High aspect ratio tapered hollow metallic microneedle arrays with microfluidic interconnector

We present a novel microfabrication method for a tapered hollow metallic microneedle array and its complete microfluidic packaging for drug delivery and body fluid sampling applications. Backside exposure of SU-8 through a UV transparent substrate was investigated as a means of fabricating a dense array of tall (up to 400 μm) uniformly tapered SU-8 pillar structures with angles in the range of 3.1–5° on top of the SU-8 mesa. Conformal electroplating of metals on top of the array of the tapered SU-8 pillars, lapping of the tip of the metallic microneedles with planarizing polymer, and removal of the SU-8 sacrificial layers resulted in an array of tapered hollow metallic microneedles with a fluidic reservoir on the backside. A microfluidic interconnector assembly was designed and fabricated using SU-8 and conventionally machined PMMA in a way that it has a male interconnector, which directly fits into the fluidic reservoir of the microneedle array at one end and the other male interconnector, which provides fluidic interconnection to external devices at the other end. The fluid flow rate was measured and it showed 0.69 μL/s. per microneedle when the pressure of 6.89 KPa (1 psi) was applied.     

Fabrication and testing of embedded microvalves within PMMA microfluidic devices

The integration of a PDMS membrane within orthogonally placed PMMA microfluidic channels enables the pneumatic actuation of valves within bonded PMMA–PDMS–PMMA multilayer devices. Here, surface functionalization of PMMA substrates via acid catalyzed hydrolysis and air plasma corona treatment were investigated as possible techniques to permanently bond PMMA microfluidic channels to PDMS surfaces. FTIR and water contact angle analysis of functionalized PMMA substrates showed that air plasma corona treatment was most effective in inducing PMMA hydrophilicity. Subsequent fluidic tests showed that air plasma modified and bonded PMMA multilayer devices could withstand fluid leakage at an operational flow rate of 9 μl/min. The pneumatic actuation of the embedded PDMS membrane was observed through optical microscopy and an electrical resistance based technique. PDMS membrane actuation occurred at pneumatic pressures of as low as 10 kPa and complete valving occurred at 14 kPa for ~100 μm by 100 μm channel cross-sections.     

In-situ fabrication of polymer microsieves for ��TAS by slanted angle holography

We present a simple, versatile method for the in-situ fabrication of membranes inside a microfluidic channel during a chip manufacturing process using only two extra slanted angle holographic exposure steps. This method combines the strengths of both inclined UV exposure and holographic lithography to produce micrometer-sized three-dimensional sieving structures. Using a common chip material, the photoresist material SU-8, together with this method, a leak-free membrane-channel connection is obtained. The resulting membranes are monodisperse, with a very well-defined pore geometry (i.e., microsieves with a pore diameter between 500 nm and 10 μm) that is easily controllable with the holographic set-up. The selectivity of in-situ fabricated microsieves with a pore diameter of 2 μm will be demonstrated using polystyrene beads of 1 and 3 μm.     

Embedding off-the-shelf filter in PDMS chip for microbe sampling

Filtration for microfluidic sample-collection devices is desirable for sample selection, concentration, preprocessing, and manipulation, but microfabricating the required sub-micrometer structures is an elaborate process. This article presents a simple method to integrate filters in polydimethylsiloxane (PDMS) devices to sample microorganisms in aqueous environments. An off-the-shelf membrane filter with 0.22-μm pores was embedded in a PDMS layer and sequentially bound with other PDMS channel layers. No leakage was observed during filtration. This device was validated by concentrating a large amount of biomass, from 15 × 10⁷ to 3 × 10⁸ cells/ml of cyanobacterium Synechocystis in simulated sample water with consistent performance across devices. The major advantages of this method are low cost, simple design, straightforward fabrication, and robust performance, enabling wide-utility of chip-based devices for field-deployable operations in environmental microbiology.     

