Note: Descriptions are shown in the official language in which they were submitted.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
1
Silicon Structure
The present invention relates to a new silicon structure and a new process for
fabricating a
silicon structure. The silicon structure may comprise one or more hydrophilic
substances.
The invention also concerns a new process of fabricating macroporous silicon,
and a new
macroporous silicon product. The process for the fabrication of macroporous
silicon may
involve the consolidation of a silicon particulate product, followed by
anodisation of the
consolidated product. The resulting macroporous silicon product may comprise
macropores that are substantially surrounded by microporous and/or mesoporous
silicon.
Porous silicon has properties that allow it to be used for a variety of
medical uses. For
example it is a biocompatible and resorbable material as described in WO
9706101; it can
be used as a scaffold for the repair or replacement of damaged bone as
described in
WO 0195952; it can be used in dermatological compositions as described in
WO 0215863; it can be used to deliver beneficial substances such as drugs as
described
in WO 9953898; and it can be used in a variety of diagnostic devices as
described in
WO 03015636. The biological properties of porous silicon are often dependent
upon
porosity and pore size. Porous silicon has been formed that has a porosity as
low as 2%,
and in excess of 90%; it may be categorised by its pore size: microporous
silicon contains
pores having a diameter less than 20 A, mesoporous silicon contains pores
having a
diameter in the range 20 A to 500 A; and macroporous silicon contains pores
having a
diameter greater than 500 A.
The two main methods by which porous silicon can be fabricated are: by
anodisation, and
by stain etching. Anodisation typically involves the immersion of a solid
sample of silicon,
such as a bulk crystalline silicon wafer, in hydrofluoric acid solution. An
electrical contact is
made with the sample of silicon, a potential difference being applied between
the silicon
and a second electrode also placed in the solution. The HF etches the silicon
to create
pores and hence porous silicon is formed. Preferably the sample is
semiconducting
throughout its volume, to allow a uniform potential difference to be
established.
Stain etching involves the immersion of a silicon sample in a hydrofluoric
acid solution
containing a strong oxidising agent. No electrical contact is made with the
silicon, and no
potential is applied. The hydrofluoric acid etches the surface of the silicon
to create pores.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
2
The technique is commonly used to etch relatively small particles of silicon,
since it would
be difficult to attach an electrode to each small particle.
Anodisation and stain etching typically result in the formation of silicon -
hydrogen bonds
at the surface of the porous silicon, making it hydrophobic. Porous silicon
may be used to
deliver drugs to animal or human patients, and this hydrophobic nature can
make the
loading of hydrophilic drug into porous silicon problematic.
One of the main disadvantages of anodisation is its relatively low throughput
and hence
high cost. The use of an electrochemical cell reduces the speed at which
silicon can be
processed, hence increasing expense. Further, the silicon used for anodisation
is
preferably semiconducting throughout its volume, and this typically means that
relatively
expensive silicon wafers are employed.
Stain etching allows the use of particulate silicon that may be obtained at a
lower price
than silicon wafers, and does not involve the use of a time consuming
electrochemical
process.
However, it is easier to control the pore size and/or porosity of porous
silicon fabricated by
anodisation than by stain etch techniques.
The following documents provide background information that is relevant to the
present
application. US 5,164,138 describes a process for manufacturing an article
having particles
comprising a silicon based material; the particles are bonded to one another
by reaction
with a liquid agent. US 4,357,443 describes a process for producing a silicon
containing
article comprising the step of coating the particle with boron oxide. US
4,040,848 describes
a process for producing a polycrystalline silicon sintered body which
comprises the step of
forming a particulate mixture of silicon powder and boron. US 4,865,245
describes a
method of joining together two semiconductor devices, each having a number of
metallic
contacts. US 6,126,894 describes a method for producing a high density
sintered article
from iron-silicon alloys. US 4,818,482 describes a process for producing
workpieces
comprising water atomising a metal alloy. US 5,711,866 describes a process for
consolidating powders comprising the step of removing an oxide from the
surface of a
metal coated composite. US 6,057,469 describes a process for the preparation
of a silicon
powder comprising the step of grinding metallurgical grade silicon. US
4,040,848 describes
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
3
a process for producing a polycrystalline sintered body. WO 01/95952 describes
a fixitor,
which may be used for the repair of damaged bone, comprising porous silicon.
WO
03/101504 describes a method of preparing a scaffold from blocks comprising
porous
silicon. US 4,767,585 describes a process for producing moulded products from
granular
silicon. US 4,759,887 describes a process for manufacturing shaped products
from silicon
granules. JP 8109012 describes press moulding at high temperatures. "The
Compaction of
Oxidised Silicon Powder", by RG Stephen & FL Riley, Journal of European
Ceramic
Society 9, (1992) 301-307 describes the fabrication of silicon dioxide coated
silicon
particles that result in agglomeration. "Production of Polycrystalline Silicon
Sheets for
Photovoltaic applications by pressing and sintering of silicon powders" by A
Derbouz
Draoua et al describes the fabrication of wafers from silicon powder by
compaction and
heating at temperatures close to the melting point of silicon. "Semiconductor
Wafer
Bonding: Science and Technology", Wiley, New York, ISBN 0471574813, 1999,
describes
bonding two planar single crystal wafer surfaces.
It is an objective of the present invention to at least partly solve at least
some of the above
mentioned problems. It is a further objective of the present invention to
provide a process
that allows the low cost, rapid fabrication of porous silicon having a well
defined porosity
and pore size.
It is a yet further objective of the present invention to provide a method of
combining a
hydrophilic compound with porous silicon. It is an even further objective to
provide a new
method of drug loading by consolidation of a silicon particulate product and a
hydrophilic
drug.
According to one aspect the invention provides a process for fabricating a
silicon structure,
the process comprising the steps:
(a) taking a silicon particulate product comprising a multiplicity of free
silicon particles; and
(b) consolidating at least part of the silicon particulate product to form a
multiplicity of
bonded silicon particles, each bonded silicon particle being bonded to at
least one of the
other bonded silicon particles.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
4
The process may comprise the further step, performed between steps (a) and
(b), of
combining at least part of the silicon particulate product with a beneficial
substance. The
beneficial substance may be a hydrophilic compound.
At least one of the bonds formed between at least two of the bonded silicon
particles may
be a covalent Si-Si bond. At least some of the bonded silicon particles may be
Si-Si
covalently bonded. Step (b) may be performed in such a manner that a Si-Si
covalent bond
is formed between at least two of the silicon particles. Step (b) may be
performed such that
sufficient pressure is applied to at least part of the silicon particulate
product that a
multiplicity of bonded silicon particles are formed.
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed,
the silicon unitary body comprising at least some of the bonded silicon
particles.
Steps (a) and (b) may be performed in such a manner that the silicon unitary
body
comprises at least 10 bonded silicon particles. Steps (a) and (b) may be
performed in such
a manner that the silicon unitary body comprises at least 100 bonded silicon
particles.
Steps (a) and (b) may be performed in such a manner that the silicon unitary
body
comprises at least 1,000 bonded silicon particles. Steps (a) and (b) may be
performed in
such a manner that the silicon unitary body comprises between 10 and 1026
bonded silicon
particles. Steps (a) and (b) may be performed in such a manner that the
silicon unitary
body comprises between 104 and 1016 bonded silicon particles.
The unitary body may be porous, the pores being formed by interstices between
the
bonded silicon particles. This porosity may result in a relatively high
surface area.
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed
having a Fracture strength between 30 MPa and 7,000 MPa.
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed
having a Fracture strength between 70 MPa and 7,000 MPa.
