WO2006110035A1

WO2006110035A1 - Microsieve membrane for emulsification and lithographic method of making the same

Info

Publication number: WO2006110035A1
Application number: PCT/NL2006/000195
Authority: WO
Inventors: Stefan Sanchez-De Vries
Original assignee: Fluxxion B.V.
Priority date: 2005-04-13
Filing date: 2006-04-13
Publication date: 2006-10-19
Also published as: NL1028759C2

Abstract

A membrane with pores is used for forming drops in an emulsion, by passing a disperse phase through the pores, whereby drops form. The membrane is manufactured by etching away a substrate under the membrane at least partly with isotropic etchant which is supplied via the pores and supplemental holes in the membrane. The supplemental holes are situated between the pores, but have a smaller diameter than the pores, such that the supplemental holes do not contribute to the emulsion formation. The supplemental holes serve to reduce the maximum etching distance over which etching needs to be done between the pores, while the emulsion formation depends only on a greater distance between the pores.

Description

MICROSIEVE MEMBRANE FOR EMULSIFICATION AND LITHOGRAPHIC METHOD OF MAKING THE SAME

The invention relates to forming an emulsion, manufacturing a membrane for forming an emulsion, to a filter for forming an emulsion and to an apparatus for forming an emulsion.

5 An emulsion contains a carrier liquid having therein drops of another liquid. The carrier liquid is designated as "continuous phase" and the other liquid as "disperse phase". In known membrane emulsification processes, disperse phase is forced through a porous membrane, along which flows the continuous phase. The membrane splits the disperse phase into drops which

10 are subsequently carried along in drop form in the continuous phase. The size distribution of the drops is an important property of the emulsion. It is desirable that it be possible to accurately realize any specified size distribution, in particular a monodisperse size distribution, with all drops having substantially the same thickness.

15 Different kinds of membranes can be used for emulsion formation.

European patent application No. 728034 describes a technique of making a porous membrane using microlithography. In this technique, first a thin prospective membrane layer is formed on a silicon substrate, with a thickness of, for instance, one micron. With photolithographic techniques

20 (such as known from the semiconductor industry), holes are provided in the membrane layer, which will later serve as pores through the membrane layer. Next, the substrate is etched away in areas under the holes. Between the areas, substrate remains present, as a support for the membrane. In these areas, microsieve fields are thus formed.

25 It is then desirable to etch away at least one layer of the substrate with etchant that is supplied from the front, that is, via the holes in the membrane layer, to the substrate. In principle, also such photolithographically manufactured membranes can be used for emulsification. A great advantage is then that the size distribution of the drops in the emulsion is determined by the distribution of the size of the pores. As the diameter of the pores is defined photolithographically, it is possible to give all pores practically the same diameter. In addition, these membranes can be made very thin, so that little excess pressure is needed for emulsion formation. In principle, this affords the possibility of making accurately monodisperse emulsions.

In practice, however, it has been found that in the use of such photolithographically manufactured membranes the drops often coalesce, so that the emulsion also contains larger drops. This proves to occur especially at the time when the drops appear out of the pores. In hindsight, this is because the pores on such a membrane are situated rather close to each other and because the position of the pores where drops form is random. As a result, the drops already come into mutual contact while they are being formed. A known method of preventing this is to place the pores further apart. A disadvantage of this, however, is that etching a layer under the membrane takes place only locally, adjacent a pore, so that the membrane in this phase does not come entirely clear of the substrate.

It is an object of the invention to provide a method for manufacturing a membrane for use in emulsification, whereby drops form at all or a majority of the pores, whereby an emulsion with an accurately controllable drop size distribution can be made without coalescence occurring at the surface of the membrane or coalescence having any adverse effect on the drop size distribution.

It is an object of the invention to provide a method for manufacturing a membrane for use in emulsification, wherein in the manufacture use is made of etching through the pores in the membrane, and wherein the maximum etching distance and the distance between the pores can be chosen independently of each other.

It is an object of the invention to provide an emulsification technique whereby an emulsion with an accurately controllable drop size distribution can be made without coalescence occurring at the surface of the membrane.

It is an object of the invention to provide a membrane and an apparatus with such a membrane for use in emulsification, whereby an emulsion with an accurately controllable drop size distribution can be made without coalescence occurring at the surface of the membrane or coalescence having any adverse effect on the drop size distribution.

