DE102011017696A1 - Microsieve and method of making a microsieve - Google Patents

Abstract

The method (S1, S2) is used to manufacture a microscreen (2) and has the following steps: firstly, a surface-area application of a photolithographically produced mask (1), in particular silicon wafer, provided with a structure (3), to a thin layer (2, 2a) and then irradiating, in particular with laser light, the thin layer (2, 2a) with the mask (1). The microsieve (2b) has been produced by means of the process (S1, S2). The microsieve can be used in particular for the enrichment or extraction of certain cells from cell-containing body fluids, e.g. B. from blood, urine, biopsy fluids, saliva, etc., including from human blood or from natural or artificially generated cell suspensions or dilutions thereof.

Description

The invention relates to a microsieve. The invention further relates to a method for producing a microsieve.

Micro sieves are increasingly used for demanding separation tasks, eg. B. in medical technology or biotechnology. For example. the enrichment or extraction of certain cells from human blood can be carried out by filtration of the blood through a microsieve (microfiltration). Microsieves, in contrast to the conventional microfilters sponge-like polymer or ceramic membranes have a defined pore geometry and are therefore much more efficient and better classifying. To optimize a filtration process, a freely selectable pore geometry, pore density and pore distribution of the microsieve are desirable, but currently not or only with considerable effort 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 a 8 micrometer pore diameter tracked-etched membrane, it is only possible to achieve a maximum void area of the membrane 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 fabricate a microsieve is to apply a layer of parylene onto a silicon carrier wafer and pattern the parylene layer by photolithography and dry etching. With this method, any pore geometries and pore arrangements can be generated. A disadvantage, however, is that this usually expensive and expensive methods of microsystem technology in the production of each microsieve must be used. In addition, the microsieve generally can only be produced by means of a material which is thin Apply layer to a wafer substrate and peel it off again after 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 by means of mask projection on small areas, since only in the central region, the corresponding imaging optics have the necessary imaging quality to produce 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 holes with a diameter of more than 80 microns.

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 microsieve, in particular 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 comprises at least the following. Comprising: laminating a patterned lithographic 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 are. This porous 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 thus is widely used. 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, particularly film, is generally understood and can be achieved by moving the mask to the thin film, moving the thin film to the mask, moving both components or even forming the thin film on the mask become.

The microsieve can be used in particular for separating solids and / or for retaining solids from a liquid and / or gas stream. A micro-sieve can therefore generally also be understood to mean a microfilter element. The microsieve may in particular be a (separating) membrane.

The microsieve can be used in particular for the enrichment or extraction of certain cells from cell-containing body fluids, eg. From blood, urine, biopsy fluids, saliva, etc., including from human blood or from natural or engineered cell suspensions or dilutions thereof.

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

The material of the mask may be a metal or a nonmetal. The non-metal may in particular comprise a semi-metal, ceramic or glass. Metal, for example, can be electrodeposited on a master mold produced by photolithography, which keeps the desired holes in the metal free. Glass and ceramics can also be structured photolithographically. Glass can alternatively be structured by sand blasting.

It is a particularly preferred embodiment that the semimetal is silicon. Silicon is particularly inexpensive as wafers, easy to structure, environmentally friendly and durable. In addition, the structuring of silicon in a simple manner over a large area by conventional structuring methods of microsystems technology, especially the silicon technology, such as etching. (eg dry etching, wet etching, so-called "photo-assisted electrochemical etching" etc.). The irradiation may thus do with few or even no step-and-repeat steps. Another advantage is the highly accurate and freely selectable shape of the. Structuring, z. With respect to a shape (e.g., cylindrical pores, slits, etc.), a size and a position of the pores thereof, or the like.

It is yet another embodiment that the silicon is porous silicon. As a result, a silicon or the like produced by a "Photoassisted Electrochemical Etching" (PAECE) method can also be used.

However, all semi-metals (B, Si, Ge, As, Se, Sb, Te Po) in pure form and / or their mixtures, compounds and / or alloys are usable.

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 comprises a 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 form of the plated-through holes of the mask, which can be specified very precisely.

Alternatively, the planar approach may involve close approach. Thus, the thin film, in particular film, possibly disturbing or even destructive contact with the mask may be avoided.

It is also a development that the structuring has a group of circular cylindrical holes. Consequently, the pores of the microsieve, at least in plan view, 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, particularly at a predetermined local density. Consequently. would also pores of the microsieve form a corresponding irregular pattern.

In yet another alternative, the holes may have a targeted (eg, gradual or locally random) variation in their spacing or local density over the face 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. B. depending on 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 limited. So like the holes also elongated, z. As oval or rectangular, holes, in particular with a width between 5 microns and 25 microns and a length between 10 microns and 200 microns.

