colloid treated tubules to the plating bath was varied from one to six 
minutes. The presence of a nickel coat on the tubules was confirmed by 
optical microscopy. 
EXAMPLE 13 
The nickel-coated tubules prepared at various plating times as described in 
Example 12 were dehydrated and embedded in epoxy according to the 
procedure of Example 11, with the exception that a flat-plate ceramic 
magnet was used to align the microstructures an the epoxy was cured at 
room temperature. The composites were sectioned, using a microtome, into 
40 nm thick slices, cut perpendicular to the axis of tubule alignment. 
Examination of the composites by SEM indicated that only tubules plated 
for more than about two minutes remained intact during the 
dehydration/embedding/ sectioning procedure. Cross-sectional views of the 
tubules showed metal coats on both the inner and outer surfaces of the 
cylinders. The thickness of the coats ranged between 17 nm and 45 nm, and 
increased monotonically with the plating time. Epoxy was clearly present 
throughout the interior of the tubules. 
Instead of employing an epoxy for the matrix, the tubules can be embedded 
in any of a wide variety of materials. Polyurethane, for example, is a 
suitable material for employment as the matrix for embedding the tubules. 
THE FLOW DIAGRAM 
Referring now to the FIG. 1 flow diagram, the procedure for producing metal 
clad lipid microstructures starts with the step of producing the lipid 
microstructures in forms which may be helical, tubular, or spheroidal. For 
simplicity the steps of washing, rinsing, and concentrating the lipid 
microstructures have been omitted from the flow diagram. Where it is 
desired to enhance the thermal, chemical or mechanical stability of the 
lipid, the lipid microstructures are irradiated with energy sufficient to 
cause polymerization of the lipids, such as by deep UV light, X-rays, 
gamma rays, or electrons. The lipid polymerization step is optional and 
may be skipped. By following the remaining steps, metal clad lipid 
microstructures will be produced. To indicate that the polymerization step 
is optional, that step is shown in FIG. 1 in a broken line box. Whether or 
not the optional step is used, the next step is to cause a catalyst 
precursor to be absorbed on the microstructures. Those microstructures are 
then subjected to the action of an electroless metal plating bath that 
deposits metal on the surfaces of the microstructures. 
In view of the obvious changes that can be made in the foregoing 
procedures, it is intended that the invention not be restricted to the 
precise examples here described. Rather, it is intended that the scope of 
the invention be construed in accordance with the appended claims, having 
due regard for changes that are obvious to those skilled in the metal 
plating art or in the associated field of surface chemistry.