WO2012146500A1

WO2012146500A1 - Micro-screen and method for producing a micro-screen

Info

Publication number: WO2012146500A1
Application number: PCT/EP2012/056896
Authority: WO
Inventors: Friedrich Lupp; Daniel Sickert
Original assignee: Siemens Aktiengesellschaft
Priority date: 2011-04-28
Filing date: 2012-04-16
Publication date: 2012-11-01
Also published as: DE102011017696A1

Abstract

The invention relates to a method (S1, S2) that is used to produce a micro-screen (2) and comprises the following steps: first, a mask (1), in particular a silicon wafer, which is provided with a structuring (3) and produced photolithographically, is moved close to a thin film (2, 2a) in a planar manner, and then the thin film (2, 2a), together with the mask (1), is irradiated, in particular with laser light. The micro-screen (2b) has been produced by means of the method (S1, S2). The micro-screen can be used in particular to enrich or extract certain cells from cell-containing body fluids, for example from blood, urine, biopsy fluids, saliva and the like, including from human blood or from natural or synthetically produced cell suspensions or dilutions thereof.

Description

description

Microsieve and Method of Making a Microsieve The invention relates to a microsieve. The invention further relates to a method for producing a microsieve.

Microsieves are increasingly used for sophisticated separation tasks, e.g. in medical technology or biotechnology. For example, the enrichment or extraction of certain cells from human blood by filtration of the blood through a microsieve done (microfiltration). In contrast to conventional microfilters made of sponge-like polymer or ceramic membranes, microsieves have a defined pore geometry and are therefore much more efficient and better classifying. In order to optimize a filtration process, a freely selectable pore geometry, pore density and pore distribution of the microsieve are desirable, but currently or only at considerable expense achievable.

One type of known microsieves are the so-called. Tracked-etched membranes. These membranes have due to their manufacturing process on a spatially irregular pore distribution. Depending on the pore size, the maximum number of pores per unit area is considerably limited. For example, with tracked-etched membranes with a pore diameter of 8 micrometers, it is only possible to achieve a maximum pore fraction of the membrane's total area of 5%. In addition, a plurality of pores does not pass through the base material of the membrane perpendicularly, but obliquely. Furthermore, double pores occur which give a common pore with a larger than the nominal diameter.

Another way to make a microsieve is to place a layer of parylene on a silicon wafer.

Apply carrier wafer and structure the parylene layer by photolithography and dry etching. Any pore geometry and po- generate rena arrangements. On the other hand, it is disadvantageous that the usually complex and expensive methods of microsystem technology must be used for the production of each individual micro-sieve. In addition, the microsieve can generally only be produced by means of a material which can be applied as a thin layer to an affer substrate and can be detached again after the processing.

Polymer microsieves can currently also be produced by means of a laser beam (laser ablation), using two different methods. In the first method, the pores are produced by scanning a polymer film with the laser beam at a high repetition rate. This is a sequential process and correspondingly expensive and time consuming. In addition, variations in hole shape and hole size can not be ruled out. In the second method, a metal mask with corresponding holes is produced and then used as an imaging mask for a subsequent laser beam ablation process. However, this method is limited to small surfaces by means of mask projection, since only in the central region the corresponding imaging optics have the necessary imaging quality for producing very small hole diameters. Consequently, the polymer film is to be processed according to the step-and-repeat method for large-scale processing. When drilling printed circuit boards, a method is known in which a metal proximity mask is used for drilling vo holes with a diameter of more than 80 micrometers. It is the object of the present invention to at least partially overcome the disadvantages of the prior art and, in particular, to provide an improved possibility for producing a micro-sieve, in particular made of plastic. This object is achieved according to the features of the independent claims. Preferred embodiments are in particular the dependent claims. The object is achieved by a method for producing a microsieve, which has at least the following steps: surface bringing a provided with a structuring lithographically produced mask to a thin film; and irradiating the side of the lithographically produced mask (hereinafter also referred to as "mask") facing away from the thin layer with a radiation which is suitable for removing the thin layer. The thin layer may in particular be a (thin) film.

The film may in particular be a prefabricated, in particular commercially available, film.

