Search

Structured microparticles, with unique shapes, customizable sizes, multiple materials, and spatially-defined chemistries, are leading the way for emerging 'lab on a particle' technologies. These microparticles with engineered designs find applications in multiplexed diagnostics, drug delivery, single-cell secretion assays, single-molecule detection assays, high throughput cytometry, micro-robotics, self-assembly, and tissue engineering. In this article we review state-of-the-art particle manufacturing technologies based on flow-assisted photolithography performed inside microfluidic channels. Important physicochemical concepts are discussed to provide a basis for understanding the fabrication technologies. These photolithography technologies are compared based on the structural as well as compositional complexity of the fabricated particles. Particles are categorized, from 1D to 3D particles, based on the number of dimensions that can be independently controlled during the fabrication process. After discussing the advantages of the individual techniques, important applications of the fabricated particles are reviewed. Lastly, a future perspective is provided with potential directions to improve the throughput of particle fabrication, realize new particle shapes, measure particles in an automated manner, and adopt the 'lab on a particle' technologies to other areas of research.

3D microparticles have promising applications in self-assembly, biomedical engineering, mechanical engineering

In the present article we report a new hybrid microfluidic device (hyFlow) comprising a disposable paper electrode and a three-dimensional (3D) printed plastic chip for the electrochemical detection of a magnetic bead-silver nanoparticle (MB-AgNP) bioconjugate. This hybrid device evolved due to the difficulty of incorporating micron-scale MBs into paper-only fluidic devices. Specifically, paper fluidic devices can entrap MB-containing conjugates within their cellulose or nitrocellulose fiber matrix. The hyFlow system was designed to minimize such issues and transport MB conjugates more efficiently to the electrochemical detection zone of the device. The hyFlow system retains the benefit of fluid transport by pressure-driven flow, however, no pump is required for its operation. The hyFlow device is capable of detecting either pre-formed MB-AgNP conjugates or conjugates formed in-situ formation. The detection limit of AgNPs using this device is 12 pM, which represents just 22 AgNPs per MB.

The ability to arrange distinct cells in specific, predefined patterns at single-cell resolution can have broad applications in cell-based assays and play an important role in facilitating interdisciplinary research for researchers in various fields. However, most existing methods for single-cell patterning are based on the complicated lithography-based microfabrication process, and require professional skills. Thus, exploiting convenient and universal strategies of single-cell preparation while maintaining high-throughput single-cell patterning remains a challenge. Here, we describe a simple approach for rapid and high-efficiency single-cell patterning using an ultrathin metal microstencil (UTmS) and common tools available in any laboratory. In this work, ultrathin steel microstencil plates with only 5 μm thickness could be fabricated with laser drilling and achieve single-cell prototyping on an arbitrary planar substrate under gravity-induced natural sedimentation without requiring additional fixation, reaction pools, and centrifugation procedures. In this method, the UTmS is reusable and single-cell occupancy could easily reach approximately 88% within 30 min on fibronectin-modified substrates under gravity-induced natural sedimentation, and no significant effect on cell viability was observed. To verify this method, the real-time and heterogeneous study of calcium release and apoptosis behaviors of single cells was carried out based on this new strategy. To our knowledge, it is the first time that a UTmS with 5 μm thickness is directly applied to facilitate the micropatterning of high-resolution single cells, which is valuable for researchers in different fields owing to its user-friendly operation.

International audience; We report the fabrication of permeable membranes for microfluidic dialysis applications in poly(dimethylsiloxane) (PDMS) channels. A maskless UV projection device was used to photo-pattern long hydrogel membranes (mm-cm) with a spatial resolution of a few microns in PDMS chips integrating also micro-valves. We show in particular that multi-layer soft lithography allows one to deplete oxygen from the PDMS walls using nitrogen gas flow and therefore makes possible in-situ UV-induced polymerization of hydro-gels. We also report a simple surface modification of the PDMS channels leading to strongly anchored hydrogel membranes that can withstand trans-membrane pressure drops up to 1 bar without leakages. We then measured the Darcy permeability of these membranes and estimated their cutoff by measuring the kinetics of diffusion of macromolecules of different sizes through the membrane. Finally, we illustrate the opportunities offered by such microfluidic chips for dialysis applications by observing in real time the crystallization of a model protein in a chamber of a few nanoliters.

