U.S. patent application number 11/632849 was filed with the patent office on 2008-10-02 for molded body, method for producing the body and use thereof.
This patent application is currently assigned to FORSCHUNGSZENTRUM KARLSRUHE GMBH. Invention is credited to Stefan Giselbrecht, Christina Trautmann, Roman Truckenmuller.
Application Number | 20080241502 11/632849 |
Document ID | / |
Family ID | 34971894 |
Filed Date | 2008-10-02 |
United States Patent
Application |
20080241502 |
Kind Code |
A1 |
Giselbrecht; Stefan ; et
al. |
October 2, 2008 |
Molded Body, Method For Producing the Body and Use Thereof
Abstract
A molded body comprises a film with a film thickness D ranging
from 1 .mu.m to 1000 .mu.m, with at least one hollow structure
configured into the film. Each hollow structure has an outside
diameter d equal to at least double value of film thickness D, a
height h is equal to or less than double the value of the outside
diameter d, a wall thickness b greater than 0.02 times the film
thickness D and less than or equal to the film thickness D and a
local curvature radius r greater than 0.2 times and less than or
equal to 5 times the wall thickness b. The film and the hollow
structure include a plurality of pores.
Inventors: |
Giselbrecht; Stefan;
(Karlsruhe, DE) ; Truckenmuller; Roman; (Flein,
DE) ; Trautmann; Christina; (Darmstadt, DE) |
Correspondence
Address: |
VENABLE LLP
P.O. BOX 34385
WASHINGTON
DC
20043-9998
US
|
Assignee: |
FORSCHUNGSZENTRUM KARLSRUHE
GMBH
Karlsruhe
DE
|
Family ID: |
34971894 |
Appl. No.: |
11/632849 |
Filed: |
June 30, 2005 |
PCT Filed: |
June 30, 2005 |
PCT NO: |
PCT/EP05/07043 |
371 Date: |
January 19, 2007 |
Current U.S.
Class: |
428/313.5 ;
264/424 |
Current CPC
Class: |
B29C 2793/0045 20130101;
B01D 71/50 20130101; Y10T 428/249972 20150401; B29C 2035/0872
20130101; B26F 1/31 20130101; B29L 2031/755 20130101; B29C 2059/023
20130101; B29C 59/022 20130101; B29C 35/08 20130101; B01D 67/0032
20130101; B01D 2323/34 20130101; B01D 69/02 20130101 |
Class at
Publication: |
428/313.5 ;
264/424 |
International
Class: |
B32B 3/28 20060101
B32B003/28 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 21, 2004 |
DE |
10 2004 035 267.4 |
Claims
1. A molded body, comprising a film with a film thickness D ranging
from 1 .mu.m to 100 .mu.m, at least one hollow structure configured
in the film and having: an outside diameter d equal to at least
double a value of the film thickness D a height h equal to or less
than double the value of the outside diameter d, a wall thickness b
greater than 0.02 times the film thickness D and less than or equal
to the film thickness D and a local curvature radius r greater than
0.2 times and less than or equal to 5 times the wall thickness b,
and wherein the film and the at least one hollow structure comprise
a plurality of pores.
2. The molded body according to claim 1, wherein the at least one
hollow structure is provided with an undercut.
3. The molded body according to claim 1, wherein the pores have a
diameter .delta. from about 10 nm to about 10 .mu.m.
4. The molded body according to claim 1, wherein the pores are
statistically distributed across the film and the hollow
structure.
5. The molded body according to claim 1, wherein the film a
thermoplastic plastic.
6. The molded body according to claim 5, wherein the thermoplastic
plastic includes at least one of polymethylmethacrylate (PMMA),
polycarbonate (PC), polyethylene-terephthalate (PET), polystyrene
(PS), polyimide (PI), polypropylene (PP), polyvinylidenefluoride
(PVDF), or cycloolefin copolymer (COC).
7. The molded body according to claim 1, wherein the at least one
hollow structure includes a plurality of hollow structures wherein
adjacent hollow structures are spaced by a distance g that
corresponds at least to the outside diameter d of the hollow
structure.
8. The molded body according to claim 7, wherein the hollow
structures are arranged in a row.
9. The molded body according to claim 7, wherein the hollow
structures are distributed across the film.