The method makes use of the surprising fact that lithographically produced material, in particular silicon, as a proximity mask or imaging mask is also suitable for radiation ablation, in particular laser ablation. By means of this method, the thin layer is selectively removed there locally, where the structuring (holes or the like) of the lithographically produced mask is present, through which

Radiation can penetrate. Other areas covered by the mask, however, are not or not significantly removed. The irradiation or removal is carried out until continuous pores or holes of desired size and / or shape have been produced in the thin film. These pore - afflicted or perforated thin film then represents the microsieve or a part thereof.

The method has the advantage that the mask is not destroyed in the process and consequently can be used many times. In addition, the thin film does not need to be further structurally processed, which keeps a range of usable materials broad. The method can therefore produce high-precision micro-sieves inexpensively.

The bringing of the mask to the thin film, in particular film, is generally understood and can by moving the mask to the thin film, moving the Thin film to the mask, by moving both Komponen ^¬ th or even be achieved by generating the thin film on the mask. The microsieve may be used in particular for separating solids and / or or for retaining solids from a liquid ^¬-speed and / or Gasström. Under a micro ^¬ sieve including a micro-filter element can verstan ^¬ be the general. The microsieve may in particular be a (separating) membrane.

The microsieve may be used in particular for Anrei ^¬ insurance or extraction of specific cells from cell-containing body fluids, such as from blood, urine, ten Biopsieflüssigkei-, saliva, etc., including from human blood or from na ^¬-natural or artificially produced cell suspensions or Ver ^¬ dilutions davo.

In particular, the lithographically produced mask may be a photolithographic (i.e., photolithographic) prepared mask. Alternatively, the lithographically produced mask may be a mask made by electron beam and ion lithography, laser lithography, or nanoimprint lithography (IL).

The material of the mask may be a metal or a nonmetal. The non-metal may in particular comprise a semi-metal, Ke ^¬ Ramik or glass. Metal can, for example galvanically deposited form on a photolithographically produced master, which maintains the desired holes ^¬ freely in the metal. Glass and ceramics can also be patterned using photolithogra- phy. Glass may alternatively be structured by means of Sandstrah ^¬ lens. It is a particularly preferred embodiment that the

Semi-metal is silicon. Si 1 iz ium is particularly inexpensive as wafers, well structurable, environmentally compatible and durable. In addition, the structuring of silicon can be in a simple manner over a large area by customary structuring methods of microsystem technology, in particular silicon technology, such as etching {z. Dry etching, wet etching, so-called "Photo-Assisted Electrochemical Etching" etc.). The irradiation may thus manage with few or even no step-and-repeat steps. Another advantage is the highly accurate and freely selectable shaping of the structuring, for example with respect to a shape (eg cylindrical pores, slits, etc.), a size and a position of the associated pores or the like

It is yet another embodiment that the silicon is porous Si 1 i zium. As a result, a silicon ion produced by a "photo-assisted electrochemical etching" (PAECE) process can also be used. be used .

However, all semi-metals (B, Si, Ge, As, Se, Sb, Te Po) can be used in Reinfor and / or their mixtures, compounds and / or alloys.

In particular, the semimetals may be present as wafers, that is, the non-metal mask may in particular be a structured half-metal wafer. However, the non-metal mask is not limited to wafers. It is an embodiment that the planar approach involves surface contact. This makes it possible to introduce particularly precise pores into the thin film, in particular film. The cross-sectional shape of these pores corresponds in particular to the contact surface of the shape of the plated-through holes of the mask, which are very precisely predetermined.

Alternatively, the planar approach may involve close approach. So like the thin film, in particular film, if necessary. disturbing or even destructive contact with the mask can be avoided.

It is also a development that the structuring has a group of circular cylindrical holes. Folg- At least in plan view, the pores of the microsieve would have a circular shape, in particular at the contact surface with the non-metal mask. It is also an embodiment that the holes form a regular pattern. The pattern may be, for example, a matrix pattern or a dense area pattern. For example, a dense pattern may have a hexagonal or cubic unit cell as the smallest unit. The holes may in particular be present in a locally same density. Consequently, the pores of the microsieve would also form such a pattern.

Alternatively, the holes may form an irregular pattern, especially at a predetermined local density. Consequently, the pores of the microsieve would also form a corresponding irregular pattern.

In yet another alternative, the holes may have a deliberate (e.g., gradual or locally random) variation in their spacing or depth. their local density over the surface of the non-metal mask. Consequently, the pores of the microsieve would also form such a pattern. It is a preferred embodiment that the holes have a, in particular uniform, diameter between about 1 micrometer and about 50 micrometers. It is a particularly preferred embodiment that the holes have a uniform diameter between 5 microns and about 25 microns, in particular between about 7 microns and about 15 microns.