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed
having a Fracture strength between 40 MPa and 250 MPa.
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed
having a Fracture strength between 50 MPa and 150 MPa.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
Steps (a) and (b) may be performed in such a manner that a silicon unitary
body is formed
having an electrical resistivity, measured across its longest dimension,
between 10 Kncm
and 10"50cm. Steps (a) and (b) may be performed in such a manner that a
silicon unitary
body is formed having an electrical resistivity, measured across its longest
dimension,
5 between 10 K S2cm and 200 K S2cm. Steps (a) and (b) may be performed in such
a manner
that a silicon unitary body is formed having an electrical resistivity,
measured across its
longest dimension, between 10 K i2cm and 60 K S2cm.
The formation of silicon - silicon covalent bonds between the bonded silicon
particles may
result in the unitary body having a relatively high mechanical strength and
low electrical
resistivity.
In general, the electrical resistivity of the bond formed between two bonded
silicon particles
will be higher than that of the silicon from which either of the particles is
formed. The
unitary body is therefore likely to have an electrical resistivity that is
significantly higher
than the silicon from which each particle is formed. The greater then number
of bonds, the
greater the resistivity, when calculated from the resistance of the unitary
body across its
largest dimension.
Steps (a) and (b) may be performed in such a manner that each of the bonded
silicon
particles from which the unitary body is formed, are integral with each of the
other bonded
silicon particles from which the silicon unitary body is formed.
The process may comprise the further step (r) of chemically reducing part of
the silicon
particulate product. The step (r) may be performed prior to step (b). The step
(r) may
comprise the step of substantially removing silicon oxide from at least part
of the surface of
the free silicon particles. The step (r) may comprise the step of treating at
least some of
the free silicon particles with a reducing agent. The step (r) may comprise
the step of
treating at least some of the free silicon particles with a reducing agent
selected from one
or more of: NaOH, KOH, and HF. The step (r) may comprise the step of treating
at least
some of the free silicon particles with a solution of hydrofluoric acid, the
solution being
selected from one or more of aqueous HF solution, ethanolic HF solution,
methanolic HF
solution, and ethanoic HF solution. The step (r) may comprise the step of
treating at least
some of the free silicon particles with HF vapour. The step (r) may be
performed in such a
manner that Si-H bonds are formed at the surface of at least some of the free
silicon
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
6
particles. The step (r) may be performed in such a manner that Si-H bonds are
formed at
the surface of most of the free silicon particles.
The treatment of the free silicon particles with hydrofluoric acid is
advantageous because it
results in the formation of free silicon particles having a surface that is at
least partly
hydrogen terminated, and because it at least partly removes any oxygen atoms
that were
bonded to the surface of the free silicon particles.
It has been discovered that the presence of oxygen atoms at the surface of the
free silicon
particles makes it more difficult to consolidate the silicon particulate
product. In other words
the presence of oxygen bonded to the surface of the silicon makes it more
difficult to form
Si-Si covalent bonds between the bonded silicon particles. The presence of
oxygen
reduces the stability of the unitary body in solutions of HF, making it more
likely to
fragment. Surface oxide may also increase the electrical resistivity of the
unitary body.
The presence of the hydrogen atoms at the surface of the free silicon
particles is also
advantageous, because this helps to prevent oxygen re-bonding to the silicon
surface prior
to consolidation.
The consolidation of a silicon particulate product comprising surface Si-H
bonds may result
in the formation of silane. The method may comprise the further step (h) of
detecting silane
gas resulting from the formation of bonded silicon particles. The formation of
silane
provides evidence of Si - H bond breaking and Si - Si bond formation.
Step (b) may comprise the step (p) of applying pressure to at least some of
the free silicon
particles.
Step (b) may comprise the steps: (ci) of placing at least some of the free
silicon particles in
a container; and (di) reducing the volume of the container.
Step (ci) and step (di) may be performed in such a manner that pressure is
applied to at
least some of the free silicon particles contained in the container.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
7
The step (b) may comprise the steps: placing at least some of the free silicon
particles in a
container, and applying a uniaxial pressure or isostatic pressure to the free
silicon particles
contained in the container.
The step (b) may comprise the steps: placing at least some of the free silicon
particles in a
container, and applying an isostatic pressure or isostatic pressure to the
free silicon
particles contained in the container.
The uniaxial pressure may be between 5,000 MPa and 50 MPa.
The uniaxial pressure may be between 1,000 MPa and 100 MPa.
The uniaxial pressure may be between 1,000 MPa and 200 MPa.
The uniaxial pressure may be between 750 MPa and 200 MPa.
The uniaxial pressure may be between 500 MPa and 10 MPa.
The isostatic pressure may be between 5,000 MPa and 50 MPa.
The isostatic pressure may be between 1,000 MPa and 100 MPa.
The isostatic pressure may be between 1,000 MPa and 200 MPa.
The isostatic pressure may be between 750 MPa and 200 MPa.
The isostatic pressure may be between 500 MPa and 10 MPa.
.20
Step (b) may comprise the steps: (cii) of placing at least some of the free
silicon particles
in a volume enclosed by at least part of a mould; and (dii) reducing the
enclosed volume.
Step (cii) and step (dii) may be performed in such a manner that pressure is
applied to at
least some of the free silicon particles contained in the mould.
The silicon particulate product may comprise semiconducting silicon. The
particulate silicon
product may comprise one or more of: polycrystalline silicon, amorphous
silicon, bulk
crystalline silicon, and metallurgical grade silicon. The silicon particulate
product may
comprise silicon particles prepared by chemical vapour deposition. The silicon
particulate
product may comprise hydrogen terminated silicon particles, each hydrogen
terminated
particle comprising semiconducting silicon and surface Si - H bonds. The
silicon
particulate product may comprise oxygen terminated silicon particles, each
oxygen
terminated particle comprising semiconducting silicon and surface Si - 0
bonds.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
8
For the purposes of this specification metallurgical grade silicon is silicon
that has been
produced by the reduction of silica by carbon in an arc furnace at a
temperature between
1500 C and 2500 C, has a purity in the range 95 to 99.9%.
At least some of the free silicon particles may comprise semiconducting
silicon. At least
some of the free silicon particles may comprise one or more of:
polycrystalline silicon,
amorphous silicon, bulk crystalline silicon, and metallurgical grade silicon.
At least some of
the free silicon particles may comprise silicon prepared by chemical vapour
deposition.
The silicon particulate product may comprise porous silicon. At least some of
the free
silicon particles may comprise porous silicon. Each of the free silicon
particles may
comprise porous silicon.
The consolidation of the silicon particulate product may result in a porous
unitary body, the
pores being formed from the spaces between the bonded silicon particles.
However, the
free silicon particles may themselves be porous prior to consolidation. For
example the free
silicon particles may have been porosified by stain etching.
The silicon particulate product may comprise one or more of the following
elements: Y, P,
Sb, In, Fe, As, La, Ca, Pd, Sr, I, Co, Ir, B, Ge, Cu, Pb, Sn, and Au. At least
some of the
free silicon particles may comprise one or more of the following elements: Y,
P, Sb, In, Fe,
As, La, Ca, Pd, Sr, I, Co, Ir, B, Ge, Cu, Pb, Sn, and Au.
Preferably the silicon particulate product may comprise one or more of the
following
elements: Y, B, P, and Sn. Preferably at least some of the free silicon
particles may
comprise one or more of the following elements: Y, B, P, and Sn.
