Patent Application
20080199362
The invention relates generally to the field of microfluidics. More specifically, the invention relates to microfluidic packages and methods of fabricating the same.
Over the past decade, growing interest in microfluidics has provided the impetus for its rapid development from a theoretical science to a field with important biological and biochemical applications. Microfluidic devices are being used for the quantitative study of molecular diffusion, fluid viscosity, pH, chemical binding, and enzyme reaction kinetics in biological samples. More recently, the use of microfluidic devices has extended to other applications such as capillary electrophoresis, isoelectric focusing, immunoassays, flow cytometry, drug analysis, sample injection of proteins for analysis via mass spectrometry, PCR amplification, DNA and RNA extraction, DNA analysis, cell manipulation, cell separation, cell patterning, and chemical gradient formation.
Microfluidic devices that are used for the analysis of biological fluid samples typically comprise one or more microfluidic chips that are used to analyze a sample and a biologically compatible substrate housing a series of fluid channels for delivering the sample to the microfluidic chip. One or more inlets may be present to allow the introduction of the sample and/or chemicals into the device.
One of the problems encountered in the manufacture of a microfluidic package arise from the lack of cost-effective integrative technologies for microscale and mesoscale components, which would allow microfluidic packages to be manufactured cheaply and yet still, be able to function acceptably. Relatively time-consuming methods are still required to establish a secure and robust fluidic interface and fluidic interconnections within the microfluidic package.
Recent attempts have been made to address this problem. Han et al. proposed the use of a specific liquid perfluoro polymer (CYTOP® Asahi Glass Company, Japan) to create an in-situ prepared amorphous polymer film that is dried and solidified to bond the microfluidic chip to the substrate of the microfluidic package. The CYTOP® film allows the microfluidic chip to be adhered onto the substrate and thereby maintains the alignment of the inlets and outlets of the microfluidic chip with the corresponding inlets and outlets on the substrate. (Micro Electro Mechanical Systems, 2000. MEMS 2000. 13th Annual International Conference on, 23-27 Jan. 2000. Pages: 414-418). Kohl et al. suggested the use of UV curable polymers to bond and align flow sensors and microvalves to microchannels on the substrate of the microfluidic package. (Micro Electro Mechanical Systems, 2004. 17th IEEE International Conference on MEMS, 2004, Pages: 288-291.) However, the use of liquid phase polymers for bonding led to the undesirable clogging of flow channels in the package and therefore required greater precision during the assembly of the package.
Apart from the above, other methods have been suggested as well. Schabmueller et al. suggested the use of anodic bonding to establish the interface between microfluidic components and the substrate of the package. (J. Micromach, Microeng, Vol 9 (1999), pp 176-179). Jo et al. suggested the use of an oxygen plasma curable silicone elastomer (SYLGARD 184, Dow Corning) mixed with a curing agent in the weight ratio of 10:1 as a suitable material for bonding components within a microfluidic package (J. MEM Systems, Vol. 9 No. 1, 2000).
More recently, Pattekar et al. described a method of establishing the fluidic interconnections for a silicon microfluidic chip in which Teflon tubes were used to form the macro-micro interconnections. The method involved the use of thermal heat to melt the Teflon tube and the use of high temperature epoxy to secure the tube to the inlet and outlet ports (J. Micromach, Microeng. 2003, pg. 337-345). Li et al. suggested the use of plasma treatment to enable the bonding of PDMS on the microfluidic chip and further employed epoxy to enhance the bond strength.
Despite these developments there remains a need for microfluidic packages that are constructed with reliable interface connections between the interconnect flow channels and the microfluidic chip. It would be desirable to have a cost effective method of manufacturing such packages. It is also desirable to provide microfluidic packages having “plug-and-pump” connections directly from the microfluidic chip to the substrate, as well as to provide chip-to-chip microfluidic interfacing. Furthermore, it is also desirable to provide off-chip fluidic circuits within the cartridge to handle large volumes of reagents.