Design and fabrication of SU-8 micro optic fiber holder with cantilever-type elastic microclips

The optic alignment module containing out-of-plane 3D micro lenses, and micro optic fiber holders have been fabricated using tilted UV lithography technique in water with SU-8 photoresist (Ling and Lian in Proc SPIE 4979:402–409, 2007). Each holder is a circumscribed quadrilateral formed by a V-groove and pairs of fixed microclips, which will hold the fiber in position through the elastic deformation when the fiber is inserted. Since these microclips were fixed cantilever beams and its effective beam length, the distance between the fixed end of the beam and beam–fiber contact point, is very short (~62.5 μm), the stress on the beam is high even under a small (few microns) deformation. The inserted optical fiber was either too loose to lose its alignment accuracy, or too tight causing the clips to break because of dimensional tolerance. It becomes very difficult, if not impossible, to use them in practical applications. Therefore, the key issue of fabricating optical alignment module is to have a suitable stiffness of microclips with an appropriate deformation during the fiber insertion, which can provide enough force to hold the fiber for accurate alignment and avoid introducing neither significant viscous deformation nor the damage to the clips. In this paper, a novel technique to fabricate SU-8 cantilever beam as elastic clamping device in optical fiber holder is proposed. Simulation based on SU-8 material properties indicates that for a 250-μm-long, 50-μm-thick SU-8 beam the clamping force per unit beam width will range from 10 to 100 Newton/m as the deflection increased from 1.4 to 14 μm. This predicted performance is comparable to or even better than that of existing silicon nitride microclips in optical fiber holding application [Bostock et al. in J Micromech Microeng 8(4):343–360, 1998]. By using a two-mask process, we have fabricated free-end cantilever beams as fiber holding clips. In order to have longer beams over V-groove, the slots in the V-groove were introduced, which allow the beams extended deeper into the sloped V-groove walls. The micro alignment module with 250-μm-length cantilever beams as microclips for housing 125-μm-diameter optical fibers has been successfully fabricated using a 300-μm-thick SU-8 photoresist layer by a two-mask UV lithography processes. This approuch offers significant advantages over other techniques with respect to costs of material, simple in equipment, and easy in manufacture. These optical fiber holders with elastic microclips combined with pre-aligned out-of-plane 3D micro lenses make it possible that to build an integrated micro optic system with precise alignment accuracy on a wafer-scale.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.

     

Two photon absorption coefficients and processing parameters for photoresists

The two photon absorption (TPA) process is currently used to write high resolution microstructures for a variety of applications. Key parameters required to predict the final structure formation for this process are experimentally determined and reported in this article for two commercially available resists, Ormocore and SU-8. The measured TPA coefficients measured at 800 nm for Ormocore and SU-8 are 27 ± 6 and 28 ± 6 cm TW⁻¹, respectively. For Ormocore and SU-8 the dose required to write 35 and 50 μm high structures, respectively, were 54 ± 8 and 3.5 ± 0.5 J cm⁻³, respectively, and the measured contrasts were 15 ± 2 μm per decade J⁻¹ cm³ and 55 ± 8 μm per decade J⁻¹ cm³, respectively.     

Surface microfluidics fabricated by photopatternable superhydrophobic nanocomposite

Surface microfluidics can be of potential use in a variety of emerging applications, including biological and chemical analysis, cellular detection and manipulation, high-throughput pharmaceutical screening, and etc. In comparison with the conventional closed-channel microfluidic system, surface microfluidics shows the distinct advantages of simple construction, direct surface access, no cavitation or interphase obstruction, clear optical path, easy fluidic packaging, and device reusability. In this article, we first present surface microfluidic networks microfabricated by a single-step lithographic process using a novel superhydrophobic photosensitive nanocomposite formula. The photopatternable superhydrophobic nanocomposite (PSN) incorporates PTFE nanoparticles into a SU-8 matrix, in which superhydrophobicity (contact angle of above 160°) is primarily contributed by the extremely low chemical energy and nano-topology of PTFE nanoparticles, while the SU-8 polymer matrix offers photopatternability (lithographic resolution of 10 μm) and substrate adhesion. Moreover, an additive intermediate layer with hydrophilic sidewall considerably reduces flow resistance while improving the substrate adhesion, as a crucial improvement from the previous surface flow configuration. Furthermore, self-propelled microfluidic networks driven by surface tension-induced pressure gradient have been fabricated and characterized to demonstrate the applicability of the novel nanocomposite fabrication approach.     

