Moreover, silicon is also not transparent and therefore unsuitable for optical sensing. Disposable microfluidic devices: Fabrication, function, and application. The key aspects addressed here were mould fabrication and manufacturing using roller embossing and microthermoforming. Another approach is selective fusing of print media in a granular bed. 
Moulds for hot embossing are typically fabricated from either silicon or metal using microfabrication or CNC milling, respectively. There are three key components: a light source as the energy input to activate some reactive species and allow reactions to occur; precursor materials with reactants, usually called photoinitiators, which are sensitive to light exposure; and a printing platform as a reaction container to hold the reaction mixture and maintain a certain reaction environment. Reyes D.R., van Heeren H., Guha S., Herbertson L., Tzannis A.P., Ducre J., Bissig H., Becker H. Accelerating innovation and commercialization through standardization of microfluidic-based medical devices.
MEMS processes along this line can be found in numerous books and are not elaborated here. Inst. Resolution is given in layer thickness with X-Y resolution in dpi. Both aspects help reduce residual stress. The hot extruded foils are directly fed into and pressed by the embossing rollers.
Thermally actuated interferometric sensors based on the thermal expansion of transparent elastomeric media. The chemical resistance of thiol-ene polymers depends on the monomers used. Fabrication of Flexible Binary Amplitude Masks for Patterning on Highly Curved Surfaces. Attia U.M., Marson S., Alcock J.R. Micro-injection moulding of polymer microfluidic devices.
An ultra high-efficiency droplet microfluidics platform using automatically synchronized droplet pairing and merging.
FIB-assisted chemical vapour deposition occurs when a gas, such as tungsten hexacarbonyl (W(CO)6), is introduced to the vacuum chamber and allowed to chemisorb onto the sample. Fabrication and Functionalization of 3D Printed Polydimethylsiloxane-Based Microfluidic Devices Obtained through Digital Light Processing. Inst. The machining is non-contact and dissolution-based, and thus no residual mechanical or thermal effects are presented on the workpiece surface [22].
), and dry (RIE and DRIE) etching, as well as FIB and e-beam. Flexible Substrate-Based Devices for Point-of-Care Diagnostics.
Jena R.K., Yue C.Y., Lam Y.C., Wang Z.Y. Chang et al.
Direct fabrication of rigid microstructures on a metallic roller using a dry film resist. The higher resolution for fs lasers does, however, come at the cost of higher investment and maintenance costs. Many hours are usually required to expose a 4 wafer area, and the need of a vacuum chamber limits the size of the workpiece; moreover, the initial capital investment required for an e-beam machine is high.
Ren et al. A CAD file of the workpiece design can generally be used directly to control the movement between the laser source and the liquid polymer.
3D printing is a form of additive manufacturing technology where a three-dimensional object is created by successive layers of material. The authors declare no conflict of interest. Dedicated equipment is less demanding in these methods. Beckwith A.L., Borenstein J.T., Velasquez-Garcia L.F. Monolithic, 3D-Printed microfluidic platform for recapitulation of dynamic tumor microenvironments.
Chang C.-Y., Yang S.-Y., Chu M.-H.
Focused ion beam (FIB) machining utilises ions with high kinetic energy to remove or add material by momentum transfer. The combination of UV and short pulses results in the removal of surface layers by one of a number of mechanismsvaporisation in the case of metals and ceramics, molecular disintegration (photoablative decomposition) for many polymers at less than 300 nm, or interface effects (stripping by exfoliation of thin films up to a few micrometres thick).
There are currently several injection moulding techniques available to transfer micron-scaled features from moulds to polymeric products [179,180,181]. Combining individual functions and integrating multiple parts can promote the usability of these devices to be competitive to existing products. Rapid fabrication of ultraviolet-cured polymer microlens arrays by soft roller stamping process. Liang Y., Liu C., Sun H.L., Li J.M., Liu J.S., Gao X.N.