These problems are solved by the microfluidic package and method of assembling the microfluidic package, amongst other aspects, having the features of the respective independent claims.
Such a microfluidic package comprises a substrate having a (at least one) surface comprising at least one fluid channel, at least one fluidic chip having a top surface, a bottom surface, at least one side surface, and at least one passage to allow a fluid to traverse from the top surface or any side surface to the bottom surface of the chip; and a sheet of which both sides are adhesive. The first adhesive side of the sheet is attached to the substrate, and the at least one fluidic chip is secured by the second adhesive side of the sheet, such that the at least one passage of the fluidic chip is in fluid communication with the at least one fluid channel of the substrate.
In a further aspect, the invention provides a method of assembling the microfluidic package, said method comprising attaching a sheet comprising of two sides, both being adhesive onto the top patterned surface of the substrate or attaching said sheet to the bottom surface of the at least one fluidic chip and securing the at least one fluidic chip on top of the top surface of the substrate.
The invention also provides a method of assembling the microfluidic package of, further comprising securing a second a sheet comprising of two sides, both being adhesive, on the top surface of the at least one fluidic chip or on any exposed portion of the top surface of the substrate and securing a cover plate to the second sheet.
The invention further provides a method of fabricating the substrate of a microfluidic package. This method comprises providing a master mold comprising at least two pins for creating at least one sealed inlet passage and one sealed outlet passage, and at least one protrusion for creating at least one fluid channel, depositing a precursor of the substrate material into the master mold, and allowing the precursor to solidify, thereby forming the substrate. In this aspect, the invention also provides for a substrate that is obtainable or obtained from this method of fabricating the substrate of a microfluidic package. Such a substrate comprises: a surface, wherein this surface comprising at least one fluid channel, at least one sealed inlet passage, and at least one sealed outlet passage.
The sheet that is used in the present invention has two sides, both of which are adhesive, and may utilize a first adhesive side to attach itself to the substrate. The fluidic chip may then be attached to the second adhesive side of the sheet. The alignment and location of the fluidics chip with respect to the substrate is such that after being secured to the second adhesive side of the sheet, there exists a means of fluid communication between the at least one passage of the fluidics chip and the at least one fluid channel of the substrate. In addition, the orientation of the fluidic chip may be regarded as being substantially parallel to the plane of the surface of the substrate that features the at least one fluid channel.
The above-mentioned sheet may be continuous, meaning that it may be formed as a one-piece element. In another embodiment, the sheet may comprise a plurality of individual sheets (discontinuous), which in combination with one another may make up a larger sheet. The larger sheet may be equivalent in size and shape to the aforementioned continuous sheet, for example. Whether the sheet is continuous or discontinuous, the sheet may take the form of a regular shape such as a rectangle, square, triangle, elliptical, circle or any other known polygonal shape wherein the geometry of the said shape has at least one line of symmetry. A further embodiment includes the sheet adopting an annular (donut shaped) geometry.
Alternatively, the said sheets, whether continuous or otherwise, may take the form of an irregular shape, wherein an irregular shape is defined as a shape whose geometry has no clearly discernable line of symmetry. Therefore the sheet as such may comprise a continuous sheet or a plurality of individual sheets, wherein each sheet may be regularly or irregularly shaped. In general, regardless of the shape of the adhesive sheet, it is preferably arranged at selected portions of the substrate where it is important to ensure the presence of a secure fluidic seal. Portions of the substrate that are considered to be important for this purpose include fluid channels, fluidic ports and areas where the microfluidic chip is to be placed. The sheet may be shaped to cover these structures either entirely or partially. The sheet may also be positioned only at the edge of the substrate as described below.
