Optimized SU-8 processing for low-cost microstructures fabrication without cleanroom facilities

The study and optimization of epoxy-based negative photoresist (SU-8) microstructures through a low-cost process and without the need for cleanroom facility is presented in this paper. It is demonstrated that the Ultraviolet Rays (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, can replace the more expensive and less available equipment, as the Mask Aligner that has been used in the last 15 years for SU-8 patterning. Moreover, high transparency masks, printed in a photomask, are used, instead of expensive chromium masks. The fabrication of well-defined SU-8 microstructures with aspect ratios more than 20 is successfully demonstrated with those facilities. The viability of using the gray-scale technology in the photomasks for the fabrication of 3D microstructures is also reported. Moreover, SU-8 microstructures for different applications are shown throughout the paper.Work supported by FEDER funds through the Eixo I do Programa Operacional Fatores de Competitividade (POFC) QREN, project reference COMPETE: FCOMP-01-0124-FEDER-020241, and by FCT- Fundação para a Ciência e a Tecnologia, project reference PTDC/EBB-EBI/120334/2010. Vânia C. Pinto thanks the FCT for the SFRH/BD/81526/2011 grant. Paulo J. Sousa thanks the FCT for the SFRH/BD/81562/2011 grant. Vanessa F. Cardoso thanks the FCT for the SFRH/BPD/98109/2013 gran

Porous Biomimetic Microlens Arrays as Multifunctional Optical Structures

Microlenses are important optical components that image, detect and couple light. Most synthetic microlenses, however, have fixed position and shape once they are fabricated. Therefore, the attainable range of their tunability and complexity is rather limited. In comparison, biological world provides a multitude of varied, new paradigms for the development of adaptive optical networks. This review discusses a few inspirational examples of biological lenses and their synthetic analogs. We focus on the fabrication and characterization of biomimetic microlens arrays with integrated pores, whose appearance and function are similar to a highly efficient optical element formed by brittlestars. The complex microlens design can be created by three-beam interference lithography. These synthetic microlenses have strong focusing ability, and the structure can be, therefore, used as an adjustable lithographic mask, and a tunable optical device coupled with the microfluidic system. The replacement of rigid microlenses with soft hydrogels provides means for changing the lens geometry and refractive index continuously in response to external stimuli, resulting in intelligent, multifunctional, tunable optics

A versatile maskless microscope projection photolithography system and its application in light-directed fabrication of DNA microarrays

We present a maskless microscope projection lithography system (MPLS), in which photomasks have been replaced by a Digital Micromirror Device type spatial light modulator (DMD, Texas Instruments). Employing video projector technology high resolution patterns, designed as bitmap images on the computer, are displayed using a micromirror array consisting of about 786000 tiny individually addressable tilting mirrors. The DMD, which is located in the image plane of an infinity corrected microscope, is projected onto a substrate placed in the focal plane of the microscope objective. With a 5x(0.25 NA) Fluar microscope objective, a fivefold reduction of the image to a total size of 9 mm2 and a minimum feature size of 3.5 microns is achieved. Our system can be used in the visible range as well as in the near UV (with a light intensity of up to 76 mW/cm2 around the 365 nm Hg-line). We developed an inexpensive and simple method to enable exact focusing and controlling of the image quality of the projected patterns. Our MPLS has originally been designed for the light-directed in situ synthesis of DNA microarrays. One requirement is a high UV intensity to keep the fabrication process reasonably short. Another demand is a sufficient contrast ratio over small distances (of about 5 microns). This is necessary to achieve a high density of features (i.e. separated sites on the substrate at which different DNA sequences are synthesized in parallel fashion) while at the same time the number of stray light induced DNA sequence errors is kept reasonably small. We demonstrate the performance of the apparatus in light-directed DNA chip synthesis and discuss its advantages and limitations.Comment: 12 pages, 9 figures, journal articl

Fabrication of 3D hydrogel-based microscale tissue analog chip with integrated optofluidics

