WO2012166053A1 - Membrane filtrante - Google Patents

Membrane filtrante Download PDF

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Publication number
WO2012166053A1
WO2012166053A1 PCT/SG2012/000191 SG2012000191W WO2012166053A1 WO 2012166053 A1 WO2012166053 A1 WO 2012166053A1 SG 2012000191 W SG2012000191 W SG 2012000191W WO 2012166053 A1 WO2012166053 A1 WO 2012166053A1
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WO
WIPO (PCT)
Prior art keywords
cross
mold
substrate
layer
holes
Prior art date
Application number
PCT/SG2012/000191
Other languages
English (en)
Inventor
Shashi Ranjan
Yong Zhang
Original Assignee
National University Of Singapore
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National University Of Singapore filed Critical National University Of Singapore
Publication of WO2012166053A1 publication Critical patent/WO2012166053A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/005—Microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/3842—Manufacturing moulds, e.g. shaping the mould surface by machining
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/42—Moulds or cores; Details thereof or accessories therefor characterised by the shape of the moulding surface, e.g. ribs or grooves
    • B29C33/424—Moulding surfaces provided with means for marking or patterning
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y10/00—Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • G—PHYSICS
    • G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
    • G03F7/0002—Lithographic processes using patterning methods other than those involving the exposure to radiation, e.g. by stamping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/021—Pore shapes
    • B01D2325/0212—Symmetric or isoporous membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/06—Surface irregularities
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/0827—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using UV radiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/0844—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using X-ray
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0805—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation
    • B29C2035/085—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using electromagnetic radiation using gamma-ray
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0866—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation
    • B29C2035/0872—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation using ion-radiation, e.g. alpha-rays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0866—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation
    • B29C2035/0877—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation using electron radiation, e.g. beta-rays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0866—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation
    • B29C2035/0883—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation using neutron radiation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/40—Plastics, e.g. foam or rubber
    • B29C33/405—Elastomers, e.g. rubber
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0888—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using transparant moulds
    • B29C35/0894—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using transparant moulds provided with masks or diaphragms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C59/00—Surface shaping of articles, e.g. embossing; Apparatus therefor
    • B29C59/14—Surface shaping of articles, e.g. embossing; Apparatus therefor by plasma treatment

Definitions

  • the present invention generally relates to a filtering membrane and a method of forming the same.
  • the present invention also relates to a mold and a method of forming the same.
  • the present invention also relates to a microfluidic device.
  • micro-scale devices for handling biologically relevant micron-sized entities, like cells or micro- beads, to satisfy ever growing biological and medical needs. Many of such biological and medical needs require either sorting or separation or patterning/trapping of these micron-sized entities and have attracted attention for developing new micro-devices.
  • a few examples of biological and medical separations include separation : of circulating tumor cells or epithelial cells from blood, separation of white blood cells from whole blood, separation of blood-cell subtypes, and isolation of stem cells from amniotic fluids.
  • An example of cell-patterning for basic studies on cell biology include individual cell studies.
  • separation and patterning of micro-beads conjugated with functional bio-molecules has provided a new tool for immunoassays .
  • Micro-particle separation has been achieved by various types of micro-devices based on either intrinsic biophysical differences (such as size, shape, polarisability or charge) or extrinsic differences (such as magnetic labeling of different cells) .
  • Track-etched membranes with different pore sizes are commercially available. However, track-etched membranes have randomly placed pores with variations in pore shape and size and have relatively low pore density. Fusion of two or more pores can also be found in track- etched membranes which reduces the efficiency of filtration. These membranes cannot be fabricated with desired structures around the pore. Also, fabrication of such membranes requires expensive equipment or harsh chemicals for etching and hence is not suitable for high- end applications.
  • porous membrane technology has a major problem of clogging or fouling during a filtration process.
  • the clogging of pores results in increased pressure build-up and eventually failure of membrane function.
  • micro-particles have been demonstrated either by creating micro-traps using properties such as electrical, mechanical or optical, or by using chemically modified micro-patterned surfaces. While some of these approaches (like electrical or mechanical traps) may be used for achieving simultaneous functionalities, the efficiency of such approaches is low and sensitive to the process parameters. Further, mechanical traps using pillars, wire or V C shaped structures suffer from low throughput, clogging and incomplete separation.
  • a filtering membrane comprising a substrate having a plurality of holes that extend through the substrate, and arresting formations provided around the openings of the holes on at least one side of the substrate, the arresting formations being configured to arrest the ingress of particulate entities of a selected particle oversize from entering the holes.
  • the filtering membrane may not suffer from problems such as pore-clogging or filter fouling.
  • the filtering membrane may be used to filter a plurality of particulate entities or particles having different particle sizes so as to separate or pattern the particulate entities or particles.
  • the particulate entities or particles that have a smaller particle size than the holes can pass through the holes while those having a larger particle size are trapped by the arresting formations.
  • the larger particles are trapped by the arresting formations, due to the interstitial gaps in between adjacent arresting formations, smaller particulate entities or particles and/or fluid can still pass through the holes.
  • the filtering membrane may not experience high pressure drops as compared to another membrane that does not have the arresting formations thereon.
  • the arresting formations may confer multi-functionalities to the filtering membrane such as enhanced ⁇ filtration, high efficiency patterning of particles and further functionality due to non-blockage e-f—-heie-s--due—- ⁇ --th-e- ⁇ the trapped. particles may be separated from the un-trapped particles (that is, those particles which pass through the holes) while not restricting the flow of smaller sized particles and fluid. ⁇
  • the ability to trap particles while allowing fluid to flow around the trapped particles to the holes may allow for enhanced interaction (due to a graeter contact area) between the trapped particles and fluid.
  • the trapped particles may be functionalized with, for example, protein, antibody or DNA, while the fluid may contain target analytes that can bind to the trapped particles while flowing to the holes.
  • a method for forming a filtering membrane comprising a substrate having a plurality of holes that extend through the substrate, and arresting formations provided around the openings of the holes on at least one side of the substrate, the method comprising the steps of:
  • a mold comprised of a layer of a cross-linkable material to a cross-linking treatment to cross-link the cross-linkable material and to thereby form imprint formation structures thereon, wherein the degree of cross-linking throughout the mold is unequal throughout;
  • a mold having imprint formation structures thereon having a first region . that has a substantially uniform cross-sectional area along the length of the first region and a second region that has a varying cross-sectional area along the length of ir ⁇ ⁇ s ⁇ corrd ⁇ 3 ⁇ 4 ⁇ g ⁇ on " :
  • a method for forming a mold having imprint formation structures thereon comprising the step of subjecting a mold comprised of a layer of a cross- linkable material to a cross-linking treatment to crosslink the cross-linkable material and to thereby form imprint formation structures thereon, wherein the degree of cross-linking throughout the mold is unequal throughout.
  • a microfluidic device comprising a channel for flow of a plurality of particulate entities having ' different particle sizes therein; and a membrane in fluid communication with the flow channel, the membrane having a plurality of holes that extend through the membrane, and arresting formations provided around the openings of the holes on at least one side of the membrane.
  • a substrate having three-dimensional structures thereon, wherein the three-dimensional structures have a varying cross-sectional area along the length of the structures.
  • a method for forming a substrate having three-dimensional structures thereon comprising the step of subjecting the substrate comprised of a layer of a cross- linkable material to a cross-linking treatment to crosslink the cross-linkable material and to thereby form three-dimensional structures thereon, wherein the degree of cross-linking throughout the substrate is unequal.
  • particulate entity or “particle” are to be interpreted broadly to include a variety of materials or substances that can be characterized in terms of its dimensions or size.
  • the particulate entity or particle may include, but is not limited to, cells, both eukaryotic (e.g., leukocytes, erythrocytes or fungi) and prokaryotic (e.g., bacteria, protozoa or mycoplasma), viruses, cell components, macromolecules , microparticles , beads (including microbeads), etc.
  • cross-link or “cross-linked” refer to an interconnection (usually chemical bonding) between monomers or co-monomers making up a polymer or between two types of discrete polymers.
  • organic polymer refers to a polymeric material which has repeating units of a backbone composed mainly of carbon atoms or a ring containing carbon atoms, and which also contains hydrogen.