The process may comprise the further step (e) of porosifying at least part of
the silicon
unitary body. The process may comprise the further step (e) of porosifying at
least part of
the silicon unitary body by anodising the silicon unitary body in a solution
of hydrofluoric
acid. The process may comprise the further step (e) of porosifying at least
part of the
silicon unitary body by anodising the silicon unitary body in a solution of
hydrofluoric acid,
the solution comprising a surfactant. The surfactant may comprise one or more
of: ethanol,
methanol, acetic acid, a cationic surfactant, an anionic surfactant.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
9
The addition of a surfactant to the HF acid solution may improve the wetting
of the silicon
unitary body by the HF solution.
The step (e) may comprise the step of allowing a solution of HF to enter the
pores of the
unitary body, the pores being formed by the spaces between the bonded silicon
particles
from which the unitary body is formed.
For porosification of the unitary body by anodisation to be effective, the
unitary body must
have a sufficiently high electrical conductivity, and must have sufficient
structural stability
1o when immersed in a solution of HF. The unitary body may be formed from a
very large
number of free silicon particles, and therefore the required stability and
conductivity may
only be achieved by forming a correspondingly large number of bonds between
the silicon
particles. The strength of the bonds formed and degree of contact between the
bonded
silicon particles will also affect the success of the anodisation process.
The use of a surfactant may assist the ingress of the hydrofluoric acid
solution into pores
located between the bonded silicon particles.
The process may comprise the further step (e) of porosifying at least part of
the silicon
unitary body by stain etching the silicon unitary body in a solution of
hydrofluoric acid.
The step (e) may be preceded by the step of attaching at least one electrode
to the silicon
unitary body.
The unitary body may comprise a plurality of macropores, each pore being
formed at least
partly by the interstices between the bonded silicon particles. The mean size
of the
macropores contained in the unitary body may have a size between 500 A and 200
microns.
The unitary body may comprise a plurality of pores, each pore being formed at
least partly
by the interstices between the bonded silicon particles. The unitary body may
comprise a
multiplicity of nanoparticles, the mean size of the pores contained in the
unitary body may
have a size between 50 A and 1 micron.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
The step (e) may comprise the step of allowing a solution of hydrofluoric acid
to pass into
at least one of the pores of the unitary body. The step (e) may comprise the
step of
allowing a solution of hydrofluoric acid to pass into substantially all the
pores of the unitary
body. The step (e) may comprise the step of allowing a solution of
hydrofluoric acid to pass
5 into some of the pores of the unitary body.
The step (e) may be performed in such a manner that at least one of the bonded
silicon
particles is porosified throughout its volume. The step (e) may be performed
in such a
manner that at least one of the bonded silicon particles is porosified through
substantially
10 its whole volume. The step (e) may be performed in such a manner that
substantially each
of the bonded silicon particles is porosified through substantially its whole
volume.
The fabrication of a macroporous silicon unitary body in this way, allows the
anodisation of
a relatively inexpensive silicon particulate product, such as metallurgical
grade silicon. The
silicon particulate product is consolidated to form a unitary body that has
sufficient
mechanical strength and size to allow the attachment of an electrode, and
hence
anodisation. The macroporous silicon body has a high surface area so that the
yield of
porous silicon is high relative to the amount of silicon used.
The step (e) may be performed in such a manner that microporous silicon and/or
mesoporous silicon is formed from the silicon unitary body.
The unitary body may already be porous, as a result of pores formed from the
spaces
between the bonded silicon particles and/or as a result of the particulate
product
comprising free porous silicon particles, before step (e) is performed.
The process may comprise the further step (g), performed after step (e), of
fragmenting
the silicon unitary body. The step (g) may comprise the step of mechanically
crushing the
unitary body. The step (g) may comprise the step of ultrasonically fragmenting
the unitary
body. The step (g) may be performed in such a manner that a multiplicity of
partially
surface porous silicon particles are generated, the surface of each partially
surface porous
particle comprising a porous area and a non-porous area.
A method that comprises the steps (e) and (g) allows the formation of small
anodised
porous silicon particles, that could not be fabricated by other prior art
methods.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
11
Each bonded silicon particle is bonded to at least one other bonded silicon
particles, the
bond or bonds may be formed by applying pressure to two or more free silicon
particles.
The silicon unitary body may comprise a first silicon bonded particle and a
second silicon
bonded particle. The first and second bonded silicon particles may be integral
with each
other without being in direct contact with each other. In other words the
first and second
bonded silicon particles may be connected by an intermediate bonded silicon
particle(s).
Step (b) may comprise the step (h) of heating the silicon particulate product.
Step (b) may
comprise the step of heating the silicon particulate product to a temperature
between 50 C
and 500 C. The step (b) may comprise the step of maintaining the silicon
particulate
product at a substantially constant temperature.
The step (b) may be performed at a temperature between -5 'C and + 5 C for an
interval
of time between 1 second and 1 hour. The step (b) may comprise the step of
maintaining
the silicon particulate product at a temperature between -20 C and + 20 C
for an interval
of time between 0.1 seconds and 1 hour. The step (b) may be performed at a
temperature
between -50 C and + 50 C for between 1 minute and 10 hours.
The step (p) of applying a pressure to at least some of the free silicon
particles may
precede the step (h) of heating the silicon particulate product.
The step (b) may comprise the step of cold pressing at least part of the
silicon particulate
product.
Steps (a) and (b) may be performed in such a manner that the silicon unitary
body has a
surface area greater than or equal to 10 cm2 per gram of silicon. Steps (a)
and (b) may be
performed in such a manner that the silicon unitary body has a surface area
greater than
or equal to 100 cmZ per gram of silicon. Steps (a) and (b) may be performed in
such a
manner that the silicon unitary body has a surface area greater than or equal
to 1,000 cmZ
per gram of silicon.
The surface area of a silicon unitary body formed by a cold pressing technique
may be
high, relative to that of a silicon unitary body formed by a hot pressing
technique. This is
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
12
because hot pressing can result in rearrangement of the surface silicon atoms,
causing
cavities and defects to be removed.
The process may further comprise the step (i) of introducing a gas to a region
in which at
least some of the free silicon particles are located; the gas may comprise one
or more of:
nitrogen, helium, argon, and hydrogen.
The process may comprise the step (v) of removing a gas from a region in which
at least
some of the free silicon particles are located. The process may comprise the
step of
removing a gas from a region in which at least some of the free silicon
particles are located
in such a manner that the pressure is reduced to less than 1 mm Hg.
The step (b) may be performed in an inert atmosphere or in an atmosphere
comprising H2
gas. The inert atmosphere may comprise a noble gas such as argon.
The step (b) and/or the step (h) may be performed after and/or during the step
(i) and/or
(v).
The process may comprise the step, performed between steps (a) and (b), of
combining
the silicon particulate product with a beneficial substance, steps (a) and (b)
being
performed in such a manner that the beneficial substance is located in the
pores between
the bonded silicon particles.
By, at least partly, trapping the beneficial substance within the consolidated
product formed
by steps (a) and (b), the release of the substance may be controlled. The
process is
therefore of particular value in the fabrication of pharmaceutical products
comprising
hydrophilic drugs, for which controlled release in physiological environments
may be
required. The fabrication of the bonded silicon particles from free porous
silicon particles
may be advantageous, since this may help to trap the beneficial substance in
the pores
formed by the bonded silicon particles.
The beneficial substance may comprise a hydrophilic compound. The beneficial
substance
may comprise a multiplicity of beneficial substance molecules, each beneficial
substance
molecule having greater than 100 atoms. The beneficial substance may comprise
a
hydrophilic compound. The beneficial substance may comprise a multiplicity of
beneficial
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
13
substance molecules, each beneficial substance molecule having greater than
1000
atoms. The beneficial substance may comprise a hydrophilic compound. The
beneficial
substance may comprise a multiplicity of beneficial substance molecules, each
beneficial
substance molecule having between 100 and 5,000 atoms.