Lab-on-a-chip (LOC) is a device that integrates one or more laboratory functions in a single chip with dimensions ranging from a micrometer to a few millimeters. On-chip optofluidics, which combines microfluidics and tunable micro-optical components, is crucial for bio-sensing applications. However, recently reported optofluidic devices have only two-dimensional (2D) dielectric or metallic regions for sensing cellular activity, which fail to mimic the three-dimensional (3D) in vivo microenvironment of cells. In this research, a 3D hydrogel-based micro-scale-tissue-analog-chip (µTAC) is fabricated with an integrated optofluidic design for biomedical applications. These 3D hydrogels act as a scaffold for the cellular studies and as a waveguide for increasing the signal efficiency in sensing applications. These 3D waveguides, embedded in a Poly(dimethylsiloxane) elastomer-based optofluidic channel, are composed of Poly(ethylene glycol)-diacrylates (PEGDA). The refractive index of the PEGDA waveguides is higher compared to the water-based cladding that surrounds the waveguide. Because of this refractive index difference, waveguides confine the light waves due to the total-internal-reflection phenomenon (TIR). Initially, the characterizations and the sensing efficiency of the µTAC device are successfully demonstrated with a fluorescein detection study. This study demonstrates that the proposed device is in accordance with Beer-Lambert’s law with a limit of detection of 2.54 µM of fluorescein. Further, the sensing efficiency of the µTAC devices is tested in cellular studies by encapsulating cells inside the waveguides. Cellular studies with µTAC devices prove that the device is capable of efficiently sensing the cell density and the cell viability changes inside the waveguides with a limit of detection of ~27 cells/waveguide. In addition, this study also proves that the proposed µTAC device has a potential for long-term cell monitoring applications without compromising cell-viability. Therefore, with integrated 3D hydrogel waveguides, this µTAC-optofluidic device could be a potential platform with a broad range of applications in the fields of diagnosis and detection

Polymer-based fluidic devices integrated with perforated micro- and nanopore membrane for study of ionic and DNA transport

This study aims to develop a process, allowing a low-cost and high-throughput fabrication technique to produce freestanding polymer membranes having perforated micro- and nanopores, and also to design 3D micro/nanofluidic devices with the membrane, enabling a study of ions and DNA transport through nanopores. Technically, we have designed and fabricated high quality silicon stamp. Then, they have been used as molds for modified nanoimprint lithography that takes advantages of a sacrificial layer to obtain freestanding polymer membrane. This technique allows easy fabrication of large area, fully released polymer membranes containing perforated micro- and sub-micropores. The membrane with perforated micropores has been successfully integrated with microfluidic channels and used for in situ formation of lipid bilayer. The membrane with nanopores (\u3c 10 nm diameter) has been directly fabricated using modified nanoimprint lithography with silicon microneedle stamp. Also, the pore size was reduced further (down to 10 nm) with a subsequent process such as pore reduction by using polymer reflowing. Then, it was utilized for sensing and characterizing the ions and DNA transport through pores

Enzymatic reactions in microdevices

Enzyme reactions conducted in microdevices for diagnostic applications minimize the enzyme usage. In this research, polydimethylsiloxane microdevices were fabricated and used to study the well studied hydrogen peroxide decomposition reaction using bovine liver catalase. Soft lithography techniques were developed to fabricate custom-made microdevices in-house. High resolution photomasks and oxygen plasma treatment followed by baking for 2--3 hours yielded microdevices with vertical walls that did not leak easily. Flow experiments were conducted with free enzyme, enzyme immobilized on microdevice walls, and carrier-free enzyme aggregates. For free enzyme and carrier-free enzyme aggregate reactions, the average reaction rate showed a maxima at ∼80 mmol/L as predicted from macroscale batch experiments. The trend for average reaction rate was consistent with the model series reactor scheme developed. Covalent binding of enzyme to the microdevice wall was not achieved as the enzyme was found to continuously leach from the microdevice walls

Development and Characterisation of High Surface Energy Microstructured Sol-gel Coatings for Sensing Applications

This study investigates the development of high surface energy photoreactive organic inorganic hybrid sol-gel coatings for the microstructuration of high-resolution microfluidic platforms and optofluidic biosensor platforms by standard photolithography processes. To achieve this, the first step of our work consisted of identifying the fundamental physico chemical processes governing the structuration and surface properties of hybrid organic inorganic sol-gel coatings. For this purpose, a reference material based on the combination of an organosilane (3-Methacryloxypropytrimethoxysilane, MAPTMS) and a transition metal (zirconium propoxide, ZPO), was firstly developed and characterised. It was highlighted that chemical, physical and combined physical and chemical processes can be performed to impact the structure, morphology and surface properties of hybrid sol-gel coatings. Therefore, our work progressed towards the investigations of chemical strategies that may impact the general properties of hybrid coatings, with a specific objective on the alteration of their surface properties. For this purpose, 3 strategies have identified including (1) to alter the content of transition metal, (2) to vary the hydrolysis degree and (3) to form core-shell nanoparticle by the surface functionalisation of the reference material during its preparation along with the curing process of the coatings. The materials were characterised employing a set of structural, thermal and surface characterisations techniques namely Contact Angle measurements (CA), DLS, DSC, FTIR, 29Si-NMR. Fundamentally, a triangular relationship between the wettability, the condensation and curing process of the coatings was taking place. More specifically, the wettability was governed by the occurrence of parallel and competitive hydroxylation and condensation processes of the coatings. Having performed the identified chemical strategies, our work has progressed towards the investigations of physical and physico-chemical treatments of the final coatings. Here, the effects of air-plasma, nitrogen-plasma and plasma treatments combined with post-silane ii surface functionalisation were performed and the durability of the treatments investigated. Although hydrophobic recovery was observed for all materials, it was found that air-plasma enabled to achieve the most stable surface properties due to the formation of hydrophilic hydroxyl groups at the surface of the coatings. The next step of the work focussed on the microstructuration fabrication of a microfluidic platform. The photolithography fabrication conditions were established to enable the successful preparation of well-defined microchannels with resolutions ranging from 50 to 500 microns. Having developed our microfluidic platform, our work concentrated on developing strategies to integrate an optical transducer onto the platform to enable the fabrication of an optofluidic device that may be applied as biosensor, thus demonstrating the potential of our technology for biosensing applications. The biosensor design we proposed consisted of integrated optical waveguides onto microfluidics that would also be fabricated employing a photolithography process. The fabrications conditions of the optofluidic platform were established by considering the required optical conditions that enable efficient light propagation in the waveguides, which can be used as an optical excitation to fluorophores located within sensor spots in the microchannels. The successful demonstration of concept of the optofluidic-based biosensor concept was successfully performed by recording optical emissions of biomolecules fluorophores under optical excitations with the optical waveguides integrated on the microfluidic platform. The work reported in this thesis has been multidisciplinary requiring chemistry, physics, biotechnology and engineering competencies which have been synergised for the development of the first “whole hybrid sol-gel optofluidic biosensor platform”. It is also showing the potential of the proposed technology for applications where functional microstructured coatings are required