Lab-on-a-chip devices, capable of culturing living cells in continuously perfused, micrometer-sized channels, have been intensively investigated to model physiological microenvironments for cell-related testing and evaluation applications. Various chemical, physical, and/or biological culture cues are usually expected in a designed chip to mimic the in vivo environment with defined spatial heterogeneity of cells and biomaterials. To create such heterogeneity within a given chip, typical methods rely heavily on sophisticated fabrication and cell seeding processes, and chips fabricated with these methods are difficult to readily adapt for other applications. In this study, laser-induced forward transfer (LIFT)-based printing has been implemented to create heterogeneous cellular patterns in a lab-on-a-chip device to achieve the efficiency in creating heterogeneous cellular patterns as well as the flexibility in adapting different evaluation configurations in lab-on-a-chip devices. Two applications, parallel evaluation of cellular behavior and targeted drug delivery to cancer cells, have been implemented as proof-of-concept demonstrations of the proposed fabrication method. For the first application, the morphology of cells in different extracellular matrix (ECM) materials cultured under varying conditions has been investigated. It is found that less stiff ECM and dynamic culturing are preferred for spreading of fibroblasts. For the second application, different drug carriers have been utilized for targeted delivery of anticancer drugs to breast cancer cells. It is found that targeted drug delivery is important to realize effective chemotherapy and drug release rate from drug carriers affects the chemotherapy effect. Consequently, the proposed laser printing-based method enables direct creation of heterogeneous cellular patterns within lab-on-a-chip devices which improves the efficiency and versatility of cell-related sensing and evaluation using lab-on-a-chip devices.

Direct laser writing (DLW) is a three-dimensional (3D) manufacturing technology that offers vast architectural control at submicron scales, yet remains limited in cases that demand microstructures comprising more than one material. Here we present an accessible microfluidic multi-material DLW (μFMM-DLW) strategy that enables 3D nanostructured components to be printed with average material registration accuracies of 100 ± 70 nm (ΔX) and 190 ± 170 nm (ΔY) - a significant improvement versus conventional multi-material DLW methods. Results for printing 3D microstructures with up to five materials suggest that μFMM-DLW can be utilized in applications that demand geometrically complex, multi-material microsystems, such as for photonics, meta-materials, and 3D cell biology.

Tape-based razor-printing is a flexible and affordable ultra-rapid prototyping approach for microscale device fabrication. However, integration of this prototyping approach into cell-based assay development has been limited to proof of principle demonstrations. This is in large part due to lack of an established or well-characterized option for biocompatible adhesive tape. Without such an option, integration of these areas will remain unexplored. Therefore, to address this critical hurdle, we characterized microscale devices made using a potentially biocompatible double-sided adhesive, ARCare 90106. We validated tape-based device performance against 96-well plates and PDMS microdevices with respect to cell viability, hydrophobic small molecule sequestration, the potential for leaching compounds, use in fluorescence microscopy, and outgassing (bubble formation). Results supported the tape as a promising tool for future cell-based assay development. Therefore, we subsequently demonstrated specific strengths enabled by the ultra-rapid (< 1hr per prototype) and affordable (~$1,200 cutting plotter, < $0.05 per prototype) approach. Specifically, data demonstrate the ability to integrate disparate materials for advanced sticker-device functionality such as bonding of polystyrene devices to glass substrates for microscopy applications, inclusion of membranes, and incorporation of different electrospun biomaterials into a single device. Likewise, the approach allowed rapid adoption by uninitiated users. Overall, this study provides a necessary and unique contribution to the largely separate fields of tape-based razor-printing and cell-based microscale assay development by addressing a critical barrier to widespread integration and adoption while also demonstrating the potential for new and future applications.