The elastic deformation of the tool and the workpiece, vibration of the machine, thermal deformation, and the tool itself all can affect the accuracy of the machining [22]. Niggemann M., Ehrfeld W., Weber L. Fabrication of miniaturized biotechnical devices.
The .gov means its official.
Van Den Berg A., Mummery C.L., Passier R., Van der Meer A.D. Personalised organs-on-chips: Functional testing for precision medicine. Sintered diamond tools seem to provide a solution with a lower wear. Such an approach could allow higher volume manufacture of microfluidic devices which combine microfluidic channels with other elements such as gratings and fluidic filters.
The procedure therefore starts with fabrication of the master mould by spin coating negative SU-8 resist onto the substrate and then a soft (first) bake by passing through a temperature cycle which is dependent on the SU-8 resist thickness. 
Double-sided structure forming has also been demonstrated [92], although alignment remains an issue for further development. 3D printed microfluidic devices: Enablers and barriers. FIB tools are designed to etch or machine surfaces; an ideal FIB could machine away one atom layer without any disruption of the atoms in the next layer, or any residual disruptions above the surface. Figure 7B shows impedimetric point-of-care diagnostic cartridge for biomarker detection, which comprises an electrode layer using PEN substrate and a hot embossed fluidic layer and with both of these layers being joined using PSA tape that is laser-structured to open selected areas of the electrode layer [222]. Theilade U.A., Hansen H.N.
Unger M.A., Chou H.P., Thorsen T., Scherer A., Quake S.R.
The film is clamped at its edges and heated to the glass transition temperature of the material; the softened material is then stretched against moulds with the assistance of pneumatic or mechanical pressure; the structure is then cooled and demoulded. Compounds that add to the epoxy group include amines, amino acid, and thiols, all of which can initiate curing of the epoxy monomer. Simple replication methods for producing nanoslits in thermoplastics and the transport dynamics of double-stranded DNA through these slits. [48], Landolt et al.
Electrochemical micromachining (EMM) is a variant of ECM at the micro-scale. Several mechanical, chemical, and optical properties of PDMS make it appealing for microfluidic applications. Weber L., Ehrfeld W., Freimuth H., Lacher M., Lehr H., Pech B. Micromolding: A powerful tool for large-scale production of precise microstructures. 
Microfluidic Multicompartment Device for Neuroscience Research. Figure 8A shows semi-additive R2R processes [224] that can be implemented for patterning of metal on a substrate, and Figure 8B shows demonstration of producing the electrode layer for impedimetric detection described in [222] as a R2R process in copper, as a proof of concept.
Lillehoj et al.
Malek C.G.K. Moreover, the world-to-chip interfaces for cast microfluidic devices is not straightforward. Some recent advances in multi-material micro- and nano-manufacturing. Rombach M., Hin S., Specht M., Johannsen B., Lddecke J., Paust N., Zengerle R., Roux L., Sutcliffe T., Peham J.R., et al. Park J., Fujita H., Kim B. Yeo L.P., Ng S.H., Wang Z., Wang Z., de Rooij N.F.
High-aspect ratio silicon structures may be achieved with deep reactive ion etching (DRIE), but this is an expensive process. Mkel T., Haatainen T., Majander P., Ahopelto J. The mould insert provides the micro/nano features of the polymer device and can be fabricated with various methods which are subsequently described further. The process of EDM usually leaves a layer of melted and re-solidified material (recast) at the machining zone, which tends to be hard and brittle with decreased fatigue strength.
Walsh D.I., Kong D.S., Murthy S.K., Carr P.A.
Microstructuring of polymer films for sensitive genotyping by real-time PCR on a centrifugal microfluidic platform. Higher applied pressure, higher embossing temperature, and longer holding time tend to reproduce micro-features closer to the mould [169]. It is relatively easy to produce monomers from the acryloyls. The most commonly used monomer chemistries include vinyl and acrylates, epoxy resins, thiol-enes, polyurethanes, and siloxanes. The alternative, however, cannot pattern continuously due to size limit of the planar mould, and will be difficult to integrate with other roller operation. The slurry is injected between the sonotrode and the workpiece constantly to replace worn-out abrasive and to carry away workpiece debris and heat generated from the impact. A variety of different approaches have been demonstrated. LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus.