  • the polymeric material may also contain other elements such as, for . example, sulphur, oxygen or nitrogen .
  • micron-sized or “micron-range” refer to a dimension that is more than about 1 pm to about 1000 pm.
  • the term "about”, in the context of concentrations of components of the formulations, typically means +/- 5% of the stated value, more typically +/- 4% of the stated value, more typically +/- 3% of the stated value, more typically, +/- 2% of the stated value, even more typically +/- 1% of the stated value, and even more typically +/- 0.5% of the stated value.
  • range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the , possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
  • the filtering membrane comprises a substrate having a plurality of holes that extend through the substrate, and arresting formations provided around the openings of the holes on at least one side of the substrate, the arresting formations being configured to arrest the ingress of particulate entities of a selected particle oversize from entering the holes.
  • the holes may allow the ingress of particulalte entities or particles of a selected particle undersize to enter the holes.
  • the arresting formations may be integrally formed with, and extend from, the substrate.
  • the arresting formations may be formed at the same time as the holes.
  • the arresting formations may be three-dimensional (that is, 3-D) structures that extend from at least one surface of the substrate.
  • a number of arresting formations may be chosen as appropriate to surround a hole while trapping a particulate entity (or particle) above the hole.
  • the number of arresting formations that surround a hole may be at least three, at least four, at least five or at least six.
  • the shape of the arresting formations is not particularly limited as long as they define a region, typically above the hole, for trapping a particulate entity or particle, while allowing fluid (and optionally smaller sized particulate entities) to enter the holes from the sides of the arresting formations.
  • the arresting -formations may prevent the ' escape of the trapped particles when subjected to a wash. Due to the ability of the filtering membrane to allow fluid through the hole, the filtering membrane may not experience high pressure-dr_o_, which would otherwise be experienced by another filtering membrane without the arresting formations. The decrease in the pressure drop (as compared to another filtering membrane without the arresting formations) may be due to the arresting formations which trap the larger sized particles such that they do not enter the holes and get trapped there.
  • the arresting formations may generally taper from a base portion adjacent the holes to a smaller end portion. As such, the distance between adjacent arresting formations surrounding a hole may not be equal when extending from the base portion to the end portion.
  • the shape of the arresting formations may be a pyramidal shape with an inclined surface being presented to the ⁇ particulate entity. Other shapes may include frustum- shape, dome-shape, doll-shape, etc.
  • the arresting formation may be of the same material as the substrate.
  • the arresting formations and substrate may be comprised of an organic polymer.
  • the organic polymer may comprise monomers selected from the group consisting of methylesiloxanes , ethylenes, propylenes, methyls, pentenes, amides, sulphones, ethersulphones, esters, carbonates, acrylonitriles , butadienes, styrenes, imides, amic acids, phenols, styrene sulphonic acids, acrylic acids, methacrylic acids, saccharides, thiophenols and combinations thereof.
  • the organic polymer may be selected from the group consisting of polydimethylsiloxanes ; polyolefins such as polyethylene, polypropylene, polymethylpentene; polyamides and polyimides, including aryl polyamides and aryl polyimides; polystyrenes or substituted polystyrenes; polysulphones such as polyethersulphones; polyesters such as polyethylene terephthalates, polybutylene terephthalates; polyacrylates ; polycarbonates ; pgJLyamic__acids ; polyphenols; polystyrene sulphonic acids; polyacrylic acids; polymethacrylic acids; polythiophenols; polysaccharides such as agarose and alginate as well as co-polymers such as polyacrylic acid/butadiene copolymer or polystyrene/butadiene copolymer.
  • polyolefins such as polyethylene, polypropylene, polymethyl
  • the arresting formations may be dimensioned in the micron-range. Accordingly, the height, length of the base portion and length of the end portion may be dimensioned in the micron-range. It is to be noted that the dimensions of the arresting formations are not particularly limited and is adjustable according to the size of the target particulate entity that is to be trapped by the arresting formations. The size and shape of the arresting formations may be dependent on the size and shape of the imprint formation structures of the mold material when forming the filtering membrane (as will be discussed further below) .
  • the peak-to-peak distance between adjacent arresting formations may also be in the micron-range.
  • the holes may have a substantially consistent cross- sectional shape when extending through the substrate.
  • the cross-sectional dimension of the holes may be in the micron-range.
  • the holes may be arranged throughout the substrate in a random distribution or in a non-random distribution .
  • the anisotropic cross-linking treatment may comprise the step of exposing the mold to one of ultraviolet (UV) light or ⁇ ionizing radiation.
  • UV ultraviolet
  • the extent of desirable cross-linking may be dependent on the exposure energy of the cross-linking treatment, which in turn may depend on the time of the exposure based on the power of the light- energy source.
  • the time of exposure to UV light may be selected from the range of about 1 second to about 2 minutes, about 10 seconds to about 2 minutes, about 20 seconds to about 2 minutes, about 30 seconds to about 2 minutes, about 40 seconds to about 2 minutes, about 50 seconds to about 2 minutes, about 60 seconds to about 2 minutes, about 70 seconds to about 2 minutes, about 80 seconds to about 2 minutes, about 90 seconds to about 2 minutes, about 100 seconds to about 2 minutes, about 110 seconds to about 2 minutes, about 1 second to about 10 seconds, about 1 second to about 20 seconds, about 1 second to about 30 seconds, about 1 second to about 40 seconds, about 1 second to about 50 seconds, about 1 second to about 60 seconds, about 1 second to about 70 seconds, about 1 second to about 80 seconds, about 1 second to about 90 seconds, about 1 second to about 100 seconds, about 1 second to about 110 seconds, about 1 second to about 5 seconds, about 20 seconds to about 40 seconds.
  • the mold may be exposed to the UV light for about 30 seconds.
  • the power used during the UV light treatment may be s-e-Le.ct_e_d,__f_rom the range of about 1 mW/cm 2 to about 10 mW/cm 2 , about 1 mW/cm 2 to about 2 mW/cm 2 , about 1 .
  • the cross-linkable material may be exposed to the UV light through a photo-mask, which is patterned as desired.
  • the cross-linking treatment may comprise the step of adding a second layer of a cross-linkable material to the first layer to thereby allow diffusion of cross-linkable material from the first layer to the second layer ' .
  • the cross-linkable material in the two layers may be of the same material.
  • the first layer may be treated with ultraviolet (UV) light or ionizing radiation as described above.
  • the second layer may not require any cross-linking treatment as the cross-linking species from the first layer is able to diffuse to the second layer, that is, the cross-linking species is able to diffuse from the exposed region to the unexposed region.
  • a cross-linking treatment may be applied to the second layer .
  • the cross-linkable material may be a photosensitive material.
  • the cross-linkable material may be a negative cross-linking photoresist.
  • the negative cross-linking photoresist may be SU-8, AZ negative photoresist., poly (vinyl cinnamate) , Novolaks or poly ( t-Boc styrene) .
  • the thickness of the cross-linkable material is not especially limited and depends on the desired height of the arresting formations.
  • the method may comprise the step of providing the layer of the cross-linkable material onto a support material.
  • the support material may be used to form channels for the subsequent micro-fluidic device.
  • the support material may be silicon wafer or may be the same material as the cross-linkable material.
  • the method may comprise the step of providing a subsequent layer of cross-linkable material before or after the subjecting step (a).
  • This layer may be treated and developed to form pillars that, ' when applied to the substrate, form complementary holes in the substrate.
  • the mold may comprise imprint formation structures that comprise two regions, the first region containing the pillars and the second region containingthe cross-linked 3D structures. When this mold is applied to the substrate, the pillars of the mold form corresponding holes in the substrate while the cross- linked structures of the mold contribute to the formation of the arresting formations on the substrate.
  • the cross-linkable material may be deposited onto the support material or first cross-linkable layer by spin-coating. After each layer of cross-linkable material is deposited, the cross-linkable material may be subjected to a soft-baking step (or pre-exposure baking step) . This soft-baking step- may aid in the evaporation of solvents which are used to dissolve the material. The solvent allows spreading of the material on a surface (like silicon wafer) during spin-coating, but has to be removed after spin-coating as the solvent may interfere with the cross-linking step.
