A Customer Programmable Microfluidic System

Microfluidics is both a science and a technology offering great and perhaps even revolutionary capabilities to impact the society in the future. However, due to the scaling effects there are unknown phenomena and technology barriers about fluidics in microchannel, material properties in microscale and interactions with fluids are still missing. A systematic investigation has been performed aiming to develop A Customer Programmable Microfluidic System . This innovative Polydimethylsiloxane (PDMS)-based microfluidic system provides a bio-compatible platform for bio-analysis systems such as Lab-on-a-chip, micro-total-analysis system and biosensors as well as the applications such as micromirrors. The system consists of an array of microfluidic devices and each device containing a multilayer microvalve. The microvalve uses a thermal pneumatic actuation method to switch and/or control the fluid flow in the integrated microchannels. It provides a means to isolate samples of interest and channel them from one location of the system to another based on needs of realizing the customers\u27 desired functions. Along with the fluid flow control properties, the system was developed and tested as an array of micromirrors. An aluminum layer is embedded into the PDMS membrane. The metal was patterned as a network to increase the reflectivity of the membrane, which inherits the deformation of the membrane as a mirror. The deformable mirror is a key element in the adaptive optics. The proposed system utilizes the extraordinary flexibility of PDMS and the addressable control to manipulate the phase of a propagating optical wave front, which in turn can increase the performance of the adaptive optics. Polydimethylsiloxane (PDMS) has been widely used in microfabrication for microfluidic systems. However, few attentions were paid in the past to mechanical properties of PDMS. Importantly there is no report on influences of microfabrication processes which normally involve chemical reactors and biologically reaction processes. A comprehensive study was made in this work to study fundamental issues such as scaling law effects on PDMS properties, chemical emersion and temperature effects on mechanical properties of PDMS, PDMS compositions and resultant properties, as well as bonding strength, etc. Results achieved from this work will provide foundation of future developments of microfluidics utilizing PDMS

MS

thesisPolymeric materials are widely used in manufacturing of microfluidic devices, and polydimethylsiloxane (PDMS) is a commonly used polymeric material in research laboratories due to its potential for rapid prototyping. However, PDMS is less desirable for mass production applications as it requires considerable processing time. With the development of micro/nano imprinting techniques, microfluidic structures can also be rapidly imprinted on other polymers such as Poly(methyl methacrylate) (PMMA) and polycarbonate using molding technologies. Even though PMMA is the material of preference for our application-a nanoporous membrane-based RNA extraction system-a PDMS membrane is an integral part for the functioning of pneumatically actuated valves and pumps. Since there is no well-established method that exists for bonding PDMS to PMMA, an attempt has been made in this thesis to increase the functionality of PMMA microfluidic parts. The work can be classified into two main categories: manufacturing of hot embossed plastic parts and development of bonding technology for PDMS and PMMA. To prepare the PMMA parts, a hot embossing template of brass is designed and manufactured for imprinting the microfluidic parts. Functional silanes such as Amino-Propyl-Tri-Ethoxy- Silane and Bis-Tri-Methoxy-Silyl-Propyl-Amine are used to obtain an irreversible chemical bond between PMMA and PDMS, which cannot be achieved effectively with existing bonding practices such as glow discharge and thin layer PDMS adhesive

Doctor of Philosophy

dissertationMicrofluidics is an emerging field that deals with the technology and science of manipulation of fluid in microchannels. Since its birth in the 1990s, it has now gradually matured into an enabling technology, like microelectronics and software engineering. A majority of current applications of microfluidics are in life sciences. Polydimethylsiloxane (PDMS) is a soft elastomer and a popular material for fabricating microfluidic devices. This is due to PDMS's unique set of material properties and low cost. Furthermore, the unique mechanical properties of thin PDMS layers/membranes (< 200 µm) can be used to increase the functionality of PDMS-based microfluidic systems. In this presentation, three unique neuroscience applications of PDMS-based microfluidic devices are presented. The working principle behind each of these devices depends on the unique properties of thin PDMS layers. In the first project a fabrication protocol was developed to stack 30 patterned 10-um thick PDMS layers on top of each other without any trapped air bubbles or wrinkles. Each PDMS layer was patterned by spin-coating uncured PDMS on a photolithographic micromold at very high spin speeds and thermally curing the layer later. The layer stacking procedure was done manually using no specialized tools and did not cause any layer deformation to inhibit functionality. This fabrication protocol was used to develop the first ever microfluidic Magnetic Resonance Imaging Phantom to stimulate brain white matter. In the second project, laser ablation was used to rapidly prototype micromolds and by using these micromolds a unique fabrication protocol was developed and characterized to build microvalve arrays (consisting of 100s of microvalves) without access to any cleanroom facility. This was achieved by manipulating the stiffness of thin PDMS layers that are inherent part of pneumatic microvalves. These microvalve arrays were used to build a microfluidic platform for manipulation of C. elegans (a type of a small round worm), which are used extensively for neuronal behavioral analysis. In the last project using similar fabrication techniques (as described in the second project) microfluidic genotyping devices are developed for zebrafish embryos that are less than 2 days old. The unique advantage of the microfluidic zebrafish genotyping devices is that they enable researchers to collect genetic material (for genotyping) from a zebrafish embryo (1 to 2 days old) without causing any harm to its health. This capability is not possible with any other model multicellular organism to date. The working principle behind one of the presented genotyping devices depends on the controlled actuation of PDMS membranes