10. The molded body according to claim 9, wherein the hollow
structures are at least one of arranged in rows and columns or
staggered.
11. The molded body according to claim 7, wherein the molded body
is singly or spirally rolled up and the hollow structures are
directed toward the inside or the outside.
12. A molded body according to claim 7, which is folded or has a
corrugated shape.
13. An arrangement of molded bodies each according to claim 7
wherein the molded bodies are arranged at least one of
side-by-side, one above another, or nestled into each other.
14. A method for producing a molded body, said method comprising:
providing a film comprising a thermoplastic plastic; irradiating of
the film with ionizing radiation, to produce irradiated regions in
the film; thermally reshaping the film into a molded body, wherein
a temperature of the thermal reshaping remains below the melting
temperature for the thermoplastic plastic; removing the irradiated
regions, to create pores in the molded body, and removing the
molded body from a mold.
15. The method according to claim 14, wherein the film is
irradiated through a mask.
16. The method according to claim 15, wherein the film is
irradiated with heavy ions.
17. The method according to claim 16, wherein the heavy ions have a
prespecified energy above 0.1 MeV/nucleon.
18. The method according to claim 14, wherein the irradiated
regions are removed via a wet-chemical etching process.
19. At least one of a filter or an atomizer including the molded
body of claim 1.
20. A housing for micro-structured components including the molded
body of claim 1.
21. A method for immobilizing inorganic or organic molecules,
bio-molecules, prokaryotic or eukaryotic cells comprising utilizing
the molded body of claim 1.
22. A method for cultivating prokaryotic or eukaryotic cells
comprising utilizing the molded body of claim 1.
23. At least one of a biosensor or a bio-reactor including the
molded body of claim 1.
Description
[0001] The invention relates to a molded body into which at least
one hollow structure is configured, wherein the film and the at
least one hollow structure contain a plurality of pores. The
invention furthermore relates to a method for producing the molded
body and the use thereof.
[0002] Commonly used methods for producing micro-perforated films
(membranes) are based either on directed physical processes such as
the ion-trace technology, the laser micro-perforation, or the
lithography, on special precipitation methods such as the phase
inversion, or on drawing processes. Whereas the latter two
processes are primarily used for producing flat micro-filtration
and ultra-filtration membranes, the directed physical processes are
generally used for the micro-perforation of micro-structures. In
combination with technical micro-structuring processes, such as the
micro injection-molding or the hot stamping, however, these
processes can be used only with already existing three-dimensional
microstructures.
[0003] To be sure, perforating all sides of a microstructure of
this type by turning and rotating the structure is conceivable in
principle, for example when subjecting it to radiation, but can be
realized only at high expense and only with individual,
free-standing structures. In the case of several adjacent
structures (structure array), at most a micro-perforation that is
perpendicular or at a slight angle to the structural plane is
possible.
[0004] Starting from this point, it is the object of the present
invention to propose a molded body, a method for producing said
body and the use thereof, which do not have the aforementioned
disadvantages and limitations. In particular, it is the object to
provide a molded body with three-dimensional, thin-walled hollow
structures of polymer that are perforated on all sides and have a
defined pore size between 10 nm and 10 .mu.m.
[0005] For the molded body, this object is solved with the features
disclosed in claim 1, for the method it is solved with the method
steps disclosed in claim 14, and for the use by the claims 19 to
23. The dependent claims respectively describe advantageous
embodiments of the invention.
[0006] A molded body according to the invention consists of a film
(membrane) having a film thickness D ranging from 1 .mu.m to 1000
.mu.m, preferably from 10 .mu.m to 100 .mu.m, wherein the film
thickness advantageously remains nearly constant over large areas
(several square meters). The film itself advantageously consists of
a thermoplastic plastic material, preferably polymethylmethacrylate
(PMMA), polycarbonate (PC), polyethyleneterephthalate (PET),
polystyrene (PS), polyimide (PI), polypropylene (PP),
polyvinylidenefluoride (PVDF), or cycloolefin copolymer (COC).