The step of combining the beneficial substance with the silicon particulate
product may
comprise the step of contacting at least part of the silicon particulate
product with one or
more of: beneficial substance vapour, beneficial substance gas, liquid
beneficial
substance, solid beneficial substance, and a solution of a beneficial
substance.
The process may comprise the further step of fragmenting the consolidated
product
formed by steps (a) and (b).
For the purposes of this specification a "beneficial substance" is something,
which when
administered to a human or animal subject, is beneficial overall: it could be
a toxin, toxic to
undesirable cells/to interfere with an undesirable physiological process. For
example,
anti-cancer substances would be considered "beneficial", even though their aim
is to kill
cancer cells.
The silicon particulate product may have a mean particle size betweenl x 10"4
and 1 x 10"2
microns. The silicon particulate product may have a mean particle size between
1 x 10"3
and I x 10"2 microns. The silicon particulate product may have a mean particle
size
between 2 x 10"3 and 1 x 10-2 microns.
The silicon particulate product may have a mean particle size between 0.01
microns and
5 mm. The silicon particulate product may have a mean particle size betweenl
micron and
500 microns. The silicon particulate product may have a mean particle size
between I
micron and 1 mm. The silicon particulate product may have a mean particle size
between
1 nm and 150 microns.
At least one tenth of the free silicon particles from which the silicon
particulate product is
formed may each have a largest dimension between I x 10"4 and 1 x 10"2
microns. At least
one tenth of the free silicon particles from which the silicon particulate
product is formed
may each have a largest dimension between 1 micron and 500 microns.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
14
According to a further aspect the invention provides a process for fabricating
a silicon
structure comprising silicon and a beneficial substance, the process
comprising the steps:
(a) combining a silicon particulate product, comprising a multiplicity of
silicon particles, with
a beneficial substance; and
(b) consolidating at least part of the silicon particulate product and at
least part of the
beneficial substance to form a silicon structure comprising silicon and a
beneficial
substance.
The silicon structure may comprise a unitary body, the unitary body comprising
at least part
of the beneficial substance, and at least part of the silicon particulate
product.
The method may comprise the further step of fragmenting the unitary body from
which the
silicon structure is at least partly formed.
The silicon particulate product may comprise one or more of porous silicon,
polycrystalline
silicon, bulk crystalline silicon, amorphous silicon, and metallurgical grade
silicon. The
silicon particulate product may comprise stain etched porous silicon and/or
anodised
porous silicon. The silicon particulate product may comprise silicon prepared
by chemical
vapour deposition.
The porous silicon may comprise one or more of: microporous silicon,
macroporous silicon,
and mesoporous silicon.
The beneficial substance may comprise a hydrophilic compound. The beneficial
substance
may comprise other drugs that are difficult to introduce into the pores of
porous silicon by
prior art methods. The beneficial substance may comprise a hydrophilic
compound. The
beneficial substance may comprise a multiplicity of beneficial substance
molecule, each
beneficial substance molecule having greater than 100 atoms. The beneficial
substance
may comprise a hydrophilic compound. The beneficial substance may comprise a
multiplicity of beneficial substance molecule, each beneficial substance
molecule having
greater than 1000 atoms. The beneficial substance may comprise a hydrophilic
compound.
The beneficial substance may comprise a multiplicity of beneficial substance
molecule,
each beneficial substance molecule having between 100 and 5,000 atoms.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
The step (a) may comprise the step of contacting at least part of the silicon
particulate
product with one or more of: beneficial substance vapour, beneficial substance
gas, liquid
beneficial substance, a solution of a beneficial substance.
5
Step (b) may comprise the steps: (ci) of placing at least some of the silicon
particles and at
least some of the beneficial substance in a container; and (di) reducing the
volume of the
container.
10 Step (ci) and step (di) may be performed in such a manner that pressure is
applied to at
least some of the free silicon particles, and to at least some of the
beneficial substance,
contained in the container.
The step (b) may comprise the steps: placing the silicon particulate product
and the
15 beneficial substance into a container, and applying a uniaxial pressure to
at least some of
the beneficial substance, and at least some of the silicon particulate product
in the
container.
The uniaxial pressure may be between 5,000 MPa and 50 MPa.
2o The uniaxial pressure may be between 1,000 MPa and 100 MPa.
The uniaxial pressure may be between 1,000 MPa and 200 MPa.
The uniaxial pressure may be between 750 MPa and 200 MPa.
The uniaxial pressure may be between 500 MPa and 10 MPa.
Step (b) may comprise the steps: (cii) placing at least some of the silicon
particles and at
least some of the beneficial substance in a volume enclosed by at least part
of a mould;
and (dii) reducing the enclosed volume.
Step (cii) and step (dii) may be performed in such a manner that pressure is
applied to at
least some of the silicon particles contained in the mould and at least some
of the
beneficial substance contained in the mould.
The silicon structure may form at least part of a medical device.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
16
The step (b) may comprise the step of maintaining the silicon particulate
product and the
beneficial substance at a temperature between -5 C and + 5 C for an interval
of time
between 1 second and 1 hour. The step (b) may comprise the step of maintaining
the
silicon particulate product and the beneficial substance at a temperature
between -20 C
and + 20 C for an interval of time between 0.1 seconds and 10 hours. The step
(b) may
comprise the step of maintaining the silicon particulate product at a
temperature between -
50 C and + 50 C for between 1 minute and 1 hour.
According to a further aspect the invention provides a process for fabricating
a silicon
structure comprising the step of sandwiching a beneficial substance between at
least two
silicon layers to form the structure.
The beneficial substance may comprise a hydrophilic compound. The beneficial
substance
may comprise a multiplicity of beneficial substance molecule, each beneficial
substance
molecule having greater than 100 atoms. The beneficial substance may comprise
a
hydrophilic compound. The beneficial substance may comprise a multiplicity of
beneficial
substance molecule, each beneficial substance molecule having greater than
1000 atoms.
The beneficial substance may comprise a hydrophilic compound. The beneficial
substance
may comprise a multiplicity of beneficial substance molecule, each beneficial
substance
molecule having between 100 and 5,000 atoms.
The silicon particulate product may comprise one or more of porous silicon,
polycrystalline
silicon, bulk crystalline silicon, amorphous silicon, and metallurgical grade
silicon. The
silicon particulate product may comprise stain etched porous silicon and/or
anodised
porous silicon. The silicon particulate product may comprise silicon prepared
by chemical
vapour deposition.
At least one of the silicon layers may comprise a porous silicon membrane. At
least one of
the silicon layers may comprise a porous silicon membrane having a largest
dimension
between 0.5mm and 20mm. At least one of the silicon layers may be
substantially planar.
At least one of the silicon layers may be substantially spherical. The
beneficial substance
may comprise one or more layers.
The porous silicon may comprise one or more of: microporous silicon,
macroporous silicon,
and mesoprous silicon.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
17
The method may further comprise the step of applying a sealant substance to at
least part
of the surface of the silicon structure. The method may comprise the further
step of
applying a sealant substance to at least part of the silicon structure, in
such a manner that
egress of the beneficial substance, other than that resulting from erosion of
the porous
silicon or from diffusion through the pores of the porous silicon, is
substantially prevented
when the silicon structure is placed in a physiological electrolyte.