We developed a highly efficient method for patterning cells by a novel and simple technique called lift-off cell lithography (LCL). Our approach borrows the key concept of lift-off lithography from microfabrication and utilizes a fully biocompatible process to achieve high-throughput, high-efficiency cell patterning with nearly zero background defects across a large surface area. Using LCL, we reproducibly achieved >70% patterning efficiency for both adherent and non-adherent cells with

Multi-electrode arrays (MEAs) have become a key element in the study of cellular phenomena in vitro. Common modern MEAs are still based on costly microfabrication techniques, making them expensive tools that researchers are pushed to reuse, compromising the reproducibility and the quality of the acquired data. There is a need to develop novel fabrication strategies, able to produce disposable devices that incorporate advanced technologies beyond the standard metal electrodes on rigid substrates. Here we present an innovative fabrication process for the production of polymer-based flexible MEAs. The device fabrication exploited inkjet printing, as this low-cost manufacturing method allows for an easy and reliable patterning of conducting polymers. Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was used as the sole conductive element of the MEAs. The physical structure and the electrical properties of the plastic/printed MEAs (pMEAs) were characterised, showing a low impedance that is maintained also in the long term. The biocompatibility of the devices was demonstrated, and their capability to successfully establish a tight coupling with cells was proved. Furthermore, the pMEAs were used to monitor the extracellular potentials from cardiac cell cultures and to record high quality electrophysiological signals from them. Our results validate the use of pMEAs as in vitro electrophysiology platforms, pushing for the adoption of innovative fabrication techniques and the use of new materials for the production of MEAs.

This study reports a simple, rapid, low-cost, robust, and multiplexed barcoded paper-based assay (BPA) compatible with mobile devices. An inkjet printer and an XYZ dispensing platform were used to realize mass-manufacturing of barcoded paper-based analytical devices (BPADs) with high precision and efficiency. We designed a new group of barcodes and developed an application (APP) for the reading of the new code. The new barcodes possess a 16 times higher coding capacity than the standard Codabar code in our experiment on drug residue detection. The BPA system allows applications in the assays of blood-transmitted infections, drug residues in milk and multiplex nucleic acids. The whole detection process and the readout of the results can be completed within 10 minutes. The limit of detection for enrofloxacin (ENR) (8 ng mL−1) satisfies the requirements of drug residue monitoring. Its high rapidity, simplicity, efficiency and selectivity make the BPA system extremely suitable to be applied in rapid and on-site detection.

Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.

The assembly of scalable liquid compartments for binding assays in array formats constitutes a topic of fundamental importance in life sciences. This challenge can be addressed by mimicking the structure of cellular compartments with biological native conditions. Here, inkjet printing is employed to develop up to hundreds of picoliter aqueous droplet arrays stabilized by oil-confinement with mild surfactants (Tween-20). The aqueous environments constitute specialized compartments in which biomolecules may exploit their function and a wide range of molecular interactions can be quantitatively investigated. Raster Image Correlation Spectroscopy (RICS) is employed to monitor in each compartment a restricted range of dynamic intermolecular events demonstrated through protein-binding assays involving the biotin/streptavidin model system.

This paper presents a simple and cost-effective polyester toner microchip fabricated with laser print and cut lithography (PCL) to use with a battery-powered centrifugal platform for fluid handling. The combination of the PCL microfluidic disc and centrifugal platform: (1) allows parallel aliquoting of two different reagents of four different volumes ranging from nL to μL with an accuracy comparable to a piston-driven air pipette; (2) incorporates a reciprocating mixing unit driven by a surface-tension pump for further dilution of reagents, and (3) is amenable to larger scale integration of assay multiplexing (including all valves and mixers) without substantially increasing fabrication cost and time. For a proof of principle, a 10 min colorimetric assay for the quantitation of the protein level in the human blood plasma samples is demonstrated on chip with a limit of detection of ∼5 mg mL(-1) and coefficient of variance of ∼7%.