[0007] At least one hollow structure (cavity) is configured into
the film, wherein the geometric dimensions of said structure are
expressed with the following values: [0008] The outside diameter d
of the hollow structure has a value that is at least double the
value of the film thickness D:
[0008] d.gtoreq.2*D (1) and especially preferred is at least three
times the value of the film thickness D. [0009] The height h
(depending on the view, it may be the depth) of the hollow
structure is at most double the value of the outside diameter
d:
[0009] h:d.ltoreq.2:1 (2) [0010] The wall strength (wall thickness)
b of the hollow structure is approximately the same or is lower by
one order of magnitude than the film thickness D, meaning it
assumes a value between 0.02 times the film thickness D and the
film thickness D:
[0010] 0.02*D.ltoreq.b.ltoreq.D (3) [0011] The value for the local
curvature radius r of the hollow structure is on the order of
magnitude of the respective local wall thickness b, meaning it has
a value between 0.2 times and 5 times the wall thickness b:
[0011] 0.2*b.ltoreq.r.ltoreq.5*b (4)
[0012] According to one preferred embodiment, the hollow structure
is provided with an undercut and consequently assumes the
cross-sectional form of a .OMEGA. structure. In cases where the
values for the film thickness D, the outside diameter d of the
hollow structure, and the height h of the hollow structure is the
same--wherein the equation (1) must still be met--this results in a
.OMEGA. structure with distinctive distribution function for the
wall thickness b.
[0013] Several hollow structures, preferably a plurality of hollow
structures, are configured into the film, wherein the respective
value for the distance g between these structures corresponds at
least to the outside diameter d of the respective hollow
structures:
g.gtoreq.d (5)
[0014] This lower limit for the spacing (minimum distance)
essentially follows from the mechanical resistance of the reshaping
tool for the film. Depending on the type of material and the
production method, extremely narrow webs having a width of a few
micrometers, which are still stable with respect to the shaping
operation, can thus be produced.
[0015] Finally, the molded body, meaning the film and the hollow
structures, contains a plurality of pores for which the respective
diameter .delta. preferably has a value between 10 nm and 10 .mu.m.
It is preferable if the pores are distributed statistically across
the complete molded body, meaning the film as well as the hollow
structures, wherein it is possible for individual pores to overlap.
According to one alternative embodiment, the pores are distributed
in an orderly arrangement and with a spacing .beta. across the film
and the hollow structures.
[0016] A molded body according to the invention can be produced
with the following method steps. According to method step a), a
film is initially provided with a thickness between 1 .mu.m and
1000 .mu.m, preferably between 10 .mu.m and 100 .mu.m, wherein this
film advantageously consists of polymethylmethacrylate (PMMA),
polycarbonate (PC), polyethyleneterephthalate (PET), polystyrene
(PS), polyimide (PI), polypropylene (PP), polyvinylidenefluoride
(PVDF), or cycloolefin copolymer (COC).
[0017] The film is subsequently irradiated with ionizing radiation,
as specified in method step b), such that irradiated regions are
created within the film. Heavy ions are preferably used for
irradiating the film, for example ions of the type
.sup.132Xe.sup.21+. The specific energy should be selected at least
high enough to ensure the penetration of the film. The fluence of
the heavy ions is selected such that it can be used to adjust the
average pore density per surface area. The heavy ions preferably
have a specific energy above 0.1 MeV/nucleon.
[0018] An approximately 90.degree. angle is advantageously used for
irradiating the film surface, meaning the film is positioned
substantially perpendicular to the direction of the heavy ion beam.
Any other type of ionizing radiation, which allows configuring
regions in the film that are removed during a later processing step
as pores of a suitable size, can be used in place of the heavy
ions. In addition, masks can also be used for irradiating the film,
so as to produce locally delimited areas and/or regions of
perforation, which are to be dissolved out completely.
[0019] It is critical for the method according to the invention
that the film is reshaped thermally into a molded body during the
following method step c), for example by using the process known as
micro-thermoforming. During the thermoforming process, the film is
reshaped in an entropy-elastic phase and not in a melting phase of
the plastic, so that the correlation between the radiation dose and
the irradiated location is not lost. It is important that the
temperature remains in the range of softening temperature
(glass-transition temperature) for the thermoplastic plastic,
meaning below its melting temperature, to avoid a healing of the
traces and/or a blurring of the locally deposited dose. This goal
is reached with the comparably low reshaping temperature and the
short reshaping duration.