The choice of the foil material can be limited because of the UV-curable property, such as foil thickness and optical property for the UV process and chemical compatibility for further processes [93].
Childs W.R., Nuzzo R.G. In practice, the processes are very similar to that of hot embossing, other than forming with either compressed gas or vacuum.
Bonded powder prints can be further strengthened by wax or thermoset polymer impregnation.
Molecular diagnostics requires considerable sample processing which needs to be integrated as different unit operations on the microfluidic device, including separation of blood or serum from whole blood before lysis, nucleic acid amplification, and amplicon detection.
The force involved is also much smaller than that in a mechanical process. Mekaru H., Goto H., Takahashi M. Development of ultrasonic micro hot embossing technology. Von Woedtke T., Abel P., Krger J., Kautek W. Subpicosecond-pulse laser microstructuring for enhanced reproducibility of biosensors. Bowen A.M., Nuzzo R.G. Upon contact with the rollers, the foil takes the pattern, followed by cooling down and retaining the pattern upon leaving the rollers.
Generally, the main considerations are speed, cost of the printed prototype, cost of the 3D printer, choice and cost of materials, and colour capabilities.
Ruchhoeft P., Colburn M., Choi B., Nounu H., Johnson S., Bailey T., Damle S., Stewart M., Ekerdt J., Sreenivasan S.V., et al. The approach was able to fabricate microchannels with widths of 50 m and obviated the need of separate step for sealing the channels. The running costs are relatively low and the skill demand of labour is not high [25].
The SU-8 is then developed to give the designed microfluidic architecture.
The greatly reduced costs of polymeric films further enhance their roles in the manufacturing of disposable microfluidic devices and offers enormous potential.
These techniques allow the mould to be fabricated with an ordinary LIGA process on planar surfaces and are relatively simple and fast. Rozkiewicz D.I., Kraan Y., Werten M.W.T., De Wolf F.A., Subramaniam V., Ravoo B.J., Reinhoudt D.N.
Bhattacharya S., Datta A., Berg J.M., Gangopadhyay S. Studies on surface wettability of poly(dimethyl) siloxane (PDMS) and glass under oxygen-plasma treatment and correlation with bond strength.
PDMS does, however, have several drawbacks for particular applications. To increase the absorption and reduce the reflection, one can utilise methods such as changing surface finish, applying surface coating, and oxidising the workpiece surface [24].
The liquid polymer is then drained from the vat, leaving the solid model.
The current practice seems to limit the ratio around one for negative forming [209], and three is possible for positive forming [198]. A PDMS soft mould on the roller cast by wrapping of PC film is also demonstrated [89,90].
High melt and mould temperatures, and high injection speed have a positive effect on the melt flow in very small cavities [189].
A roller embossing process for rapid fabrication of microlens arrays on glass substrates. Xia Y., Whitesides G.M. Decal transfer microlithography: A new soft-lithographic patterning method.
UV roller embossing uses UV-curable resin as the process material [89,90,91,204,205]. Foils can also provide protective and insulation functions for degradable contents and can be easily punctured to provide an easy mechanism for reagent transfer. The cycle time of the process is strongly affected by the tool design. Lewis et al. For the direct impact effect, the workpiece is abraded upon direct pounding by the tool through the abrasive particles caught in between the tool and the workpiece. The reduction in size, weight, and power consumption; improvement in sensitivity; and the characteristics of low-cost batch manufacturing of these devices have made the technology very appealing for numerous applications. Certain considerations are vital for the quality of hot embossed parts. Bilayer metal wire-grid polarizer fabricated by roll-to-roll nanoimprint lithography on flexible plastic substrate.
For the additive process, a gas injection system (GIS) is used and a precursor gas is injected close to the surface of the substrate (typically 100 m).