  • the soft-baking step may be &a-r-r-i-ed- out—f-o-r—-a— eriod—-of—time—s-eLected—.from—t.he__ aag_e of about 1 minute to about 20 minutes, about 1 minute to about 5 minutes, about 1 minute to about 10 minutes, about 1 minute to about 15 minutes, about 5 minutes to about 20 minutes, about 10 minutes to about 20 minutes and about 15 minutes to about 20 minutes.
  • the soft-baking step may be conducted at a temperature selected from the range of about 60°C to about 100°C, about 65°C to about 100°C, about 70°C to about 100°C, about 75°C to about 100°C, about 80°C to about 100°C, about 85°C to about 100°C, about 90°C to about 100°C, about 95°C to about 100°C, about 60°C to about.65°C, about 60°C to about 70°C, about 60°C to about 75°C, about 60°C to about 80°C, about 60°C to about 85°C, about 60°C to about 90°C and about 60°C to about 95°C.
  • the soft-baking step may be carried out over two time periods and temperature. As such, the soft- baking step may be carried out for about 1 minute to about 3 minutes at a temperature of 65°C and then rampedto 15 minutes at a temperature of 95°C.
  • the method may comprise the step of baking the exposed layer (or postexposure baking step) .
  • this may either control the degree of cross-linking in the exposed region or complete the cross-linking process.
  • the post-exposure bake can be carried out for a shorter period of time (such as from about 30 seconds to about 2 minutes) and a lower temperature (such as from about 60°C to about 95°C) as compared to the post-exposure bake for completing the cross-linking (which . can take place at about 15 minutes at 96°C) .
  • the post-exposure baking step may be carried out for a period of time from about 30 seconds to about 2 minutes, about 40 seconds to about 2 minutes, about 50 seconds to about 2 minutes, about 60 seconds to about 2 minutes, about 70 seconds to about 2 minutes, about 80 seconds to about 2 minutes, about 90 seconds to about 2 minutes, about 100 seconds to about 2 minutes, about 110 seconds to about 2 minutes, about 30 seconds to about 40 seconds, about 30 seconds to about 50 seconds, about 30 seconds to about 60 seconds, about 30 seconds to about 70 seconds, about 30 seconds to about 80 seconds, about 30 seconds to about 90 seconds, about 30 seconds to about 100 seconds and about 30 seconds to about 110 seconds.
  • the temperature during this period may be from about 60°C to about 95°C, about 65°C to about 95°C, ' about 70°C to about 95°C, about 75°C to about 95°C, about 80°C to about 95°C, about 85°C to about 95°C, about 90°C to about 95°C, about 60°C to about 65°C, about 60°C to about 70°C, about 60°C to about 75°C, about 60°C to about 80°C and about 60°C to about 85°C.
  • the post-exposure bake may be carried out at two temperatures for two time periods, such as for one minute at 65°C and then for 1 minute at 95°C.
  • the final post-exposure baking step may be carried out for about 10 minutes to about 20 minutes, about 12 minutes to about 20 minutes, about 14 minutes to about 20 minutes, about 16 minutes to about 20 minutes, about 18 minutes to about 20 minutes, about 10 minutes to about 12 minutes, about 10 minutes to about 14 minutes, about 10 minutes to about 16 minutes and about 10 minutes to about 18 minutes.
  • the temperature may be selected from about 95°C to about 100°C, about 95°C ' to about 96°C, about 95°C to about S7°C,—about 95°C to about 98 ;; C.,.. . about _ .
  • the final post-exposure, bake may include baking for about 3 minutes at 65°C, ramping to 96°C within 2 minutes and then 15 minutes at this temperature.
  • the mold may be subjected to a cooling step.
  • the cooling step may be carried out for about 25 to about 35 minutes, or 30 minutes.
  • the cooled mold may be developed in order to obtain the imprint formation structures.
  • the cooled mold may be developed in a developer solution which dissolves the material which is not cross-linked such that only the desired cross-linked material is left as the mold.
  • the applying step (b) may comprise the step of spin- coating the substrate layer onto ' the mold.
  • the substrate layer may be subjected to a baking step in order to speed up the cross-linking process and solidify the substrate layer.
  • the baking step may also allow the imprint formation structures to indent into the substrate and form the corresponding holes and arresting formations.
  • the substrate layer may be baked for a certain period of time (such as from about 5 minutes to about 30 minutes) at a certain temperature (such as from 50°C to about 70°C) .
  • the method may further comprise the step of removing the substrate layer from the mold.
  • the substrate layer may be removed from the mold through the use of solvents such as Iso-propanol or subjecting to heat at, for example, 70°C for about .30min.
  • the removed substrate layer may be subjected to a plasma treatment.
  • the plasma treatment may result in the generation of charged species on the surface of the removed—s-ubs-txa ⁇ -e Layjer so s___to_ allow ⁇ bonding of two layers of the substrate.
  • the plasma treatment may be an oxygen-plasma treatment for a period of about 20 seconds to about 1 minute at a power of about 150 W to about 250 W. In one embodiment, the oxygen plasma treatment is carried out for 30 seconds at 200 W.
  • the mold comprises imprint formation structures which have a first region that has a substantially uniform cross-sectional area along the length of the first region and a second region that has a varying cross-sectional area along the length of the second region.
  • the mold may be comprised of a cross-linkable material.
  • the cross-linkable material may be a photosensitive material.
  • the cross-linkable material may be a negative cross-linking photoresist.
  • the negative cross-linking photoresist may be SU-8, AZ negative photoresist, poly (vinyl cinnamate) , Novolaks or poly(t- Boc styrene) .
  • the first region of the imprint formation structures may be pillars which when applied to a substrate, form corresponding holes in the substrate.
  • the pillars ⁇ may be randomly or non-randomly distributed throughout the mold.
  • the cross-sectional shape of the pillars is not particularly limited and may be circular, squarish or any other shape.
  • the cross-sectional dimension (length or diameter as appropriate) of the pillar may be in the micro-scale.
  • the second region results in the formation of the arresting formations on the substrate.
  • the second region may be 3-D structures that are formed of cross-linked species.
  • the mold may be subjected to a cross-linking r-ea-t-me-n-t—a-s—defined above in order to form the 3-D structures.
  • the 3-D structures may have a varying cross- sectional area along the length of the second region such that the 3-D structures taper from one end towards the other end.
  • the base portion may have a greater dimension as compared to the end portion, which is connected to the first region.
  • the 3-D structures converge at the end portion.
  • the dimensions of the 3-D structures may be in the micron-range.
  • the method comprises the step of subjecting a mold comprised of a layer of a cross-linkable material to an anisotropic cross-linking treatment to cross-link the cross-linkable material, wherein the degree of cross-linking throughout the mold is unequal, to thereby form imprint formation structures thereon.
  • The- anisotropic cross-linking treatment may comprise the step of exposing the mold to one of ultraviolet (UV) light or ionizing radiation.
  • UV light treatment The conditions for the UV light treatment are as described above.
  • the cross-linkable material may be exposed to the UV light through a photo-mask, which is patterned as desired .
  • the cross-linking treatment may comprise the step of adding a second layer of a cross-linkable material to the first layer to thereby allow diffusion of cross-linkable material from the first layer to the second layer.
  • the cross-linkable material in the two layers may be of the same material.
  • the first layer may be treated with ultraviolet (UV) light or ionizing radiation as described above.
  • the second layer may not require any cross-linking treatment as the cross-linking species from the first la-yer is ⁇ _able__to diffuse to the second layer, that is, the cross-linking species is able to diffuse from the exposed region to the unexposed region.
  • a cross-linking treatment may be applied to the second layer.
  • the microfluidic device comprises a channel for flow of a plurality of particulate entities having different particle sizes therein; and a membrane in fluid communication with the flow channel, the membrane having a plurality of holes that extend through the membrane, and arresting formations provided around the openings of the holes on at least one side of the membrane.
  • the membrane may be as described above with regard to the filtering membrane.
  • the microfluidic device may be used to separate ⁇ particles that are larger than the holes from those that are smaller than the holes.
  • the smaller particles that pass through ' the holes may be collected in a collector.