The step of sandwiching the beneficial substance may comprise the step of
mechanically
contacting the beneficial substance with at least part of said at least two
silicon layers. The
step of sandwiching the beneficial substance may comprise the step of applying
pressure
to both or each of the layers in such a manner that the beneficial substance
contacts at
least part of both or each of the layers.
By stacking alternating layers of silicon and a beneficial substance and
optionally applying
a sealant to the edges of the sandwich structure, a variety of configurations
may be
achieved. This allows greater control over the loading and release of a
beneficial
substance, and is of particular value with regard to loading of hydrophilic
substances.
Release of the beneficial substance, when the structure is immersed in a
physiological
environment, may occur as a result of diffusion through macropores formed by
contact
between the silicon layers; alternatively it may occur as a result of
diffusion through, or
erosion of, the silicon layer.
The method may comprise the further step of fragmenting the sandwich
structure.
According to a further aspect the invention provides a product obtainable by a
process as
defined in any of the above aspects.
According to a further aspect, the invention provides a silicon unitary body
comprising a
silicon skeleton.
The silicon unitary body may further comprise macroporous silicon having a
mean pore
size between 500 A and 200 microns; and microporous silicon and/or mesoporous
silicon.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
18
The silicon unitary body may further comprise macroporous silicon having a
mean pore
size between 500 A and 10 microns; and microporous silicon and/or mesoporous
silicon.
The silicon unitary body may further comprise macroporous silicon having a
mean pore
size between 1 micron and 100 microns; and microporous silicon and/or
mesoporous
silicon.
The silicon unitary body may have a largest dimension between 1 mm and 5 cm.
The
silicon unitary body may have a largest dimension between 1 cm and 50 cm.
The at least 0.1 la of the surface silicon atoms of the unitary body may each
be bonded to
a hydrogen atom. The at least 1% of the surface silicon atoms of the unitary
body may
each be bonded to a hydrogen atom. The at least 10% of the surface silicon
atoms of the
unitary body may each be bonded to a hydrogen atom.
The silicon unitary body may have a surface area between 10 cmZ and 200 cm2
per gram
of silicon. The silicon unitary body may have a surface area between 50 cm2
and 500 cm2
per gram of silicon. The silicon unitary body may have a surface area between
10 cmZ and
10,000 cm2 per gram of silicon.
At least one tenth of the boned silicon particles, from which the silicon
unitary body is
formed, may each have a largest dimension between 0.01 microns and 500
microns.
At least one tenth of the bonded silicon particles, from which the silicon
unitary body is
formed, may each have a largest dimension between 1 nm and 10 microns.
The silicon unitary body may comprise bonded silicon particles having a mean
particle size
between 0.01 microns and 5 mm. The silicon unitary body may comprise bonded
silicon
particles having a mean particle size between 1 micron and 500 microns. The
silicon
unitary body may comprise bonded silicon particles having a mean particle size
between 1
micron and 1 mm. The silicon unitary body may comprise bonded silicon
particles having a
mean particle size between 1 nm and 150 microns.
The silicon unitary body may comprise bonded silicon nanoparticles, having
largest
dimension in the range 1 to 50 nm, it may comprise micro and/or mesopores,
formed by
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
19
the spaces between the bonded nanoparticies, and may be resorbable in
physiological
environments.
The silicon unitary body may further comprise microporous silicon having a
mean pore size
between I x 10-4 and 1 x 10"2 microns, the micropores being formed by the
spaces
between the silicon particles.
The silicon unitary body may further comprise microporous silicon having a
mean pore size
between 1 x 10"3 and 1 x 10"2 microns.
The silicon unitary body may further comprise microporous silicon having a
mean pore size
between 2 x 10-3 and 1 x 10"2 microns.
For the purposes of this specification an interconnected macropore is a
macropore that is
connected to at least one other macropore by one or more mesopores and/or one
or more
micropores.
The unitary body may comprise at least one interconnected macropore, the
unitary body
may comprise at least ten interconnected macropores. The unitary body may
comprise at
least 100 interconnected macropores. The unitary body may comprise at least
1,000
interconnected macropores.
The unitary body may comprise at least one interconnected macropore per 10
adjacent
macropores. The unitary body may comprise at least one interconnected
macropore per
100 adjacent macropores. The unitary body may comprise at least one
interconnected
macropore per 1,000 adjacent macropores.
At least one of the macropores may be defined by at least part of a
microporous surface
and/or mesoporous silicon surface. At least some of the macropores may be
defined by at
least part of the microporous silicon surface and/or mesoprorous silicon
surface. Each of
the macropores may be defined by at least part of the microporous silicon
surface and/or
mesoprorous silicon surface.
At least some of the macropores may be formed in at least part of the silicon
skeleton, and
the or part of the silicon skeleton from which the macropores are formed may
comprise at
least part of the microporous silicon and/or mesoporous silicon.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
The silicon unitary body may have an electrical resistivity, when measured
across its
longest dimension, between 10 KQcm and 10"50cm The silicon unitary body may
have an
electrical resistivity, when measured across its longest dimension, between 10
K i2cm and
5 250 KDcm. The silicon unitary body may have an electrical resistivity, when
measured
across its longest dimension, between 10 K S2cm and 100 K f2cm.
The silicon unitary body may have a fracture strength between 30 MPa and 1,000
MPa.
The silicon unitary body may have a fracture strength between 70 MPa and 7,000
MPa.
10 The silicon unitary body may have a fracture strength between 40 MPa and
250 MPa.
The silicon unitary body may have a fracture strength between 50 MPa and 150
MPa.
The silicon unitary body may comprise one or more of the following elements:
Y, P, Sb, In,
Fe, As, La, Ca, Pd, Sr, I, Co, Ir, B, Ge, Cu, Pb, Sn, and Au. The silicon
unitary body may
15 comprise one or more of the following isotopes: 90Y 32P, 124Sb 1141n 59Fe,
76As, 140 La, 47Ca,
103Pd' 89Sr, 1311, 1251, 60CO, 192 lr, 12B,10B 71Ge, 64Cu 203Pb and 198Au.
The silicon unitary body may form at least part of a cancer treatment device
comprising a
radionucleotide and/or a cyotoxic agent for use in the treatment of cancer.
The silicon unitary body may form at least part of a cancer treatment device
comprising a
radionucleotide selected from one or more of the following radionucleotides
90Y, 32P, 124Sb,
114In, 59Fe, 76AS, 140 La, 47Ca, 103Pd, 89Sr, 1311, 1251, 60CO' 1921r,
1213,1013 71Ge 64Cu 203 Pb and
198Au for use in the treatment of cancer.
The silicon unitary body may form at least part of a cancer treatment drug
delivery device
comprising a cytotoxic agent selected from one or more of: an alkylating agent
such as
chlorambucil, a cytotoxic antibody such as doxorubicin, an antimetabolite such
as
fluorouracil, a vinca alkaloid such as vinblastine, a hormonal regulator such
as GNRH, and
a platinum compound such as cis platin.
The silicon unitary body may form at least part of a drug delivery device
comprising a
beneficial substance. The silicon unitary body may form at least part of a
drug delivery
device comprising a hydrophilic beneficial substance.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
21
The silicon unitary body may form at least part of a cancer treatment device
having one or
more of the following radionucleotides 90Y, 32P, 124Sb, 1141n, 59Fe,76As, 140
La, 47Ca, 103Pd,
89Sr, 1311, 1251, 60CO 192ir 12B 71Ge, 64Cu, 203Pb and 198Au for use in the
treatment of one or
more of the following cancers: prostate cancer, liver cancer, pancreatic
cancer, breast
cancer, lung cancer, brain cancer, and testicular cancer.