Micro-/nanofabrication-based lab-on-a-chip (LOC) technologies have recently been substantially advanced and have become widely used in various inter-/multidisciplinary research fields, including biological, (bio-)chemical, and biomedical fields. However, such hybrid-scale LOC devices are typically fabricated using microfabrication and nanofabrication processes in series, resulting in increased cost and time and low throughput issues. In this review, after briefly introducing the conventional micro-/nanofabrication technologies, we focus on unconventional micro-/nanofabrication technologies that allow us to produce either in situ micro-/nanoscale structures or master molds for additional replication processes to easily and conveniently create novel LOC devices with micro- or nanofluidic channel networks. In particular, microfabrication methods based on crack-assisted photolithography and carbon-microelectromechanical systems (C-MEMS) are described in detail because of their superior features from the viewpoint of the throughput, batch fabrication process, and mixed-scale channels/structures. In parallel with previously reported articles on conventional micro-/nanofabrication technologies, our review of unconventional micro-/nanofabrication technologies will provide a useful and practical fabrication guideline for future hybrid-scale LOC devices.

In this work, we first report a facile, low-cost and high-throughput method for photolithographical fabrication of microfluidic cloth-based analytical devices (μCADs) by simply using a cotton cloth as a substrate material and employing an inexpensive hydrophobic photoresist laboratory-formulated from commercially available reagents, which allows patterning of reproducible hydrophilic-hydrophobic features in the cloth with well-defined and uniform boundaries. Firstly, we evaluated the wicking properties of cotton cloths by testing the wicking rate in the cloth channel, in combination with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analyses. It is demonstrated that the wicking properties of the cloth microfluidic channel can be improved by soaking the cloth substrate in 20 wt% NaOH solution and by washing the cloth-based microfluidic patterns with 3 wt% SDS solution. Next, we studied the minimum dimensions achievable for the width of the hydrophobic barriers and hydrophilic channels. The results indicate that the smallest width for a desired hydrophobic barrier is designed to be 100 μm and that for a desired hydrophilic channel is designed to be 500 μm. Finally, the high-throughput μCADs prepared using the developed fabrication technique were demonstrated for colorimetric assays of glucose and protein in artificial urine samples. It has been shown that the photolithographically patterned μCADs have potential for a simple, quantitative colorimetric urine test. The combination of cheap cloth and inexpensive high-throughput photolithography enables the development of new types of low-cost cloth-based microfluidic devices, such as "microzone plates" and "gate arrays", which provide new methods to perform biochemical assays or control fluid flow.

© The Royal Society of Chemistry. Long-term culture and monitoring of individual multicellular spheroids and embryoid bodies (EBs) remains a challenge for in vitro cell propagation. Here, we used a continuous 3D projection printing approach - with an important modification of nonlinear exposure - to generate concave hydrogel microstructures that permit spheroid growth and long-term maintenance, without the need for spheroid transfer. Breast cancer spheroids grown to 10 d in the concave structures showed hypoxic cores and signs of necrosis using immunofluorescent and histochemical staining, key features of the tumor microenvironment in vivo. EBs consisting of induced pluripotent stem cells (iPSCs) grown on the hydrogels demonstrated narrow size distribution and undifferentiated markers at 3 d, followed by signs of differentiation by the presence of cavities and staining of the three germ layers at 10 d. These findings demonstrate a new method for long-term (e.g. beyond spheroid formation at day 2, and with media exchange) 3D cell culture that should be able to assist in cancer spheroid studies as well as embryogenesis and patient-derived disease modeling with iPSC EBs.

The diagnosis of infectious disease is typically carried out at the point-of-care (POC) using the lateral flow assay (LFA). While cost-effective and portable, LFAs often lack the clinical sensitivity and specificity required for accurate diagnoses. In response to this challenge, we introduce a new digital microfluidic (DMF) platform fabricated using a custom inkjet printing and roll-coating process that is scalable to mass production. The performance of the new devices is on par with that of traditional DMF devices fabricated in a cleanroom, with a materials cost for the new devices of only US $0.63 per device. To evaluate the usefulness of the new platform, we performed a 13-step rubella virus (RV) IgG immunoassay on the inkjet printed, roll-coated devices, which yielded a limit of detection of 0.02 IU mL^(−1), well below the diagnostic cut-off of 10 IU mL^(−1) for RV infection and immunity. We propose that this represents a breakthrough for DMF, lowering the costs to a level such that the new platforms will be an attractive alternative to LFAs for the diagnosis of infectious disease at the POC.