  • the larger particles may be retained by the arresting formations while allowing fluid (and optionally smaller particles) ' to pass through the holes.
  • the particle may be tagged with a ligand that reacts with a target analyte such that if the target analyte is present in the fluid sample, the target analyte will bind to the ligand and this interaction between the ligand and its target analyte can be dectected.
  • the microfluidic device may be used for the patterning of microparticles or microbeads .
  • the particulate entities are not particularly limited and may include microbeads, cells, bacteria, fungi, yeasts, virus.
  • a substrate having three- dimensional structures thereon, wherein the three- dimensional structures have a varying cross-sectional area along the length of the structures.
  • This substrate may be of the same material as the mold described above.
  • the three-dimensional structures of this substrate are similar to the imprint formation structures of the mold and may be formed as described above.
  • a method for forming a substrate having three-dimensional structures thereon comprising the step of subjecting the substrate comprised of a layer of a cross-linkable material to a cross-linking treatment to cross-link the cross-linkable material and to thereby form three- dimensional structures thereon, wherein the degree of cross-linking throughout the substrate is unequal.
  • the cross-linking treatment is as described above.
  • Fig. 1(a) shows a diagram of a photo-mask with transparent circles.
  • Fig. 1(b) shows a diagram of a photo-mask with opaque circles.
  • Fig. 2 (a) (i) is a schematic diagram showing the arresting formations trapping particulate entities of different particle ' sizes while allowing. smaller particulate entities to pass through the holes.
  • Fig. 2 (a) (ii) is a schematic diagram of a single trapped particulate entity surrounded by a number of arresting formations .
  • Fig. 2(b) (i) is a schematic diagram of one process to make the master mold by way of UV light exposure.
  • Fig. 2 (b) (ii) is a schematic diagram of another process to make the master mold by way of diffusion.
  • Fig. 2(c) is a schematic diagram of the process to form the substrate.
  • Fig. 3(a) (i) shows a top view schematic representation of a microfluidic device incorporating the filtering membrane while the right side shows the bottom view of the microfluidic device.
  • Fig. 3(a) (ii) is an expanded view of the filtering membrane.
  • Fig. 3(b) is a schematic diagram of the fluid flow in the microfuidic device.
  • Fig. 4(a) shows a scanning electron microscopic (SEM) micrograph image of the master-mold obtained from Example 2 at ⁇ , ⁇ magnification.
  • Fig. 4(b) shows an SEM image of the porous PDMS film being peeled off from the master-mold from Example 3 at 55x magnification.
  • Figs. 4(c) to (f) show the SEM images of the top, bottom, side and the 45°-angled view of the final porous membrane film obtained from Example 3 at l,100x, l,200x, l,100x and ⁇ , ⁇ magnification respectively.
  • Fig. 5 shows an SEM ⁇ image and the associated measurements of a trap of the porous membrane obtained from Example 3.
  • Fig. 6(a) shows an SEM image at 850x magnification of the un-patterned clumps of beads on the membrane film integrated into the microfluidic device of Example 4.
  • Fig. 6(b) shows an SEM image at 80 Ox magnificatTohT """ of ⁇ "" larger beads of size ⁇ and 12 m being patterned on the film in Example 4.
  • Fig. 6(c) shows a graph of the patterning efficiency of the different sizes of beads in Example 4.
  • Fig. 6(d) shows the separation and patterning efficiencies of bead ratio groups for 5 ⁇ beads to ⁇ beads of 1:3, 1:2, 1:1, 2:1 and 3:1 in Example 4.
  • Fig. 6(e) shows an SEM image at 750x magnification of patterned yeast and cancer cells on the membrane film integrated into the microfluidic device of Example 5.
  • Fig. 6(f) shows the separation and patterning efficiencies of the cells in Example 5.
  • Fig. 7 shows the patterning efficiency of different bead concentrations in Example .
  • Fig. 8(a) shows a schematic diagram of the model used for studying the fluid flow velocity through the pores in Example 6.
  • Fig. 8(b) shows the velocity profile in m/s obtained by the COMSOL Multiphysics.
  • Figs. 9(a) to (c) show the SEM images at l,800x, l,700x and 2,500x magnifications respectively of trapped beads with a size of ⁇ , 12 ⁇ and 20 ⁇ respectively in the membrane filter obtained from Example 3 and used in Example 6.
  • Figs. 9(d) to (f) show the SEM images at 500x, ⁇ , ⁇ and 500x magnifications respectively of the normal filter used in Example 6.
  • Fig. 9(g) shows a plot of the percentage of beads that passed through the pores of the normal filter and the structured filter against the flow speed in Example 6.
  • Figs. 10(a) and (b) show the ,SEM images of the flow of ⁇ beads . through the micro-structured filter at l,900x magnification and the normal filter l,800x magnification respectively in Example 6.
  • Figs. 10(c) and (c) show the ,SEM images of the flow of ⁇ beads . through the micro-structured filter at l,900x magnification and the normal filter l,800x magnification respectively in Example 6.
  • FIG. 10(e) show the SEM images of the flow of 3 ⁇ beads through the rnicro-st IIctured ⁇ fiTEer " at ⁇ 7 ⁇ 7 ⁇ magiii ' fTeation ancf the normal filter at l,200x magnification respectively in Example 6.
  • Figs. 10(e) and (f) show the SEM images at 2,000x and ⁇ , ⁇ magnifications respectively of the flow of ⁇ and .3 ⁇ beads through patterned 12 ⁇ beads on the micro-structured filter in Example 6.
  • Fig. 10(g) shows the percentage of ⁇ and 3 ⁇ beads that passed through the interstitial gaps between the trapped ⁇ beads and the micro-structures of the normal filter and the structured filter used in Example 6.
  • Fig. 10(g) shows the percentage of ⁇ and 3 ⁇ beads that passed through the interstitial gaps between the trapped ⁇ beads and the micro-structures of the normal filter and the structured filter used in Example 6.
  • FIG. 10(h) shows the percentage of ⁇ and 3 ⁇ beads that passed through the interstitial gaps between the trapped 12 ⁇ beads and the micro-structures of the normal filter and the structured filter used in Example 6.
  • Fig. 10 (i) shows the efficiency in percentage of ⁇ , 3 ⁇ and 5 ⁇ beads that passed through the interstitial gaps between trapped MDA-MB-231 ' cells and the normal filter and the structured filter- used in Example 6.
  • Figs. 11(a) and (b) show the bright-field images of the target sample mold and the control sample mold respectively obtained in Example 7 to study the anisotropic cross-linking by the low-dose exposure method.
  • Figs. 11(c) and (d) show the SEM images of the target sample mold at l,400x magnification and the control sample mold respectively obtained in Example 7 to study the anisotropic cross-linking by the diffusion method .
  • Figs. 12(a) to (f) show the SEM images of the different shapes of structures, such as hour-glass shaped, popsicle-shaped and doll-shaped, obtained from Example 8.
  • the SEM images in Figs. 12(a) to (e) are at 350x magnification and the SEM image in Fig. 12(f) are at 330x magnification.
  • Figs. 12(g) to (i) show the graphs of the normalized values of different defining features against a variation of exposure energy at a PEB ramp-up temperature of 85°C to 90°C, 90°C to 96°C and 96°C to 100°C respectively in Example 8.
  • Figs. 13(a) and (b) show the SE images at 350x magnification of the film obtained at different exposure energies in Example 9.
  • Fig. 13(c) show the graph of the normalized values of different defining features against the variation of exposure energy in Example 9.
  • Figs. 14(a) and (b) show the SEM images at 350x magnification of the film obtained from Example 10.
  • Figs. 14(c) and (d) show the SEM images at 350x magnification of the film obtained in Example 11.
  • Figs. 14(e) and (f) show the graph of the normalized values of different defining features against the different exposure energies obtained from Examples 10 and 11 respectively.
  • Figs. 15(a) and (b) show the SEM images at 350x magnification of the film obtained from Example 12.
  • Fig. 15(c) shows the graph of the normalized values of different defining features against the different exposure energies obtained from Example ' 12.
  • Fig. 1(a) and Fig. 1(b) there are shown respective photo-masks 10.
