Microsystems technology: objectives

This contribution focuses on the objectives of microsystems technology (MST). The reason for this is two fold. First of all, it should explain what MST actually is. This question is often posed and a simple answer is lacking, as a consequence of the diversity of subjects that are perceived as MST. The second reason is that a map of the somewhat chaotic field of MST is needed to identify sub-territories, for which standardization in terms of system modules an interconnections is feasible. To define the objectives a pragmatic approach has been followed. From the literature a selection of topics has been chosen and collected that are perceived as belonging to the field of MST by a large community of workers in the field (more than 250 references). In this way an overview has been created with `applications¿ and `generic issues¿ as the main characteristics

Development of a light-powered microstructure : enhancing thermal actuation with near-infrared absorbent gold nanoparticles.

Development of microscale actuating technologies has considerably added to the toolset for interacting with natural components at the cellular level. Small-scale actuators and switches have potential in areas such as microscale pumping and particle manipulation. Thermal actuation has been used with asymmetric geometry to create large deflections with high force relative to electrostatically driven systems. However, many thermally based techniques require a physical connection for power and operate outside the temperature range conducive for biological studies and medical applications. The work presented here describes the design of an out-of-plane bistable switch that responds to near-infrared light with wavelength-specific response. In contrast to thermal actuating principles that require wired conductive components for Joule heating, the devices shown here are wirelessly powered by near -infrared (IR) light by patterning a wavelength-specific absorbent gold nanoparticle (GNP) film onto the microstructure. An optical window exists which allows near-IR wavelength light to permeate living tissue, and high stress mismatch in the bilayer geometry allows for large actuation at biologically acceptable limits. Patterning the GNP film will allow thermal gradients to be created from a single laser source, and integration of various target wavelengths will allow for microelectromechanical (MEMS) devices with multiple operating modes. An optically induced temperature gradient using wavelength-selective printable or spinnable coatings would provide a versatile method of wireless and non-invasive thermal actuation. This project aims to provide a fundamental understanding of the particle and surface interaction for bioengineering applications based on a “hybrid” of infrared resonant gold nanoparticles and MEMS structures. This hybrid technology has potential applications in light-actuated switches and other mechanical structures. Deposition methods and surface chemistry are integrated with three-dimensional MEMS structures in this work. The long-term goal of this project is a system of light-powered microactuators for exploring cells\u27 response to mechanical stimuli, adding to the fundamental understanding of tissue response to everyday mechanical stresses at the molecular level

Development of novel micropneumatic grippers for biomanipulation

Microbjects with dimensions from 1 μm to 1 mm have been developed recently for different aspects and purposes. Consequently, the development of handling and manipulation tools to fulfil this need is urgently required. Micromanipulation techniques could be generally categorized according to their actuation method such as electrostatic, thermal, shape memory alloy, piezoelectric, magnetic, and fluidic actuation. Each of which has its advantage and disadvantage. The fluidic actuation has been overlooked in MEMS despite its satisfactory output in the micro-scale. This thesis presents different families of pneumatically driven, low cost, compatible with biological environment, scalable, and controllable microgrippers. The first family demonstrated a polymeric microgripper that was laser cut and actuated pneumatically. It was tested to manipulate microparticles down to 200 microns. To overcome the assembly challenges that arise in this family, the second family was proposed. The second family was a micro-cantilever based microgripper, where the device was assembled layer by layer to form a 3D structure. The microcantilevers were fabricated using photo-etching technique, and demonstrated the applicability to manipulate micro-particles down to 200 microns using automated pick-and-place procedure. In addition, this family was used as a tactile-detector as well. Due to the angular gripping scheme followed by the above mentioned families, gripping smaller objects becomes a challenging task. A third family following a parallel gripping scheme was proposed allowing the gripping of smaller objects to be visible. It comprises a compliant structure microgripper actuated pneumatically and fabricated using picosecond laser technology, and demonstrated the capability of gripping microobject as small as 100 μm microbeads. An FEA modelling was employed to validate the experimental and analytical results, and excellent matching was achieved

Advanced medical micro-robotics for early diagnosis and therapeutic interventions