Research in microfluidic biosensors has led to dramatic improvements in sensitivities. Very few examples of these devices have been commercially successful, keeping this methodology out of the hands of potential users. In this study, we developed a method to fabricate a flexible microfluidic device containing electrowetting valves and electrochemical transduction. The device was designed to be amenable to a roll-to-roll manufacturing system, allowing a low manufacturing cost. Microchannels with high fidelity were structured on a PET film using UV-NanoImprint Lithography (UV-NIL). The electrodes were inkjet-printed and photonically sintered on second flexible PET film. The film containing electrodes was bonded directly to the channel-containing layer to form sealed fluidic device. Actuation of the multivalve system with food dye in PBS buffer was performed to demonstrate automated fluid delivery. The device was then used to detect Salmonella in a liquid sample.

A microfluidic chip approach utilising integrated electrically connected stationary SERS targets based on inkjet-printed silver nanoparticles is presented. It enables multiple interference-free consecutive surface-enhanced Raman measurements inside chip channels by electrically assisted regeneration of the stationary SERS substrate. Thereby it circumvents common adsorption and memory effect problems associated with stationary SERS targets allowing multiple consecutive measurements in a continuous-flow system.

In this study, we report on a simple and versatile plug-n-play microfluidic system that is fabricated from flexible assembly of glass-based flow-control modules for flexibly manipulating flows for versatile emulsion generation. The microfluidic system consists of three basic functional units: a flow-control module, a positioning groove, and a connection fastener. The flow-control module that is based on simple assembly of low-cost glass slides, coverslips, and glass capillaries provides excellent chemical resistance and optical properties, and easy wettability modification for flow manipulation. The flexible combination of the flow-control modules with 3D-printed positioning grooves and connection fasteners enables creation of versatile microfluidic systems for generating various higher-order multiple emulsions. The simple and reversible connection of the flow-control modules also allows easy disassembly of the microfluidic systems for further scale-up and functionalization. We demonstrate the scalability and controllability of flow manipulation by creating microfluidic systems from flexible assembly of flow-control modules for controllable generation of multiple emulsions from double emulsions to quadruple emulsions. Meanwhile, the flexible flow manipulation in the flow-control module provides advanced functions for improved control of the drop size, and for controllable generation of drops containing distinct components within multiple emulsions to extend the emulsion structure. Such modular microfluidic systems provide flexibility and versatility to flexibly manipulate micro-flows for enhanced and extended applications.

Microfluidic systems based on polydimethylsiloxane (PDMS) have gained popularity in recent years. However, microelectrode patterning on PDMS to form biosensors in microchannels remains a worldwide technical issue due to the hydrophobicity of PDMS and its weak adhesion to metals. In this study, an additive technique using inkjet-printed silver nanoparticles to form microelectrodes on PDMS is presented. (3-Mercaptopropyl)trimethoxysilane (MPTMS) was used to modify the surface of PDMS to improve its surface wettability and its adhesion to silver. The modified surface of PDMS is rendered relatively hydrophilic, which is beneficial for the silver droplets to disperse and thus effectively avoids the coalescence of adjacent droplets. Additionally, a multilevel matrix deposition (MMD) method is used to further avoid the coalescence and yield a homogeneous pattern on the MPTMS-modified PDMS. A surface wettability comparison and an adhesion test were conducted. The resulting silver pattern exhibited good uniformity, conductivity and excellent adhesion to PDMS. A three-electrode electrochemical biosensor was fabricated successfully using this method and sealed in a PDMS microchannel, forming a lab-on-a-chip glucose biosensing system.

Precise and quantitative control of extracellular signalling cues using surface-engineered chips has facilitated various neurobiological assays in vitro. Although the formation of axon collateral branches is important for the establishment and refinement of the neuronal connections during the development and regeneration, surface designs for controlling branch phenotypes have been rarely proposed. In this work, we fabricated a surface-printed microdot array for controlling axon branch formation. Following the culture of hippocampal neurons on a 5 μm dot array patterned by micro-contact printing of poly-D-lysine, we found that most axon collateral branches were initiated from axonal regions on a microdot and terminated on neighboring dots. In addition, the length of branches increased as the spacing between dots increased. Surprisingly, other morphological features were not significantly different from the neurons cultured on a conventional unpatterned surface. Further investigation of this phenomenon indicated that the branch-forming machineries, such as actin patches, were focused on the dot. According to these investigations, we concluded that discontinuous adhesion spots given by dot arrays arranged the branching formation on the expectable location and direction. Therefore, microdot arrays will be applicable as the surface design parameter of bio-chip platforms to reduce branching complexity and quantize branching formation for the simple and easy assay in neurobiological studies.