  • Fig. 1(a) shows a photo- mask 10 with transparent circles 12 while
  • Fig. 1(b) shows a photo-mask 10 with opaque circles (14). Exemplary dimensions of the circles and inter-circle distances are also shown.
  • the photo-masks are used during the production of- the master mold ' during UV treatment.
  • Fig. 2(a) (i) is a schematic diagram showing the arresting formations 16 trapping particulate entities of different particle sizes such as particles 20a and 20b while allowing smaller particulate entity such as particle 22a to pass through the holes 18.
  • the larger .sized particulate entities particles 20a and 20b
  • the larger .sized particulate entities are trapped by the inclined surface of the arresting formations 16 and do not completely block the holes 18.
  • . fluid and optionally smaller-sized particulate entities
  • Fig. 2(a) (ii) is a schematic diagram of a single trapped particulate entity 24 surrounded by a number of arresting formations 16. As can be seen in Fig. 2(a) (ii) , the fluid (with flow direction depicted by arrow 26) is able to enter the hole 18 through the gaps provided between the arresting formations 16.
  • Fig. 2(b) (i) is a schematic diagram of one process 100 to make the master mold 30 by way of UV light exposure.
  • a layer of photosensitive material 34 is coated onto a substrate 32.
  • the photosensitive material may be baked for a period of time.
  • the photosensitive material 34 is exposed through a photo-mask- 38 (for channels) to UV light 35 and is baked for a short time.
  • a second layer 37 of the same ' photosensitive material is coated onto the exposed layer 36 and soft-baked.
  • the second layer 37 is exposed to a low dose of UV light 40 (without any photomask) and subjected to a post-exposure bake to generate partially cross-linked species 44.
  • a third layer of photosensitive material 39 is coated onto the second layer and soft-baked to allow interaction with partially cross-linked species 44.
  • the third layer 39 is then exposed ⁇ to UV light 35 via another photo-mask 42 (with patterns to form the pillars) and then subjected to a post-exposure bake.
  • the layered photosensitive material is developed to form the master mold 30 having the imprint formation structures thereon 46.
  • Fig. 2(b) (ii) is a schematic diagram of another process 110 to make the master mold by way of diffusion.
  • the first step is identical to that in process 100 of Fig. 2 (b) (i) above.
  • the difference between process 110 and process 100 is that the second layer 37 is exposed to UV light 35 via a photo-mask 42.
  • the photo-mask of Fig. 1(a) is used as the photo-mask 42 here.
  • the post-exposure bake after this UV exposure is also carried out for a shorter period of time as compared to that in the second step of process 100. The shorter post-exposure bake prevents complete cross-linking and allows diffusion to occur in the subsequent steps.
  • the short post-exposure bake after the second exposure controls the cross-linking of the exposed layer 36 and does not allow complete cross-linking of the exposed layer 36.
  • the coating of the third layer 39 allows for a non-uniform distribution of cross- linking species 44 from the exposed layer 36 to the unexposed third layer 39.
  • the remaining step is identical to the fourth step of process 100.
  • Fig. 2(c) is a schematic diagram of the process 120 to form the substrate 50.
  • a layer of the substrate 48 is deposited onto the master mold 30 to cover the imprint formations structures 46 and baked.
  • the thickness of the substrate 48 ' is controlled to allow formation of through- holes by pillars in the mater mold. It is then removed from the master mold using 2-propanol to form a porous substrate 50 having the arresting formations 52 and holes 54 therethrough.
  • Fig. 3(a) (i) shows a top view schematic representation of a microfluidic device 80 incorporating the filtering membrane 50' on the left and a bottom view of the microfluidic device 80 on the right.
  • Fig. 3(a) (ii) is an expanded view of the filtering membrane 50' showing the arresting formations 52' and the holes 54'.
  • Fig. 3(b) is a schematic diagram of the fluid flow in the microfuidic device 80.
  • the fluid may contain a plurality of particulate entities and is introduced into the microfluidic device 80 via inlet 84.
  • the fluid then flows in the channel 82 with outlet 88 open and outlet 80 closed.
  • the particulate entities encounter the filtering membrane 50' where larger sized particulate entities are captured by the arresting formations (not shown) while smaller sized particulate entities pass through the holes 54' to a collector 90.
  • Non-limiting examples of the invention and a comparative example will be further described in greater detail by reference to specific Examples, which should not be construed as in any way limiting the scope of the invention.
  • a master-mold was fabricated using the low dose exposure energy method, in accordance with the schematic process diagram in Fig. 2(b) (i).
  • the oxygen plasma treatment was done using a PX-250 plasma chamber from March Instruments Incorporated, Massachusetts, USA. Thereafter, the silicon wafer was soft-baked twice, the first for 2 min at 65 ° C and the second for 10 min at 95 ° C on a hot-plate to remove solvents (Sawatec AG, Germany) .
  • the patterned photo-mask schematically shown in Fig. 1(a) has a rectangular, array of circular open windows of 5 ⁇ diameter each separated by 15 ⁇ .
  • the patterned photo-mask acts as a design for creating imprint formation structures, also termed in the examples as "micro- structures", as the patterned mask blocks UV exposure on the SU-8 under the mask.
  • the photo-activated UV-exposed regions are thus able to form micro-structures.
  • a second layer of SU-8 was coated thereon at 6000 rpm. It was soft-baked twice, the first for 3 min at 65 ° C and the second for 15 min at 95 ° C.
  • PEB post-exposure bake
  • a third layer of SU-8 was coated thereon at 5000 rpm. It was soft-baked twice, the first for 1 min at. 65 ° C and the second for 15 min at 92 ° C.
  • a master-mold was fabricated using the diffusion method, in accordance with the schematic . process diagram in Fig. 2(b) (ii).
  • a second layer of SU-8 was coated thereon at 5000 rpm. It was soft-baked twice, the first for 3 min at 65°C and the second for 15 min at 95°C.
  • PEB was then performed for 30s at temperatures ramping from 78 °C to 85 °C. This short PEB permitted the partial cross-linking at the UV ⁇ exposed region of the first and second SU-8 layers.
  • a third SU-8 ' layer was then coated at 5000 rpm, which allowed mixing of the exposed and unexposed regions, thereby permitting some amount ⁇ of ⁇ dTffus " ion ⁇ fTom ' the exposed (photo-activated) layer to the unexposed layer. Due to such diffusion, a non-uniform distribution of cross-linked species was. observed. Thereafter, the third layer was soft-baked twice, the first for 1 min at 65 c C and the second for 15 min at 92°C.
  • the substrate was then baked at this temperature for 15 min. Thereafter, the substrate was cooled down for 30 min before developing it for a further 8 min. The master- mold was therefore obtained.
  • FIG. 4(a) A scanning electron microscopic (SEM) image of the master-mold obtained is shown in Fig. 4(a) at ⁇ , ⁇ magnification.
  • the micro-structures of the master-mold is seen as bright circles in Fig. 4(a).
  • Example 2 The master-mold obtained from Example 2 was used to fabricate a porous membrane in accordance with an embodiment of the present invention. This example was performed in accordance with the schematic process diagram of Fig. 2(c).
  • a polydimethylsiloxane (PDMS) base solution was thoroughly mixed with a curing ' agent in a ratio of 10:1 to obtain a PDMS solution.
  • the PDMS solution was degassed in vacuum desiccators for 30 min.
  • a small amount of PDMS solution was first dropped onto the arrayed structures of the master-mold to cap the structures and was baked for 15 min at 70 ° C.
  • the PDMS was then spun-coated at 1400 rpm onto the master-mold to cover the channels and baked for 10 min at 70 ° C.
  • the cap was then removed and another layer of PDMS was coated at 2500 rpm. A weight was applied to remove excess PDMS and the coated array was baked for 5 min at 50°C. The weight was then removed and the arrayed pillars of the master-mold were wiped with a small piece of silicon wafer.
  • a PDMS-containing collector was aligned to the arrayed structures and the collector was bonded to the array using oxygen-plasma treatment.
  • FIGs. 4(c), (d) , (e) and (f) SEM images of the top, bottom, side and the 45°- angled view of the final porous membrane film obtained are shown in Figs. 4(c), (d) , (e) and (f) respectively.
