Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B3/00—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form
  • B32B3/26—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer
  • B32B3/30—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer characterised by a layer formed with recesses or projections, e.g. hollows, grooves, protuberances, ribs
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
  • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B27/00—Layered products comprising a layer of synthetic resin
  • B32B27/06—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material
  • B32B27/08—Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B38/00—Ancillary operations in connection with laminating processes
  • B32B38/06—Embossing
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/12—Specific details about materials
  • B01L2300/123—Flexible; Elastomeric
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2307/00—Properties of the layers or laminate
  • B32B2307/50—Properties of the layers or laminate having particular mechanical properties
  • B32B2307/51—Elastic
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2307/00—Properties of the layers or laminate
  • B32B2307/70—Other properties
  • B32B2307/704—Crystalline
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2307/00—Properties of the layers or laminate
  • B32B2307/70—Other properties
  • B32B2307/728—Hydrophilic
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2307/00—Properties of the layers or laminate
  • B32B2307/70—Other properties
  • B32B2307/73—Hydrophobic
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2309/00—Parameters for the laminating or treatment process; Apparatus details
  • B32B2309/08—Dimensions, e.g. volume
  • B32B2309/10—Dimensions, e.g. volume linear, e.g. length, distance, width
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2310/00—Treatment by energy or chemical effects
  • B32B2310/04—Treatment by energy or chemical effects using liquids, gas or steam
  • B32B2310/0445—Treatment by energy or chemical effects using liquids, gas or steam using gas or flames
  • B32B2310/0463—Treatment by energy or chemical effects using liquids, gas or steam using gas or flames other than air
  • B32B2310/0481—Ozone
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B2319/00—Synthetic rubber
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B32—LAYERED PRODUCTS
  • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
  • B32B38/00—Ancillary operations in connection with laminating processes
  • B32B38/0008—Electrical discharge treatment, e.g. corona, plasma treatment; wave energy or particle radiation

Definitions

• a first aspect of the invention relates to a method of making a microfluidic device that includes the steps of: forming a mold substrate having a relief pattern formed in a surface thereof and a device substrate having a relief pattern formed in a surface thereof, wherein the relief patterns formed into the surface of the mold and device substrates are identical or nearly identical except the relief pattern of the mold substrate has a depth that is smaller than a depth of the relief pattern of the device substrate;
• Figure IB is a cross section of a prior art microfluidic device formed using a reduced thickness substrate (e.g., silicon wafer) that is etched to form one or more reduced height microchannels, and an elastomeric polymer (e.g., PDMS) cap over the substrate.
• a reduced thickness substrate e.g., silicon wafer
• an elastomeric polymer e.g., PDMS
• the thinned substrate while sufficient to reduce the microchannel height, is problematic insofar as the substrate is much more fragile and prone to damage.
• the materials identified are exemplary.
• Figures 2A-B illustrate a method of preparing the mold and device substrates, fabricating the elastomeric polymer layer, and combining the device substrate and elastomeric polymer layer to form the microfluidic device of the present invention.
• the materials identified are exemplary.
• Figure 3 is a cross section of a microfluidic device formed using the present invention, which includes one or more reduced height microchannels formed between the patterned substrate (e.g., silicon) and the conforming surface of the elastomeric polymer (e.g., PDMS) cap.
• the patterned substrate e.g., silicon
• the conforming surface of the elastomeric polymer e.g., PDMS
• the materials identified are exemplary.
• Figure 4 illustrates a microfluidic device prepared in accordance with the present invention, which includes a plurality of parallel microfluid channels that are fed by a common passage from the inlet port and relieved by a common passage to the outlet port.
• the bottoms of the microfluid channels are porous and communicate via the pores with a common channel that passes a separate fluid via inlet and outlet.
• Figure 5 is a cross sectional view of PDMS sheet capping micromachined channels shows the height reduction of the channels, which have a trapezoidal cross section.
• the PDMS was bonded to a multichannel membrane device and reduced the channel height from 300 ⁇ to 200 ⁇ .
• the cross section is created with a razor blade which creates grooves in the PDMS and leaves debris on the rough exposed edge of the Si.
• the present invention relates to methods for making microfluidic devices, the resulting microfluidic devices, and kits that can be used to prepare the same.
• the microfluidic device is formed of a substrate and an elastomeric polymer layer, which together define the features of the microfluidic device. These features may include, without limitation, one or more microfluidic channels, one or more inlet and outlet ports, one or more sample chambers, one or more mixing chambers, one or more heating chambers, one or more valve structures, and one or more nanoporous or microporous membrane structures. These features can be connected together so as to achieve a desired function (e.g., mix, pump, redirect, allow reactions to occur, filter, etc.).
• a desired function e.g., mix, pump, redirect, allow reactions to occur, filter, etc.
• the materials and structures formed in accordance with the present invention are particularly, though not exclusively, suitable for photolithography and electrochemical etching processes for the formation thereof.