Active material micro-actuator arrays fabricated with SU-8 resin

 Active materials such as piezoelectric ceramics and shape memory metal alloys commonly actuate active control and intelligent material systems. Commercially available piezoelectric materials exhibit small actuation stroke and shape memory metal alloys have limited bandwidth. The proposed micro-actuator array design and fabrication process increases the actuation stroke of piezoceramic material by a factor of 1.5 for a 2 × 2 array; two active material segments connected in parallel and two in series, and doubles the response time of a 1 × 4 shape memory alloy driven array; four active materials segments connected in series. A high aspect ratio fabrication method incorporating SU-8 resin and conventional lithography is the process that forms the array linkages. The SU-8 resin array structures are 300 μm tall.     

Design and fabrication of an electrostatically suspended microgyroscope using UV-LIGA technology

A micromachined electrostatically suspended gyroscope, with a wheel-like rotor housed by top stator and bottom stator, using UV-LIGA microfabrication technology, was presented. The designed structure and basic operating principle of the gyroscope are described. The key steps in the fabrication process, such as wet etching of Pyrex glass pits for soldering, and integration of thick nickel structures by removal of SU-8 mold, were considered in detail and well solved. Cr/Pt/photoresist was used as etching mask and the etched pits, in depth of near 30 μm, with aspect ratio (depth to undercutting) of 0.75, were obtained. With metal foundations constructed for consolidation, successful integration of the nickel structures, in thickness of 200 μm, was achieved by successful removal of the SU-8 mold using oleum. After the two stators and the rotor were fabricated separately, they were assembled and soldering bonded to form axial and radial small gaps, hence, the initial prototype of the microgyroscope was realized. The key techniques described in this paper can be applied to fabrication of other micro devices. The metal foundation method, associated with removal of SU-8 mold by oleum, is expected to make SU-8 wider applications in making integrated microstructures with fabricated circuitry on the same chip.     

New production method of convex microlens arrays for integrated fluorescence microfluidic detection systems

A new method for producing microlens array with large sag heights is proposed for integrated fluorescence microfluidic detection systems. Three steps in this production technique are included for concave microlens array formations to be integrated into microfluidic systems. First, using the photoresist SU-8 to produce hexagonal microchannel array is required. Second, UV curable glue is injected into the hexagonal microchannel array. Third, the surplus glue is rotated by a spinner at high velocity and exposed to a UV lamp to harden the glue. The micro concave lens molds are then finished and ready to produce convex microlens in poly methsiloxane (PDMS) material. This convex microlens in PDMS can be used for detecting fluorescence in microfluidic channels because a convex microlens plays the light convergence role for optical fiber detection.     

Prototyping of microfluidic systems using a commercial thermoplastic elastomer

This article describes the fabrication of microfluidic networks (μFNs) from a commercially available (styrene)–(ethylene/butylene)–(styrene) (SEBS) block copolymer (BCP). The unique combination of hard and elastomeric properties provided by this material promotes high-throughput replication of fluidic structures using thermoforming technologies, while retaining the advantage of quick and easy assembly via conformal contact, as commonly achieved for devices fabricated from poly(dimethylsiloxane (PDMS). We employ Versaflex CL30, which is optically transparent, available at low cost (e.g., $2.50/Lbs), and likely to be compatible with a broad range of biological species. We demonstrate excellent fidelity in replication of fluidic structures using hot embossing lithography in conjunction with a photolithographically prepared Si/SU-8 master mold. Moreover, we introduce rapid prototyping of high-quality structures using an approach that we call soft thermoplastic lithography (STPL). Thanks to the rheological characteristics of the SEBS copolymer, STPL enables thermoforming on a heated master at temperatures around 170°C. Using this approach, replication can be completed within a very short period of time (e.g., less than 3 min) without the need of resorting to pressure- or vacuum-assisted instrumentation. Serving as a proof-of-concept, we devise a μFN that is suitable for the formation of miniaturized arrays comprising fluorescently labeled oligonucleotides and proteins on hard plastic substrates. Resultant spots are characterized by high fluorescent contrast, excellent edge definition, and uniform distribution of probes within the modified areas.     

