Proceedings Volume 7593

Microfluidics, BioMEMS, and Medical Microsystems VIII

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Proceedings Volume 7593

Microfluidics, BioMEMS, and Medical Microsystems VIII

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Volume Details

Date Published: 11 February 2010
Contents: 10 Sessions, 38 Papers, 0 Presentations
Conference: SPIE MOEMS-MEMS 2010
Volume Number: 7593

Table of Contents

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Table of Contents

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  • Front Matter: Volume 7593
  • MOEMS-MEMS Plenary Session
  • Optical Methods in Microfluidics
  • Manufacturing Technologies
  • Cell and Particle-based Systems
  • Diagnostics
  • Microfluidic Devices and Biosensors
  • BioMEMS and Medical Devices
  • Special Session: Dip-Pen Lithography
  • Poster Session
Front Matter: Volume 7593
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Front Matter: Volume 7593
This PDF file contains the front matter associated with SPIE Proceedings Volume 7593, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.
MOEMS-MEMS Plenary Session
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Emerging research in micro and nano systems: opportunities and challenges for societal impact
Yogesh B. Gianchandani
In just a few decades, micro and nano technologies have changed the way that we live - how we work and communicate; the food and medicine that we consume; the clothing that we use; and the entertainment that we seek. While these technologies are being actively investigated in several research communities, the potential for continued societal impact is constrained by resources available for system-level research. Given the long time-lines and levels of investment that are typically necessary to develop functional systems, strategic prioritization of research directions from the perspective of societal needs can be helpful. This paper outlines the findings of an NSF-sponsored road-mapping workshop that was held in 2009, with the intention of initiating a conversation about the opportunities and challenges for micro and nano systems. Four areas of need were discussed: environmental sensing; health care; infrastructure monitoring; and energy alternatives. Possible research trajectories were identified by envisioning technological goals for the year 2040, and linking these to horizons for 2015 and 2025. This paper also provides few examples of current research in each of the four application domains. It is noted that a systems perspective can help to keep the research focused, accelerating and amplifying the societal gain with available resources. Practical and affordable solutions at the system level will require partnerships between specialists, and also between academia and industry.
Optical Methods in Microfluidics
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SERS measurements in microfluidic devices: a promising way for online-monitoring of lowest agent concentrations
Jürgen Popp, Anne März, Katrin Ackermann, et al.
The observation of agent concentrations is of major importance for a lot of areas such as medicine, process and environmental analysis. The aim of this research work is the development of an analytical tool with the potential to online-monitor concentration changes. For this purpose the combination of surface enhanced Raman spectroscopy (SERS) and a microfluidic device seems to be a promising approach. This approach is capable for a qualitative as well as quantitative analysis. In summary the great potential of surface enhanced Raman spectroscopy in combination with a microfluidic device for a quantitative analysis will be shown.
Investigating fast enzyme-DNA kinetics using multidimensional fluorescence imaging and microfluidics
Tom Robinson, Hugh B. Manning, Christopher Dunsby, et al.
We have developed a rapid microfluidic mixing device to image fast kinetics. To verify the performance of the device it was simulated using computational fluid dynamics (CFD) and the results were directly compared to experimental fluorescence lifetime imaging (FLIM) measurements. The theoretical and measured mixing times of the device were found to be in agreement over a range of flow rates. This mixing device is being developed with the aim of analysing fast enzyme kinetics in the sub-millisecond time domain, which cannot be achieved with conventional macro-stopped flow devices. Here we have studied the binding of a DNA repair enzyme, uracil DNA glycosylase (UDG), to a fluorescently labelled DNA substrate. Bulk phase fluorescence measurements have been used to measure changes on binding: it was found that the fluorescence lifetime increased along with an increase in the polarisation anisotropy and rotational correlation time. Analysis of the same reaction in the microfluidic mixer by CFD enabled us to predict the mixing time of the device to be 46 μs, more than 20 times faster than current stopped-flow techniques. We also demonstrate that it is possible to image UDG-DNA interactions within the micromixer using the signal changes observed from the multidimensional spectrofluorometer.
Optofluidic generation of color and shape encoded microparticle for multiplexed bioassay
Hyoki Kim, Jianping Ge, Yadong Yin, et al.
We present a new method for in-situ synthesis of multiple color and shape encoded particles in microfluidic channel using single material. Material developed in this work is M-Ink whose color is magnetically tunable and lithographically fixable. By combining novel material system and special instrumentation enables generation of limitless number of codes and greatly simplify the manufacturing process of encoded particles.