The invention provides a manufacturing method according to claim 1. In it, when etching away substrate through the holes in the membrane, use is made of holes for use in emulsion formation and of supplemental holes between the pores, having such a diameter that the supplemental holes do not contribute to the emulsion formation. As the supplemental holes are situated between the pores, the maximum etching distance that is to be etched away starting from a pore or supplemental hole to where the substrate is etched away starting from other pores or supplemental holes, is smaller than it would be if the etchant were administered solely through pores. Thus, etching away is simplified without increased risk of coalescence. The pressure across the membrane in the emulsion formation is preferably chosen such that a flux of the disperse phase occurs through the first holes, but not through the supplemental holes.

In one embodiment, after etching away, an extra layer is provided on the membrane, whereby diameters of the pores and the supplemental holes are reduced such that they do not contribute to the emulsion formation. This allows etching with fairly large supplemental holes. In a further embodiment, the extra layer is even so thick that the extra holes are at least substantially closed. In one embodiment, the supplemental holes are positioned according to a periodically repeating grid, and the pores are positioned according to a subgrid which repeats itself with a multiple of a period of the periodically repeating grid. This enables a simple pattern without risk of coalescence. The invention also provides a microsieve for use in emulsification, provided with a membrane having therethrough a pattern of pores for forming drops in an emulsion, wherein between the pores in the pattern supplemental holes are provided having a diameter such that the supplemental holes do not contribute to the emulsion formation. Further, the invention provides a method for forming an emulsion according to claim 12, wherein use is made of a membrane with holes for emulsification and supplemental holes and wherein a pressure is applied across the membrane whereby the supplemental holes do not contribute to the emulsification.

These and other objectives and advantageous aspects of the invention will be further illustrated in and by the description of the following figures.

Figure 1 shows a part of an emulsification apparatus. Figure 2 shows a geometry of a pore.

Figures 3-4 schematically show top plan views of sieve membranes.

Figure 1 shows a part of an emulsification apparatus. It comprises a cross-flow channel 10 with a wall having therein a drain surface of a microsieve 12. Further, the apparatus comprises a supply channel 14 for supplying disperse phase to a supply surface of microsieve 12.

In operation, a cross-flow of a continuous phase through cross-flow channel 10 is realized. Simultaneously, under excess pressure with respect to the continuous phase, disperse phase is supplied to the supply surface of microsieve 12. As a result, the disperse phase is forced through pores in microsieve 12, whereby drops form which are entrained by the cross-flow of the continuous phase. Thus, an emulsion is created which comprises the carrier liquid and drops of the disperse phase.

The probability that a drop has a particular size is partly determined by the diameter of the pores and the pressure difference applied across the membrane. According as the pressure difference is greater, the spread in the probability distribution increases.

The geometry of the pores determines a minimum pressure difference that is needed to form drops. To be able to form a drop through the pores, a critical pressure needs to be overcome. This pressure is given, in approximation, by

Pcrtt

wherein γ is the interface surface tension (N/m) between the continuous phase and the disperse phase.

Figure 2 shows the geometry of a pore in cross section, in which one diameter di is indicated in the pore opening. d2 is the diameter perpendicular to the plane of the drawing. In the case of a circular opening, di and d2 are equal to each other. In the case of slotted openings, di and d2 correspond respectively to the width and length of the slot. The critical pressure can also depend on the geometric shape of the cross section of the pore. In practice, for that reason, the critical pressure can also be determined experimentally. In the cross section, the continuous phase 20 and the disperse phase 22 are indicated, with an interface in the pore, θ is the contact angle that occurs between the interface and the wall 24 of the pore opening. In practice, however, a higher pressure difference is needed than the critical pressure difference. Only at a pressure difference higher than the critical pressure will a flux of the disperse phase through the membrane occur. The size of the flux depends on the pressure difference and the thickness of the membrane. According as the membrane is thicker, a greater pressure difference will be needed to maintain a reasonable flux. In practice, the pressure used is expressed as a factor with respect to the critical pressure. This factor is typically from 1.1 to ca. 10, the higher factors being used to obtain a higher flux. A high excess pressure, however, has been found to be at the expense of the monodispersity of the emulsion, that is, it is accompanied by a greater spread in the size of the drops. When thin membranes are used, this excess pressure can remain low, so that the spread in the drop size can be limited. In membrane emulsification, it always holds that the drop formed is larger than the pore from which the drop is formed. Accordingly, the distance between two pores should be at least greater than the drop size in order to prevent coalescence. The ratio between drop size and pore size is typically a factor of 3 to 10. This means directly that it is desirable that the pores be situated at a fairly large distance from each other, preferably at a distance of greater than 3 times the pore size.

