Optical biosensors have emerged in the past decade as the most promising candidates for portable, highly-sensitive bioanalytical systems that can be employed for in-situ measurements. In this work, a miniaturized optoelectronic system for rapid, quantitative, label-free detection of harmful species in food is presented. The proposed system has four distinctive features that can render to a powerful tool for the next generation of Point-of-Need applications, namely it accommodates the light sources and ten interferometric biosensors on a single silicon chip of a less-than-40mm2 footprint, each sensor can be individually functionalized for a specific target analyte, the encapsulation can be performed at the wafer-scale, and finally it exploits a new operation principle, Broad-band Mach-Zehnder Interferometry to ameliorate its analytical capabilities. Multi-analyte evaluation schemes for the simultaneous detection of harmful contaminants, such as mycotoxins, allergens and pesticides, proved that the proposed system is capable of detecting within short time these substances at concentrations below the limits imposed by regulatory authorities, rendering it to a novel tool for the near-future food safety applications.
In this work, interferometric silicon chips with monolithically-integrated light-emitting devices coupled to co-integrated monomodal waveguides shaped as Young interferometers through mainstream silicon technology, are presented. Although the light sources are broad-band emitters, Young interferometry is possible through filtering. Chips with arrays of ten multiplexed interferometers have been employed for the label-free determination of pesticides in drinking water currently achieving detection limits in the ng/ml range.
The increasing demand of enhanced sensitivity in the detection of various biochemical analytes paves the way for the development of a new generation of biosensors. Label free multianalyte immunosensing methods utilizing photonic probing have proven to result in better sensitivity and reliability than other types of biosensing methods. Here we described a monolithic silicon optoelectronic transducer capable of label-free and multianalyte determinations. The transducer includes ten Mach-Zehnder interferometers each of which is coupled to its own broad band light emitting device. The adlayers on the sensing arm cause spectral shifts detected at the output of the interferometers by coupling a portable spectrometer through an external fiber. Fourier transform techniques are employed to determine with a high degree of accuracy the shifts of the sinusoidal spectral outputs. The microphotonic chip was integrated with a microfluidic module and a model binding assay (mouse-antimouse) was run to demonstrate the operation.
The existing technological approaches employed in the realization of optical sensors still face two major challenges: the
inherent inability of most sensors to integrate the optical source in the transducer chip, and the need to specifically
design the optical transducer per application. We have introduced a unique Optoelectronic chip that consists of a series
of light emitting diodes (LEDs) coupled to silicon nitride waveguides allowing for multi-analyte detection. Each
optocoupler is structured as Broad-Band Mach-Zehnder Interferometer and has its own excitation source and can either
have its own detector or the entire array can share a common detector. The light emitting devices (LEDs) are silicon
avalanche diodes which when biased beyond their breakdown voltage emit in the VIS-NIR part of the spectrum. The
optoelectronic chip is fabricated by standard silicon technology allowing for potential mass production in silicon
foundries. The integrated nature of the optoelectronic chip and the ability to functionalize each transducer independently
allows for the development of miniaturized optical transducers tailored towards multi-analyte tests. The platform has
been successfully applied in bioassays and binding assays monitoring in a real-time and label-free format and is
currently being applied to ultra-sensitive food safety applications.
Label-free optical sensors are considered ideal for biomedical analysis since they provide the advantages of multiplex
and real-time detection. They still suffer; however, from lower sensitivity and/or more sophisticated equipment as
compared to indirect detection methods. Here, we propose a label-free sensor based on White Light Reflectance
Spectroscopy that overcomes the limitation of high cost and low detection sensitivity. The optical setup consists of a
VIS-NIR light source, a spectrometer and a reflection probe. The sensor is Si with 1-μm thick thermal SiO2 and
functionalized with antibodies. The incident light is directed vertically to sensor surface and the reflected interference
spectrum is recorded through the spectrometer. The evolution of the biomolecular reactions are monitored in real-time
by monitoring the shifts in the interference spectrum. Up to seven different reactions sites have been created onto the
same sensing surface allowing for multi-analyte determinations. The analytical capabilities of the proposed sensor were
demonstrated through the development of a sensitive immunoassay for the detection of C-Reactive Protein (CRP) in
human serum samples. CRP, a biomarker related to acute inflammatory incidents, it has attracted particular interest as a
marker of inflammation associated with cardiovascular diseases. The lowest CRP concentration detected was 10 ng/mL,
and the dynamic range of the assay was extended up to 500 ng/mL. Regeneration of antibody coated sensing areas for up
to 20 times without loss of immobilized antibody reactivity is also presented. In conclusion, the proposed sensing system
is characterized by low cost, high assay sensitivity and, reliability.