Feasibility study of micro-optical diffusion sensor based on laser-induced dielectrophoresis
K. Itani, A. Ebisui, Y. Taguchi, et al.
A real-time monitoring of the diffusion coefficient using a micro sensing device is valuable for analyzing the dynamic change of protein-protein interactions and the protein conformation, such as the molecular size and the higher order structure. In the present study, we have developed a novel micro-optical diffusion sensor (MODS) based on a laserinduced dielectrophoresis (LIDEP) enabling small sample volume and high-speed measurement. This paper reports the measurement principle, chip design, and the validity of the proposed method. MODS consists of a pair of transparent electrodes and a photoconductive layer sealing the liquid sample. AC voltage is applied between transparent electrodes, and two excitation lasers are intersected on the photoconductive layer. The electrical conductivity distribution of the a- Si:H layer due to the photoconductive effect generates a non-uniform electric field followed by the dielectrophoresis (DEP), and then the concentration distribution is induced by LIDEP force. After cutting the AC voltage, the mass diffusion is occurred, and the diffusion coefficient can be obtained by observing the one dimensional diffusion process along with the interference fringe pattern. In the preliminary measurement, the prototype of the DEP cell was fabricated by the micro electro mechanical systems (MEMS) technique in order to verify the applicability of MODS, and we confirmed the lattice-shaped concentration distribution of polystyrene beads in distilled water. The decay time of the diffusion of the concentration distribution agreed well with the theoretical calculation. As a result, the applicability of MODS as the diffusion coefficient measurement method was verified.
Pressure mediated tunable elastomeric optofluidic devices
We introduce a novel tuning mechanism based on pressure actuating force, which can enable a broad spectrum of tunable elastomeric optofluidic devices. Thanks to the flexibility of the Polydimethylsiloxane (PDMS) material, the local deformation inside PDMS chip can be generated by filling the compressed air/liquid into the embedded channels. Such tuning method turns out to be very simple for fabrication and control, also being compatible with microfluidic chips. To this end, we have demonstrated the pressure mediated tunable optofluidic gratings, tunable optofluidic laser, and microfluidic 2×2 optical switch.
Manufacturing Technologies
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A research factory for polymer microdevices: muFac
Brian W. Anthony, David E. Hardt, Melinda Hale, et al.
As part of our research on the manufacturing science of micron scale polymer-based devices, an automated production cell has been developed to explore its use in a volume manufacturing environment. This "micro-factory" allows the testing of models and hardware that have resulted from research on material characterization and simulation, tooling and equipment design and control, and process control and metrology. More importantly it has allowed us to identify the problems that exist between and within unit-processes. This paper details our efforts to produce basic micro-fluidic products in high volume at acceptable production rates and quality levels. The device chosen for our first product is a simple binary micromixer with 40×50 micron channel cross section manufactured by embossing of PMMA. The processes in the cell include laser cutting and drilling, hot embossing, thermal bonding and high-speed inspection of the components. Our goal is to create a "lights-out" factory that can make long production runs (e.g. an 8 hour shift) at high rates (Takt time of less than 3 minutes) with consistent quality. This contrasts with device foundries where prototypes in limited quantities but with high variety are the goal. Accordingly, rate and yield are dominant factors in this work, along with the need for precise material handling strategies. Production data will be presented to include process run charts, sampled functional testing of the products and measures of the overall system throughput.
Hybrid tooling technologies for injection molded and hot embossed polymeric microfluidic devices
The growing complexity of microfluidic devices is currently leading to an increased dimensional scale dynamics, i.e. the range of sizes of features on the microfluidic device is steadily increasing, from centimeter-sized features like reservoirs over millimeter-sized features like fluidic connections and micrometer-sized features like microchannels to nanometersized features like surface textures. In order manufacture these devices with polymer replication technologies like injection molding and hot embossing, molding tools (masters) have to be fabricated which contain the same structural dynamic range. Often, this is not possible using a single tooling technology. We therefore present examples of such tools which have been fabricated using two techniques on the same master structure, namely precision mechanical machining, single-point diamond turning (SPDT) and stereolithography.
LABONFOIL: investigations regarding microfluidic skin patches for drug detection using flexible OLEDs
M. Scholles, L. Kroker, U. Vogel, et al.
This contribution describes first results concerning the overall and especially optical system design of microfluidic skin patches for drug detection based on fluorescence analysis of sweat samples. This work has been carried out within the European project LABONFOIL which aims to develop low-cost lab-on-chip systems for four different applications, one of them for the detection of cocaine abuse by professional drivers. To date work has focused on the integrated design of the skin patch itself including methods for sweat collection as well as studies concerning the feasibility of OLEDs for optical excitation of the fluorescence signal.
Tuning parameters of metal ion implantation within a microfluidic channel
Jae-Woo Choi, Samuel Rosset, Muhamed Niklaus, et al.
Applying electrical fields is a simple and versatile method to manipulate and reconfigure optofluidic devices. Several methods to apply electric fields using electrodes on polymers or in the context of lab-on-a-chip devices exist. In this paper, we utilize an ion-implanted process to pattern electrodes within a fluidic channel made of polydimethylsiloxane (PDMS). Electrode structuring within the channel is achieved by ion implantation at a 40° angle with a metal shadow mask. In previous work using the ion-implantation process, we demonstrated two possible applications in the context of lab-on-a-chip applications. Asymmetric particles were aligned through electro-orientation. Colloidal focusing and concentration was possible with negative dielectrophoresis. In this paper, we discuss the different electrode structures that are possible by changing the channel dimensions. A second parameter of ion implantation dosage prevents the shorting of electrodes on the side wall or top wall of the fluidic channel to the bottom. This allows for floating electrodes on the side wall or top wall. These type of electrodes help prevent electrolysis as the liquid is not in direct contact with the voltage source. Possible applications of the different electrode structures that are possible are discussed.