Alternatively, the diameter or the flow cross section can be selectively varied, for example as a function of a position of the respective hole on the non-metal mask. Consequently, the pores of the microsieve would also have a varied diameter or flow area. However, the shape of the holes (in plan view) is not be ^¬ limits. Thus, the holes may be oblong, for example oval or rectangular, holes, in particular having a width Zvi ^¬ rule 5 micrometers and 25 micrometers and a length be- see 10 micrometers and 200 micrometers.

It is yet an embodiment that the irradiating a Be ^¬ rays of light, in particular laser light, comprising. This can preferably be carried out over a large area over the entire structure of the mask. The light can be insbeson ^¬ broader visible light and / or UV light. In particular, the light may have a wavelength of less than 400 nm.

It is still an embodiment that the light used, in particular laser light, has short pulse times, in particular ^¬ dere pulse times less than 1 ps, preferably less than 100 ns.

It is a further development that the incorporated in the thin film ^¬ brought pores is a (surface in the direction of the Lichteinstrahl- to the light exit surface) of tapering shape, in particular ^¬ sondere frusto rtige shape,. This can be achieved by the present method without further aids in a simple manner. The truncated cone-like shape of the ^pores allows a reduction in the pressure required for filtration or more effective particle retention. In previously known micro-sieves, the pores are cylindrical and have over their: entire length and the course through the Schichtma ^¬ material the same diameter. Thus, the necessary for Filtra ^¬ tion pressure with the layer thickness grows, so herkömmlich- enough, only a limited layer thickness can be used for example to avoid a destruction or alteration of the retained particles during the filtration process by excessive pressure. With conically widened pores, this problem can be avoided.

But generally also not widening pores forth are ^¬ adjustable. It is a further embodiment that a best ahlungsin ^¬ intensity for obtaining a signal dependent on the intensity of irradiation opening angle of the thin film introduced into the pores is defined. This embodiment makes use of the surprising finding that the opening angle of the pores (tapering) introduced into the thin film can be adjusted by predetermining the radiation intensity. In other words, the opening angle of the pores can be varied as a function of the radiation intensity. This results in an easily implementable option for the targeted setting of the opening angle.

An opening angle may, in particular, be understood as meaning an angle between a longitudinal axis of the pore and a line coplanar with the longitudinal axis on the lateral surface of the pore. Alternatively, under an opening angle, in particular an angle between two opposite lines coplanar to a longitudinal axis of the pore on the lateral surface of the pore can be understood.

It is yet another refinement that a frequency of irradiation for obtaining an opening angle dependent on the frequency of irradiation is predetermined for voids introduced into the thin layer and tapered, in particular frustoconical. This embodiment makes use of the equally surprising finding that the opening angle of the pores (tapering) introduced into the thin film can be adjusted by predefining an irradiation frequency (or radiation duration). In other words, the opening angle of the pores can be varied depending on the frequency of irradiation. This results in a further easily implementable option for the targeted setting of the opening angle. It is also an embodiment that a divergence angle of the radiation used for lithography, in particular light, in particular laser light, to obtain one of the Divergenzwinke! dependent opening angle from to the thin Push introduced, constricting, in particular frustoconical, pores is given. This refinement thus makes use of the knowledge that the opening angle of the pores introduced into the thin film can be adjusted by predetermining the divergence angle of the radiation. In other words, the opening angle of the pores can be varied depending on the divergence angle. This provides a further easily implementable option for the targeted setting of the opening angle.

Overall, therefore, by specifying an irradiation intensity, an irradiation frequency and / or a divergence angle of the irradiated light, an opening angle (phi) of pores to be introduced into the thin film can be set.

It is yet another embodiment that a layer thickness of the thin film, in particular film, for obtaining smaller diameter of the introduced into the thin film, in particular film, introduced tapered, in particular truncated cone, pores is given. This refinement makes use of the knowledge that the smaller diameter of the (tapered) pores introduced into the thin film can be set by predefining a layer thickness.

In other words, the smaller diameter of the pore can be varied depending on the layer thickness of the thin film. This results in yet another easily implementable option for the targeted setting of the smaller diameter of the pore.

The intensity of irradiation, the frequency of irradiation, the divergence angle and / or the layer thickness can be set in any desired combination.