[0020] The method according to the invention is based on inserting
the intermediate technical step of reshaping through
micro-structuring between the step of irradiating the polymer
substrate and the processing step that would normally follow it.
Critical for the proposed method is the thermoforming of a locally
modified polymer material with the aid of ionizing radiation to
allow a later removal of these regions to generate perforated or
net-type thin-walled three-dimensional hollow structures.
[0021] In order to perforate the side walls and the bottom of
thin-walled, three-dimensional micro cavities, a flat semi-finished
technical film is subjected to an ionizing radiation, preferably
with ionizing particles. In contrast to the traditional method for
producing perforated membranes, the irradiated film with the
existing latent traces is therefore micro-structured before (!) the
pores are generated by means of etching and then dissolving.
[0022] For this type of reshaping, micro-technical processes can be
used for which the polymer does not transition to a liquid-melt
phase since all traces are otherwise healed and/or a blurring of
the locally deposited dose occurs. Micro-thermoforming, however, is
a micro-technical process with an entropy-elastic state during the
forming process, so that the material cohesion of the polymer is
ensured since the thermoplastic material is deformed only in the
range immediately surrounding its plasticizing temperature.
[0023] In the same was as for the macroscopic thermoforming,
thermoplastic semi-finished products are spatially drawn in a
negative form in order to thin the wall thickness. By drawing the
thermoplastic materials, the applied traces are retained per se,
but change their position relative to each other, corresponding to
the respective local drawing, meaning the trace density per surface
unit decreases with increasing drawing.
[0024] Following the three-dimensional micro structuring through
micro-thermoforming of the thermoplastic film, which continues to
be closed, the irradiated regions can then be freely etched and/or
dissolved with a suitable substance because of their changed
physical properties, as disclosed in method step d). As a result,
pores are formed in the molded body, which preferably have a
diameter .delta. between 10 nm and 10 .mu.m. According to a
particularly preferred embodiment, the irradiated regions in the
molded body are removed (dissolved) with the aid of wet chemical
etching, for example by using a strong alkaline solution. The
desired pore diameter is adjusted via the parameters (duration,
temperature) for the etching step.
[0025] Finally, according to method step e), the molded body
produced according to the invention is removed from the mold. This
molded body represents a three-dimensional hollow structure with
thin walls, provided with pores of a defined size in all regions of
the side walls and the bottom, wherein these are furthermore
aligned in all regions mostly perpendicular to the wall.
[0026] The molded bodies produced with the method according to the
invention have many different uses. A molded body comprising a
single or several hollow structures can be used as housing for
micro-structured parts (components) or for collecting
micro-particles and/or nano-particles. The surfaces of the
aforementioned particles can be functionalized, for example,
through perfusion of various reaction means.
[0027] Molded bodies with hollow structures that have an inside
diameter d.sub.i, obtained by using the outside diameter d minus
double the wall thickness b, as well as a height h in the range of
10-50 .mu.m, can furthermore be used for individual biological or
pharmaceutical analyses of bio-molecules, as well as prokaryotic or
eukaryotic cells.
[0028] Molded bodies with hollow structures that have an inside
diameter d.sub.i as well as a height h in the range of 50-500
.mu.m, for which the dimensions are consequently in the range of
standard spheroids, can be used for the three-dimensional
cultivation of prokaryotic or eukaryotic cells. Examples for this
are the cultivation of cells for studying angiogenesis,
invasiveness (tumor research), or cell-to-cell communication.
[0029] According to one preferred embodiment, several and/or a
plurality of hollow structures are arranged in a single plane,
wherein it is possible to arrange the hollow structures in a row or
to have a planar distribution across the complete film or parts of
the film. In the latter case, the hollow structures are preferably
arranged in rows and columns and/or are in a staggered
arrangement.
[0030] Molded bodies of this type can be used as addressable
cavities for immobilizing and/or magazining micro-particles or
nano-particles, for which the surfaces can be functionalized
through perfusion of reaction media.