It is yet another embodiment that the irradiation comprises irradiation with light, in particular laser light. This can preferably be carried out over a large area over the entire structure of the mask. The light may, in particular, be 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 pulse times of less than 1 μs, preferably less than 100 ns.

It is a further development that the pores introduced into the thin film have a shape (in particular in the form of a truncated cone) that tapers (in the direction from the light irradiation surface to the light exit surface). This can be achieved by the present method without further aids in a simple manner. The frusto-conical shape of the pores allows a reduction in pressure necessary for filtration or more effective particle retention. In previously known micro-sieves, the pores are cylindrical and have the same diameter over their entire length and the course through the layer material. Thus, the pressure required for filtration increases with the layer thickness, so that conventionally only a limited layer thickness can be used, for example, to avoid destruction or change of the retained particles during the filtration process by excessive pressure. With conically widened pores, this problem can be avoided.

However, non-expanding pores are generally produced.

It is a further embodiment that an irradiation intensity for obtaining an irradiation intensity dependent opening angle of introduced into the thin film pores is specified. This embodiment makes use of the surprising finding that the opening angle of the pores (tapered) introduced into the thin film can be adjusted by a predetermining 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, by 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 still an embodiment that an irradiation frequency, for obtaining an opening angle dependent on the frequency of irradiation, of tapered, in particular frusto-conical, pores introduced into the thin layer is specified. This embodiment makes use of the equally surprising finding that the opening angle of the in the Thin-layered (tapered) pores can be adjusted by predetermining 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, for obtaining a dependent of the divergence angle opening angle of introduced into the thin film, tapered, in particular frustoconical, pores is specified. This refinement thus makes use of the knowledge that the opening angle of the pores (tapering) introduced into the thin film can be set 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 results in 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 incident light, an opening angle (phi) of pores to be introduced into the thin film can be set.

It is still a further embodiment that a layer thickness of the thin film, in particular film, for obtaining smaller diameter of in the thin film, in particular film, introduced tapered, in particular frusto-conical, pores is given. This refinement makes use of the knowledge that the smaller diameter of the pores (tapering) introduced into the thin layer can be set by specifying 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 provides yet another easy-to-implement way to selectively set the smaller diameter of the pore.

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

It is a further embodiment that a diameter of a larger opening of a frusto-conical pore inserted into the thin film is between 5 micrometers and 25 micrometers and / or a diameter of a smaller opening of a frustoconical pore inserted between the thin layer is between 5 micrometers and 20 micrometers.

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 approximately 10 micrometers. However, the sizes, in particular diameter, of the pores are basically not limited.

In general, however, other than tapered pores are introduced, z. B. cylindrical, in particular circular cylindrical, 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 layer or the microsieve comprises or consists of polycarbonate and / or polyarylate. Under polyarylates, in particular pure aromatic polyester (APE) and polyester carbonates (PEC) can be understood. 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, depending on a differential pressure, at least substantially the same flow-through behavior (volume flow, speed, etc.) 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 of small pore diameter to large pore diameter). This suppresses clogging of the pores and reduces a flow resistance and consequently the required pressure in the filtration while maintaining the pore diameter and the pore density.

The microsieve can be arranged for filtering but also in the flow direction that narrow its pores (filtration of large pore diameter to small pore diameter), for example, for more effective capture of particles, eg. As 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 film, 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. In this case, the same or equivalent elements may be provided with the same reference numerals for clarity.

1 shows a sectional view in side view one with a structuring provided mask, which rests flat on a thin film;

2 shows a sectional view in side view of the mask with the polymer film 1 during an irradiation process with a magnifying section; and

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

1 shows a provided with a structuring mask in the form of a silicon wafer 1 which is on a thin film in the form of a thin, untreated polymer film 2 . 2a flat rests and with this a contact surface 6 forms.

The silicon wafer 1 has a Durchstrukturierung, which is a group of arranged in the surface in a regular pattern, vertically introduced circular cylindrical holes 3 having. 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.

1 may in particular correspond to a first step S1 of a method for producing a microsieve.

2 shows the silicon wafer 1 with the polymer film 2 during an irradiation process. The polymer film 2 Here is a present at the end of the irradiation process, substantially finished polymer film 2 B ,

In the irradiation process, that of the polymer film 2 opposite side 4 of the silicon wafer 1 irradiated with laser light P over a large area. The laser light P is suitable for the material of the polymer film 2 ablate (so-called laser ablation). The laser light P penetrates through the holes 3 on the polymer film 2 and is otherwise shaded. The silicon wafer 1 thus serves as a mask during laser ablation.