In an embodiment of the invention, the membrane is manufactured with a photolithographic process, in which the size and position of the pores are photolithographically defined by a pattern in a mask. Then, preferably, for all pores from which drops are formed, the same pore size is defined. Thus, it becomes possible for all drops formed to obtain the same size. Without departing from the invention, however, it is possible to define different pore sizes for the pores from which drops are formed, for instance when it is desirable to obtain a predetermined size distribution of the drops. This is done by choosing the fraction of pores with different sizes in accordance with the desired size distribution. In this embodiment, in addition to the pores from which drops are formed, photolitho graphically also extra pores are defined which are too small for drops to be formed during emulsification at the employed pressure difference across the membrane. These pores are provided to enable a substrate layer to be etched away through the pores under the whole defined membrane area.

Figures 3 and 4 shows examples of useful pore patterns. Shown here is a periodic grid of relatively smaller pores 30 (for instance of a diameter of 1.4 micrometers) on which each time after a number of grid periods a relatively larger pore 32 (for instance of a diameter of 5 micrometers) is included instead of a smaller pore. More generally, larger pores 32 form a subgrid of the grid of the smaller pores 30. As shown in Figure 3, use can be made of a rectangular grid. But also other grids are possible. Thus, Figure 4 shows a grid in which the grid vectors are at an angle with respect to each other. Preferably, an angle of about 60 degrees is used because it enables an optimum pore density. A condition is that the grid continues to meet the requirement that the shortest distance between the pores 32 is chosen such that in practice coalescence is prevented.

For the rest, use can be made of any available manufacturing process. In an example, the starting point is a silicon wafer as substrate, on which a silicon nitride layer is provided of a thickness of for instance one micrometer (or for instance 0.4 micrometers or other desired thickness). In the silicon nitride layer, holes are provided by photolithographic technique. This can be done with any suitable technique, for instance by first depositing the silicon nitride layer, then providing a photoresist on this layer, next exposing this photoresist via a mask which defines the shape and size of the holes, developing the photoresist and then locally etching away the silicon nitride layer through holes in the photoresist. This is only an example: from the prior art, other techniques are known to make layers with holes and these can be used too. In other techniques, the holes may already be present when providing the silicon nitride layer, for instance when pads are provided on the substrate to which the silicon nitride layer does not adhere, or later removed by planarization.

With an isotropic etchant, next, etchant is supplied through the holes in the silicon nitride layer, with which the substrate in a layer under the silicon nitride layer is etched away. Isotropic means that the etchant does not etch predominantly along predetermined crystal planes. The etchant is preferably an isotropic etching liquid, but this etching step can also be carried out with an isotropic plasma etch, using a gaseous etchant. With the isotropic etchant, the silicon nitride layer is underetched, so that around the holes the underside of the silicon nitride layer is cleared of silicon. Etching is continued at least to the extent where the etched-away areas around the holes merge, so that a number of sieve fields are created, in each of which a number of holes are situated and in which no silicon is situated at the underside of the silicon nitride layer. Etching further than is needed to clear the underside of the silicon nitride in the sieve fields of silicon is, in principle, not necessary. The etching depth used is, for instance, between five and ten micrometers. The largest distance between the smallest pores is determined by the etching depth used, such that the distance is preferably twice the etching depth or less.

In addition, areas of the substrate are etched away with an anisotropic etchant from the rear side of the substrate (i.e. from the side opposite the side on which is the silicon nitride layer). This can be done before or after etching through the holes. Preferably, it is done before etching. Thus, open areas are formed under the sieve fields, with between them residual silicon serving as support for the silicon nitride layer.

After etching of the rear side and etching away a first layer through the hole pattern, the etched-away layer can be enlarged, in effect the space be deepened by the use of an anisotropic etching step without the lateral dimensions thereby being significantly enlarged. In this way, it is possible to use a large part of the silicon nitride layer for sieve fields. When etching is done from the rear, a slanting substrate surface is formed which continues at an angle unequal to ninety degrees with the membrane layer as far as the membrane layer. The hole at the membrane surface determines which part of the membrane surface can be used for sieve fields. If etching were done solely from the rear, the etched hole in the substrate would thereby be smaller at the membrane surface than further away from the substrate. Thus, the part of the membrane surface available for sieve fields remains relatively small. When etching is done through the holes as well, it is possible with high accuracy to remove the silicon under areas where holes are situated. As a result, a maximum part of the silicon nitride surface can be used for holes.