Towards rapid 3D direct manufacture of biomechanical microstructures

The field of stereolithography has developed rapidly over the last 20 years, and commercially available systems currently have sufficient resolution for use in microengineering applications. However, they have not as yet been fully exploited in this field. This thesis investigates the possible microengineering applications of microstereolithography systems, specifically in the areas of active microfluidic devices and microneedles. The fields of micropumps and microvalves, stereolithography and microneedles are reviewed, and a variety of test builds were fabricated using the EnvisionTEC Perfactory Mini Multi-Lens stereolithography system in order to define its capabilities. A number of microneedle geometries were considered. This number was narrowed down using finite element modelling, before another simulation was used to optimise these structures. 9 × 9 arrays of 400 μm tall, 300 μm base diameter microneedles were subjected to mechanical testing. Per needle failure forces of 0.263 and 0.243 N were recorded for the selected geometries, stepped cone and inverted trumpet. The 90 μm needle tips were subjected to between 30 and 32 MPa of pressure at their failure point - more than 10 times the required pressure to puncture average human skin. A range of monolithic micropumps were produced with integrated 4 mm diameter single-layer 70 μm-thick membranes used as the basis for a reciprocating displacement operating principle. The membranes were tested using an oscillating pneumatic actuation, and were found reliable (>1,000,000 cycles) up to 2.0 PSIG. Pneumatic single-membrane nozzle/diffuser rectified devices produced flow rates of up to 1,000 μl/min with backpressures of up to 375 Pa. Another device rectified using active membrane valves was found to self-prime, and produced backpressures of up to 4.9 kPa. These devices and structures show great promise for inclusion in complex, fully integrated and active microfluidic systems fabricated using microstereolithography alone, with implications for both cost of manufacture and lead time

Microfluidic Technology and Application in Urinal Analysis

Microfluidic technology offers numerous advantages in minimizing and integrating the traditional assays. However, the lack of efficient control components of the microfluidic systems has been hindering the widely commercialization of the technology. The research work in this dissertation focused on the development of effective control components for microfluidic applications. A linear peristaltic pump was firstly designed, fabricated, and tested for conventional microfluidics by synchronously compressing the microfluidic channel with a miniature cam-follower system in Chapter 2. The miniature cam-follower system and microfluidic chip was prototyped using three-dimensional (3D) printing technology and soft lithography technology. Results from experimental test showed that the pump is self-priming and tolerant of bubbles. The pumping flowrate and back pressure could be controlled by changing the driving speed of the motor. Then a novel pinch-type valving system that can be used to realize both normally closed and normally open valves for centrifugal microfluidics was demonstrated in Chapter 3. A sliding wedge was actuated by centrifugal force to drive the valves. Experimental test and theoretical predication showed that the burst frequency of the valves could be tuned by changing the physical parameters of the valving system. In Chapter 4, the pinch type valving system was then further improved for better integration of multiple valves in limited space to realize sequential control of microfluidics. A valve chip with grooves on the surface was used to drive multiple valves. A flow switch which is capable of working at low rotation frequency and constant rotation direction is realized. Finally, the microfluidic platform was utilized for automatic urinalysis for the application at point of care (POC) to eliminate the difficulties in control of sample distribution and read-out time in manually conducted colorimetric urinalysis. 3D printed prototype of the microfluidic chip was used to test the proposed system. Commercial urinalysis strips was integrated with the microfluidic system for detecting glucose, specific gravity, PH, and protein from simulated urine sample. The color change of the pads was recorded using smartphone camera and analyzed to quantify the interested parameters