In one embodiment, the first adhesive side of the sheet is attached to the surface of the substrate wherein the at least one fluid channel is located on said surface of the substrate, such as the top surface, for example. In this embodiment, the sheet may be continuous, meaning that the sheet comprises a single piece of material. The single continuous sheet may cover the entire top surface of the substrate or it may cover only a portion of the top surface. If the top surface of the substrate is rectangular (or regularly shaped), for example, then correspondingly, the sheet will take the form of a continuous rectangular sheet spanning from one peripheral edge of the substrate to the next thereby covering the entire top surface of the substrate. Alternatively, the sheet may be triangular in shape. In such an embodiment, the sheet may not cover the entire top surface of the substrate but is restricted to selected portions of the top surface of the substrate. In other embodiments in which the continuous sheet does not cover the entire top surface of the substrate, the centre portion of the sheet is removed so that it assumes a frame-like or border-like shape which can be placed, for example, along the perimeter or peripheral edge of the top surface of the substrate (see
In a further embodiment the sheet may be irregularly shaped. Again, as mentioned above, the sheet may only cover selected portions of the surface of the substrate. Furthermore, in the embodiment of an irregularly shaped but continuous sheet, the sheet may also span from one peripheral edge of the substrate to the next. Accordingly, the sheet, though continuous, due to its irregular shape, may only cover selected portions of the substrate.
In a further embodiment, the sheet may also comprise a plurality of smaller sheets. Should the sheets be regularly shaped, it is possible that the sheets may be arranged in such a manner that allows the top surface of the substrate to be covered in entirety. For example, it is possible that the sheet may be of a different shape from the substrate or may not cover the surface of the substrate entirely, but takes up the form of the bottom shape of the microfluidic chips either partially or entirely. However, if the said plurality of smaller sheets is irregularly shaped, it may be possible to also cover the entire surface of the substrate although it may be preferable that the surface of the substrate is only partially covered by the said plurality of irregularly shaped sheets. This may leave irregularly shaped portions of the substrate uncovered.
Hereinafter, when reference is made to the ‘sheet’, it is to be understood that the ‘sheet’ may be, as defined above, continuous, discontinuous and comprising a plurality of individual sheets and may further be regularly or irregularly shaped.
In a further embodiment, the sheet may be secured to the top surface of the substrate such that the sheet covers the at least one fluid channel of the substrate. In this embodiment, the sheet may not cover the remaining areas of the top surface of the substrate. In another embodiment, the sheet may cover all other portions of the top surface of the substrate that do not comprise of the at least one fluid channel. In other words, the sheet may cover also the non-fluid channel portions of the top surface of the substrate.
In the above-mentioned embodiment, the sheet may be secured only to the periphery of the top surface of the substrate. In such an embodiment, the sheet may include a membrane attached in a frame-like manner to the sheet, with the sheet being situated along the peripheral edge of the membrane. In this embodiment, the centre portion of the sheet may be removed thus retaining the sheet in a frame-like manner. The centre portion of the sheet may be substituted for a suitable membrane or any other material that may serve the function of covering (and sealing) the fluid channel portions on the top surface of the substrate.
In a further embodiment, the sheet may further comprise of a membrane that is either partially or fully integrated into said sheet. The partially or wholly integrated membrane may then be aligned with the at least one fluid flow channel of the substrate such that when the sheet is secured, the at least one fluid flow channel is sealed in the manner as described above.
The membrane may be selected from any biologically compatible or inert material. Examples of such materials include polyethyleneterephthalate (PET)), polycarbonate (PC) and polyimide.