• silicon is by far the most common substrate used in forming microfluidic devices of this type, persons of skill in the art should appreciate the other materials can be used including, without limitation, undoped germanium, p-doped silicon or germanium, n-doped silicon or germanium, a silicon-germanium alloy, and Group III element nitrides.
• Dopants are well known in the art and may include, without limitation, (CH 3 ) 2 Zn, (C 2 H 5 ) 2 Zn, (C 2 H 5 ) 2 Be, (CH 3 ) 2 Cd, (C 2 H 5 ) 2 Mg, B, Al, Ga, In, H 2 Se, H 2 S, CH 3 Sn, (C 2 H 5 ) 3 S, SiH 4 , Si 2 3 ⁇ 4, P, As, and Sb.
• the dopants can be present in any suitable amount.
• the elastomeric polymer material is preferably a silicone elastomeric material such as polydimethylsiloxane ("PDMS", e.g., Dow Corning Sylgard ® 184) (McDonald et al, "Fabrication of Microfluidic Systems in Poly(dimethylsiloxane),” Electrophoresis 21 :27-40 (2000), which is hereby incorporated by reference in its entirety).
• PDMS polydimethylsiloxane
• Dow Corning Sylgard ® 184 Dow Corning Sylgard ® 184
• PDMS is a particularly well studied material for the construction of microfluidic systems. It is optically transparent, and has a refractive index that is much lower than that of silicon.
• PDMS has a hydrophobic surface after polymerization, but the surface of PDMS can be treated with a surfactant, oxygen and plasma, or atmospheric RF to become hydrophilic (Hong et al., "Hydrophilic Surface Modification of PDMS Using Atmospheric RF Plasma,” Journal of Physics: Conference Series 34:656-661 (2006), which is hereby incorporated by reference in its entirety).
• This hydrophilicity assists not only in bonding the polymer layer to the substrate, but also decreases surface tension and bio fouling within the microchannels to allow fluids to move easily along those channels.
• microstructures in a variety of substrates particularly those described above.
• a masking agent is applied to the surface of a material using lithography to form an array of elements that will dictate the manner in which the unprotected substrate will be etched.
• the portions of the surface that are not protected by the masking agent are then chemically etched using an etchant. Any of a variety of suitable anisotropic or isotropic (i.e., wet) etchants can be used.
• Exemplary anisotropic etchants include, without limitation, buffered oxide etchant solutions containing about 5 to about 25 wt %, more preferably about 5 to about 15 wt % HF; KOH (potassium hydroxide) etchants containing about 20 wt% to about 60 wt% KOH, TMAH (tetramethylammonium hydroxide) etchants containing about 2 wt% to about 10 wt% TMAH, and EDP etchants (containing ethylenediamine, pyrocatechol, pyrazine, and water).
• KOH potassium hydroxide
• TMAH tetramethylammonium hydroxide
• EDP etchants containing ethylenediamine, pyrocatechol, pyrazine, and water.
• Exemplary isotropic etchants include, without limitation, various combinations and mixtures of HNO 3 , HF, CH 3 COOH, HCIO 4 , or KMn0 4 .
• the substrate can be removed from the etch cell, rinsed with ethanol, then water, and dried under a stream of N 2 gas.
• the mask can be removed with an appropriate solvent such as acetone, methyl ethyl ketone (MEK), or methyl isobutyl ketone (MIBK). Used in this manner, lithography and etching can produce highly detailed microfluidic structures in the substrate.
• the resulting device substrate can have the bottom of its microfluidic channels formed into nanoporous membranes that are less than 500 nm thick, more preferably less than 100 nm thick, and have properties that include a porosity of at least about 1% percent, a pore size cutoff below 100 nm, and combinations thereof.
• Nanoporous membranes of this type can be formed according to the techniques described in U.S. Patent No. 8,182,590 to Striemer et al, Fang et al, "Methods for Controlling the
• microporous membranes can be formed using deep reactive ion etching (DRIE) for pore drilling through the silicon (Zazpe et al., "Ion- transfer voltammetry at silicon membrane-based arrays of micro -liquid-liquid interfaces,” Lab Chip 7: 1732-1737 (2007), which is hereby incorporated by reference in its entirety.
• DRIE deep reactive ion etching
• the mold substrate 60 is used to form the elastomeric polymer layer 62 that will be used with the device substrate 40 to form the microfluidic device.
• the elastomeric polymer layer 62 is formed by introducing a liquid composition that includes the polymer precursors onto the surface of the mold substrate 60, and then allowing the liquid composition to cure under conditions suitable to form the elastomeric polymer layer.
• the base and curing agents are thoroughly mixed together in a roughly 10: 1 weight ratio, although variations in this ratio can also be used.
• the liquid mixture should be placed in a desiccator under vacuum (e.g., 22 in. Hg) until the liquid mixture is free of bubbles, which should take about 10-20 minutes.