Nishiyama H., Mizoshiri M., Kawahara T., Nishii J., Hirata Y. SiO_2-based nonplanar structures fabricated using femtosecond laser lithography. Technol. Experimental study of polymer microlens fabrication using partial-filling hot embossing technique. Federal government websites often end in .gov or .mil. Lasers can be used for fabrication of moulds that can then be used for higher volume replication of microfluidic devices. Ochoa M., Rahimi R., Ziaie B. Cavities, holes, channels, and 3D structures are common applications (see Datta et al. The pattern from a photomask is transferred onto the SU-8-coated substrate by exposing to UV light and then a post exposure bake to accelerate the SU-8 polymerisation. The X-Y resolution is comparable to that of laser printers. Fabrication of Microfluidic Reactors and Mixing Studies for Luciferase Detection.
Nath P., Fung D., Kunde Y.A., Zeytun A., Branch B., Goddard G. Rapid prototyping of robust and versatile microfluidic components using adhesive transfer tapes. There is enough time for the laser energy to be absorbed in the workpiece and the thermal wave propagates into the material. (A) Hybrid integrated temperature sensor label from [224] under creative commons 3.0.
We have previously described addressing a 24 element array of microchambers through a series of row and columnar pneumatically actuated normally closed (NC) valves [120]. Printing Meets Lithography: Soft Approaches to High-Resolution Patterning.
RespiDisk: A point-of-care platform for fully automated detection of respiratory tract infection pathogens in clinical samples.
For simplicity, the discussion here will be limited to PDMS. Alting L., Kimura F., Hansen H.N., Bissacco G. Micro Engineering. [168] have demonstrated that 3D printed metal moulds can be used for high quality replication of hot embossed microfluidic devices.
The dynamically changed SLM has greatly increased the process efficiency. Li et al.
First, the material swells if in contact with several nonpolar organic solvents, such as diisopropylamine, triethylamine, pentane, and xylenes [105], presenting difficulty for maintaining feature sizes. Here, we will refer to the two parts as the tool and the mould insert [13].
McGeough J.A., Leu M.C., Rajurkar K.P., De Silva A.K.M., Liu Q. Electroforming Process and Application to Micro/Macro Manufacturing. Siloxanes have an alternating siliconoxygen polymer backbone.
HHS Vulnerability Disclosure, Help Fabrication of three-dimensional microstructures by electrochemically welding structures formed by microcontact printing on planar and curved substrates. [209] has given the variants on the microthermoforming process, which include micro matched-die moulding, rubber-assisted hot embossing, micro-backing moulding, and micro-pressure forming. Therefore the feasible ways to fabricate moulds include both the traditional MEMS approaches and micro-engineering [17]. A microfluidic device for capturing circulating tumour cells (CTCs) was fabricated using a fs laser combined with micromilling and solvent-assisted assembly of the different layers [134].
Learn more The pulse length of laser predominantly determines the characteristics the outcome of the machining. Simple approaches to minimally-instrumented, microfluidic-based point-of-care Nucleic Acid Amplification Tests. Kern P., Veh J., Michler J. Wang S.Q., Chinnasamy T., Lifson M.A., Inci F., Demirci U. Struct. Striegel et al. Proceedings of the Microfluidic Devices and Systems, Proceedings of the Micromachining and Microfabrication, Santa Clara, CA, USA, 2024 September 1998. Large-Area Roll-to-Roll and Roll-to-Plate Nanoimprint Lithography: A Step toward High-Throughput Application of Continuous Nanoimprinting.
Convery N., Gadegaard N. 30 Years of Microfluidics. A foil-based approach is also convenient for borrowing of approaches from the longer established printing and packaging industries. Fused deposition modelling uses a nozzle to deposit molten polymer onto a support structure, layer by layer. To achieve better replication of parts during the moulding process, one needs to optimise certain process parameters.
These factors will lead to different fluidic outcome, such as pressure drop or mixing in the channels, as well as process time. (B) Nineteen-layer London underground map against a UK 50 pence coin from [129] under Creative Commons 4.0 International license. Ng S.H., Wang Z.F.