  • the 45°-angled view of the porous membrane shown in Fig. 4(f) shows that 3-D structures on top of 2- D pillars are created on one side of the film, evidenced by the pyramidal structures that surround funnel-like through-holes.
  • the reverse side of the film does not have any micro-structures, as seen in Fig. 4(d).
  • the porous membrane obtained from Example 3 was integrated into a microfluidic device as shown in the schematic diagram of Fig. 3(a) (i) .
  • the microfluidic device was used for separation of beads based on size and patterning of beads on the porous membrane .
  • each feature in a single through-hole of the porous membrane termed "trap" herein, was measured and the size .measurements are shown in Fig. 5.
  • the solid lines indicate the distance measured, while the dotted lines represent the line of feature between which the distance is measured.
  • the dimensions indicate that each trap is capable of holding any particle in the size-range of 6pm to 20 ⁇ . Consequently, it is hypothesized that particles having a size less than 6 m would be able to flow out of the microfluidic device.
  • the beads that passed through the pores of the device were collected from the sink and were counted. Single beads that were either not positioned in a single trap or not separated were washed away from the device and were collected back. These beads were then pumped again into the device. The above process was repeated for about 2 to 3 times.
  • the beads that did not pattern on the porous membrane in the device or that were not singly patterned on a single trap were counted in order to determine the number and the percentage of singly- patterned beads. Separation and patterning efficiencies were calculated as per the formulae below.
  • Fig. 6(c) The patterning efficiency of the different sizes of beads was charted in Fig. 6(c). From Fig. 6(c), it can be seen that beads of size ⁇ and 12 ⁇ were patterned at the highest efficiency at more than 90%, which is expected for the given dimensions of traps in this example.
  • the 7 ⁇ beads were patterned with slightly lower efficiency of about 85% since a single trap can capture more than one such bead and these beads may get stuck between the micro-structures of the pores during washing.
  • the efficiency for patterning of 19 ⁇ beads is low at about 30%. This is because the trapping of bigger particles may block the passageway of the neighboring pores which in turn hinder other big particles to be trapped in the vicinity.
  • the simultaneous separation and patterning of beads were also studied in this example by using a mixture of 5pm and ⁇ beads in varying ratios.
  • the concentration of the ⁇ beads was fixed to 10 5 beads/mL and the concentration of 5 ⁇ beads was varied according to the desired ratio.
  • Example 4 Cancer cells from cell-line MDA-MB-231 were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented by 10% fetal bovine serum (FBS) in a cell-culture flask. Cells were trypsinized and were counted using a hemocytometer . The cell solution was diluted in complete cell-culture medium to a concentration of 10 5 cells/mL.
  • DMEM Dulbecco's Modified Eagle Medium
  • FBS fetal bovine serum
  • Yeast cells were taken from an agar plate and mixed in the cell-culture medium. Yeast cells represent smaller sized cells, while cancer cells represent bigger sized cells. The concentration was adjusted by dilution. Accordingly, the mixture of cancer cells and yeast cells was obtained in different ratios keeping the concentration of cancerous cells constant at 10 5 cells/mL in the mixture .
  • Trapped cells were fixed in the device by using 4% paraformaldehyde in phosphate-buffered saline (PBS) for one hour. The cells were then dehydrated by using different concentrations of ethanol solution varying from 10 vol% to 100 vol% of ethanol ⁇ with an increment of 10 vol% for 5 min incubation at each point. Thereafter, the cells were dried on the device by using different ratios of ethanol to hexamethyldisilazane (HMDS) with increasing concentration of HMDS (3:1, 2:1, 1:1, 1:2 and 1:3) and left to dry overnight.
  • PBS phosphate-buffered saline
  • the sample was sputter-coated using Jeol Sputter (JEOL Ltd, Japan) for about 30s to 40s at 30 mA before obtaining an .SEM image at 750x magnification of patterned cells on the membrane film integrated into the microfluidic device.
  • the SEM image is shown in Fig. 6 (e.) .
  • The. trapped cells in this SEM image looked smaller than the r "_ -3 ⁇ 4 " rmaI — size ' ⁇ of ⁇ a 1 bout ⁇ 4 ' ⁇ to Z0 " pm _ b aTy ⁇ 3 ⁇ 4ue to shrinkage of cells during sample preparation, i.e. fixation and dehydration, for SEM. Also, it can be seen from Fig. 6(e) that the cells were successfully patterned on the film, with an efficiency of about 85%.
  • Fluid flow for filtration processes is essential to ensure that the porous membrane of a " microfluidic device does not get clogged or fouled easily.
  • FIG. 9(a) shows a lOum bead
  • Fig. 9(b) shows, a 12 ⁇ bead
  • Fig. 9(c) shows a 20 ⁇ bead.
  • FIG. 8(a) A schematic diagram of the model is shown in Fig. 8(a). As seen in Fig. 8(a), the model is an array of through-holes surrounded by 3-D structures with two columns of through-holes filled with solid spheres which represents cells. The model was solvecT ⁇ By ⁇ 'tRe ⁇ COMSOE — so ⁇ ff7ware ⁇ al3 ⁇ 4d TM h ⁇ ⁇ ve ⁇ lbjl;y prbfTle " in " m/s obtained is shown in Fig. 8(b). In Fig.
  • Example 3 To prove the theory that the interstitial gaps between trapped cells and pores are not blocked and allow fluid to flow through, a study was done using the porous membrane filter of Example 3 and a normal filter without any micro-structures. The normal filter was obtained by reversing the membrane of Example 3 as the other side of the membrane did not have any micro-structures.
  • ⁇ sized beads were used in this example.
  • the beads were patterned in the microfluidic device and fluid flow at flow-rates from 100 ⁇ /min to 500 pL/min was maintained to study the relative difference- in the pressure drop due to blocking or partial blocking of pores .
  • the pores of the filter can be fully or partially blocked when beads are patterned on the device.
  • the liquid passing through the device would cause a pressure drop, depending on the extent of pore blockage.
  • the pressure drop increases with increasing fluid flow- rate.
  • fully blocked pores would have .a higher pressure drop as compared to partially blocked pores. If the pressure drop is too high, the film may be damaged.
  • Fig. 9(d) shows beads pushed into the pores of the normal filter.
  • Fig. 9(e) shows complete blocking of pores oy beads. The increased pressure drop caused some of beads to pass through pores in spite of their bigger size, as seen in Fig. 9(f) .
  • PDMS is a soft and flexible material, thus beads which are bigger than the pore size may also be pushed through the pore at a higher pressure drop.
  • the difference between the percentage of beads that passed through the two different types of filters used in this example indicates the relative difference in the pressure drop to thereby conclude on the amount of blockage of pores.
  • a plot of the percentage of beads that passed through the pores against the flow speed was obtained for both types of filters and is shown in Fig. 9(g). It can be seen from Fig. 9(g) that the percentage of beads that passed through the micro-structured filter ' was much lower as compared to the normal filter. This indicates a lower pressure drop in the micro-structured filter compared to normal filter.
  • the lower pressure drop indicates that the fluid-flow is maintained around the pore according to Bernoulli's principle and the continuity principle, and can be attributed to the absence or at least a lower level of pore blockage by beads in the micro-structured filter. Though all pores may not be blocked or partially blocked and the pressure drop in the device may be a complex function of different parameters, but the relative difference in the pressure drop for the two type of filters is instructive.
  • Fig. 10(g) The percentage of lpm and 3 ⁇ beads that passed through the pores of both types of filter devices is shown in Fig. 10(g). It can be seen in Fig. 10(g) that there is a significant difference in the percentage of l m beads passing through the micro-structured filter as compared to the normal filter. Specifically, the percentage of ⁇ beads passing through the . micro- structured filter is about twice that of the normal filter. However, the percentage of 3 ⁇ beads passing through the micro-structured filter is about half that of the normal filter.
  • FIGs. 10(a) and (b) show the SEM images of the flow of ⁇ beads through the micro-structured filter and the normal filter respectively. It can be seen from the arrow in Fig. 10(a) that the ⁇ beads that were unable to pass throug —the—rntex-s-ttt-i-a-l—g-a-p-s—w-e-re—t-r-appe-d—-arou d—the— patterned ⁇ beads. In contrast, Fig. 10(b) shows that the ⁇ beads were scattered over the whole surface of the normal filter. Also from . Fig.