A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

Inexpensive, quickly producable X-ray mask for LIGA

 The capability to produce X-ray masks inexpensively and rapidly is expected to greatly enhance the commercial appeal of the LIGA process. This paper presents a process to fabricate X-ray masks both inexpensively (under $1000) and rapidly (within a few days). The process involves one UV lithography step and eliminates the need for an intermediate X-ray mask. The X-ray mask produced by this process consists of a 125 μm thick graphite membrane that supports a gold-on-nickel absorber pattern. The thickness of the absorber structures is great enough to supply sufficient contrast even when radiation sources with high characteristic photon energies up to 40 keV are utilized and/or when deep exposures are desired. The mask fabrication process is initiated by spin coating 30–50 μm of SU-8 directly on a graphite membrane. The SU-8 is then patterned using a UV mask. Gold-on-nickel absorber structures are electroplated directly onto the SU-8 covered graphite. Once the remaining SU-8 is removed, attaching the graphite membrane to a frame completes the mask. To test the performance of the mask, a nickel mold insert was fabricated. A sheet of PMMA 500 μm in thickness was bonded to a nickel substrate, then exposed to X-rays through the mask, and developed. Electroplating nickel into the patterned PMMA sheet produced a mold insert. SEM pictures taken of the SU-8, the X-ray mask, and the mold insert are shown. This method of rapidly producing an inexpensive X-ray mask for LIGA resulted in a mold insert with smooth, vertical sidewalls whose dimensions were within two micrometers of the UV mask dimensions. Received: 12 December 1998/Accepted: 2 February 1999     

Low-stress fabrication of 3D polymer free standing structures using lamination of photosensitive films

Free-standing microstructures such as cantilevers, membranes or microchannels are building blocks of microfluidic systems and MEMS. As a complement to silicon, the large family of polymers offers many opportunities for micro and nanotechnologies. Their low temperature processing and the planarizing properties of many resists is a definitive advantage for system integration, paving the way to complete lab-on-chips. In this article, we investigate a fabrication process of polymeric free standing structures based on the lamination of SU-8, a thick epoxy photoresist. Our motivation is the hybrid integration of polymer microfluidic or MEMS components with silicon chips (e.g., integrated circuits or sensors). Compared to rigid substrates used in more conventional SU-8/SU-8 bonding process, the flexible photosensitive films used within this lamination technique allows a more homogeneous and reliable bonding at low pressure and temperature, and a 3D fabrication with an excellent level-to-level alignment. A parametric optimization of the lamination process is presented. The fabrication of a leakage-free 3D microfluidic network is demonstrated by stacking up to five layers. A polyethylene terephtalate layer has been employed to easily release the SU-8 devices. We show that this release layer also significantly decrease the curvature of the substrate by 32% and the related residual stress in a 100 μm SU-8 layer by at least 10%. Finally, we briefly describe the hybrid integration of a silicon sensor in a microfluidic network as a direct application of our lamination process to the fabrication of lab-on-chips.

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Continuous-flow ATP amplification system on a chip

In this study, we constructed a novel microfluidic device for continuous-flow ATP amplification, using the SU-8:PDMS method. Sepharose beads immobilized with adenylate kinase and pyruvate kinase was packed into a microfluidic chamber to form lamination layer. Dry film type SU-8 was suitable to form a very thick mold for beads column reactor and its dam structure. A good correlation between amplified luminescence and initial ATP concentration was observed in this system. The gradient of amplification when performing six cycles of continuous-flow ATP amplification was 1.72^N.     