Patterning of PMMA microfluidic parts using screen printing process
Aminreza Ahari Kaleibar, Mona Rahbar, Marius Haiducu, et al.
An inexpensive and rapid micro-fabrication process for producing PMMA microfluidic components has been presented. Our proposed technique takes advantages of commercially available economical technologies such as the silk screen printing and UV patterning of PMMA substrates to produce the microfluidic components. As a demonstration of our proposed technique, we had utilized a homemade deep-UV source, λ=254nm, a silk screen mask made using a local screen-printing shop and Isopropyl alcohol - water mixture (IPA-water) as developer to quickly define the microfluidic patterns. The prototyped devices were successfully bonded, sealed, and the device functionality tested and demonstrated. The screen printing based technique can produce microfluidic channels as small as 50 micrometers quite easily, making this technique the most cost-effective, fairly high precision and at the same time an ultra economical plastic microfluidic components fabrication process reported to date.
Effect of surface treatments/coatings and soft bake profile on surface uniformity and adhesion of SU-8 on a glass substrate
Samantha Grist, Jasbir N. Patel, Moeed Haq, et al.
We present the effect of surface treatments/coatings and soft bake temperatures aimed at improving adhesion and surface uniformity of SU-8 on glass substrates. While the adhesion strength of SU-8 to metal layers on glass and silicon has been previously investigated, our research examines the influence of additional surface treatments (RCA, Acetone/IPA rinse) and coatings (fresh/one-day-aged Ti, fresh/one-day-aged Cr, SU-8 2005®) on adhesion strength as well as surface uniformity for 100 μm thick SU-8 films. Additionally, we vary the soft bake times and temperatures while keeping all other process parameters constant, to correlate adhesion strength with surface uniformity of SU-8 films for each surface modification. We have found that for all surface treatments/coatings, a soft bake temperature of 65°C for 90 minutes yielded a more uniform SU-8 film (σ = 5.18 μm) as compared to the manufacturer-recommended soft bake temperature of 95°C (σ = 12.66 μm) for 30 minutes. Consequently, a more uniform SU-8 film provided excellent adhesion strength (> 2 MPa, as determined by stress testing using an Instron® microtester) for both metallic seed layers while the adhesion strength of films baked at 95°C was determined to be < 0.5 MPa. This study, for the first time, has been able to quantitatively determine the adhesion strength of SU-8 films on different seed layers deposited on glass substrates, for varying soft bake temperatures.
Cell and Particle-based Systems
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From bioseparation to artificial micro-organs: microfluidic chip based particle manipulation techniques
Martin Stelzle
Microfluidic device technology provides unique physical phenomena which are not available in the macroscopic world. These may be exploited towards a diverse array of applications in biotechnology and biomedicine ranging from bioseparation of particulate samples to the assembly of cells into structures that resemble the smallest functional unit of an organ. In this paper a general overview of chip-based particle manipulation and separation is given. In the state of the art electric, magnetic, optical and gravitational field effects are utilized. Also, mechanical obstacles often in combination with force fields and laminar flow are employed to achieve separation of particles or molecules. In addition, three applications based on dielectrophoretic forces for particle manipulation in microfluidic systems are discussed in more detail. Firstly, a virus assay is demonstrated. There, antibody-loaded microbeads are used to bind virus particles from a sample and subsequently are accumulated to form a pico-liter sized aggregate located at a predefined position in the chip thus enabling highly sensitive fluorescence detection. Secondly, subcellular fractionation of mitochondria from cell homogenate yields pure samples as was demonstrated by Western Blot and 2D PAGE analysis. Robust long-term operation with complex cell homogenate samples while avoiding electrode fouling is achieved by a set of dedicated technical means. Finally, a chip intended for the dielectrophoretic assembly of hepatocytes and endothelial cells into a structure resembling a liver sinusoid is presented. Such "artificial micro organs" are envisioned as substance screening test systems providing significantly higher predictability with respect to the in vivo response towards a substance under test.
Device for in-vivo study of the tumor micro-environment
Waseem Khan Raja, Bojana Gligorijevic, Michael R. Padgen, et al.
In-vivo cancer cells create a unique microenvironment which enables their spread to other organs. To understand the tumor microenvironment, special tools and devices are required to monitor the interaction among different cell types as well as the effects of particular chemical gradients. We are reporting on the status of a new device (the NANIVID: NANoIntraVItal Device) that will collect chemotactic cells from the tumor environment. Due to the transparency of this implantable device, direct in-vivo cell imaging both inside and outside the device is possible. The cell collection chamber of the device consists of a micro-electrode system based on patterning of transparent, conducting films that deliver real time data including cell density and dynamics. The current development and testing status of the device will be presented. This will include the modeling of ligand gradient profile results produced from the device and the cell migration in the EGF (epidermal growth factor) gradient created by the device. Further, prototype electrode arrays were designed, fabricated and cells were cultured on the arrays at selected degrees of confluence to measure the device sensitivity. The development path of the NANIVID will be integrated with an existing animal model protocol for in-vivo testing. This will result in a clearer understanding of the dynamics of a tumor's metastatic progression.