The unitary body may form at least part of an orthopaedic scaffold for use in
the repair or
replacement of bone. The unitary body may form at least part of a tissue
engineering
scaffold for use in the repair or replacement of soft tissue.
The silicon unitary body may comprise semiconducting silicon. At least some of
the free
silicon particles may comprise one or more of: polycrystalline silicon,
amorphous silicon,
bulk crystalline silicon, and metallurgical grade silicon.
The silicon skeleton may comprise a multiplicity of bonded silicon particles,
each bonded
silicon particle being bonded to at least one of the other bonded silicon
particles.
At least some of the bonded silicon particles may comprise one or more of
macroporous
silicon, mesoporous silicon, and microporous silicon.
The silicon unitary body may form at least part of a drug delivery implant
comprising a
beneficial substance and a binder substance, the binder substance having a
structure and
composition such that it binds at least part of the beneficial substance to at
least part of the
silicon skeleton.
The silicon unitary body may form at least part of a drug delivery implant
comprising a
beneficial substance and a fragmenting substance, the fragmenting substance
having a
structure and composition such that, when immersed in a physiological
electrolyte, reacts
with the electrolyte to release a gas.
According to a further aspect the invention provides a composite unitary body
comprising a
composite skeleton, the composite skeleton comprising silicon and a beneficial
substance.
The silicon particulate product may comprise one or more of porous silicon,
polycrystalline
silicon, bulk crystalline silicon, amorphous silicon, and metallurgical grade
silicon. The
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
22
silicon particulate product may comprise stain etched porous silicon and/or
anodised
porous silicon.
The silicon particulate product may comprise one or more of: microporous
silicon,
macroporous silicon, and mesoporous silicon.
The beneficial substance may comprise a hydrophilic compound.
The composite unitary body may comprise a plurality of macropores. The mean
size of the
macropores contained in the unitary body may have a size between 50 A and 200
microns.
The composite unitary body may form part of a pharmaceutical product for the
delivery of
the beneficial substance to an animal or human subject. The unitary body may
form part of
an implant for the delivery of the beneficial substance to an animal or human
subject.
The composite unitary body may form at least part of a pharmaceutical product
comprising
a beneficial substance and a binder substance, the binder substance having a
structure
and composition such that it binds at least part of the beneficial substance
to at least part
of the silicon.
The composite unitary body may form at least part of a pharmaceutical product
comprising
a beneficial substance and a fragmenting substance having a structure and
composition
such that, when immersed in a physiological electrolyte, reacts with the
electrolyte.
According to a further aspect the invention provides a multilayer silicon
structure
comprising two or more silicon layers, and one or more beneficial substance
layers, the
beneficial substance being sandwiched between the or at least two of the
silicon layers.
The multilayer structure may comprise alternating layers of beneficial
substance and
silicon.
The beneficial substance may comprise a hydrophilic compound.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
23
The silicon, from which both or each of the silicon layers is formed, may
comprise one or
more of: porous silicon, polycrystalline silicon, amorphous silicon, and bulk
crystalline
silicon.
At least one of the silicon layers may comprise a porous silicon membrane. The
or at least
one of the silicon membranes may have a largest dimension between 0.5mm and
20mm.
At least one of the silicon layers may be substantially planar. At least one
of the silicon
layers may be substantially spherical. The beneficial substance may comprise
two or more
layers.
The porous silicon may comprise one or more of: microporous silicon,
macroporous silicon,
and mesoprous silicon.
The silicon structure may comprise a sealant substance that is in contact with
at least part
of said at least two silicon layers. The silicon structure may comprise a
sealant substance
that is in contact with at least part of said at least two silicon layers in
such a manner that
egress of the beneficial substance, other than that resulting from erosion of
the porous
silicon or from diffusion through the pores of the porous silicon, is
substantially prevented
when the pharmaceutical product is placed in a physiological electrolyte.
According to a further aspect the invention provides a partially surface
porous silicon
particulate product comprising a multiplicity of partially surface porous
silicon particles, the
surface of each partially surface porous particle comprising a porous area and
a non-
porous area.
At least one of the partially surface porous silicon particles may have at
least two discrete
non-porous areas. At least some of the partially porous silicon particles may
each have two
or more discrete non-porous areas.
At least one of the partially surface porous silicon particles may comprise a
first non-
porous area and a second non-porous area, the first and second non-porous area
being
spatially separate from each other by a porous area.
The partially surface porous silicon particulate product may comprise at least
100 partially
surface porous silicon particles. The partially surface porous silicon
particulate product may
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
24
comprise between 100 and 1026 partially surface porous silicon particles. The
partially
surface porous silicon particulate product may comprise between 100 and 106
partially
surface porous silicon particles. The partially surface porous silicon
particulate product may
comprise between 100 and 103 partially surface porous silicon particles.
Substantially each partially surface porous silicon particle may have a size
between 0.5
microns and 200 microns.
Between 10% and 90% of all of the partially surface porous silicon particles
may have a
size between 1 and 150 microns.
At least one of the partially surface porous silicon particles may comprise
one or more of
the following elements: Y, P, Sb, In, Fe, As, La, Ca, Pd, Sr, I, Co, Ir, B,
Ge, Cu, Pb, Sn,
and Au. At least one of the partially surface porous silicon particles may
comprise one or
more of the following isotopes: 90Y, 32P' 124Sb, 1141n, 59Fe, 76As, 140 La 47
Ca, 103Pd, 89Sr, 1311,
1251, 60Co, 192ir' 126' 10671Ge' 6a'.uI 203Pb and 198Au.
The partially surface porous silicon particulate product may comprise one or
more of the
following elements: Y, P, Sb, In, Fe, As, La, Ca, Pd, Sr, I, Co, Ir, B, Ge,
Cu, Pb, Sn, and
Au. The partially surface porous silicon particulate product may comprise one
or more of
the following isotopes:90Y, 32P, 124Sb, 1141n, 59Fe,76AS, 140La, 47Ca, 103Pd,
89Sr, 1311, 1251'
60C0' 1921r' 12B,1oB 71Ge, 64Cu 203Pb and 1saAu.
At least one of the partially surface porous silicon particles may be bonded
to one or more
of the other partially surface porous silicon particles from which the
particulate product is
formed.
At least one of the partially surface porous silicon particles may be
covalently bonded to
one or more of the other partially surface porous silicon particles from which
the particulate
product is formed.
According to a further aspect the invention provides a silicon structure, as
defined in any of
the above aspects, for use as a medicament.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
According to a further aspect the invention provides a unitary body, as
defined in any of the
above aspects, for use as a medicament.
According to a further aspect the invention provides a fragmented silicon
unitary body, as
5 defined in any of the above aspects, for use as a medicament.
According to a further aspect the invention provides metallurgical grade
silicon for use as a
medicament. The metallurgical grade silicon may comprise calcium and/or iron.
The
metallurgical grade silicon may comprise calcium, the molar concentration of
the calcium
10 being grater than that of any other impurity contained in the silicon. The
metallurgical grade
silicon may comprise iron, the molar concentration of the iron being greater
than that of
any other impurity contained in the silicon. The metallurgical grade silicon
may comprise a
toxic component selected from one or more of: arsenic, cadmium, lead, and
mercury. The
toxic component preferably has a concentration less than 10ppm. The
metallurgical grade
15 silicon may comprise aluminium; the aluminium may be present at a
concentration less
than 1,000 ppm.