High-efficiency transfection of genes, proteins, or drug compounds into cells without causing permanent damage is a prerequisite for many cell biology experiments. Here, we report a printed circuit board (PCB)-based electroporation device for high-throughput delivery of exogenous molecules into cells in an individually addressable manner. This device incorporates an array of 96 through-holes on the PCB with a pair of gold coated symmetric electrodes plated on the wall of each through-hole. A mixture of cell suspension and exogenous molecules is top-loaded, electroporated, and bottom-ejected with cell culture medium into the corresponding well of a 96-well plate placed under the PCB. One group of electrodes on the same side of the 96 through-holes were connected to eight top pads via connecting row wires plated on the top surface of the PCB and the other group of electrodes were connected in a column format to twelve bottom pads. Therefore, each pair of electrodes can be selectively energized, guaranteeing that appropriate electroporation parameters can be applied to different holes. We demonstrate the use of the present device to effectively introduce plasmid DNA and synthetic interfering RNA into cultured and primary cells with high cell viability and transfection efficiency. The high performance and low cost features make our device an ideal platform for cellular and molecular research and high-throughput screening.

Digital microfluidics is introduced as a novel platform with unique advantages for performing single-molecule detection. We demonstrate how superparamagnetic beads, used for capturing single protein molecules, can be printed with unprecedentedly high loading efficiency and single bead resolution on an electrowetting-on-dielectric-based digital microfluidic chip by micropatterning the Teflon-AF surface of the device. By transporting droplets containing suspended superparamagnetic beads over a hydrophilic-in-hydrophobic micropatterned Teflon-AF surface, single beads are trapped inside the hydrophilic microwells due to their selective wettability and tailored dimensions. Digital microfluidics presents the following advantages for printing and sealing magnetic beads for single-molecule detection: (i) droplets containing suspended beads can be transported back and forth over the array of hydrophilic microwells to obtain high loading efficiencies of microwells with single beads, (ii) the use of hydrophilic-in-hydrophobic patterns permits the use of a magnet to speed up the bead transfer process to the wells, while the receding droplet meniscus removes excess beads off the chip surface and thereby shortens the bead patterning time, and (iii) reagents can be transported over the printed beads multiple times, while capillary forces and a magnet hold the printed beads in place. High loading efficiencies (98% with a CV of 0.9%) of single beads in microwells were obtained by transporting droplets of suspended beads over the array 10 times in less than 1 min, which is much higher than previously reported methods (40–60%), while the total surface area needed for performing single-molecule detection can be decreased. The performance of the device was demonstrated by fluorescent detection of the presence of the biotinylated enzyme β-galactosidase on streptavidin-coated beads with a linear dynamic range of 4 orders of magnitude ranging from 10 aM to 90 fM.

Advances in microfluidics now allow an unprecedented level of parallelization and integration of biochemical reactions. However, one challenge still faced by the field has been the complexity and cost of the control hardware: one external pressure signal has been required for each independently actuated set of valves on chip. Using a simple post-modification to the multilayer soft lithography fabrication process, we present a new implementation of digital fluidic logic fully analogous to electronic logic with significant performance advances over the previous implementations. We demonstrate a novel normally closed static gain valve capable of modulating pressure signals in a fashion analogous to an electronic transistor. We utilize these valves to build complex fluidic logic circuits capable of arbitrary control of flows by processing binary input signals (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12-bit shift register built using static gain valves. This fluidic logic shows cascade-ability, feedback, programmability, bi-stability, and autonomous control capability. This implementation of fluidic logic yields significantly smaller devices, higher clock rates, simple designs, easy fabrication, and integration into MSL microfluidics.

Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

A novel facile method of fabricating disposable and highly reproducible surface-enhanced Raman spectroscopy (SERS) arrays using screen printing was explored. The screen printing ink containing silver nanoparticles was prepared and printed on supporting materials by a screen printing process to fabricate SERS arrays (6 × 10 printed spots) in large batches. The fabrication conditions, SERS performance and application of these arrays were systematically investigated, and a detection limit of 1.6 × 10(-13) M for rhodamine 6G could be achieved. Moreover, the screen printed SERS arrays exhibited high reproducibility and stability, the spot-to-spot SERS signals showed that the intensity variation was less than 10% and SERS performance could be maintained over 12 weeks. Portable high-throughput analysis of biological samples was accomplished using these disposable screen printed SERS arrays.

Exposure of a negative photoresist-coated glass slide with diffused light from the backside through a mask with disconnected features provides multi-level rounded channels with narrow orifices in one exposure. Using these structures, we construct microfluidic systems capable of creating aqueous two-phase system droplets where one aqueous phase forms droplets and the other aqueous phase forms the surrounding matrix. Unlike water-in-oil droplet systems, aqueous two-phase systems can have very low interfacial tensions that prevent spontaneous droplet formation. The multi-level channels fabricated by backside lithography satisfy two conflicting needs: (i) the requirement to have narrowed channels for efficient valve closure by channel deformation and (ii) the need to have wide channels to reduce the flow velocity, thus reducing the capillary number and enhancing droplet formation.

The transformative potential of silicon photonics for chip-scale biosensing is limited primarily by the inability to selectively functionalize and exploit the extraordinary density of integrated optical devices on this platform. Silicon biosensors, such as the microring resonator, can be routinely fabricated to occupy a footprint of less than 50 × 50 µm; however, chemically addressing individual devices has proven to be a significant challenge due to their small size and alignment requirements. Herein, we describe a non-contact piezoelectric (inkjet) method for the rapid and efficient printing of bioactive proteins, glycoproteins and neoglycoconjugates onto a high-density silicon microring resonator biosensor array. This approach demonstrates the scalable fabrication of multiplexed silicon photonic biosensors for lab-on-a-chip applications, and is further applicable to the functionalization of any semiconductor-based biosensor chip.

A new method for making superhydrophobic (SH) paper based on spraying a nanocomposite film is developed. Furthermore, manipulating the wetting characteristics of SH paper has been demonstrated through a new method, i.e. printing solid grey patterns of different intensities with simple printing technology (home or office grade ink-jet and laser printers). It has been found that for a range of ink intensities (0-85%), water drop mobility can be changed at a different rate (almost independently) from repellency. The repellency of water decreases minimally up to 85% ink intensity with a sharp decrease up to 100% ink intensity. Drop mobility remains constant up to 30% ink intensity with a steady decrease up to 100% ink intensity. It was observed that using ink-jet or laser printing would yield different results for the change of mobility or repellency with higher amounts of ink/toner used. Being able to achieve almost independent control of water drop mobility over water drop repellency on SH paper would allow inexpensive lab-on-paper devices to be used for sampling, mixing and transport of liquids.

We report the design, fabrication, and characterization of practical microfluidic valves fabricated using laser printer lithography. These optofluidic valves are opened by directing optical energy from a solid-state laser, with similar power characteristics to those used in CD/DVD drives, to a spot of printed toner where localized heating melts an orifice in the polymer layer in as little as 500 ms, connecting previously isolated fluidic components or compartments. Valve functionality, response time, and laser input energy dependence of orifice size are reported for cyclo-olefin polymer (COP) and polyethylene terephthalate (PET) films. Implementation of these optofluidic valves is demonstrated on pressure-driven and centrifugal microfluidic platforms. In addition, these “one-shot” valves comprise a continuous polymer film that hermetically isolates on-chip fluid volumes within fluidic devices using low-vapor-permeability materials; we confirmed this for a period of one month. The fabrication and integration of optofluidic valves are compatible with a range of polymer microfabrication technologies and should facilitate the development of fully integrated, reconfigurable, and automated lab-on-a-chip systems, particularly when reagents must be stored on chip for extended periods, e.g. for medical diagnostic devices, lab-on-a-chip synthetic systems, or hazardous biochemical analysis platforms.