Despite the advances in optical biosensors, the existing technological approaches still face two major challenges: the inherent inability of most sensors to integrate the optical source in the transducer chip, and the need to specifically design the optical transducer per application. In this work, the development of a radical optoelectronic platform is demonstrated based on a monolithic optocoupler array fabricated by standard Si-technology and suitable for multi-analyte detection. The platform has been specifically designed biochemical sensing. In the all-silicon array of transducers, each optocoupler has its own excitation source, while the entire array share a common detector. The light emitting devices (LEDs) are silicon avalanche diodes biased beyond their breakdown voltage and emit in the VIS-NIR part of the spectrum. The LEDs are coupled to individually functionalized optical transducers that converge to a single detector for multiplexed operation. The integrated nature of the basic biosensor scheme and the ability to functionalize each transducer independently allows for the development of miniaturized optical transducers tailored towards multi-analyte tests. The monolithic arrays can be used for a plethora of bio/chemical interactions becoming thus a versatile analytical tool. The platform has been successfully applied in bioassays and binding in a real-time and label-free format and is currently being applied to ultra-sensitive food safety applications.
Miniaturized bioanalytical devices find wide applications ranging from blood tests to environmental monitoring. Such
devices in the form of hand held personal laboratories can transform point-of-care monitoring provided miniaturization,
multianalyte detection and sensitivity issues are successfully resolved. Optical detection in biosensors is superior in
many respects to other types of sensing based on alternative signal transduction techniques, especially when both
sensitivity and label free detection is sought. The main drawback of optical biosensing transducers relates to the
unresolved manufacturability issues encountered when attempting monolithic integration of the light source. If the
mature silicon processing technology could be used to monolithically integrate optical components, including light
emitting devices, into complete photonic sensors, then the lab on a chip concept would materialize into a robust and
affordable way. Here, we describe and demonstrate a bioanalytical device consisting of a monolithic silicon optocoupler
properly engineered as a planar interferometric microchip. The optical microchip monolithically integrates silicon light
emitting diodes and detectors optically coupled through silicon nitride waveguides designed to form Mach-Zehnder
interferometers. Label free detection of proteins is demonstrated down to pM sensitivities.
KEYWORDS: Monte Carlo methods, Photomasks, Optical simulations, Electron beam lithography, Metrology, Extreme ultraviolet, Electron beams, Software development, Laser scattering, Scattering
Electron Beam writing process is essential for EUV mask manufacturing and direct writing. Electron beam lithography
simulation tools can provide critical information in the way of obtaining high accuracy results. In the present work a
software tool which performs e-beam writing simulation, resist development simulation and automated metrology has
been developed and applied in the case of Mo/Si multilayer substrates. Simulation results are compared with
experimental ones in order to evaluate the simulation's accuracy.
Strong candidate lithography for the mass production of devices at the 32nm technology node and beyond is extreme
ultra violet lithography (EUVL). The mask used in EUVL is a complex set of layers. The material composition and
thickness of each layer should be considered explicitly in an attempt to model the deposited energy in the resist film
during fabrication of mask features using electron-beam lithography. Targeting to sub-32nm technology even with the
reduction by 4 of the mask features on the wafer level, lithography should consider accurate fabrication features on the
mask level of the order of 50nm. Therefore, detailed simulation of the electron-beam fabrication process, as well as the
resist dissolution mechanism and etching is demanding. In this work an attempt is initiated targeting in combining two
simulation techniques i.e., the electron-beam simulation, with the stochastic lithography simulation, in a common
simulation platform. This way it will be possible to get detailed information of the fine details of the fabricated features,
taking into account the multilayer substrate of the mask, and the resist material properties. The e-beam simulation
algorithm is presented and used to expose a layout. The calculated energy deposition in the resist level, initially
determined considering resist material to be continuous, is used in the discrete representation of the resist. With
appropriate threshold in the exposure energy, also acid diffusion could be taken into consideration. Stochastic
development of the resist material, delivers line-edge roughness (LER) and critical dimension (CD) on the resist level, in
terms of polymer chain architecture.
The whole process of stochastic lithography simulation combined with an electron-beam
simulation module, could be useful in the validation of design rules taking into account fine details
such as line-edge roughness, and for simulating the layout before actual fabrication for design
inconsistencies. Material and process parameters can no more be considered of second order
importance in high-density designs. Line-width roughness quantification should accompany CD
measurements since it could be a large fraction of the total CD budget. An example of the effects of
exposure, material and processes on layouts are presented in this work using a combination of
electron beam simulation for the exposure part, stochastic simulations for the modeling of resist
film, the post-exposure bake, resist dissolution, and a simple analytic model for resist etching.
Particular examples of line-width roughness and critical dimension non-uniformity due to, material,
and process effects on the gate of a standard CMOS inverter layout are presented.