Theoretical investigation of capillary flow under gravity with microbead suspension
Prashant R. Waghmare, Sushanta K. Mitra
In the present study, gravity assisted capillary transport of microbead suspension is investigated theoretically. An additional gravitational head from the reservoir which is placed at the top of the capillary is considered as pressure force at the inlet of capillary. The pressure field distribution at the inlet of capillary is deduced to calculate this inlet pressure force. The non-dimensional governing equation is derived by taking into account the surface, viscous and gravity forces which act on the fluid front. Presence of microbeads delays the capillary transport. It is observed from the numerical solution of the governing equation that, not only the aspect ratio of the capillary but the aspect ratio of reservoir also plays a vital role in the flow front transport in the capillary. Although higher fluid level in the reservoir has added advantage towards higher gravitational head, the resistance from reservoir makes the progress of the flow front movement slow at the beginning of the transport. The physical properties of the fluid also play an important role in deciding the progression fluid flow front.
Mesoscale to microscale controlled manipulation of microscale objects using MEMS based microgripper and haptic interface
Ashwin P. Vijayasai, Ganapathy Sivakumar, Matthew Mulsow, et al.
In this work, we describe the development and testing of a three degree of freedom (DOF) meso/micro manipulation system for handling biological cells (SF-9) and micro objects. Three axis control is obtained using stepper motors coupled to three micromanipulators. One motor is coupled to a linear X-stage which holds the test specimen. The remaining two stepper motors are coupled to Y and Z axis micromanipulators. The stepper motor - micromanipulator arrangement has minimum step resolution of ~0.45μm with a total travel of 10mm and the stepper motor - X stage arrangement has a minimum resolution of ~0.3μm. The shaft end of the micromanipulator has a commercially available electrostatic MEMS microgripper from Femtotools™ which has a gripping range of 0 - 100μm. As the gripping action is performed, a commercially available 3 DOF haptic device (Novint Falcon) is programmed to give force feedback to the user. Both mesoscale and microscale control are important, as mesoscale control is required for the travel motion of the test object whereas microscale control is required for the gripping action. A LabView based system is used to control the position of the microgripper, to control the opening of the microgripper, and to provide force-feedback through the haptic.
Development of an integrated microsystem for the multiplexed detection of breast cancer markers in serum using electrochemical immunosensors
Alex Fragoso, Noemi Laboria, Mary Luz Botero, et al.
A microsystem integrating electrochemical biosensoric detection for the simultaneous multiplexed detection of protein markers of breast cancer is reported. The immobilization of antibodies against each of carcinoembryonic antigen (CEA), prostate specific antigen (PSA) and cancer antigen 15-3 (CA15-3) was achieved via crosslinking to a bipodal dithiol chemisorbed on gold electrodes. This bipodal dithiol had the double function of eliminating non-specific binding and optimal spacing of the anchor antibodies for maximum accessibility to the target proteins. Storage conditions were optimized, demonstrating a long-term stability of the reporter conjugates jointly stored within a single reservoir in the microsystem. The final system has been optimized in terms of incubation times, temperatures and simultaneous, multiplexed detection of the protein markers was achieved in less than 10 minutes with less than ng/mL detection limits. The microsystem has been validated using real patient serum samples and excellent correlation with ELISA results obtained.
Diagnostics
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Microfluidic diagnostics for low-resource settings
Kenneth R. Hawkins, Bernhard H. Weigl
Diagnostics for low-resource settings need to be foremost inexpensive, but also accurate, reliable, rugged and suited to the contexts of the developing world. Diagnostics for global health, based on minimally-instrumented, microfluidicsbased platforms employing low-cost disposables, has become a very active research area recently-thanks, in part, to new funding from the Bill & Melinda Gates Foundation, the National Institutes of Health, and other sources. This has led to a number of interesting prototype devices that are now in advanced development or clinical validation. These devices include disposables and instruments that perform multiplexed PCR-based assays for enteric, febrile, and vaginal diseases, as well as immunoassays for diseases such as malaria, HIV, and various sexually transmitted diseases. More recently, instrument-free diagnostic disposables based on isothermal nucleic-acid amplification have been developed. Regardless of platform, however, the search for truly low-cost manufacturing methods that would enable affordable systems (at volume, in the appropriate context) remains a significant challenge. Here we give an overview of existing platform development efforts, present some original research in this area at PATH, and reiterate a call to action for more.
Portable microfluidic cytometer for whole blood cell analysis
Meggie M. Grafton, Michael D. Zordan, Han-Sheng Chuang, et al.
