We report the design and fabrication of a novel single cell electroporation biochip fabricated by the Proton Beam Writing
technique (PBW), a new technique capable of direct-writing high-aspect-ratio nano and microstructures. The biochip
features nickel micro-electrodes with straight-side walls between which individual cells are positioned. By applying
electrical impulses across the electrodes, SYTOX® Green nucleic acid stain is incorporated into mouse neuroblastoma
(N2a) cells. When the stain binds with DNA inside the cell nucleus, green fluorescence is observed upon excitation from
a halogen lamp. Three parameters; electric field strength, pulse duration, and the number of pulses have been considered
and optimized for the single cell electroporation. The results show that our biochip gives successfully electroporated
cells . This single cell electroporation system represents a promising method for investigating the introduction of a wide
variety of fluorophores, nanoparticles, quantum dots, DNAs and proteins into cells.
The use of microfluidics for biofluid analysis offers a cheaper alternative to conventional techniques in disease diagnosis. However, traditional microfluidics design may be complicated by the need to incorporate separation elements into the system in order to facilitate specific molecular detection. Alternatively, an optical technique known as surface-enhanced Raman spectroscopy (SERS) may be used to enable identification of analyte molecules directly from a complex sample. This will not only simplify design but also reduce overall cost. The concept of SERS-based microfluidics is however not new and has been demonstrated previously by mixing SERS-active metal nanoparticles with a model sample, in situ, within the microchannel. Although the SERS reproducibility of these systems was shown to be acceptable, it is, however, not stable toward variations in the salt content of the sample, as will be shown in this study. We have proposed a microfluidics design whereby periodic SERS-active metal nanostructures are fabricated directly into the microchannel via a simple method of spin coating. Using artificial as well as human urine samples, we show that the current microfluidics is more stable toward variations in the sample's ionic strength.
Proton beam writing (p-beam writing) is a process which uses a focused beam of MeV protons to pattern resist material
at nanodimensions. This makes p-beam writing the only one tool for fast prototyping of high aspect ratio structures with
vertical walls up to 60μm and high aspect ratio values with details down to the 20 nm level. The process, although
similar in many ways to direct writing using electrons, nevertheless offers some interesting and unique advantages.
Protons, being more massive, have deeper penetration in materials whilst maintaining even energy deposition along a
straight path, enabling p-beam writing to fabricate 3D high aspect ratio structures with vertical smooth sidewalls and low
line edge roughness. Calculations have also indicated that p-beam writing exhibits minimal proximity effects, since the
secondary electrons induced in proton/electron collisions have low energy. A platform technology to integrate 3D
nanowires is proposed through high aspect ratio nanofabrication using p-beam writing.
Proton beam writing (PBW) is a lithographic technique that utilizes MeV protons in a direct write mode to
fabricate micro/nano features in suitable resist material (E.g PMMA, SU-8, silicon, Foturan). These micro/nano
structures may be used in an electroplating step to yield robust metallic stamps/molds for the replication of
the original and lends itself to the fabrication of micro/nano fluidic channels that are important components in
devices such as biophotonic chips. Another feature of proton bombardment is its ability to induce an increase
in refractive index along the ions path, in particular at the end of its range where there is substantial nuclear
scattering. This allows PBW to directly write buried waveguides that can be accurately aligned with fluidic
channels.
Polydimethylsiloxane (PDMS) is an optically clear, biocompatible polymer that can be readily used with a
mold (such as that created with PBW) and easily sealed so as to produce biophotonic chips containing micro/nano
fluidic channels. This has lead us to favour PDMS as the base material for our work on the development of these
biophotonic chips. The present work is concerned with the production of integrating channel waveguides in
PDMS chips, so as to have a working device that may be used to detect fluorescently tagged biological samples.
For this we have adopted two approaches, namely(1) directly embedding optical fibres in the polymer and (2)
using PBW to directly write buried waveguides in the polymer.
Proton beam writing is a lithographic technique that can be used to fabricate microstructures in a variety of materials including PMMA, SU-8 and FoturanTM. The technique utilizes a highly focused mega-electron volt beam of protons to direct write latent images into a material which are subsequently developed to form
structures. Furthermore, the energetic protons can also be used to modify the refractive index of the material at a precise depth by using the end of range damage. In this paper we apply the proton beam writing technique to the fabrication of a lab-on-a-chip device that integrates buried waveguides with microfluidic channels. We have chosen to use FoturanTM photostructurable glass for the device because both direct patterning and refractive index modification is possible with MeV protons.
Surface enhanced Raman spectroscopy (SERS) discovered some 30 years ago has gained popularity as a powerful analytical tool for developing chemo- and bio-sensing. The combination of SERS with the microfluidics technology can provide a miniaturized and portable device for bio-fluid analysis. However, as will be pointed out in this study, heat generated in a SERS-active substrate as a result of laser-induced plasmon resonance can unfavorably affect the sensitivity of a SERS-based microfluidic device. We will show that the plasmon-induced heat associated with SERS can significantly reduce the signal strength from the analyte under certain circumstances, and show heat-induced morphological changes in the SERS-active substrate as a primary cause of the observed signal changes. This study indicates that sufficient heat dissipation is crucial for the proper working of a SERS-based microfluidic device.