• the elastomeric polymer layer 62 is then bonded to the device substrate 40. This is carried out by contacting the conforming surface 64 of the elastomeric polymer layer 62 to the relief patterned surface of the device substrate 40. To facilitate handling and placement of the elastomeric polymer layer, it may be wetted in water or ethanol prior to initiating contact with the device substrate. (Contacting with the device substrate should be made carried out without significant delay after surface activation of PDMS, because the PDMS surface will return to its hydrophobic state after time.) Once dry, bonding is complete. To facilitate a thorough fluid-tight seal between the elastomeric polymer layer 62 and the device substrate 40, slight pressure can be applied while contacting, i.e., during the bonding process.
• fluid ports can be designed for either introduction through the device substrate or through the elastomeric polymer layer.
• ports can be formed by creating vertical channels in the elastomeric polymer layer such that short glass tubing may be inserted into channels formed in the PDMS (defined by the SU-8 on the mold substrate). Flexible tubing can be attached to these short glass tubes.
• a common or shared channel in the elastomeric polymer layer can be carried to the edge of the device substrate and accessed from a single port. Side entrance to the device will allow multiple devices to be stacked upon each other in parallel.
• microchannels that are less than about 500 ⁇ in height.
• the microchannels are less than about 400 ⁇ in height, less than about 300 ⁇ in height, less than about 200 ⁇ in height, or less than about 100 ⁇ in height.
• the microchannels are less than about 90 or about 80 ⁇ in height, less than about 70 or about 60 ⁇ in height, less than about 50 or about 40 ⁇ in height, less than about 30 or about 20 ⁇ in height, or less than about 10 ⁇ in height.
• microfluidic devices possess a microchannel volume to membrane surface area ratio that in some embodiments is lower than that found in other microfluidic devices.
• a microfluidic device with 300 ⁇ deep, 1mm wide channel (at membrane) has a V/A ratio of 0.345, whereas a channel reduced to 100 ⁇ but having the same width has a V/A ratio of 0.105 and a channel reduced to 10 ⁇ but having the same width has a V/A ratio of 0.01005.
• the microfluidic device 80 includes a device substrate 90 formed of silicon and having a plurality of parallel, reduced-height microchannels with a porous nanocrystalline membrane (less than 500 nm thick) formed at the base of each microchannel.
• a polymer layer 82 that has a conforming lower surface that partially defines the plurality of microchannels.
• a pair of lateral microchannels 84, 86 are Formed in the polymer layer 82, which allow for coupling of the plurality of parallel, reduced-height microchannels to a common inlet 88 that communicates with the microchannel 84 and a common outlet 90 that communicates with the microchannel 86.
• the polymer layer 82 is capped by a layer 92, which is formed by PDMS, glass, or a thermoplastic material.
• a polymer layer 94 that defines a common chamber communicating with each of the plurality of parallel, reduced-height microchannels via the porous nanocrystalline membranes.
• the common chamber is also capped by a layer 96, which is formed by PDMS, glass, or a thermoplastic material.
• the common chamber includes an inlet 98 and an outlet 100.
• This embodiment can be used as a parallel flow filtration system for, e.g., dialysis.
• a fluid to be filtered is delivered via inlet 88 through each of the microchannels, where the fluid flows above the porous membrane, and exits via outlet 90 as a filtered fluid.
• a counter-flow fluid is delivered via inlet 98 to the common chamber, where it collects the filtered materials before exiting via outlet 100.
• a silicon wafer was used to form both a mold substrate and device substrate.
• the lower side of the device substrate was first prepared to generate a porous nanocrystalline nanolayer in accordance with the techniques described in U.S. Patent No. 8,182,590 to Striemer et al., Fang et al., "Methods for Controlling the Morphology of Ultra-thin Porous Nanocrystalline Silicon Membranes," J. Phys: Condens Matter
• mold substrate surface was printed with SU-8 and both substrates were masked with a nitride film. After masking, the substrates were etched with EDP etchant. The mold substrate was etched for a shorter duration to form a 100 ⁇ deep channel, whereas the device substrate was etched to a depth of 300 ⁇ . This allowed for a reduction in channel height from 300 ⁇ to 200 ⁇ . After removal of the nitride mask, the mold substrate was cleaned, dried, and then surface treated with Cole-Parmer® Micro-90® as a release agent. Thereafter, PDMS was prepared, applied to the mold substrate, and cured. After curing, the PDMS layer was removed from the mold substrate.
• FIG. 5 A cross sectional image of the finished device is illustrated in Figure 5. The cross section was created by cutting the device with a razor blade, which created grooves in the PDMS and left debris on the rough exposed edge of the Si.
• Figure 5 the location of the bulk silicon (forming the trapezoidal channel sidewalls), the porous nanoscale nc-Si membrane, and PDMS are identified. The reduction of the channel height from 300 ⁇ to 200 ⁇ is also illustrated.

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• 2013
  • 2013-08-19 WO PCT/US2013/055541 patent/WO2014031523A2/fr not_active Ceased

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