The irradiation process is carried out until locally through the holes 3 the silicon wafer predetermined pores 5 in the polymer film 2 have arisen. The pores 5 show at the contact surface 6 the same shape and size, here: the same diameter, as the adjacent hole 3 in the silicon wafer 1 , The pores 5 Consequently, at the contact surface also have a diameter a of about 8 microns. Because the holes 3 The pores can also be provided with a very high precision and free shaping and position 5 according exactly, freely mouldable and can be generated.

By irradiating, no pores 5 created that have a same shape over their length. Rather, it has surprisingly been found that the pores 5 in the direction of radiation taper depending on the adjusted process parameters, ie have a smaller flow cross section, as shown in the enlarged section A. In the present in plan view round pores 5 This means that they have a basic shape of a truncated cone whose larger diameter a is at the contact surface 6 and its smaller diameter b at the free surface 7 the polymer film 2 located. The diameters a and b, together with the layer thickness d of the polymer film 2 . 2 B an opening angle phi of a lateral surface of the truncated cone with respect to its longitudinal axis L.

It has also surprisingly been found that an irradiation intensity, an irradiation frequency or irradiation duration and the layer thickness d are the opening angle phi and the smaller diameter of a pore 5 can specifically influence and so by a corresponding adjustment of these parameters, the opening angle phi is easily adjustable in a simple manner. In the exemplary embodiment shown, the smaller diameter b is preferably 5 to 7 micrometers.

2 may in particular correspond to a second step S2 of a method for producing a microsieve.

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

The microsieve serving polymer film 2 . 2 B is arranged in the flow direction S so that its pores 5 widening (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 during filtration.

The same polymer film 2 . 2 B Alternatively, however, in the flow direction S, it may also be arranged so that its holes narrow (filtration of large pore diameter a to small pore diameter b). This improves locally targeted retention of particles.

Of course, the present invention is not limited to the embodiment shown.

Claims (14)

Method (S1, S2) for producing a microsieve ( 2 ), comprising at least the following steps: - surface bringing one with a structuring ( 3 ) provided lithographically prepared mask ( 1 ) to a thin layer ( 2 . 2a ); - irradiation of the thin film ( 2 . 2a . 2 B ) facing away from the mask ( 1 ) with a radiation (P), which is suitable, the thin film ( 2 . 2a . 2 B ). A method (S1, S2) according to claim 1, wherein the planar approach comprises a surface contacting. Method (S1, S2) according to one of the preceding claims, wherein the non-metal mask consists of silicon. The method (S1, S2) of claim 3, wherein the silicon is porous silicon. Method (S1, S2) according to one of the preceding claims, wherein the structuring comprises a group of regularly arranged holes ( 3 ) having. Method (S1, S2) according to one of the preceding claims, wherein the structuring holes ( 3 ) having a diameter (a) between about 5 microns and about 25 microns. Method (S1, S2) according to one of the preceding claims, wherein the structuring comprises oblong holes ( 3 ), in particular with a width between 5 microns and 25 microns and a length between 10 microns and 200 microns. Method (S1, S2) according to one of the preceding claims, wherein the irradiation comprises an irradiation with light, in particular laser light (P). Method (S1, S2) according to one of the preceding claims, wherein an irradiation intensity, an irradiation frequency and / or a divergence angle of the irradiated light for setting an opening angle (phi) of into the thin film ( 2 . 2a . 2 B ) pores to be introduced ( 5 ) is given. Method (S1, S2) according to one of the preceding claims, wherein a layer thickness (d) of the thin layer ( 2 . 2a . 2 B ) for obtaining a targeted value of a smaller diameter (b) from into the thin film ( 2 . 2a . 2 B ) to be introduced frusto-conical pores ( 5 ) is given. Method (S1, S2) according to one of the preceding claims, wherein a diameter (b) of a larger opening in the thin film ( 2 . 2 B ) introduced frusto-conical pore ( 5 ) between 5 and 25, in particular between 7 and 15, micrometers and / or a diameter (a) of a smaller opening of a introduced into the thin-film frustoconical pore between 5 and 10, in particular between 6 and 8, micrometers. Microsieve ( 2 B ), whereby the microsieve ( 2 B ) from a thin layer ( 2a ) has been prepared by a method (S1, S2) after Eifern the preceding claims. Microsieve ( 2 B ) according to claim 12, wherein the microsieve ( 2 B ) Polycarbonate, polyimide and / or polyarylate. Microsieve ( 2 B ) according to any one of claims 12 to 13, wherein the microsieve ( 2 B ) widening, in particular frustoconical widening, pores ( 5 ) having a substantially same opening angle (phi).

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