We report an alternative technique which utilizes fast proton or helium ion irradiation prior to electrochemical etching for three-dimensional micro-fabrication in bulk p-type silicon. The ion-induced damage increases the resistivity of the irradiated regions and slows down porous silicon formation. A raised structure of the scanned area is left behind after removal of the un-irradiated regions with potassium hydroxide. The thickness of the removed material depends on the irradiated dose at each region so that multiple level structures can be produced with a single irradiation step. By exposing the silicon to different ion energies, the implanted depth and hence structure height can be precisely varied. We demonstrate the versatility of this three-dimensional patterning process to create multilevel cross structure and free-standing bridges in bulk silicon, as well as sub-micron pillars and high aspect-ratio nano-tips.
Proton beam writing is a new direct write lithographic technique that utilizes a high energy (MeV) submicron focused proton beam to machine or modify a material, usually a polymer. Structures made using p-beam writing have very smooth side walls, high aspect ratio, and a scale that can be easily matched to existing optical fiber
technology (0.1 to 1000 μm). In this paper we demonstrate the use of proton beam writing for prototyping micro-optical components such as microlens arrays and gratings in positive and negative resist. The structures that are fabricated can be used for both rapid prototyping and for large scale replication with nanoimprint
lithography.
Proton beam writing is a new direct-write micromachining technique capable of producing 3-dimensional (3-D), high aspect ratio micro-structures with straight and smooth sidewalls. It uses a focused sub-micron beam of 2.0 MeV protons to direct-write on a suitable polymer, such as the photoresists: poly-methylmethacrylate (PMMA) and SU-8, a negative tone photoresist from MicroChem. In this paper, we report on the application of proton beam writing to fabricate low-loss passive polymer waveguide structures such as symmetric y-branching waveguides in SU-8. SU-8 channel waveguides are fabricated by first direct-writing the pattern using a proton beam and subsequently chemically developing the latent image formed. A UV-cured resin, Norland Optical Adhesive 88 (NOA-88) is used as the cladding layer. Being a direct-write technique, proton beam writing offers us great flexibility to fabricate waveguides of arbitrary patterns and this is an asset that can be applied to the rapid prototyping of optical circuits. With all its unique characteristics, proton beam writing is an excellent technique for waveguide fabrication.
The production of high aspect ratio microstructures requires a lithographic technique capable of producing microstructures with vertical sidewalls. There are few techniques (eg proton beam micromachining, LIGA and Stereolithoghaphy) capable of producing high aspect ratio microstructures at sub-micron dimensions. In Proton Beam Micromachining (PBM), a high energy (eg 2 MeV) proton beam is focused to a sub-micron spot size and scanned over a resist material (eg SU-8 and PMMA). When a proton beam interacts with matter it follows an almost straight path, the depth of which is dependent on the proton beam energy. These features enable the production of multilevel microstructures with vertical sidewalls of high orthogonality. Proton beam micromachining is a fast direct write lithographic technique; in a few seconds a complicated pattern in an area of 400 x 400 micrometers 2 can be exposed down to a depth of 150 micrometers . These features make proton beam micromachining a technique of high potential for the production of high-aspect-ratio-structures at a much lower total cost than the LIGA process, which requires a synchrotron radiation source and precision masks. Research is currently under way to improve the process that employs the SU-8 negative photo-resist as a mold to electroplate Ni. Experiments have shown that post-bake and curing steps are not required in this SU-8 process, reducing the effects of cracking and internal stress in the resist. Plated Ni structures can be easily produced which are high quality negative copies of the SU-8 produced microstructures.
IBIC imaging of buried structures of semiconductor devices is carried out with a scanned focussed MeV ion beam. The large range of these ions allows direct imaging of sub- surface through passivation layers, a feature not available to the well established EBIC technique. As multi-level designs become more prevalent this deep penetration is a significant advantage. The nuclear microscope is briefly described here. Recent examples of the IBIC analysis of CMOS and diffused junction devices are given, and the degradation of IBIC images with increasing ion dose is discussed. It is demonstrated that contrast is present in IBIC images even from junctions not directly connected to the preamplifier. The production of significant charge signals from unconnected junctions allows the imaging of such junctions, a highly desirable feature in the case of complex microcircuits. The contrast from unconnected junctions vanishes if these junctions are shortened, as will be shown.
LIGA and its defining process deep x-ray lithography, is an important method for machining high-aspect ratio microstructures, and a diverse range of applications are presently being investigated. One limitation of the technique is associated with the restriction on the 3D shape of the machined structures to essentially prismatic geometry. Further technical problems concerning the fabrication of a suitable mask for deep x-ray lithography are associated with the limited thickness of resist which can be patterned using electron beam lithography, and the undesirable exposure of resist by secondary radiations in an intervening x-ray lithography step which is used to produce a thicker mask. A deep lithography process using a focused beam of high energy light ions has the potential to overcome many of the geometrical restrictions inherent in deep x-ray lithography. An alternative use of deep ion bema lithography is to pattern a thick resist layer for the production of masks for deep x-ray lithography. This paper reports progress on the development of a system for deep ion bema lithography using a scanned 2.0 MeV proton beam of approximately 1 micron diameter. The result of computer simulations of the capabilities of deep ion beam lithography for the fabrication of thick DXL masks is presented.
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