Lab-on-a-chip (LOC) systems allow complex laboratory assays to be carried out on a single chip using less time, reagents, and manpower than traditional methods. There are many chips addressing PCR and other DNA assays, but few that address blood cell analysis. Blood analysis, particularly of the cellular component, is highly important in both medical and scientific fields. Traditionally blood samples require a vial of blood, then several processing steps to separate and stain the various components, followed by the preparations for each specific assay to be performed. A LOC system for blood cell analysis and sorting would be ideal. The microfluidic-based system we have developed requires a mere drop of blood to be introduced onto the chip. Once on chip, the blood is mixed with both fluorescent and magnetic labels. The lab-on-a-chip device then uses a syringe drive to push the cells through the chip, while a permanent magnet is positioned to pull the magnetically labeled white blood cells to a separate channel. The white blood cells, labeled with different color fluorescent quantum dots (Qdots) conjugated to antibodies against WBC subpopulations, are analyzed and counted, while a sampling of red blood cells is also counted in a separate channel. This device will be capable of processing whole blood samples on location in a matter of minutes and displaying the cell count and should eventually find use in neonatology, AIDS and remote site applications.
Experimental and theoretical investigation of capillary flow with BSA and microbead suspensions
Prashant R. Waghmare, Sushanta K. Mitra
The present study reports an investigation of capillary transport with a suspension of microbeads and biomolecules. Series of experiments are performed to deduce the concentration based surface tension and contact angle expression for microbead and biomolecule suspension. It is observed that, the microbead suspension restricts the spreading of the fluid front. Hence a decrease in the surface tension and an increase in the contact angle is observed as the concentration of suspension is increased. Different expressions for contact angle and surface tension depending on the range of the microbead concentrations are deduced. Theoretical model to predict the capillary transport in rectangular microchannel considering the change in physical and surface properties of the fluid is developed. The capillary transport in a microfabricated silicon microchannel is observed for fluid with and without microbead. Theoretical and experimental observations match quite well, whereas the quantitative difference in case of transport with microbead suspension is observed. Thus, the effect of suspension on the fluid properties can not be neglected in a capillary transport.
Microfluidic Devices and Biosensors
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Microfluidic cell separation: applications and challenges in tissue engineering
Brian D. Plouffe, James V. Green, Shashi K. Murthy
In tissue engineering, the enrichment of a particular cell type typically precedes in vitro culture on scaffolds. Another separation challenge that has emerged recently in tissue engineering is the need to isolate stem or progenitor cells that are naturally present in certain tissue types and have the ability to differentiate into functional cells. In both contexts, the ability of microfluidic systems to handle small sample volumes and achieve highly selective separation presents an attractive alternative to traditional techniques such as pre-plating, cell straining and sorting with fluorescent or magnetic tags.
Design and fabrication of a PDMS microchip based immunoassay
Guocheng Shao, Wanjun Wang, Jun Wang, et al.
In this paper, we describe the design and fabrication of a polydimethylsiloxane (PDMS) microchip for on-chip multiplex immunoassay applications. The microchip consists of a PDMS microfluidic channel layer and a micro pneumatic valve control layer. By selectively pressurizing the pneumatic microvalves, immuno reagents were controlled to flow and react in certain fluidic channel sites. Cross contamination was prevented by tightly closed valves. Our design was proposed to utilize PDMS micro channel surface as the solid phase immunoassay substrate and simultaneously detect four targets antigens on chip. Experimental results show that 20psi valve pressure is sufficient to tightly close a 200μm wide micro channel with flow rate up to 20μl/min.
Sample to answer: a fully integrated nucleic acid identification system for bacteria monitoring
Jungkyu Kim, John Elsnab, Michael Johnson, et al.
A fully integrated microfluidic system was developed and incorporates an EC-MWCNT (electrochemical multiwalled carbon nanotube) sensor for the detection of bacteria. Sample metering, reagent metering and delivery was implemented with microvalves and pumps embedded inside the microfluidic system. The nucleic acid extraction was performed using microchannels controlled using automated platforms and a disposable microfluidic silica cartridge. The target samples were flowed and hybridized with probe ssDNA (single strand DNA) across the MWCNT-EC sensor (built on a silicon chip), which was embedded in a microfluidic cell. The 9-pad sensor was scanned before and after hybridization to measure the quantity of RNA (Ribonucleic acid) bound to the array surface. A rapid and accurate sample-in answer-out nucleic acid system was realized with automated volume metering, microfluidic sample preparation, and integrated nano-biosensors.
BioMEMS and Medical Devices
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MEMS-based sensing and algorithm development for fall detection and gait analysis
Piyush Gupta, Gabriel Ramirez, Donald Y. C. Lie, et al.
Falls by the elderly are highly detrimental to health, frequently resulting in injury, high medical costs, and even death. Using a MEMS-based sensing system, algorithms are being developed for detecting falls and monitoring the gait of elderly and disabled persons. In this study, wireless sensors utilize Zigbee protocols were incorporated into planar shoe insoles and a waist mounted device. The insole contains four sensors to measure pressure applied by the foot. A MEMS based tri-axial accelerometer is embedded in the insert and a second one is utilized by the waist mounted device. The primary fall detection algorithm is derived from the waist accelerometer. The differential acceleration is calculated from samples received in 1.5s time intervals. This differential acceleration provides the quantification via an energy index. From this index one may ascertain different gait and identify fall events. Once a pre-determined index threshold is exceeded, the algorithm will classify an event as a fall or a stumble. The secondary algorithm is derived from frequency analysis techniques. The analysis consists of wavelet transforms conducted on the waist accelerometer data. The insole pressure data is then used to underline discrepancies in the transforms, providing more accurate data for classifying gait and/or detecting falls. The range of the transform amplitude in the fourth iteration of a Daubechies-6 transform was found sufficient to detect and classify fall events.