In another embodiment, the sheet may further comprise at least one through-hole. The through-hole may allow for the at least one channel of the top surface of the substrate to be in fluid communication with the at least one passage of a microfluidic chip. The term ‘microfluidic chip’ refers to a device that is well-known in the art and that comprises a network of microchannels and interconnects defined in a polymer substrate, the microchannels having typical channel dimensions in the region of 10-100 micrometers inclusive (cf. Han et al. supra or as disclosed in PCT applications WO 2005/009616 A1 and WO 2005/010377 A1). The microchannels are accessible via inlet/outlet apertures on 1 or more sides of the chip. The chip may be arranged such that the inlet/outlet apertures are facing the substrate, or it may also be arranged such that the inlet/outlet apertures face away from the substrate. In the former arrangement, fluidic communication with the microfluidic chip can be established by fluid channels or inlet/outlet ports in the substrate, while in the latter arrangement, the inlet/outlet apertures of the chip is in communication with inlet/outlet ports of the cover. Through-holes on the sheet may be achieved by any suitable means including punching, shearing, die-cutting as well as laser drilling.
With the exception of one of the above-mentioned embodiments, when the sheet covers the at least one fluid channel of the substrate, the sheet seals the at least one fluid channel of the substrate from the surroundings while maintaining the fluid communication between the at least one fluid flow channel of the substrate and the at least one fluid flow passage of the chip.
In a further embodiment the through-hole located on the sheet may be connected to the at least one fluid channel of the substrate and to the at least one passage of the fluidics chip. This allows a fluid to traverse from the top surface or any side surface of the fluidics chip to the at least one fluid channel of the top surface of the substrate.
One function of the sheet defined in the independent claim includes securing the microfluidic chip onto the substrate. For this purpose, the sheet should have an adhesive quality in order to allow secure attachment of the microfluidic chip thereon.
In one embodiment, the sheet comprises at least one supporting layer obtained from a material such as, but not limited to, elastic polymers, thermoplastic polymers and thermosetting polymers. If the supporting layer itself has inherent adhesive qualities, the supporting layer alone can be used to secure the microfluidic chip onto the substrate, without the need for any coating of additional adhesives onto the supporting layer. If the supporting layer is a non-adhesive, e.g. thermoplastic polymer such as those selected from carbon chain polymers and heterochain polymers, both surfaces of the supporting layer can be rendered adhesive by coating with adhesives. Examples of non-adhesive thermoplastic polymers from which the supporting layer may be obtained, are polyvinyl acetates and polyvinyl alcohols. In this conjunction, it is noted that it is not necessary to render the entire surface(s) of the supporting layer adhesive. Rather, it is possible for example, to only render the periphery of the surface of the side of the sheet that faces the microfluidic chip adhesive (cf.,
Any biocompatible adhesive which is resistant to corrosion by reagents such as alcohols, acidic or alkaline substances, for example, and which is able to provide a sufficient amount of adhesion strength to secure the microfluidic chip, may be used as the adhesive. Suitable materials for the adhesive include the general class of pressure and/or heat-sensitive polymers. Specific examples include, but are not limited to, acrylic-based adhesives, silicone-based adhesives, phenolic-based adhesives, cyanoacrylates, amino resins, and epoxies. The adhesive is preferably present in a gel, elastomeric or resin form for convenience of use. In a presently preferred embodiment, the sheet is a medical grade double-sided adhesive tape.
The microfluidic chip may further comprise at least one fluid inlet port and at least one fluid outlet port. The at least one inlet port and the at least one outlet port may be located on the top surface, bottom surface, any of the side surfaces and in any combination of the aforementioned surfaces. In any of the above-mentioned embodiments, at least one fluidics chip is secured to the sheet. It is possible to secure the bottom surface of the fluidics chip to the sheet. The fluidics chip may also be connected, via electronic means, to a printed circuit board. The printed circuit board may contain a means, such as an algorithm, for running the microfluidic chip.
The substrate of the present device may further comprise at least one inlet port and at least one outlet port through which fluid flow occurs. The top surface of the substrate comprises of at least one fluid flow channel and one fluidic reservoir or chamber. In a further embodiment, the substrate may comprise of a plurality of fluid flow channels that are inter-connected with each other. In addition, the substrate may further comprise of at least one sample storing reservoir, which may be used to store the products or by-products that may arise as a result of the fluid flow. The reservoir may further comprise of at least one inlet port or outlet port to allow for the said products or by-products to be recovered if necessary or disposed off.