Electrokinetic Transport, Trapping, and Sensing in Integrated Micro- and Nanofluidic Devices

Thesis (Ph.D.) - Indiana University, Chemistry, 2009Microfluidics is rapidly becoming a mature field, and improved fabrication methods now routinely produce sub-micrometer features. As device dimensions shrink, physical phenomena that are negligible at larger length scales become more important, and by integrating nanofluidic elements with microchannels, new analytical techniques can be developed based on the unique behavior of matter at the nanoscale. This work addresses the fabrication, operation, and application of in-plane nanochannels and out-of-plane nanopores in lab-on-a-chip devices. In planar nanofluidic devices, we demonstrate a method to produce micro- and nanoscale features simultaneously with a single UV exposure step and evaluate flow control and sample dispensing with nanofluidic cross structures. Modification of the pinched injection method makes it applicable to variable-volume, attoliter-scale injections, including the smallest volume electrokinetically-controlled injections to date. As an alternative approach, track-etch nanopore membranes are explored as out-of-plane nanofluidic components. The random distribution of pores in these membranes is overcome by lithographic and microchannel-based methods to isolate and address specific pores. Microfluidic isolation improves mass transport to the pore(s), provides easy coupling of electrical potentials, and facilitates additional sample processing steps up- and downstream. These integrated microchannel-nanopore devices are used for diffusion-based dispensing, electrokinetic trapping, and resistive pulse sensing. In a high pore density device, diffusion-based dispensing establishes a stable chemical gradient for bacterial chemotaxis assays. For lower pore density devices, the nanopores are the most resistive components in the fluidic circuit, and application of an electric potential produces localized regions of high electric field strength and field gradient. These high field regions are applied to electrokinetic trapping of particles and cells in multiple-pore devices and to single particle detection by resistive pulse sensing in devices with a single isolated pore. To better understand factors influencing ion current in single nanoscale conduits, we systematically examine ion current rectification as a function of pore diameter, ionic strength, and pH to improve understanding of ion current through nanopores and to characterize preferred operating parameters for sensing applications. These results are applied to detection of virus capsids, and future work is proposed to investigate capsid assembly

Development of microfabricated optical chemical sensor platforms using polymer processing technology

This work describes the design and fabrication of enhanced polymer waveguide platforms for absorption-based optical chemical sensors and the use of soft lithographic techniques for the fabrication of optical sensor chips. The design of the enhanced polymer waveguide platforms was based on a previously reported theoretical model that was verified experimentally in this work. The platforms were fabricated by micro-injection moulding and subsequently coated with sol-gelderived sensing layers doped with a colorimetric indicator compound. The sensor response to both gaseous ammonia and solution pH was examined using a LEDbased prototype sensor head. Soft lithographic patterning techniques, based on the use of a poly(dimethylsiloxane) (PDMS) patterning element, were employed to produce a variety of sol-gel-based structures with applications in optical sensing. These included discrete sensor spots, surface corrugation grating couplers and ridge waveguides. As a proof of principle, these techniques were applied to the development of an integrated optical oxygen sensor based on the quenching of fluorescence from a sol-gel-encapsulated ruthenium complex that was deposited as a sensor spot onto a ridge waveguide. This work highlights the feasibility of using rapid prototyping technology to fabricate sensitive, mass-producible sensor platforms that employ generic configurations, thereby facilitating their use in a broad range of applications