According to the invention, then, etching is done through both larger holes and smaller holes. The extent to which etching is to be done around these holes is thus determined by the distance between neighboring holes, virtually independently of whether these are larger or smaller holes. As a result, also the distance over which etching is done along the edge of a sieve field remains limited, so that the support structure of the silicon can remain close to the larger holes. Thus, the useful sieve surface is enlarged. After etching of the structures, preferably an extra silicon nitride layer is provided (for instance with LPCVD). This has as an effect that the holes will become smaller. This extra layer is for instance 0.6 micrometers thick, which will cause the diameter of the holes to decrease by approximately 1.2 microns. The photolithographically defined size of the larger holes is preferably chosen so large that the eventual diameter has the desired size for the emulsification process. For the smaller holes, this is not necessary. In one embodiment, these smaller holes are even at least substantially wholly closed by the extra layer. In another embodiment, these smaller holes remain open. The extra layer can moreover protect the residual silicon of the substrate from aggressive substances. During the emulsification process, the pressure difference between the disperse phase and the continuous phase is made so large as to be higher than the critical pressure difference for forming drops through the larger pores 32, but lower than the critical pressure difference for the formation of drops through the smaller pores 30 (at least, if they are still open). Thus, only the larger pores 32 will contribute to the size distribution of the drops in the emulsion. The distance between the larger pores 32 is chosen such that coalescence of the drops during the formation through the holes is avoided but the larger pores are otherwise as close as possible to each other as is consistent with the desired drop size, to achieve a highest possible yield. The required distance can be determined experimentally. In practice, the drops prove to be typically 3 to 10 times as large as the pore diameter, so that the pore distance between large pores 32 needs to be commensurately large (for instance greater than or equal to the drop diameter). Depending on the circumstances, however, a different distance may be necessary.

Although the invention has been described on the basis of a specific embodiment, it will be clear that the invention is not limited to this specific embodiment. Thus, for instance, other materials than silicon and/or silicon nitride can be used. Also, the holes can be defined with other techniques than lithographic techniques, for instance with punch and die techniques.

Although preferably use is made of holes which are arranged in periodic grids, it will be clear that also other distributions of hole positions can be used, for instance quasi-random distributions, provided that, so doing, supplemental holes are situated between the pores. As the supplemental holes are situated between the pores, the maximum necessary etching distance starting from a pore will generally be smaller than the distance between pores mutually. That supplemental holes are situated between the pores is understood to mean that the supplemental holes are situated in or at the edge of a polygonal area which has the centers of pores as corner points and itself does not further contain any pores. In the sense in which the term "between" is used here, it is hence not requisite that supplemental holes be situated in a line between a pair of pores, although this is naturally not excluded and actually preferred because this limits the maximum etching distance in an efficient manner. The use of a grid of pores and supplemental holes has the advantage that a maximum packing degree is possible, which leads to a high efficiency.

The holes in the membrane layer are preferably circular in cross section. However, the invention is not limited thereto. Alternatively, holes of an elongate cross section can be used. Further, the larger holes 32 are mutually preferably equally large (barring differences due to process fluctuations) and the smaller holes 30 are mutually preferably equally large (barring differences due to process fluctuations). However, the invention is not limited to this either. Thus, the smaller holes 30 can have mutually different diameters without this affecting the emulsification, provided that they remain small enough not to permit drops being formed through them at the pressure difference used.

The larger holes 32, too, can intentionally be given different diameters, for instance to realize a specified non-monodisperse drop size distribution in the emulsion. Thus, for instance, an emulsion with drops of two different sizes in a particular concentration ratio can be realized by using two sizes of larger holes in a numerical ratio corresponding to the desired concentration ratio.

Any desired ratio between the size of larger holes 32 and smaller holes 30 can be used, provided that it is sufficiently great to enable the setting of a pressure difference at which there is a flux through the larger holes 32 but not through the smaller holes 30. To be taken into account here is some spread in the size as a result of process fluctuations and pressure fluctuations. According as these are better controllable, the diameters can differ less. Preferably, the surface of the larger pores is at least a factor of 2.25 larger than the surface of the smaller pores 30. This is a safe margin for practice. A smaller surface ratio of for instance 1.2 at a minimum can also be used, but then the safe margin for the pressure during use is very small. A greater ratio of 1.5 or 1.8 at a minimum yields more of a margin, but 2.25 at a minimum will afford an advantageous margin in practice. It is safer still, if the surface ratio is four at a minimum. The minimum surface ratio can be made smaller by using pores of differently shaped cross section. If the large pores are made elongate, and the small pores circular or at least less elongate than the large pores, a wider safe margin can be realized with the same surface ratio. It is desirable to properly control the uniformity of the diameters.