The substrate may be fabricated from any material that is resistant to corrosion induced by test reagents used in the package, as well as biologically compatible with the sample to be analyzed. In one embodiment, the substrate material is selected from a group consisting of, but not limited to, semiconducting materials and electrically insulating materials. Examples of such materials include elemental silicon, glass and polymeric silicone. As used herein, the term polymeric silicone includes all silane polymers, silicone polymers, siloxane polymers, and inorganic silicon-nitrogen based polymers.
Specific examples of polymeric silicone, which can be used in the substrate, are polydimethylsiloxane (PDMS), polydiethylsiloxane and polydipropylsiloxane. PDMS is a presently preferred material as when an injecting needle punctures it, for example, it is self-sealing due to its ability to conform to the shape of the needle, thereby ensuring minimal exposure of the internal components and contents of the microfluidic package from to the air as well as to external contaminants. In order to modify the surface quality of the substrate for improved solid-liquid interface between the substrate and a liquid sample, the surface of the substrate may also be modified with any suitable material, e.g. polyethylene glycol or polyfluoropolyether for conferring hydrophilic or hydrophobic qualities. Other examples of (biocompatible) polymerisable material from which the substrate may be made, include monomers or oligomeric building blocks (i.e. every suitable precursor molecule) of polycarbonate, polyacrylic, polyoxymethylene, polyamide, polybutylenterephthalate, polyphenylenether, mylar, polyurethane, polyvinylidene fluoride (PVDF), flourosilicone or combinations and mixtures thereof.
The microfluidic package may further comprise a cover plate secured by means of a second sheet either to the top surface of the at least one microfluidics chip or to the top surface of the substrate. The cover plate may comprise of at least one recess fabricated such that the fluidics chip may fit into said recess when the cover is placed onto the microfluidics package. The second sheet may be positioned in-between the cover plate and the top surface of the substrate. Alternatively, the second sheet may be positioned on the top surface of the fluidics chip in order to secure the cover plate. The cover plate may have 1, 2, 3, 4 or more (i.e. a plurality of) fluidic holes or inlet/outlet ports. At least one of these fluidic holes is aligned to the channel on the top surface of the substrate in order to introduce a sample or a reagent into the microfluidic package.
In one embodiment, the top cover may comprise the same material as that which is used for the substrate, for example, semiconductor materials or electrically insulating materials such as elemental silicon, glass and polymeric silicones. Specifically, the silicone may be selected from, but is not limited to polydimethylsiloxane (PDMS), polydiethylsiloxane and polydipropylsiloxane. The top cover may also be surface modified with a suitable material, e.g. polyethylene glycol or polyfluoropolyether. Likewise, the cover may be made from a (biocompatible) polymerisable such as include monomers or oligomeric building blocks (i.e. every suitable precursor molecule) of polycarbonate, polyacrylic, polyoxymethylene, polyamide, polybutylenterephthalate, polyphenylenether, mylar, polyurethane, polyvinylidene fluoride (PVDF), flourosilicone or combinations and mixtures thereof.
Another aspect of the invention relates to a method of fabricating the substrate. The method comprises first providing a master mold comprising at least two pins for creating at least one sealed inlet passage and one sealed outlet passage, and at least one protrusion for creating at least one fluid channel. Subsequently, a precursor of the substrate material is deposited into the master mold. Finally, the precursor is allowed to solidify, thereby forming the substrate.
In accordance with the above method, the master mold is designed and constructed according to the desired layout of the fluid channels and the inlet/outlet ports. Where fluid channels are to be constructed, the surface of the master mold is provided with horizontal protrusions, which correspond to the desired layout of the fluid channels in the substrate. In order for sealed fluidic ports to be made efficiently, upright pin-like protrusions are formed in the master mold, typically orientated substantially perpendicularly to the horizontal protrusions, to provide corresponding inlet/outlet port structures in the substrate. The height of the pins are designed to be lower than the height of the substrate material filling the mold so that the passageway left in the substrate by each pin-like structure is sealed off from the opposing surface of the substrate, thereby creating a sealed fluidic port in the substrate. The fabrication begins with the deposition of liquefied substrate material is into the master mold. Thereafter, the substrate material is allowed to solidify, for example, under thermal or ultraviolet curing. Once the substrate has solidified, the substrate is removed from the mold.