Recent technological advances in micro-robotics have demonstrated their immense potential for biomedical applications. Emerging micro-robots have versatile sensing systems, flexible locomotion and dexterous manipulation capabilities that can significantly contribute to the healthcare system. Despite the appreciated and tangible benefits of medical micro-robotics, many challenges still remain. Here, we review the major challenges, current trends and significant achievements for developing versatile and intelligent micro-robotics with a focus on applications in early diagnosis and therapeutic interventions. We also consider some recent emerging micro-robotic technologies that employ synthetic biology to support a new generation of living micro-robots. We expect to inspire future development of micro-robots toward clinical translation by identifying the roadblocks that need to be overcome

Genetic Analysis and Cell Manipulation on Microfluidic Surfaces

Personalized cancer medicine is a cancer care paradigm in which diagnostic and therapeutic strategies are customized for individual patients. Microsystems that are created by Micro-Electro-Mechanical Systems (MEMS) technology and integrate various diagnostic and therapeutic methods on a single chip hold great potential to enable personalized cancer medicine. Toward ultimate realization of such microsystems, this thesis focuses on developing critical functional building blocks that perform genetic variation identification (single-nucleotide polymorphism (SNP) genotyping) and specific, efficient and flexible cell manipulation on microfluidic surfaces. For the identification of genetic variations, we first present a bead-based approach to detect single-base mutations by performing single-base extension (SBE) of SNP specific primers on solid surfaces. Successful genotyping of the SNP on exon 1 of HBB gene demonstrates the potential of the device for simple, rapid, and accurate detection of SNPs. In addition, a multi-step solution-based approach, which integrates SBE with mass-tagged dideoxynucleotides and solid-phase purification of extension products, is also presented. Rapid, accurate and simultaneous detection of 4 loci on a synthetic template demonstrates the capability of multiplex genotyping with reduced consumption of samples and reagents. For cell manipulation, we first present a microfluidic device for cell purification with surface-immobilized aptamers, exploiting the strong temperature dependence of the affinity binding between aptamers and cells. Further, we demonstrate the feasibility of using aptamers to specifically separate target cells from a heterogeneous solution and employing environmental changes to retrieve purified cells. Moreover, spatially specific capture and selective temperature-mediated release of cells on design-specified areas is presented, which demonstrates the ability to establish cell arrays on pre-defined regions and to collect only specifically selected cell groups for downstream analysis. We also investigate tunable microfluidic trapping of cells by exploiting the large compliance of elastomers to create an array of cell-trapping microstructures, whose dimensions can be mechanically modulated by inducing uniform strain via the application of external force. Cell trapping under different strain modulations has been studied, and capture of a predetermined number of cells, from single cells to multiple cells, has been achieved. In addition, to address the lack of aptamers for targets of interest, which is a major hindrance to aptamer-based cell manipulation, we present a microfluidic device for synthetically isolating cell-targeting aptamers from a randomized single-strand DNA (ssDNA) library, integrating cell culturing with affinity selection and amplification of cell-binding ssDNA. Multi-round aptamer isolation on a single chip has also been realized by using pressure-driven flow. Finally, some perspectives on future work are presented, and strategies and notable issues are discussed for further development of MEMS/microfluidics-based devices for personalized cancer medicine