Defect tolerance in microfluidic chambers for capacitive biosensors
Biomedical sensors combining microfluidic and electronics capabilities require defect avoidance in both the electronic processing circuits and microfluidic areas. Microfluidic sensors involve sealed channels through which sample fluids containing biomedical materials flow. Inserting microchannels between capacitive plates enable the detection of biomaterials by the changes in capacitance. However, faults occur when foreign particles, or fluid bubbles get lodged in the paths blocking a channel, thereby affecting the measured C. To achieve fault tolerance we investigate a Cathedral Chamber design, with pillars supporting the roof at regular intervals. This prevents single blockages from stopping fluid flow through the system in a channel, as there are many paths. We discuss the potential causes and effects of such blockages. Monte Carlo simulations show that the Cathedral Chamber design significantly increases lifetime of the system, an average of 6 times more particles are required before full blockage occurs compared to an array of parallel channels. Fluid flow modeling shows parallel channels show rapid rise of pressure with the number of blockages while the Cathedral chamber shows much slower rise, which reaches a plateau pressure until it is blocked. The impact of defects on the capacitive measurement is also discussed. Finally, an interesting application, one that uses patches of single chain Fragment variables (scFv's), the active part of antibodies, is also discussed.
Electrochemical impedance monitoring of immunochemical reactions using varying IDE geometries for signal enhancement
Robin H. Page, Calum McNeil
Electrochemical Impedance Spectroscopy (EIS) has been applied to the detection of analytes for immunosensors [1-3]. The development of hand held devices based on this technique is a very promising prospect for point-of-care applications and is an attractive alternative to laboratory-based immunochemical analysis [1, 4]. The work in this paper will focus primarily on the development of an EIS method of transduction for immunoassay detection that could be potentially introduced into a hand held point-of-care device. Varying geometries of IDEs will be reported and discussed to improve the detection of antigen.
Compact and fast read-out for wavelength-encoded biosensors
Konrad Bellmann, Peter Kiesel, Noble Johnson
Many established and recently-introduced optical biosensor concepts rely on the detection of a small wavelength change in response to change of temperature, adhesion of bio-particles, strain, or chemical environment. Special coatings are used to sensitize them to specifically bound molecules (e.g., biomarkers). We describe a compact and fast wavelength monitor that can resolve sub-pm wavelength changes. The unit was demonstrated by reading out a FBG sensor and can resolve wavelength changes as small as 50fm with a bandwidth of more than 100Hz.
Special Session: Dip-Pen Lithography
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Multiplexed Dip Pen Nanolithography patterning by simple desktop nanolithography platform
Jae-Won Jang, Alexander Smetana, Paul Stiles
Multiplexed patterning in the micro-scale has been required in order to accomplish functional bio-materials templating on the subcellular length scale. Multiplexed bio-material patterns can be used in several fields: high sensitivity DNA/protein chip development, cell adhesion/differentiation studies, and biological sensor applications. Especially, two or more materials' patterning in subcellular length scale is highly demanding to develop a multi-functional and highintegrated chip device. The multiplexing patterning of two or more materials is a challenge because of difficulty in an alignment and a precision of patterning. In this work, we demonstrate that multiplexed dip pen nanolithography® (DPN®) patterning up to four different material inks by means of using recently developed new generation nanolithography platform (NLP 2000™, NanoInk, Inc., Skokie, IL). Ink materials were prepared by adding different colored fluorescent dyes to matrix carrier materials, such as poly(ethylene glycol) dimethacrylate (PEG-DMA) and lipid material (1,2- dioleoyl-sn-glycero-3-phosphocholine, DOPC). Finally, dot-array patterns of four different inks were obtained in 50 × 50 μm2 area. This lithography platform is capable of patterning 12 separate materials within micrometer areas by efficient use of the available MEMS accessories. This number can be scaled up further with development of new accessories.
Biomimetic nanolithography and its application for biosensor chip fabrication
Hiroshi Matsui
Various nano-structures and complex patterns have been fabricated by top-down or bottom-up approaches, which have own strength and weakness. Here we combined the top-down and the bottom-up fabrications to take advantages on both strengths. We demonstrated that two different ways of the top-down/bottom-up combination could be very effective for the future nano-fabrications. One way is to assemble nanometer-sized building blocks into the device configurations such as electronics and sensor. Our strategy is to use those functionalized peptide nanowires, which can recognize and selectively bind a well-defined region on antigen-patterned substrates, as building blocks to assemble nanoscale architectures at uniquely defined positions, patterned by AFM-based nanolithography. The second method of the topdown/ bottom-up combination is to pattern mineralization peptides with nanolithography and grow metals along the peptide lines. For example, when an Au-mineralizing peptide was written in the line-array, the biomineralization yielded monodisperse Au-NPs along the peptide lines. We were also succeeded to grow and pattern semiconductors at room temperature as precursors were patterned with dip-pen nanolithography. This crystallization was induced by energy gain from the shape change caused by DPN. Then, hydrophobic-hydrophilic pattern that mimics protein-binding sites in nature could be patterned by DPN and this pattern geometry can induce the attachment-detachment switching of proteins. At last, the electronic pathogen sensor chips will be introduced as another example for the DPN application. Here the DPN was applied to attach single cell at a time on transducer surface, which unambiguously determined the single cell detection limit of the sensors.