Device shrinking combined with material manipulation under various process conditions becomes a
difficult task if specific optimization conditions should be met. Nanolithography is limited by effects
as line-edge and line-width roughness (LER and LWR respectively) and secondary electron blur
(SEB). Simulation studies could show the direction of solving design for manufacturing problems. In
the current article a simulation methodology is presented, based on the concept of stochastic modeling
of exposure, material, and process aspects of lithography and pattern transfer with plasma etching in
order to get information about the evolution of critical dimensions (CD), LER and LWR in the layout.
The study reveals that under certain process conditions, the effect of acid diffusion on LER is more
important than the one of SEB, although both deal with blurring, because acid diffusion is supposed
to extend in longer radius. However, when resists of low degree of polymerization are used, SEB
should also be considered explicitly since the deteriorations from blurring on both LER and CD are
enhanced due to the graining nature of the material. In any case, etching smoothing effects of high
frequency LER components should be considered in terms of CD loss.
Effects of process variables, such as film thickness, type of substrate and thermal processing conditions on Tgfilm were explored using Optical Interferometry; a novel, low-cost, rapid methodology. This methodology is applied for in-situ measurement of the glass transition temperature in thin resist films (Tgfilm) spin-coated on flat reflective substrates. The presented methodology enabled studies on Tg changes during resist processing in characteristic positive and negative tone chemically amplified (CA) resist materials allowing deeper insight in resist optimization issues. The film thickness and substrate effects on Tgfilm were studied in the case of one positive chemically amplified resist (commercial for DUV) as well as the exposure effect on Tgfilm in the case of a negative chemically amplified resist formulations. Also a series of POSS-based new copolymers under evaluation for use in 157nm lithography are studied in order to reveal the film quality. In the last case new copolymers with components interacting strongly with the substrate surface were examined and the calculated Tgfilm from the OPTI method differs from the corresponding DSC bulk values.
Evangelia Tegou, Evangelos Gogolides, Panagiotis Argitis, Ioannis Raptis, George Patsis, Nikos Glezos, Zoilo Tan, Kim Lee, Phuong Le, Yautzong Hsu, Michael Hatzakis
An epoxidized novolac resist (EPR) has been evaluated for high resolution negative and positive tone electron beam lithography. EPR is a chemically amplified experimental resist developed in 'Demokritos' for e-beam lithography. It is characterized by high resolution, high sensitivity and very good post-exposure bake (PEB) latitude. Wet development after the post exposure bake (PEB) step gives a negative tone process while silylation and dry development gives a positive tone process. In this work, EPR's high resolution capabilities (below 0.25 micrometer) are demonstrated for both processes. Critical process parameters such as the photo acid generator (PAG) content of the resist, the PEB temperature and the effect of the delay time between exposure and PEB are examined. Delay effects are studied both for directly e-beam written resist profiles as well as for silylated profiles. The experimental work is accompanied by detailed modeling of lithographic processes, including acid diffusion, gel formation, silylation and delay effects.
KEYWORDS: Monte Carlo methods, Silicon, Gold, Electron beam lithography, Optical simulations, Scattering, Chemically amplified resists, Polymethylmethacrylate, Electron beams, Diffusion
A fast simulator for electron beam lithography called SELID, is presented. For the exposure part, an analytical solution based on the Boltzmann transport equation is used instead of Monte Carlo. This method has been proved much faster than Monte Carlo. All important phenomena are included in the calculation. Additionally, the reaction/diffusion effects occurring during post exposure bake in the case of chemically amplified resists are taken into account. The result obtained by the simulation are compared successfully with experimental and other simulation results for conventional and chemically amplified resists. The case of substrates consisting of more than one layer is considered in depth as being of great importance in electron beam patterning. By using SELID, it is possible to forecast the resist profile with considerable accuracy for a wide range of resists, substrates and energies. Additionally, proximity effect parameters are extracted easily for use in any proximity correction package.
KEYWORDS: Monte Carlo methods, Electron beam lithography, 3D displays, Backscatter, Optical simulations, Diffusion, Lithography, Electron beams, Scattering, Laser scattering
In the e-beam world a simulator, comparable to well established optical simulators, has not been available so far. SELID (Simulation of E-Beam Lithography in 3 Dimensions) closes this gap by providing a comprehensive simulation tool covering most aspects of today's advanced e- beam lithography, such as process optimization and parameter determination for the e-beam proximity effect correction. SELID consists of 4 major parts: the simulation of the exposure step, the post-exposure bake and the resist development, and the analysis part. On output it displays many different views into the exposed image, 2D exposure images, as well as 2D resist profiles and resist structures in full 3D rendering. This paper presents first results using SELID. The application to direct write will be demonstrated. A commercially available positive e-beam resist was used for electron beam direct write lithography applications. Process optimization and the accuracy of the simulator will be demonstrated. Moreover, the agreement between experiment and simulation will be investigated.
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