Any suitable conventional methods may be used for fabricating the substrate. Examples include, but are not limited to casting, molding or lithography. In one embodiment, the substrate is formed by a method selected from a group consisting of casting, molding and lithography. Exemplary methods of casting include, but are not limited to investment casting, centrifugal casting, cold casting and potting.
In another embodiment, the substrate is fabricated by molding. Exemplary methods of molding include, but are not limited to, compression molding and injection molding.
In another embodiment, the substrate is fabricated by lithography. Exemplary methods of lithography include, but are not limited to soft lithography, ultraviolet lithography and imprint lithography.
In any of the above embodiments of the method of the invention, a precursor may be selected from any suitable materials. In a presently preferred embodiment, the precursor may be selected from the group consisting of polydimethylsiloxane, polydiethylsiloxane, polycarbonate, polyethylene, polyvinylchloride, polyamides, polyethyleneterephthalate (PET)), polycarbonate (PC), polyimide and polydipropylsiloxane.
A further aspect of the invention relates to a substrate, which may be used in any microfluidics package. The substrate may be fabricated as mentioned above and may comprise of at least one surface, said surface comprising at least one fluid channel, at least one sealed inlet passage, and at least one sealed outlet passage.
It is to be noted that the substrate, in particular holes and channels in the substrate, may be formed using any suitable standard micro-machining procedure and is not limited to casting, molding or lithography, although the latter methods are preferred methods of doing so. For example, the substrate may be fabricated using injection molding, casting, machining. laser drilling, dry etching and mechanical drilling.
The master mold can be made of any suitable material for holding molten substrate material while it is being allowed to solidify in the mold. The cover plate fabrication process may be selected from a group consisting of injection molding, soft lithography, casting, chemical machining, electrical discharge machining (EDM), wire EDM, laser ablation and electron-beam machining, or by any of the above-mentioned fabrication methods as well.
The microfluidic package of the invention may be assembled by the following method comprising:
attaching a sheet, of which both sides are adhesive, to any surface of the substrate that may comprise fluid channels such as the top surface, for example, and
securing the at least one fluidic chip onto the substrate by means of the second adhesive side of the sheet thereby forming a sealed channel comprising the fluid flow passage of the fluidics chip and the fluid flow channel of the substrate.
In a further embodiment, the method of assembling the microfluidic package may further comprise:
attaching a second sheet to the top surface of the at least one microfluidic chip or to any exposed portion of the substrate that may be in contact with the cover, and
attaching the cover, to the second sheet when said cover is placed onto the microfluidics package.
The microfluidic package of the present invention is applicable in a wide range of fields. In the chemical processing industry, microfluidic packages can be used, for example, in reactors, mixers, dispensers, heat exchangers and separators for carrying out fundamental ‘unit operations’ analysis at the microfluidic scale. In the life sciences industry, microfluidic packages can be used, for example, for high throughput screening and drug discovery. As an example of the application in the field of genomics, DNA amplification can be carried out as well as cell analysis (e.g. screening, counting, sorting). In addition, diagnostic tools and biochemical monitoring of materials such as soil, water, and pesticides may also employ the microfluidic package of the invention. Other applications include miniaturized microtitre plates, dispenser components, implantable drug delivery systems, micro-combustors, fluidic micro thrusters, DNA amplification, separation, hybridization and sequencing.