It is also a further embodiment that a diameter of a larger opening of a introduced into the thin-film frusto-conical pore between 5 microns and 25 microns and / or a diameter of a smaller one

The opening of a truncated cone-shaped pore inserted into the thin film is between 5 microns and 20 microns.

It is particularly preferred that the diameter of the smaller opening of a pore is between 5 and 10, in particular between 6 and 8, micrometers and the diameter of the larger opening of the pore is between 7 and 15 micrometers, in particular e about 10 micrometers , However, the sizes, in particular diameter, of the pores are basically not limited.

In general, however, other than constricting pores are introduced, for. cylindrical, in particular kreiszylin- derförmige, pores.

The object is also achieved by a microsieve, wherein the microsieve has been produced from a thin layer by means of a method as described above.

It is an embodiment that the thin film, in particular film, consists of polymer. It is a special embodiment that the thin film or. the microsieve has polycarbonate and / or polyarylate or. it consists. Polyarylates can be understood in particular to be purely aromatic polyesters (APE) and polyestercarbonates (PEG). Other polymers may be, for example, polyimides or polyvinyl fluorides.

It is still an embodiment that the microsieve has widening, in particular frusto-conically widening, pores with an essentially identical opening angle. This results in the advantage that a flow-through behavior (volume flow, velocity, etc.) which is at least substantially the same as a function of a differential pressure and / or retention behavior results from the continuous pores. The microsieve can be arranged in the flow direction for filtering so that its pores widen {filtration from small pore diameter to large pore diameter). This suppresses pore clogging and reduces one

Flow resistance and thus the required pressure in the filtration while maintaining the pore diameter and the pore density. The microsieve may also be arranged in the flow direction for filtering purposes, such that its pores narrow (filtration from a large pore diameter to a small pore diameter), for example for more effective capture of particles, e.g. Cells, and for the localized arrangement of the particles during filtration. This allows z. B. a simplified automated recovery and reuse of the cells.

It is a development that a layer thickness of the thin layer, in particular film, is between 5 and 50 micrometers, in particular about 10 micrometers.

In general, the features of the described method can also be used as features of the device described, and vice versa.

In the following figures, the invention will be described schematically with reference to an embodiment schematically. For the sake of clarity, identical or equivalent elements can be provided with the same reference symbols.

Fig.l shows a SchnittdarStellung in side view provided with a structuring mask, wel ^¬ cher rests flat on a thin film;

Fig.2 shows as a sectional representation in side view the

Mask with the polymer film from Fig.l during an irradiation process with a magnifying cut and

FIG. 3 shows a sectional side view of the polymer film finished as a microsieve during filtration with a magnifying section.

Fig.l shows a provided with a structuring Mas ke in the form of a silicon wafer 1, which on a thin film in the form of a thin, not yet treated polymer film 2, 2a rests flat and forms a contact surface 6 with this.

The silicon wafer 1 has a through structure, which has a group of vertically introduced, circular cylindrical holes 3 arranged in the surface in a regular pattern. A diameter of the holes 3 is about 8 microns. The polymer film 2 consists of any polymer, for example, polycarbonate or polyarylate, with a layer thickness d of about 10 micrometers.

In particular, FIG. 1 can correspond to a first step S1 of a method for producing a microsieve.

FIG. 2 shows the silicon wafer i with the polymer film 2 during an irradiation process. The polymer film 2 here is a present at the end of the irradiation process, in esent lent completed polymer film 2b.

In the irradiation process, the polymer film 2 abge facing side 4 of the Sil iziumwa Fers 1 is irradiated großflä Chig with laser light P. The laser light P is suitable for removing the mate rial of the polymer film 2 {so-called. Laser ablation). The laser light P penetrates through the holes 3 on the polymer film and is otherwise shaded. The silicon wafer 1 thus serves as a mask in laser ablation. The irradiation process is carried out until given locally through the holes 3 of the Silizxumwafers given through pores 5 in the polymer film 2. The pores 5 have at the contact surface 6 the same shape and size, here: the same diameter, as the adjacent hole 3 in the Silizxumwafer 1. The pores 5 have at the contact ^¬ surface consequently also has a diameter a of about 8 microns ^¬ rometer on. Since the holes 3 can be made available with a very high precision and free shape and position, Kings ^¬ NEN the pore 5 corresponding exactly be freely produced malleable and arranged.