  • Figs. 10(c) and (d) show the SEM images of the flow of 3 ⁇ beads through the micro-structured filter and the normal filter respectively. It can be seen from Fig. 10(c) that the 3 ⁇ beads were concentrated around the patterned ⁇ beads in the micro-structured filter, indicating that fluid flow was maintained through the gap.
  • Fig. 10(g) Another point to note from Fig. 10(g) is that the percentage of 3 ⁇ beads passing through the micro- structured filter was significantly reduced as compared to ⁇ beads. For the normal filter, the difference was not significant. Accordingly, the significant reduction of percentage of ⁇ or 3 ⁇ beads passing through the micro-structured filter can be used as a measure for studying the percentage of different sized beads passing through the interstitial gaps, as will . be discussed below.
  • the percentage of beads passing through were calculated as shown in Fig. 10(h) and compared with the corresponding percentage for the ⁇ beads.
  • the result shown in Fig. 10(h) shows a significant increase in percentage , " of smaller beads passing through the interstitial gap created by 12 ⁇ beads as compared to ⁇ beads.
  • the relative percentage values of the ⁇ and 12 ⁇ beads is useful to prove that the fluid as well as smaller beads can pass through the interstitial gaps.
  • the above results were further confirmed by patterning cells on both types of filters. Cancer cells from cell-line MDA-MB-231 were patterned on the micro- structured filter and normal filter and ⁇ , 3 m and 5 ⁇ beads were passed through the respective filter membranes thereafter.
  • Example 1 were varied to study the anisotropic cross- linking of partially cross-linked polymeric chains between the SU-8 layers.
  • the hypothesis being tested in this example is that exposing a layer of SU-8 with low energy would partially activate the layer to thereby induce partial cross-linking.
  • the behavior of partially cross-linked chains can thus be studied by exposing the SU-8 again at certain regions only.
  • a first ' layer of SU-8 was coated at a final rotational speed of 4000 rpm and was baked twice, the first for 2 min at 65°C and the second for 10 min at 96°C to remove solvents.
  • the first exposure was performed for 2s (about 14 mJ/cm 2 ) without any photo-mask.
  • the second exposure was done for 40s (about 280 mJ/cm 2 ) through the photo-mask. Again, the photo-mask shown in Fig. 1(a) was used here.
  • the PEB was performed twice, the first for 1 min at 65°C and the second for 5 min at 96°C.
  • a control was prepared in which the first and second exposures were both performed for 40s (about 280 mJ/cm 2 ) .
  • FIGs. 11(a) and (b) Bright-field images of the target sample mold and the control sample mold are shown in Figs. 11(a) and (b) respectively. From Fig. 11(a), pillars are shown as the bright circles which were developed due to exposure through the photo-mask. Unexpected connecting structures, as indicated by the arrow, were additionally observed between adjacent pillars. However, no such connecting structures were observed in the control sample, as evidenced in Fig. 11(b). This proves that the partially cross-linked chains were anisotropically cross-linked towards the cross-linked pillars.
  • Example 2 the parameters of the method of Example 2 were varied to study the anisotropic cross-linking of partially cross-linked polymeric chains between the SU-8 layers.
  • a first layer of SU-8 of the target sample was exposed to UV light without any photomask, thereby activating the layer.
  • PEB was not performed ' for this layer.
  • PEB was performed for the exposed first SU-8 layer at 95°C. PEB helped to ' complete the cross-linking of the photo- activated layer. A second layer was then coated for both samples. This allowed diffusion of the activated species from the first layer of the target sample to the second layer to create a partially cross-linked interface. However, in the control sample, inter-diffusion was restricted between the two layers.
  • One layer of SU-8 was coated at a final rotational speed of 2000 rpm for 40s on a clean silicon wafer using the spin-coater. It was then baked twice, the first for 5 min at 65°C and the second for 20 min at 96°C to remove solvents. Thereafter, it was cooled down for 10 min and was exposed to UV light at a required dose of exposure energy by using a UV light source through the photo-mask by a mask aligner-. The schematic diagram of the photomask used in this example is shown in Fig. 1(b). PEB was then performed at ramp-up temperatures of 85°C to 90°C, 90°C to 96°C and 96°C to 100°C.
  • Figs. 12(a) to (c) The SEM images of the film obtained from a ramp-up temperature of 85°C to 90°C at different exposure energies are shown in Figs. 12(a) to (c). Specifically, Fig. 12(a) was obtained ' at an exposure energy of 700 mJ/cm 2 , Fig. 12 (b) was obtained at an exposure energy of 750 mJ/cm 2 and Fig. 12 (c) was obtained at an exposure energy of 800 mJ/cm 2 . It can be seen from Figs. 12(a) to (c) that hourglass shaped micro-structures were formed.
  • Fig. 12(g) the plot showing the normalized values of different defining features against a variation of exposure energy at this ramp-up temperature is shown in Fig. 12(g) .
  • the normalized values represent the variation of the different features of the micro-structures.
  • the points marked with (*) indicate that a double-level structure was formed at exposure energies from about 700 mJ/cm 2 to about 800 mJ/cm 2 , while a conical structure was formed at an exposure energy of 850 mJ/cm 2 .
  • the normalized values did not vary very significantly and thus, a ramp-up temperature of 85°C to 90°C is empirically classified as a less sensitive zone.'
  • Figs. 12(d) and (e) The SE images of the film obtained from a ramp-up temperature of 90°C to 96°C at different exposure energies are shown in Figs. 12(d) and (e) .
  • Fig. 12(d) was obtained at an exposure energy of 700 mJ/cm 2
  • Fig. 12(e) was obtained at an exposure energy of 750 mJ/cm 2 . It can be seen from Figs. 12(d) and (e) that doll- shaped micro-structures were formed.
  • the plot of the normalized values of different defining features against the variation of exposure energy at this ramp-up temperature is shown in Fig. 12(h) .
  • Fig. 12(f) The SEM image of the film obtained from a ramp-up temperature of 96°C to 100°C at different exposure energies is shown in Fig. 12(f). Specifically, Fig. 12(f) was obtained at an exposure energy of about 650 mJ/cm 2 to produce doll-shaped micro-structures. The plot of the normalized values of different defining features against the variation of exposure energy at this ramp-up temperature is shown in Fig. 12 (i) . The double-level structure was formed at an exposure energy of about 650 mJ/cm 2 , while a conical structure was formed at other exposure energies. As seen in Fig.
  • a single layer of SU-8 was exposed, without any photo-mask, to UV light at a low value of exposure energy of 14 mJ/cm 2 . It was then exposed through a photo-mask to an exposure energy ranging from 400 to 800 mJ/cm 2 . PEB was performed at a temperature of 80°C.
  • Figs. 13(a) and (b) The SEM images of the film obtained at different exposure energies are shown in Figs. 13(a) and (b) . Specifically, ⁇ Fig. 13(a) was obtained at an exposure energy of 400 mJ/cm 2 to produce an hour-glass shaped micro-structure. Fig. 13(b) was obtained at an exposure energy, of 500 mJ/cm 2 to produce a doll-shaped micro- structure.
  • Fig. 13(c) The plot of the normalized values of different defining features against the variation of exposure energy is shown in Fig. 13(c).
  • Fig. 13(c) it can be seen that a double-level structure was formed at an exposure energy 15 " f ⁇ " 0 ⁇ 1 ⁇ 7cm 2 1and ⁇ 5 ⁇ 0 " 0 ⁇ m ⁇ J;/cm 2 -.- Example 10
  • the double-layer method can be useful for fabrication of dome-like structures .
  • the first layer of SU-8 was coated at a final rotational speed of 4000 rpm and was baked twice, the first for 2 min at 65°C and the second for 10 min at 96°C to remove solvents. It was then cooled down for 8 min and exposed to UV light for 40s at 280 mJ/cm 2 .
  • the second layer of SU-8 was immediately coated without performing PEB of the first layer. Thereafter, it was soft-baked and exposed through the photo-mask at different exposure energies. Finally, PEB was performed at 80°C.