Surface assembly of pyridyl-substituted porphyrins on Au(111) investigated in situ using scanning probe lithography
Zorabel M. LeJeune, Matt McKenzie, Erhong Hao, et al.
Scanning probe characterizations of porphyrin patterns created by nanografting were used to provide insight for the molecular orientation and surface assembly of porphyrins with pyridyl and phenyl substituents. In-situ AFM provides highly local views of the assembly of pyridyl-substituted porphyrins on surfaces of Au(111). Matrix self-assembled monolayers(SAMs) of n-alkanethiols furnish a molecular ruler for calibrating height measurements. Nanografting can be used for local measurements of the thickness of porphyrin films in situ by comparison with heights of n-alkanethiol nanopatterns. When nanografted, pyridyl porphyrins were found to assemble onto gold directly into an upright configuration, and surface binding is likely mediated through nitrogen-gold chemisorption.
Self-leveling 2D DPN probe arrays
Jason R. Haaheim, Vadim Val, Ed Solheim, et al.
Dip Pen Nanolithography® (DPN®) is a direct write scanning probe-based technique which operates under ambient conditions, making it suitable to deposit a wide range of biological and inorganic materials. Precision nanoscale deposition is a fundamental requirement to advance nanoscale technology in commercial applications, and tailoring chemical composition and surface structure on the sub-100 nm scale benefits researchers in areas ranging from cell adhesion to cell-signaling and biomimetic membranes. These capabilities naturally suggest a "Desktop Nanofab" concept - a turnkey system that allows a non-expert user to rapidly create high resolution, scalable nanostructures drawing upon well-characterized ink and substrate pairings. In turn, this system is fundamentally supported by a portfolio of MEMS devices tailored for microfluidic ink delivery, directed placement of nanoscale materials, and cm2 tip arrays for high-throughput nanofabrication. Massively parallel two-dimensional nanopatterning is now commercially available via NanoInk's 2D nano PrintArray™, making DPN a high-throughput (>3×107 μm2 per hour), flexible and versatile method for precision nanoscale pattern formation. However, cm2 arrays of nanoscopic tips introduce the nontrivial problem of getting them all evenly touching the surface to ensure homogeneous deposition; this requires extremely precise leveling of the array. Herein, we describe how we have made the process simple by way of a selfleveling gimbal attachment, coupled with semi-automated software leveling routines which bring the cm^2 chip to within 0.002 degrees of co-planarity. This excellent co-planarity yields highly homogeneous features across a square centimeter, with <6% feature size standard deviation. We have engineered the devices to be easy to use, wire-free, and fully integrated with both of our patterning tools: the DPN 5000, and the NLP 2000.
Poster Session
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Microfluidic sorting system based on optical force switching
Siew-Kit Hoi, Chammika Udalagama, Chorng-Haur Sow, et al.
We report a versatile, and automatic method for sorting cells and particles in a three dimensional polydimethylsiloxane (PDMS) structure consisting of two crossmicrochannels. As microspheres or yeast cells are fed continuously into a lower channel, a line shaped focused laser beam is applied (perpendicular to the direction of flow) at the crossing junction of the two channels. The scattering force of the laser beam was employed to push microparticles matching specific criteria upwards from one channel to another. The force depends on the intrinsic properties of the particles such as their refractive index and size, as well as the laser power and the fluid flow speed. The combination of these parameters gives a tunable selection criterion for the effective and efficient sorting of the particles. The introduction of the cylindrical lens into the optical train allows for simultaneous manipulation of multiple particles which has significantly increased the efficiency and throughput of the sorting. A high aspect ratio microchannel (A.R. = 1.6) was found to enhance the sorting performance of the device. By careful control of the microparticle flow rate, near 100% sorting efficiency was achieved.
Fabrication and properties of conductive micromoldable thermosetting polymer for electronic routing in highly flexible microfluidic systems
We present the preparation, characterization and electrical properties of a flexible electrically conducting nanocomposite polymer which has been prepared by shear mixing of 80nm - 500nm silver particles in polydimethylsiloxane (PDMS). We have characterized and compared the resistivity of films 3cm × 1 cm × 0.01cm in size as a function of weight percentage of silver nanoparticles (ranging from 10 to 50) with the result that the percolation threshold is achieved at 32.5 weight percent. The resistivity level achieved at 50 weight percentage is equal to 2.3 × 10-5 Ω-m which is better than bulk carbon. Microelectrodes were fabricated with a height of 30μm, width of 100μm, and lengths (l) ranging from 1mm to 10mm with a maximum current of 40mA achieved for the 1mm electrode at 1V. The fabricated microelectrodes maintain electrical continuity on being bent, flexed or twisted and can be used for electronic routing on a flexible circuit board of non-conductive PDMS.