The invention will now be described, by way of example only, with reference to
the
following drawings:
Figure 1 shows the variation of the release of neutral red with time, measured
in days,
from a silicon structure according to the present invention;
Figure 2 shows the effect of pre-loading neutral red on the rate of release
from a silicon
structure according to the present invention;
Figure 3 shows the variation of accumulative concentration of Interferon gamma
with
time, measured in days, from a silicon structure according to the present
invention;
Figure 4 shows the variation of the accumulative concentration of Placental
alkaline
phosphate with time, measured in days, from a silicon structure according to
the present invention;
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
26
Figure 5 shows SEM images of a porous silicon membrane after it has been
immersed
in Trizma buffer for an interval of several days;
Figure 6a shows a photograph of a first cold pressing device used to fabricate
a silicon
unitary body according to the present invention;
Figure 6b shows a photograph of some of the components from which the figure
6a first
cold pressing device is formed;
Figure 7a shows a SEM micrograph of part of a silicon unitary body according
to the
invention;
Figure 7b shows a SEM micrograph, of part of the same silicon unitary body
shown in
figure 7a, at a higher magnification;
Figure 8'shows a photograph of the components of a second cold pressing device
used
to fabricate a silicon unitary body according to the present invention, the
second cold pressing device comprises a 5mm die 81;
2o Figure 9 shows a silicon unitary body fabricated using the second cold
pressing device,
the components of which are shown in figure 8;
Figure 10 shows a porosified surface of part of a silicon anodised unitary
body according
to the invention; and
Figure 11 shows the porosified surface shown in figure 10 at higher
magnification.
The following description is divided into two sections. The first provides an
account of the
combination of silicon with a beneficial substance, particularly by
consolidation of a silicon
particulate product. The second contains a disclosure of silicon consolidation
and
anodisation of the resulting silicon unitary body.
(I) Silicon structure comprising a beneficial substance
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
27
Approximately 5 mg of neutral red, which is a hydrophilic dye, was mixed with
60 mg of a
silicon particulate product, and the mixture was consolidated by loading it
into a clamped
stainless steel press having two interlocking halves. Pressure was applied to
the mixture
by means of the press for 20 seconds. This method of consolidation will be
referred to as
Method A. Three different mixtures were prepared using particulate products
comprising
stain etched porous, anodised porous, and polycrystalline silicon. The three
consolidated
samples were then immersed in a Trizma buffer, and the release of the dye was
determined by measuring the change absorbance at 573 nm. The results,
presented in
figure 1, show that the use of anodised porous silicon gives the slowest rate
of release,
labelled AN, that of stain etched porous silicon gives an intermediate rate of
release,
labelled SE, and that of polycrystalline silicon gives a relatively fast
release, labelled
PolySi. These results are particularly relevant to drug delivery, because they
show that the
rate of drug release may be controlled, by varying the form of silicon used.
Figures 2 (a) and (b) show the accumulative release of neutral red from
anodised porous
silicon and stain etched porous silicon respectively.
The results labelled 2ai are for stain etched porous silicon and neutral red
mixture that was
been consolidated by method A. The results labelled 2aii are for stain etched
porous silicon
that was preloaded with neutral red by rotary evaporation or freeze drying
before
compression by method A. The results show that preloading provides better
sustainable
release over a 7 day dissolution period relative to the un-preloaded sample.
Similar results
are shown in figure 2(b); those labelled 2bi are for an anodised porous
silicon and neutral
red mixture silicon that has been consolidated by method A, and those labelled
2bii are for
anodised porous silicon that has been preloaded with neutral red before method
A
consolidation.
Similar experiments were performed by replacing the neutral red with:
Placental alkaline
phosphate (PLAP) and Interferon gamma (y-IFN). Figure 3 shows the accumulative
release of y-IFN using anodised porous silicon which has been pre-loaded by
freeze-
drying. The sample was recovered at the termination of the 4 day study,
crushed, and
release was again measured for the crushed sample. A further 3% of the
remaining y-IFN
was released after crushing.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
28
Figure 4 shows the release of PLAP from samples prepared using method A from
anodised (plot 4a) and from stain etched (plot 4b) porous silicon.
Accumulative release
was measured by the pNP method. Over 3 days there was approximately a 20%
release of
PLAP.
Similar experiments were also performed using neutral red compressed between
two
porous silicon membranes. Sealant was applied to the edges of the sample so
that release
of the neutral red was predominantly through the pores of the porous silicon,
or as a result
of erosion of the porous silicon. Figures 5 (a) and (b) show SEM images of the
porous
silicon membrane after immersion for several days in the Trizma buffer
solution. The
results show that the pore size of the membrane have been enlarged as a result
of
dissolution, which, it is believed, enhances the rate of diffusion of the dye
through the
membrane.
(II) Silicon structure, and anodised silicon structure
A silicon particulate product having a mean particle size between 1 and 50
microns was
treated with 40 wt %(w/w) aqueous hydrofluoric acid to remove surface oxide
present from
the silicon product, and to create a hydrogen terminated surface. The silicon
particulate
product may comprise metallurgical grade silicon particles, that has been
heavily p+ or n+
doped.
The hydrofluoric acid was removed from the silicon particulate product by
washing with
deionised water before rapid drying on filter paper in air for 15 minutes. The
particles were
then rapidly loaded into a stainless steel cold pressing device 1, which is
shown in Figure
6a. The drying and loading steps were carried out as quickly as possible to
minimise or
prevent reaction with oxygen, and to retain the hydrogen terminated
particulate surface.
An estimated uniaxial pressure of between 1,000 and 5,000 psi may then applied
by
means of the cold pressing device 1, the temperature of the silicon
particulate product may
be maintained at 20 C. The resulting silicon unitary body may have the form of
a cylindrical
consolidated macroporous silicon block having a diameter of 5 mm and a length
of 46 mm.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
29
A small opening was formed in cold pressing device to allow gas produced
during the
pressing process to escape. Figure 6b shows components, generally indicated by
2, of the
stainless cold pressing device.
Figure 7a shows a SEM micrograph of part of a silicon unitary body 3 according
to the
invention. The silicon body is in the form of a cylindrical unitary body. The
figure 7a image
shows a fracture surface 4 at which the cylinder has been broken to more
clearly show the
macroporous nature of the unitary body. Figure 7b shows a higher magnification
SEM
micrograph, of the macroporous fracture surface 4.
An electrode may be attached to the silicon unitary body, and it may then be
immersed in
10-40 wt % (w/w) aqueous hydrofluoric acid with a surfactant such as ethanol,
and a
current density of between I mAcm"2 and 10 Acm"a, measured with respect to the
external
surface area of the block, the current may be passed for between 1 to 200
minutes.
The hydrofluoric acid may pass into the macroporous network of the silicon
block,
anodisation resulting in the formation of a porous layer on the interior
surfaces of the
macropores, and on the external surface of the silicon block.
Once anodisation is complete, the block may be washed, by repeated immersion
in
deionised water or methanol, and then air dried.
Finally, if a silicon particulate product is required, the block may be
mechanically crushed
to yield a multiplicity of partially surface porous silicon particles. Each
partially surface
porous particle having a non-porous surface area, corresponding to the region
that bonded
it to an adjacent silicon particle when still located in the unitary body.
A unitary silicon body according to the invention may be used as a scaffold to
provide
protection for, or to assist, the regrowth of damaged or diseased tissue. A
unitary body
3o having an appropriate size and shape is placed in the region in which
tissue re-growth is to
occur. Macropores, having a size between 10, 000 pm2 and 62, 500 iam2, formed
in the
unitary body allow the tissue to pass through the silicon scaffold. The
scaffold may also
comprise mesporous silicon, which may be engineered to erode once tissue
growth is
complete. This process is described in WO 0195952, which is herein
incorporated by
reference in its entirety.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
Five examples will now be given which describe the consolidation of a variety
of silicon
particulate products under a variety of conditions. Examples 4 and 5 describe
the
treatment of the silicon particulate product with an aqueous solution of HF
prior to
5 consolidation. Details of this HF pre-treatment, and details of the
consolidation process,
are both given in separate sections that follow the five examples.