[0031] One preferred use of the molded bodies according to the
invention is in the form of a micro-structured cell culture carrier
for the three-dimensional cultivation of prokaryotic or eukaryotic
cells, for example as disclosed in reference DE 41 32 379 A1. This
allows the immobilizing of cells supplied by perfusing media,
wherein the preferred parameters are: [0032] foil thickness D:
20-100 .mu.m [0033] wall thickness b: 5-10 .mu.m [0034] hollow
structure: [0035] inside diameter d.sub.i: 100-300 .mu.m [0036]
height h: 100-300 .mu.m [0037] 10.sup.6-10.sup.7 pores/cm.sup.2
with diameter .delta. 1-5 .mu.m
[0038] Molded bodies according to the invention are furthermore
suitable for immobilizing enzymes or surface-active catalysts
because of their increased surface area. Immobilized enzymes on the
increased surface area make it possible to configure a biosensor,
with the medium (fluid) flowing directly through it and not just
around it.
[0039] Molded bodies according to the invention can be used with
mechanical, thermal, electric, magnetic or chemical separation
processes. In connection with suitable parameters for the film,
molded bodies of this type can be used for the filtering out of
micro-organisms, including viruses, bacterio-phages and/or or
bacteria, or bio-molecules such as soluble proteins from a medium
that is flowing through.
[0040] Molded bodies according to the invention are furthermore
suitable for use as atomizers. Substances which do not mix while in
the liquid phase are transferred from the pores of adjacent hollow
structures in the form of finely-distributed drops (aerosols) and
are mixed in this way.
[0041] According to a different preferred embodiment, a molded body
according to the invention is rolled up simply or spirally, wherein
the hollow structures are oriented either toward the inside or the
outside. Alternatively, a molded body according to the invention
can also be folded or have a corrugated shape. Finally, several
molded bodies with the same or different parameters can be arranged
side-by-side, one above the other, or can be nestled into each
other and can be used, for example, for the membrane
filtration.
[0042] In addition to the use for immobilizing enzymes or as
surface-active catalysts, micro-particles or nano-particles can be
separated serially according to their size, by means of several
layers with a graduated pore size. Molded bodies of this type are
also suitable for use as three-dimensional filters with defined
pore size, for example for the material separation in the
pharmaceutical industry, the biotechnical industry, and the
like.
[0043] One or several molded bodies according to the invention in
the form of a tube represent a module, having a considerably larger
surface area as compared to a standard hollow fiber. A module of
this type can be used, for example, for producing monoclonal
antibodies or as extra-corporeal organ support system.
[0044] For a different area of application, these bodies can be
used as thin-walled microscopic channel structures and reservoir
structures with defined localized openings and/or pores of a
defined size, which are used for taking samples, for the
ventilation, for the material separation, and the like. Molded
bodies of this type are also used, for example, in .mu. capillary
electrophoresis chips or in lab-on-a-chip systems.
[0045] The invention in particular has the following advantages:
[0046] easy irradiation of the flat polymer film prior to the
micro-structuring process; [0047] easy irradiation of large
unstructured surfaces, e.g. continuous webs of film; [0048] making
it easier to use masks (direct mask contact) for producing locally
delimited areas of perforation or regions, which must be are to be
completely dissolved out; [0049] making possible the
micro-perforation on all sides of three-dimensional micro-cavities;
[0050] higher production safety since the step of irradiating the
material is realized on cheaper semi-finished films, prior to the
generally involved and cost-intensive micro-structuring operation,
thereby avoiding the problem of rejects of existing and expensive
micro-structures with defects caused by radiation.
[0051] In the following, the invention is explained in further
detail with the aid of exemplary embodiments and the Figures, which
show in:
[0052] FIG. 1 A schematic cross section through a molded body with
perforated hollow structures.
[0053] FIG. 2 A schematic cross section through a molded body with
a hollow structure that is provided with an undercut (.OMEGA.
structure).
[0054] FIG. 3 A schematic cross section through an arrangement of
several hollow structures in a single plane: [0055] a) in a row;
[0056] b) planar, in the form of rows and columns; [0057] c)
planar, in a staggered arrangement.
[0058] FIG. 4 Schematic cross-sections through three-dimensional
arrangements of hollow structures: [0059] a) rolled up singly with
hollow structures directed toward the inside; [0060] b) rolled up
spirally with hollow structures directed toward the inside; [0061]
c) rolled up singly with hollow structures directed toward the
outside.
[0062] FIG. 5 Schematic cross sections through three-dimensional
arrangements of two molded bodies.