Experimentation and Multiphysical Modeling of Bioanalytical Microdevices

Bioanalytics involves quantitative measurements of complex biological samples that contain metabolites, DNA, RNA, and proteins. Efficient sample preparation for downstream analysis and sensitive detection of analytes can be achieved via bioanalytical microdevices. Fully realizing the potential of these devices requires tool characterization and bioprocess optimization, in addition to understanding device physics. Therefore, this thesis introduces multiphysical modeling and experimentation of microdevices, with applications to diabetes care and single-cell analysis. To understand the physics of viscometric glucose microsensors, this thesis presents a model of the sensor, which couples the fluid flow with vibrating diaphragms. The model is used to predict the sensor response to glucose via theory of squeeze-film damping and vibrations of pre-stressed plate. A first-principle-based model resulting from the theory can be evaluated from the device's geometric and material properties, and quantitatively determines the device response to vibrational excitations at varying glucose concentrations. Next, this thesis introduces a theoretical model for viscometric glucose microsensors that employ harmonic microcantilever oscillation in the sensing liquid. The presented model associates the unsteady Stokes equation with the motion of a bounded viscous liquid to understand the hydrodynamic impact on the cantilever. With a proper consideration of the viscosity and bounded geometry of liquid media, the model relaxes the thin-film assumption required for the diaphragm-based model, enabling an accurate representation of fluid-structure interactions based on fundamental structural vibration and fluid flow equations. Next, this thesis presents an experimental exploration of a hydrogel-based affinity microsensor for glucose monitoring via dielectric measurements. The microsensor incorporates a synthetic hydrogel that is attached to the device surface via in situ polymerization, which eliminates mechanical moving parts required in the viscometric glucose sensors. Changes in the dielectric properties of the hydrogel when binding reversibly with glucose molecules have been measured using a MEMS capacitive transducer to determine the glucose concentration. Experimental results demonstrate that in a glucose concentration range of 0–500 mg/dL and with a resolution of 0.35 mg/dL or better, the microsensor exhibits a repeatable and reversible response, and can potentially be useful for continuous glucose monitoring in diabetes care. Additionally, this thesis presents a microfluidic preprocessing method that integrates single-cell picking, lysing, reverse transcription and digital polymerase chain reaction to enable the isolation, tracking and gene expression analysis at single-cell level for individual cells. The approach utilizes a photocleavable bead-based microfluidic device to synthesize and deliver stable complementary DNA for downstream gene expression analysis, thereby allowing chip-based integration of multiple reactions and facilitating the minimization of sample loss or contamination. Finally, this thesis ends with concluding remarks and directions of future work towards continuous glucose monitoring and high-throughput single-cell genetic analysis

Smart Platform for Low-Cost MEMS Sensors – Pressure, Flow and Thermal Conductivity

In a technological world that is trending towards smart and autonomous engineering, the collection of quality data is of unrivalled importance. This has led to a huge market demand for the development of low-cost, small and accurate sensors and thus has resulted in significant research into sensors, with the aim of advancing the price/performance ratio in commercial solutions. Micro Electro Mechanical Systems (MEMS) have recently offered an attractive solution to miniaturise and drastically improve the performance of sensors. In this thesis, MEMS technology is exploited to create a multi-sensor technology platform that is used to fabricate several sensing technologies. Piezo-resistive and piezo-electronic pressure sensors are designed, fabricated and tested. Different doping profiles, stress-engineered structures and electronic devices for pressure transduction are investigated, with focus on their sensitivity and non-linearity. A ring is fabricated in the metal layer around the circumference of the membrane that alleviates the effects of over/under etching. This is achieved by creating a new rigid edge of the membrane in the metal layer, which has tighter fabrication tolerances. A piezo-MOSFET is developed and shown to have greater sensitivity than similar state-of-the-art devices. Flow sensors based on a heated tungsten wire are designed, fabricated, tested and substantiated with numerical modelling. Calorimetric and anemometric driving modes are optimised with regards to device structure. Thermodiodes are also used as the temperature transduction devices and are compared to the traditional resistor method and showed to be preferable when further miniaturising the sensor. Thermal conductivity gas sensors based on a heated tungsten resistor are designed, tested and substantiated with numerical modelling. Holes through the membrane are used to improve the sensitivity to measuring carbon dioxide by 270%. Asymmetric holes are utilised to prove a novel method of measuring thermal conductivity in a calorimetric method. Designs improving this new concept are outlined and substantiated with analytical and numerical models. Linear statistical methods and artificial neural networks are used to differentiate flow rate and gas concentration using three on-membrane resistors. With membrane holes, the discrimination between gases in the presence of flow is improved. Neural networks provide a viable solution and show an increase in the accuracy of both flow rate and gas concentration. The main objective of the work in this thesis was to develop low-cost, low-power, small devices capable of high-volume production and monolithic integration using a single smart technology platform for fabrication. The smart technology platform was used to create pressure sensors, flow sensors and thermal conductivity gas sensors. Within each sensing technology, proof-of-concepts and optimisations have been carried out in order to maximise performance whilst using the low-cost, high-volume fabrication process, ultimately helping towards smart and autonomous engineering solutions driven by data