  • a combination of the double-layer method and single- layer double-exposure method ' was used in this example to fabricate dome-shaped micro-structures.
  • the double-layer method was performed on a sample by coating a second layer of SU-8 without performing PEB of the first SU-8 layer. Thereafter, the sample was exposed, without a photo-mask, to UV light at a low dose of exposure energy of 7 mJ/cm 2 . The sample was then exposed through the photo-mask schematically represented in Fig. 1(b) at different exposure energies. Finally, the sample was baked at 80°C.
  • a first layer of SU-8 was exposed to UV light at a low dose of exposure energy of 14 mJ/cm 2 and then another SU-8 layer was coated. Thereafter, the second exposure was done at varying exposure energies of about 400 to 800 mJ/cm 2 . It was then baked at a PEB temperature of 80 °C.
  • the disclosed filtering membrane provides an improved membrane for biological and medical applications.
  • the disclosed filtering membrane may advantageously provide simultaneous functionalities of patterning and separation.
  • the disclosed filtering membrane may advantageously possess a lower probability of fouling when used in filtration processes.
  • the maintenance period of the disclosed membrane may advantageously be lengthened.
  • the disclosed method for forming ' a filtering membrane may advantageously possess higher efficiency and reproducibility than current methods.
  • the disclosed method does not need to be performed in special environments such as in clean-room facilities.
  • the disclosed microfluidic device may be useful for different bead and cell based applications. Some of these applications are listed in the following.
  • a bead-pattern can be generated by the disclosed device at high efficiency to provide a functional micro- array.
  • Each bead, functionalized with desired proteins, antibodies or DNA, can act ' as a functional micro-array used for detection and medical diagnosis.
  • the bead- pattern can .also be used for studying interactions between biomolecules .
  • the bead-pattern may advantageously possess high efficiency of detection or interaction as .
  • the sample fluid flows around each p ⁇ t eTne ⁇ bea " d " . Th3 ⁇ 4 fur.cti or.alizea beaas may be par.terr.ed on the disclosed device for use in bacterial diagnosis, such as multiplex bacterial detection from a pathological sample.
  • the disclosed microfluidic device may be used in the isolation of rare cells, such as circulating tumor cells (CTCs) or epithelial cells, from blood for diagnostic or prognostic applications.
  • CTCs circulating tumor cells
  • epithelial cells such as circulating tumor cells (CTCs) or epithelial cells
  • the disclosed microfluidic device may also be used in leukapheresis , which is the separation of cancerous blood cells from blood in order to reduce white blood cell count. This is possible because blood cancer cells are stiffer than normal cells and thus can be filtered out from the blood using the disclosed device.
  • the disclosed device may be modified to be used in the continuous separation of cells for the management of leukemia.
  • the disclosed device may be used for single-cell micro-arrays in drug testing. Drug discovery may thus be done based on an individual cell response.
  • Cells trapped using the disclosed device may be used as cell-based biosensors for toxin detection or point-of- care diagnosis.
  • Cell encapsulation is important for cell-based therapy and single-cell encapsulation is reguired for better mass-transfer.
  • the disclosed device can be used for encapsulation of single-cells. As arrayed cells do not block the holes, each cell can be accessed from the encapsulating solution.
  • the encapsulated cells can either be removed from the device or can be cultured on the device itself. Singly encapsulated ⁇ cells can be used for cell-therapy in the treatment of diseases.
  • the encapsulated cells on the device can also be used as a cell-based platform for treatment of diseases.
  • the singly encapsulated cells on the device can further be used for 3-D single-cell based drug testing.
  • a cell-based . artificial pancreas for diabetes treatment may be possible by using singly- encapsulated cells on the device.
  • This can be developed as a wearable device containing cells that can produce insulin ( ⁇ -cells). Blood can pass through the device by interfacing the device with the body. The encapsulated cells can then sense and respond to glucose levels in the blood and control glucose levels by producing insulin accordingly.
  • This same principle can be used for treating patients with liver failure by detoxification of blood.
  • the disclosed method for forming a mold having imprint formation structures thereon can be used for fabrication of optical components (such as micro-lens, mirror arrays or as a part of optical- microelectromechanical systems (MEMS) devices. These .devices can also be used as a part of photo-electronic devices and possibly for solar-cell applications for concentrating light.
  • optical components such as micro-lens, mirror arrays or as a part of optical- microelectromechanical systems (MEMS) devices.
  • MEMS optical- microelectromechanical systems
  • The. disclosed structures may also be developed as part of MEMS devices.
  • the double-level structures may be used for generating or sensing mechanical movements in MEMS devices. These structures can possibly be used for developing sensitive pressure-sensors, micro-valves, micro-nozzles or micro-needles.
  • the disclosed structures may be used as filters for particle separation due to the targeted trapping of bigger particles.
  • the disclosed structures may also be used as an efficient trap for cells. These structures may anchor the trapped cells to facilitate single-cell studies. Further, the patterned structures may be modified for growth of -s-t-em ⁇ ceLLs—tha e ⁇ rL-fQrJja er stem-cell studies. It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

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Abstract

L'invention propose une membrane filtrante et son procédé de formation. La membrane filtrante comprend un substrat ayant une pluralité de trous qui s'étendent à travers le substrat et des formations d'arrêt disposées autour des ouvertures des trous sur au moins un côté du substrat, les formations d'arrêt étant configurées pour arrêter l'entrée d'entités particulaires d'une dimension trop grande choisie de particules, pour les empêcher d'entrer dans les trous. L'invention concerne également un moulage et un procédé de formation de celui-ci ainsi qu'un dispositif microfluidique incorporant la membrane filtrante.
PCT/SG2012/000191 2011-05-31 2012-05-31 Membrane filtrante WO2012166053A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016149394A1 (fr) * 2015-03-17 2016-09-22 President And Fellows Of Harvard College Système automatisé de fabrication de membrane
WO2016137555A3 (fr) * 2014-12-10 2017-01-19 The Charles Stark Draper Laboratory, Inc. Microcales polymères et procédés pour les fabriquer
US10458448B2 (en) 2017-04-18 2019-10-29 The Charles Stark Draper Laboratory, Inc. Surface affix-able device incorporating mechanically actuated dry adhesive

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US20040028875A1 (en) * 2000-12-02 2004-02-12 Van Rijn Cornelis Johannes Maria Method of making a product with a micro or nano sized structure and product
US20090061152A1 (en) * 2003-12-19 2009-03-05 Desimone Joseph M Methods for fabricating isolated micro- and nano- structures using soft or imprint lithography
US20090218275A1 (en) * 2005-12-07 2009-09-03 General Electric Company Membrane structure and method of making
US20110062634A1 (en) * 2009-09-17 2011-03-17 Commissariat A L' Energie Atomique Et Aux Energies Alternatives Thermal nanoimprint lithography mould, process for producing it, and thermal nanoimprint process employing it

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US20040028875A1 (en) * 2000-12-02 2004-02-12 Van Rijn Cornelis Johannes Maria Method of making a product with a micro or nano sized structure and product
US20090061152A1 (en) * 2003-12-19 2009-03-05 Desimone Joseph M Methods for fabricating isolated micro- and nano- structures using soft or imprint lithography
US20090218275A1 (en) * 2005-12-07 2009-09-03 General Electric Company Membrane structure and method of making
US20110062634A1 (en) * 2009-09-17 2011-03-17 Commissariat A L' Energie Atomique Et Aux Energies Alternatives Thermal nanoimprint lithography mould, process for producing it, and thermal nanoimprint process employing it

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WO2016137555A3 (fr) * 2014-12-10 2017-01-19 The Charles Stark Draper Laboratory, Inc. Microcales polymères et procédés pour les fabriquer
US10791779B2 (en) 2014-12-10 2020-10-06 The Charles Stark Draper Laboratory, Inc. Polymer microwedges and methods of manufacturing same
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US11654399B2 (en) 2015-03-17 2023-05-23 President And Fellows Of Harvard College Method for micromolding a polymeric membrane having a pore array
US10458448B2 (en) 2017-04-18 2019-10-29 The Charles Stark Draper Laboratory, Inc. Surface affix-able device incorporating mechanically actuated dry adhesive

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