The invention is further illustrated by reference to the following non-limiting examples and drawings in which;
The adhesion strength and bio-compatible with chemical reagents used in bio-analysis were the main selection criteria for the adhesive material. Three types of medical-grade adhesive were evaluated. These adhesives were supplied by Adhesives Research Pte Ltd (SG). The tape carrier is polyethylene (PET)-based and the adhesives used are, namely, silicone-based {Part number 02-50-01}, acrylic-based {Part number 02-76-01A} or phenolic-based {Part number 02-82-01}. The performance of the thin-film on bio-compatible and adhesion strength was evaluated by means of chemical soaking test and peel test respectively.
Bio-analysis such as Deoxyribonucleic Acids extraction or Viral Nucleic Acids extraction required chemical reagents. They were ethanol, lysis, Phosphate Buffered Saline (PBS) and solution with high salt concentration. The three selected adhesive thin-film were soaked in these chemical reagents for 10 minutes. The adhesive thin-film was observed under microscope for any visual defect after the chemical reagent soaking.
The adhesion strength between the adhesive thin-film and PDMS substrate will affect the quality of the package in terms of maximum fluid pressure package before fluidic leakage or even cross-contamination between channels. Peel test was used to quantify the adhesion strength between adhesive thin-film and the PDMS substrate.
PDMS was cast into a rectangle substrate of size 50 mm×75 mm×1.5 mm thick. The Acrylic-based and Phenolic-based thin-film were placed on top of the PDMS substrate. During the Peel Test, the PDMS substrate was secured on the test-bed and one end of the adhesive thin-film was held by a clamp [
The prepared specimens were subjected to heat treatment for 20 min at room temperature and at 80° C. separately before the peel test. The test results were shown in
Fluidic Testing was conducted on the assembled PDMS package to understand the pressure drop of the package with regard to the ratio of the diameter of the tube fitting and the diameter of the inlet port, and the maximum fluidic pressure that the package can withstand without leakage [
The maximum pressure drop across the PDMS package was an indication of the quality of the macro-micro fluidic interconnects. The disposable PDMS package used a plug and play concept for its macro-micro fluidic interconnects. The quality of the macro-micro fluidic interconnects depended on the pressure acting on the tube fitting by the PDMS material. The pressure acting by the PDMS material depended on the ratio of the diameter of the tube fitting and the inlet port diameter.
The test was conducted to understand the maximum pressure drop of the package with respect to the ratio. The fluidic test setup was shown in
Three different tube fittings were used in this test. The test fluid was water. The results indicated the allowable pressure drop across the package increased as the ratio increases [Table 2]. This relationship helped in the selection process of the correct tube fitting with respect to the pressure drop across the package.
Water was the working fluid in the first fluidic test and was introduced at a fixed flow rate. In the present example, the disposable PDMS package was subjected to three different flow-rates. Results indicated that the pressure drop across the package increased as flow rate increased [
In a subsequent test, chemical reagents used in bio-analysis were used to investigate the biocompatibility of PDMS package. The chemical reagents were Phosphate Buffered Saline (PBS), lysis buffer, high salt and ethanol. With 10 μl/min flow rate, chemicals flowed smoothly through the package. The duration of the test was 10 min. No fluidic leakage and blockage were detected on PDMS package.
The disposable PDMS package was then subjected to a biomedical application for extraction of viral nucleic acids (RNA) from blood sample. The blood was spiked with plant virus particles and pumped along with other chemical reagents through the package containing the chip. The elute solution collected from the package was analyzed by the conventional laboratory techniques and the viral RNA was successfully amplified and detected within the elute solution. This result indicated that the adhesive thin-film used and the PDMS package did not inhibit the subsequent stages of nucleic acid amplification and detection. It was also observed that the chemical reagents used for the extraction process did not react with the adhesive and the PDMS material. Thus, the package remained intact with fluidic channels clear, providing a leak-proof interface to the chip throughout the bio analysis process.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/SG05/00038 | 2/15/2005 | WO | 00 | 5/5/2008 |