A spread of less than 10% in diameter has been found to be feasible with existing photolithographic processes.

Generally, the number of smaller pores 30 will be greater than the number of larger pores 32. Thus, it is possible to position the larger pores at a sufficient distance to prevent coalescence. The greater and smaller pores can be of different shape or of identical shape.

The outer shape of the sieve fields (areas with holes in the membrane under which substrate material has been etched away) is largely determined by the position of the smaller pores 30. The positions of these smaller pores 30 are preferably between the larger pores 32 without extending beyond the connecting lines between the larger pores 32 at the edge of the sieve field, or at least without extending outside those connecting lines by more than a fraction (less than 1, for instance less than 0.5 or 0.1) of the distance between neighboring larger pores 32, or within the connecting lines up to less than such a fraction from the connecting lines. This enables efficient utilization of the membrane surface.

Claims

1. A manufacturing method for manufacturing a membrane with pores for forming drops in an emulsion, in which manufacturing method the membrane is formed by etching away a substrate under the membrane at least partly with isotropic etchant which is supplied via the pores and supplemental holes in the membrane, wherein the supplemental holes are situated between the pores and have a smaller diameter than the pores, such that the supplemental holes do not contribute to the emulsion formation.

2. A manufacturing method according claim 1, for use under a pressure difference across the membrane during the formation of the emulsion, wherein the diameter of the pores is so large that at the pressure difference a flux of the disperse phase through the first holes occurs, and the diameter of the supplemental holes is so much smaller than the diameter of the pores that at the pressure difference no flux of the disperse phase through the second holes occurs.

3. A manufacturing method according to claim 1 or 2, wherein after etching away, an extra layer is provided on the membrane, with which diameters of the pores and the supplemental holes are reduced, wherein the diameter of the supplemental holes at least after the reduction is so small that the supplemental holes do not contribute to the emulsion formation.

4. A manufacturing method according to claim 3, wherein the extra layer is made so thick that the supplemental holes are at least substantially closed.

5. A manufacturing method according to any one of the preceding claims, wherein the supplemental holes are positioned according to a periodically repeating grid, and the pores are positioned according to a subgrid which repeats itself with a multiple of a period of the periodically repeating grid.

6. A microsieve for use in emulsification, provided with a membrane having therethrough a pattern of pores for forming drops in an emulsion, wherein between the pores in the pattern supplemental holes are provided with such a diameter that the supplemental holes do not contribute to the emulsion formation.

7. A microsieve according to claim 6, wherein the supplemental holes are placed according to a periodically repeating grid, and the pores are placed according to a subgrid which repeats itself with a multiple of a period of the periodically repeating grid.

8. A microsieve according to claim 6 or 7, wherein a surface of the pores is at least a factor of 2.25 greater than a surface of the supplemental holes.

9. A microsieve according to claim 6, 7 or 8, wherein more supplemental holes are included than the pores.

10. A microsieve according to any one of claims 6 to 9, provided with a support structure against which the membrane rests, which support structure comprises openings over which the membrane continues, and opposite each of the openings the membrane comprises a number of the pores and the supplemental holes, while a circumference of the openings corresponds substantially to a circumference of an area with pores and supplemental holes.

11. A microsieve according to any one of claims 6 to 9, provided with a support structure against which the membrane rests, which support structure comprises openings over which the membrane continues, and opposite each of the openings the membrane comprises a number of the pores and the supplemental holes, while an edge of the openings corresponds substantially to a circumference of an area with pores, and wherein the supplemental holes are spread as far as the circumference of said area up to not less than a first fraction of a minimum distance between the pores and not more than a fraction of a minimum distance between the pores outside the circumference of said area.

12. An emulsification method for forming an emulsion, comprising the steps of:

- supplying a disperse phase to a supply side of a membrane through which extend first pores of a first diameter and second pores of a second diameter, wherein the first pores are placed in a pattern with the second pores therebetween, so that a maximum distance between the first and second pores is less than distances between neighboring first pores;

- supplying a continuous phase on a drain side of the membrane;

- maintaining a pressure difference between the supply side and the drain side which is so great that a flux of the disperse phase occurs through the first pores, but not through the second pores.

13. An emulsification method according to claim 12, wherein the membrane is manufactured by etching away a substrate under the membrane at least partly with isotropic etchant which is supplied via the first and second pores.