Dual thermopile integrated microfluidic calorimeter for biochemical thermodynamics

This article presents a new design of a silicon-based microcalorimeter made with dual thermopiles and a microchannel. The dual thermopile was fabricated with chromium and copper using a microelectromechanical system (MEMS) technique, and the microchannel was made of PDMS using soft-lithography. Each thermopile consists of 26 thermocouple pairs and 50 μm wide electrodes. The total sensitivity of thermopile is 428 μV/K. The dual thermopile system enables the microcalorimeter to acquire reliable data in a rapid and convenient manner because it detects the reaction and reference temperatures simultaneously. This self-compensation allows our device to analyze a few microliters of sample solution without the need for a surrounding adiabatic vacuum.     

Development of microfluidic alginate microbead generator tunable by pulsed airflow injection for the microencapsulation of cells

Recently, microbead generation and microencapsulation of cells using microfluidic technology have been actively pursued for various applications. However, most of the proposed systems are not only technically demanding, but might also be harmful to the encapsulated cells. To tackle these issues, this study reports a microfluidic alginate microbead generator consisting of a polydimethylsiloxane (PDMS) microfluidic chip and an integrated quartz microcapillary tube. The working principle is based on the use of a pulsed airflow to segment a continuous alginate suspension flow to form suspension fragments in a microchannel and then alginate microbeads when they were delivered out the microfluidic system to a sterile calcium chloride solution through a microcapillary tube. In this study, the alginate suspension fragments with varied sizes in the microchannel can be generated either by modulating the alginate suspension flow rate or the pulsation frequency of airflow injection. By fine tuning the size of them, the alginate microbeads can be generated in a size-controllable manner. Results showed that alginate microbeads with the size ranging from 150 to 370 μm in diameter can be generated at the suspension flow rate and airflow injection frequency ranges of 2–4 μl/min and 0.6–35 Hz, respectively. Besides, the alginate microbeads generated by the system were tested with excellent size uniformity (CV: 3.1–5.1%). Moreover, its application for the microencapsulation of chondrocytes in alginate microbeads was also demonstrated with high cell viability (96 ± 2%). As a whole, the proposed device has paved an alternative route to perform alginate microbead generation or microencapsulation of cells in a simple, continuous, controllable, uniform, cell friendly, and less contaminated manner.     

SU-8 microchannels for live cell dielectrophoresis improvements

In this work a novel highly precise SU-8 fabrication technology is employed to construct microfluidic devices for sensitive dielectrophoretic (DEP) manipulation of budding yeast cells. A benchmark microfluidic live cell sorting system is presented, and the effect of microchannel misalignment above electrode topologies on live cell DEP is discussed in detail. Simplified model of budding Saccharomyces cerevisiae yeast cell is presented and validated experimentally in fabricated microfluidic devices. A novel fabrication process enabling rapid prototyping of microfluidic devices with well-aligned integrated electrodes is presented and the process flow is described. Identical devices were produced with standard soft-lithography processes. In comparison to standard PDMS based soft-lithography, an SU-8 layer was used to construct the microchannel walls sealed by a flat sheet of PDMS to obtain the microfluidic channels. Direct bonding of PDMS to SU-8 surface was achieved by efficient wet chemical silanization combined with oxygen plasma treatment of the contact surface. The presented fabrication process significantly improved the alignment of the microstructures. While, according to the benchmark study, the standard PDMS procedure fell well outside the range required for reasonable cell sorting efficiency. In addition, PDMS delamination above electrode topologies was significantly decreased over standard soft-lithography devices. The fabrication time and costs of the proposed methodology were found to be roughly the same.

     

Fabrication of large-volume microfluidic chamber embedded in glass using three-dimensional femtosecond laser micromachining

We report on fabrication of large-volume, square-shaped microfluidic chamber embedded in glass by scanning a tightly focused femtosecond laser beam inside a porous glass immersed in water. After the hollow structure is created in the porous glass substrate, the fabricated glass sample is post-annealed at 1,050°C during which it can be sintered into a compact glass. By the use of this technique, a 1 mm × 1 mm × 100 μm microchamber connected to four microfluidic channels is created inside the transparent glass substrate, showing that our technique allows for fabrication of not only thin channel structures with arbitrary lengths and configurations, but also hollow structures with infinitely large sizes.