Xurography: Rapid prototyping of microstructures using a cutting plotter. Other methods use combination of various approaches [78,86,87], and many of these techniques are adapted for pattern creation on rollers. [206] have described a roll-to-roll (R2R) UV nanoimprint lithography approach with biofunctionalised channels for multiplexed DNA detection.
It is also a non-contact machining without mechanical wear and may work well in atmosphere environment.
The part-to-part replication in mass production of small devices is also problematic. Engineering materials with light: Recent progress in digital light processing based 3D printing. The pre-heated upper heater with negative mould is lowered onto a PE membrane and a hybrid ethylene-vinyl acetate copolymer/polyethylene terephthalate (EVA/PET) membrane stacked coaxially on a PDMS-coated lower stage of the embosser set at room temperature. Lithography is the most general usage of e-beam machining in fabricating micro parts. Fabrication of metallic microstructure on curved substrate by optical soft lithography and copper electroplating. Diamond or diamond-coated tools are used for high-surface finish on soft materials and cubic boron nitride (CBN) for hard materials. The possible capability of polymeric microfluidic devices will be almost unlimited. Investigation on modifying the temperature profile of the embossed film with an aim to improve duplication fidelity by using a conveyer-belt mould is also worth noting [203]. The flushing process is important because the burned material re-solidifies in fluid as particles and can quickly accumulate; the build-up of particles can cause electrical short and stop the machining. Thin walls are manually deformable and are used frequently in blister packages for pills. Truckenmller R., Giselbrecht S., Van Blitterswijk C., Dambrowsky N., Gottwald E., Mappes T., Rolletschek A., Saile V., Trautmann C., Weibezahn K.F., et al. Pirskanen J., Immonen J., Kalima V., Pietarinen J., Siitonen S., Kuittinen M., Mnkknen K., Pakkanen T., Suvanto M., Pkknen E.J. This research was supported by the European Commission through the DVT-IMP (34256) and GateOne (644856) projects. Thermoplastic polymers soften when the material is heated above the glass transition temperaturethe point where polymers become rubber-like and are deformablewhich makes them suitable to be shaped with injection moulding or hot embossing.
The processes are then arranged into low- and high-volume manufacturing techniques. Becker H., Dietz W. Microfluidic devices for TAS applications fabricated by polymer hot embossing. Excimer beams have a typically broad spatial profile and poorly defined mode structure. The mould masters were produced by electroplating nickel through a SU-8 photo lithographically patterned mask. Open Channel Electrochromatography on a Microchip. PCR adhesive tape can offer easy, low-cost, and reversible bonding with manual pressing and no requirement for heating [127]. Lu et al.
Truckenmuller et al. Polymeric microfluidic devices have attracted a large amount of attention.
From the cost perspective, the thin-film geometry requires less material; as Velten et al.
Stephens L.S., Siripuram R., Hayden M., McCartt B. Deterministic Micro Asperities on Bearings and Seals Using a Modified LIGA Process.
Electrons from the electron gun are accelerated and focused through electrostatic or magnetic optics and bombard the workpiece at high speed. Ideally the cost of each phase should be considered, whilst the product is still at the conceptual stage. Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring. In the case of negative photoresist, exposure to UV light hardens the material whilst the unexposed areas remain soluble and can be washed away during development (Figure 2A). The high-volume processessuch as hot embossing, micro-injection moulding, and film or sheet processeshave a particularly important role for the commercial production of microfluidic devices.
A key requirement is for patterning of metals for a variety of functions, including wiring to provide interconnections between the components, data transmission, electrochemical transduction, fluid driving, and heating, and for R2R processes, these can be conveniently carried out using screen printing or microfabrication processes.
Effenhauser C.S., Bruin G.J.M., Paulus A., Ehrat M. Integrated Capillary Electrophoresis on Flexible Silicone Microdevices: Analysis of DNA Restriction Fragments and Detection of Single DNA Molecules on Microchips.
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