By irradiation, no pores 5 are created which have the same shape over their length. Rather, it has surprisingly wei se shown that the pores 5 taper in the radiation direction depending on the adjusted process parameters, so aufwei ^¬ sen a smaller flow cross-section, as shown in the enlarged section A. In the present round in plan view pore 5, this means that they have a basic shape of a truncated cone whose RESIZE ^¬ ßerer diameter is a located on the contact surface 6 and whose smaller diameter b at the free surface 7 of the polymer film. 2 The diameters a and b, together with the layer thickness d, of the polymer film 2, 2b result in one

Publ opening angle phi a lateral surface of the truncated cone in Be ^¬ train on its longitudinal axis L.

It has also surprisingly been found that an irradiation intensity, irradiation frequency or Be ^¬ radiation time and the layer thickness d of the opening angle phi and the smaller diameter of a pore 5 specifically can ^¬ influence stunning and so simple by an appropriate setting of these parameters of the Publ ungswinkel phi on Way is specifically adjustable. In the embodiment shown, the smaller diameter b is preferably 5 to 7 Mikrome ^¬ ter. In particular, FIG. 2 may correspond to a second step S2 of a method for producing a microsieve.

3 shows the finished polymer film 2, 2b during filtration, in a section B enlarged.

The polymer film 2, 2b serving as a microsieve is arranged in the flow direction S so that its pores 5 expand (filtration from the small pore diameter b to the large pore diameter a). This suppresses clogging of the pores 5, reduces flow resistance and consequently the pressure required in the filtration.

The same polymer film 2, 2b may alternatively also be arranged in the flow direction S, however, so that their holes narrow (filtration of a large pore diameter a to a small pore diameter b). This improves locally targeted retention of particles. Of course, the present invention is not limited to the embodiment shown.

Claims

claims

Method (Sl, S2) for producing a microsieve (2), comprising at least the following steps:

- applying a lithographically produced mask (1) provided with a structuring (3) to a thin layer (2, 2a);

- Irradiation of the thin film {2, 2a, 2b) facing away from the mask (1) with a radiation (P), wel che is adapted to the thin film (2, 2a, 2b) ablate.

A method (Sl, Ξ2) according to claim 1, wherein the planar approach comprises a surface contacting.

Method (Sl, S2) according to one of the preceding claims, wherein the non-metal mask is made of silicon.

The method (Sl, S2) of claim 3, wherein the silicon is porous silicon.

Method (Sl, S2) according to one of the preceding claims, wherein the structuring comprises a group of regularly arranged holes (3).

Method (Sl, S2) according to one of the preceding claims, wherein the structuring comprises holes (3) with a diameter (a) between approximately 5 micrometers and approximately 25 micrometers.

Method (Sl, S2) according to one of the preceding claims, wherein the structuring has elongate holes (3), in particular with a width between 5 microns and 25 microns and a length between 10 microns and 200 microns.

8. Method (Sl, S2) according to one of the preceding claims, wherein the irradiation comprises irradiation with light, in particular special laser light (P), includes.

Method (Sl, S2) according to one of the preceding claims, wherein a radiation intensity, an irradiation frequency and / or a divergence angle of the irradiated light for setting an opening angle (phi) of in the thin film {2, 2a, 2b) pores (5) to be introduced becomes .

Method (Sl, 32) according to one of the preceding claims, wherein a layer thickness (d) of the thin layer (2, 2a, 2b) for obtaining a targeted value of a smaller diameter (b) of in the thin film (2, 2a, 2b) to be introduced truncated cone-shaped pores (5) is given.

Method (Sl, S2) according to one of the preceding claims, wherein a diameter (b) of a larger opening of a frustum-shaped pore (5) introduced into the thin layer (2, 2b) has between 5 and 25, in particular between 7 and 15, micrometers, and / or a diameter (a) of a smaller opening of a frustoconical pore inserted into the thin film between 5 and 10, in particular between 6 and 8 microns.

Microsieve (2b), wherein the microsieve (2b) has been produced from a thin layer (2a) by means of a method (S1, 52) according to one of the preceding claims.

The microsieve (2b) of claim 12, wherein the microsieve (2b) comprises polycarbonate, polyimide and / or polyarylate.

Microsieve (2b) according to any one of claims 12 to 13, wherein the microsieve (2b) has widening, in particular truncated cone-shaped widening pores (5) with a substantially same opening angle (phi).