Example 1
1o An experiment was performed on a first silicon particulate product
comprising silicon kerf,
having a particle size between 6 and 30 microns, which had been obtained by
sawing
multi-crystalline silicon ingots. The particulate product comprising the kerf
was compressed
uni-axially at a pressure less than 1000 MPa under vacuum at 293 K, in the 5mm
diameter
hardened stainless steel die 81, shown in figure 8, using a hydraulic press.
The consolidation of the particulate product resulted in the formation of a
silicon unitary
body, in the form of a pellet. However, when the process was repeated at an
increased
pressure of 1000 MPa, it was not possible to form a single unitary body from
the particulate
product. This shows that it is possible to apply too much pressure to the
particulate
product, which can result in fracture of or damage to the unitary body upon
removal from
the die.
Example 2
A second silicon particulate product comprising metallurgical grade silicon
having a particle
size in the range 32 to 125 microns, which has been surface oxidised, was
compressed
uni-axially at 250 MPa, in the 5mm die 81, to form a single silicon unitary
body, in the form
of a pellet. Shortly after removal from the die 81, the unitary body was
immersed a solution
comprising equal volumes of ethanol and 40% w/w aqueous HF. After 5 seconds in
the
solution, the unitary body disintegrated.
This experiment showed that bonding between the silicon particles is possible,
even in the
presence of the native surface silicon oxide, however, the bonds exhibit
relatively poor
resistance to HF. It follows that the presence of surface oxide would be
disadvantageous
for the purposes of anodisation.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
31
Example 3
A silicon particulate product comprising silicon particles, comprising surface
Si-H bonds,
and having a size in the range 0.005 to 0.5 microns, were uni-axially
compressed in the 5
mm die 81 at a pressure of 500 MPa. The resulting silicon unitary body, in the
form of a
pellet, was immersed in a solution comprising equal volumes of ethanol and 40%
w/w
aqueous HF. The silicon body was stable in the solution for 30 minutes.
This shows that the presence of surface Si-H bonds in the particulate product,
allows the
formation of a greater number of silicon - silicon bonds between the silicon
particles when
compressed, and that the bonds are more resistant to HF. This property should
facilitate
anodisation, and porosification, of the unitary body.
Example 4
A silicon particulate product comprising metallurgical grade silicon, having
particles sizes
between 32 and 125 microns, and comprising surface native silicon oxide, was
treated with
aqueous HF solution for ten minutes, washed in deionised water for ten
minutes, before
being air dried on filter paper for ten minutes. 100 mg of the resulting dried
powder were
transferred to the 5 mm die 81 and compressed uni-axially under vacuum at 1000
MPa.
Small amounts of silane gas were detected when the compacted pellet was
removed from
the die 81. The density of the resulting silicon unitary body, in the form of
a pellet, was 73%
of solid non-porous metallurgical grade silicon. The electrical resistance of
the silicon
unitary body, combined with that of the electrical contacts, was 80,000 ohms.
After 16 days
exposure to air, the unitary body was immersed in a solution comprising equal
volumes of
ethanol and 40% (w/w) aqueous HF. The unitary body was stable in the solution
for 20
minutes.
This result contrasts with that of example 2 and shows the effectiveness of
the HF pre-
treatment to replace the surface silicon oxide with Si-H bonds. The
application of a uni-
axial pressure causes consolidation of the silicon particulate product, the Si-
H bonds are
broken and replaced by Si-Si covalent bonds between adjacent silicon
particles. The
release of silane is a by-product of the unitary body formation, resulting
from hydrolysis of
the silicon - hydrogen surface.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
32
Example 5
A silicon particulate product comprising metallurgical grade silicon, having
particles sizes
between 32 and 125 microns, and comprising a native surface silicon oxide
layer, was
treated in aqueous HF solution for 10 minutes, washed in de-ionised water for
10 minutes,
and air dried on filter paper for 10 minutes, before rapid transfer of the
dried particulate
product to the 5mm die 81. A 750 MPa uni-axial pressure was applied to
consolidate a
silicon particulate product, a silicon unitary body in the form of a pellet
being formed, the
pellet having a mass of 100 mg. The porosity of the unitary body was
approximately 30%.
A platinum base was place in electrical contact, using silver paste, with the
lower surface of
the silicon unitary body. Approximately 1 ml droplet of electrolyte comprising
equal
volumes of ethanol and 40% (w/w) aqueous HF was dispensed onto the upper
surface of
the silicon pellet with a pipette. A thin platinum wire was then lowered into
the electrolyte
drop, and a 12 to 15 volt potential difference was applied, resulting in a
current flow of
30mA for 20 seconds. The HF droplet gradually reduced in volume as a result of
the
combined effect of evaporation from the electrical heating and penetration
into the pores of
the pellet. SEM images, shown in figures 10 and 11, of the surface of the
anodised pellet
revealed that the bonded silicon particles had been porosified, mesopores
being formed.
Consolidation procedure
Figure 8 shows a photograph of the components of a second cold pressing device
used to
fabricate a silicon unitary body according to the present invention, the
second cold
pressing device comprises a 5mm diameter die 81, and one moveable plunger 82
formed
both from hardened stainless steel. The die 81 is designed so that it may be
evacuated.
Typically 100 mg of a silicon particulate product was loaded into the 5mm die
81. The die is
then placed between the platens of a ten tonne laboratory press (not shown in
the figures)
having a digital pressure display accurate to 0.1 tonne. A vacuum line (not
shown in the
figures) was connected to the die, and the die was evacuated to a pressure of
approximately 104 Torr. An axial pressure between 50 and 1000 MPa was then
applied to
the silicon particulate product for five minutes. The vacuum line was then
removed, and the
axial pressure was removed from the resulting silicon unitary body 91, shown
in figure 9.
CA 02564591 2006-10-24
WO 2005/113467 PCT/GB2005/001910
33
before its removal from the die. A silane sensor was positioned over the
unitary body as it
was removed.
HF Pre-treatment
The silicon particulate product was placed in a beaker containing 100 ml 40%
(w/w) and
ml ethanol for ten minutes, the mixture being agitated occasionally. The
presence of the
ethanol was required to enable wetting of the silicon particles. As much of
the solution as
possible was then decanted, to leave the particulate product in the beaker.
The beaker
10 was then filled with 100 ml of de-ionised water and ethanol, before pouring
the mixture into
a drying vessel attached to a Buckner pump. The excess solution was removed,
through a
PTFE membrane, as a result of the pressure difference. The remaining silicon
particulate
product was rinsed with fresh water or ethanol, and an HF detector was used to
ensure
that substantially no residual HF remained. The Buckner pump was then
dismantled and
the PTFE membrane, on which the particulate product remained, was removed. The
membrane was then placed on filter paper, so that the particulate product
contacted the
filter paper, and was peeled back to leave the silicon powder. Filter paper
was used to
remove much of the liquid, before leaving the powder in air for ten minutes to
dry. The time
taken between the initial decanting of the HF solution to the start of the air
drying
procedure was typically 10 minutes, so that the total time for the complete
procedure is 30
minutes (10 minutes treatment with ethanoic HF, 10 minutes washing with water,
and 10
minutes air drying).