Analysis on the effect of geometrical design parameters on maximum shear stresses in an electromagnetic micropump
A. T. Al-Halhouli
In this work, the concept of recently introduced electromagnetic pump has been presented. This pump has been proposed for pumping biomedical fluids carrying particles sensitive to shear stresses. Its working concept depends on controlling the rotation of two pistons placed in a circular channel in opposing polarity under the influence of a moving electromagnetic field. Analytical and numerical investigations on the effect of pump geometrical parameters on shear stresses at different boundary conditions are performed. The geometrical parameters include: channel aspect ratio (channel width to height) and channel radius ratio (inner to outer radius). Non-dimensional simple analytical shear stress expressions that are valid for a wide range of geometrical design parameters and variety of fluids are derived. CFD simulations have been used to verify the analytical expressions within the range of studied parameters. Obtained results showed that the analytical models predict the wall maximum shear stresses with an error less than 5% for w / h≤1.0 at high radius ratios and with an error less than10% for Ri / Ro ≥0.3. These results help the designer in fabricating the micropump to be suitable for biomedical applications, where saving the particles carried in fluids from damage is of high importance.
Fabrication and testing of integrated permanent micromagnets for microfluidic systems
A. Khosla, J. L. Korčok, B. L. Gray, et al.
We present fabrication of a novel (Nd0.7Ce0.3)10.5Fe83.9B5.6 magnetic powder and polydimethysiloxane bonded material that can be micropatterned into micromagnets. The magnetic powder, with an average particle size of 5μm-6μm, has been prepared from an alloy ingot of raw materials which are put in a vacuum induction furnace and melt spun to obtain ribbons with nanocrystalline microstructure. The ribbons are crushed using vibrating ball milling under inert atmosphere to obtain coarse powder (average particle size of 200μm). In order to obtain 5μm fine powder the course powder is jet milled at 6000rpm under inert atmosphere. The fine magnetic powder (referred to as MQFP-15) is ultrasonically uniformly dispersed in a polydimethylsiloxane matrix (PDMS) using a horn tip probe operating at a frequency of 42 kHz. Micromagnets (diameter of 50μm, height 30μm) are fabricated from the prepared composite via soft lithography and are tested using a SQUID magnetometer, showing a remanent magnetization (Mr) of 60.10 emu/g and coercivity (Hc) of 5260 G at 75 weight percentage of magnetic powder in the PDMS matrix.
PDMS surface modification in the application of waveguide claddings for evanescent field sensing
We fabricated SU-8 based slab waveguides on surface-modified poly(dimethyl siloxane) PDMS lower claddings for application in evanescent field sensing. In this application, higher sensitivity is obtained by generating stronger penetrating power above the waveguide into the analyte. This can be achieved by reducing the refractive index of the substrate. Compared with glass substrates that have a refractive index of 1.5, PDMS has a refractive index of 1.42 at 633 nm, thus serving as a better lower cladding material for high-sensitivity sensing with an evanescent field or as claddings in multilayer waveguide applications. In order to increase the adhesion of PDMS surfaces for successful SU-8 application we treated PDMS thin films in low-frequency (40 kHz) oxygen plasma for varied length of exposure time. The treatment process made PDMS hydrophilic and created nano-structures on the surfaces. The resultant surface topography with different exposure time was studied by an interferometric profiler on PDMS lower claddings and the later spin-coated SU-8 waveguides. Measurement results showed that longer plasma treatment on PDMS claddings significantly improved the uniformity and waviness of the waveguides. Light propagation tests performed with a prism coupler and an end-butt coupling setup proved that PDMS can be used as a proper material for SU-8 waveguides.
A PDMS sample pretreatment microdevice to enable downstream electrokinetic manipulations in bovine serum
The notion of sample preconditioning, or pretreatment, as a micro-unit operation in a Lab on a Chip (LOC) system has yet to be realized in commercial practice. As is well known, Biomarker detection in complex, biological samples, such as blood, requires a series of pretreatment steps to enable detection of specific markers. On chip, such a process usually relies on "off-chip" sample pretreatment prior to "on-chip" analyte manipulations and detection. Presented in this paper is a PDMS, pretreatment chip based on the design of Oddy et al.1 with a view to enable a self-contained LOC platform. The chip was designed to directly manipulate the suspended species while adjusting fluid properties using buffer volumes less than 1 ml. Using previous literature related to capillary electrophoresis, a bench-scale pretreatment protocol was developed to tune specific fluidic parameters to an optimal range, namely pH, conductivity, and viscosity. A PDMS device was fabricated and used to combine a raw, bovine serum sample with specific buffer solutions. Off-chip electrodes were used to induce DC-electrokinetic micro-mixing of the target analyte in the mixing chamber, where a homogeneous analyte distribution was achieved in less than one second using an 800V DC pulse wave. Additionally, the desired solution viscosity and pH were achieved using less than 1 ml of buffer solution. Adjustment of sample conductivity, which is driven by sample fluid volume, remains an open area of research.