[0063] FIG. 6 Scanning electron microscope image of the section
through a hollow structure, prior to the method step d).
[0064] FIG. 7 Scanning electron microscope image of a section
through the hollow structure shown in FIG. 6, following the method
step d).
[0065] FIG. 8 Scanning electron microscope image of a different
section through a hollow structure, following the method step
d).
[0066] FIG. 9 A section through the outside region of the molded
body shown in FIGS. 6 to 8 (single structure).
[0067] FIG. 10 A detail from FIG. 9 for further demonstrating the
interconnectedness of the pores.
[0068] The view in FIG. 1 shows a schematic cross section through a
molded body with perforated hollow structures. The individual
parameters included with this Figure are: [0069] D thickness of the
film [0070] d outside diameter of the hollow structure [0071] h
height of the hollow structure [0072] b wall thickness of the
hollow structure [0073] r curvature radius for the hollow structure
[0074] g spacing between two adjacent hollow structures [0075]
.delta. pore diameter [0076] .beta. spacing between pores
[0077] FIG. 2 shows a schematic cross section through a molded body
comprising a hollow structure with a real undercut, meaning a
so-called .OMEGA. structure. The distinctive distribution function
of the wall thickness b is visible in this view.
[0078] FIG. 3 shows several options for arranged hollow structures
in a single plane, while FIG. 4 shows possible spatial arrangements
of molded bodies according to the invention. FIG. 5 shows several
options for arranging two molded bodies in stacked or sandwich-type
arrangements. The hollow structures of the individual molded bodies
in this case can be oriented in the same (a, d) or in opposing
directions (b, c, e, f), either in a row (a-c) or staggered (d-f)
and/or can be directed toward the inside or the outside (c versus
b; f versus e).
[0079] The method according to the invention was realized with a
cast film of poly carbonate (PC), having a thickness of 50 .mu.m.
The film was irradiated at the linear accelerator UNILAC by the
"GESELLSCHAFT FUR SCHWERIONEN-FORSCHUNG" [Company for Heavy Ion
Research] (GSI) in Darmstadt, Germany, using heavy ions of the type
.sup.132Xe.sup.21+ with a specific energy of 11.4 MeV/nucleon and a
fluence of 10.sup.6 ions/cm.sup.2. The angle of irradiation
relative to the surface of the film was 90.degree..
[0080] The film was subsequently dried in a vacuum for 45 minutes
at 80.degree. C. to prepare for the following micro thermoforming
step. For the micro thermoforming, a mechanical pressure of 80 000N
was applied, given a forming temperature of 164.degree. C. and a
gas pressure of 5 MPa (50 bar). The form release temperature was
approximately 70.degree. C. Obtained were hollow structures with a
depth of approximately 240 .mu.m to 250 .mu.m.
[0081] A solution of 5N NaOH with 10% methanol was used as etching
medium for the pore formation. The etching occurred over a period
of 6 hours, at a temperature of 50.degree. C., and result in pores
ranging in size from 4 .mu.m to 5 .mu.m.
[0082] FIG. 6 shows the scanning electron microscope image of a
section through a hollow structure (cavity) configured in a micro
thermoformed 50 .mu.m thick film of polycarbonate (PC). The maximum
depth of the structure is approximately 250 .mu.m while the depth
in the cutting plane is somewhat lower. The film was irradiated
with heavy ions prior to the thermoforming operation.
[0083] FIG. 7 shows a scanning electron microscope image of the
section through the hollow structure in the micro thermoformed film
of polycarbonate (PC), previously shown in FIG. 6, following the
etching step. The interconnectedness of the pores is clearly
visible in some areas. The orientation of the pores does not
precisely coincide with the cutting plane, so that the cross
sections of only a few pores can be seen in their full length.
[0084] FIG. 8 illustrates the scanning electron microscope image of
a different section through a hollow structure in the micro
thermoformed film of polycarbonate (PC) that is already shown in
FIG. 6, following the method step d). The interconnectedness of the
pores is again clearly visible in some areas.
[0085] FIG. 9 contains a section through the outside region of the
micro thermoformed film of polycarbonate (single structure),
already shown in FIGS. 5 to 8. FIG. 10 contains an enlarged detail
from FIG. 9, which also shows the interconnectedness of the
pores.
* * * * *