Frequency-controlled wireless passive microfluidic devices

Microfluidics is a promising technology that is increasingly attracting the attention of researchers due to its high efficiency and low-cost features. Micropumps, micromixers, and microvalves have been widely applied in various biomedical applications due to their compact size and precise dosage controllability. Nevertheless, despite the vast amount of research reported in this research area, the ability to implement these devices in portable and implantable applications is still limited. To date, such devices are constricted to the use of wires, or on-board power supplies, such as batteries. This thesis presents novel techniques that allow wireless control of passive microfluidic devices using an external radiofrequency magnetic field utilizing thermopneumatic principle. Three microfluidic devices are designed and developed to perform within the range of implantable drug-delivery devices. To demonstrate the wireless control of microfluidic devices, a wireless implantable thermopneumatic micropump is presented. Thermopneumatic pumping with a maximum flow rate of 2.86 μL/min is realized using a planar wirelessly-controlled passive inductor-capacitor heater. Then, this principle was extended in order to demonstrate the selective wireless control of multiple passive heaters. A passive wirelessly-controlled thermopneumatic zigzag micromixer is developed as a mean of a multiple drug delivery device. A maximum mixing efficiency of 96.1% is achieved by selectively activating two passive wireless planar inductor-capacitor heaters that have different resonant frequency values. To eliminate the heat associated with aforementioned wireless devices, a wireless piezoelectric normally-closed microvalve for drug delivery applications is developed. A piezoelectric diaphragm is operated wirelessly using the wireless power that is transferred from an external magnetic field. Valving is achieved with a percentage error as low as 3.11% in a 3 days long-term functionality test. The developed devices present a promising implementation of the reported wireless actuation principles in various portable and implantable biomedical applications, such as drug delivery, analytical assays, and cell lysis devices

Microdroplet Technology Based Functional Microcapsules Generation, Handling and Applications

制度:新 ; 報告番号:甲3593号 ; 学位の種類:博士(工学) ; 授与年月日:2012/2/25 ; 早大学位記番号:新593

Simplified fabrication of complex multilayer microfluidics: enabling sophisticated lab-on-a-chip and point-of-care platforms

Complex multilayer microfluidics have generated a lot of interest in recent years. Early research introduced elastomer microvalves and postulated they would bring about a revolution for microfluidic systems, similar in scale to introduction of the transistor for electronic systems. In the following years, many researchers have been active in the use of complex multilayer microfluidic systems, with numerous high impact research outcomes using these systems as precise and active control components, providing fluidic isolation, switching or fluidic actuation, and allowing unprecedented sophistication and precise control and automation of experimental conditions. While application of complex multilayer microfluidic platforms has been demonstrated in numerous research settings, there is little evidence that the technology has become ubiquitously accepted, with a lack of evidence for point-of-care application, or widespread acceptance within the research community. While the advantages that the technology offers have been well documented, the field seems to have failed to gain traction, or facilitate the revolution that was predicted on its introduction. There are various possible explanations for this lack of acceptance, as with any technology, there are caveats to the application of complex multilayer microfluidic systems, however given the broad range of demonstrated applications, it is unlikely that the bottleneck in their application is related to a fundamental application related limitation. In contrast, fabrication technology utilised in realisation of complex multilayer microfluidic systems, has not advanced at the same rate to the multitude of application-based publications in the past decade. This thesis explores the hypothesis that one of the fundamental limiting factors in widespread application of complex multilayer microfluidic systems, is related to the challenges associated with fabrication of these systems. To explore this hypothesis, firstly, a new fabrication approach is introduced which aims to eliminate many of the challenges associated with traditional multilayer fabrication methods, this technique is demonstrated in a proof of concept capacity, fabricating common multilayer microfluidic structures and doing so with surprising ease. Having developed method with simpler fabrication, it is possible to explore whether overcoming the multilayer fabrication bottleneck would allow the advantages inherent to complex multilayer microfluidic systems to be applied to fields which would otherwise be considered prohibitively difficult, if reliant on traditional fabrication methods. This hypothesis is investigated through harnessing the new, simplified fabrication technique to advance point-of-care photonic biosensor research through short term collaborative engagements.&amp;nbsp; It is found that the use of modular building blocks and the simple, rapid fabrication enables sophisticated microfluidic chip prototypes to be developed in a very short period of time achieving multiple iterations over a matter of weeks and even facilitating collaboration on these integrated platforms remotely. The outcomes of these short-term collaborations have produced publications automating the fluid handling of highly sensitive interferometric waveguide biosensors and environmental control for a single cell analysis platform utilising integrated plasmonic biosensors.&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp; Having demonstrated that simplifying complex microfluidic fabrication can accelerate the development and deployment of these systems to enhance research platforms, the next step was to explore whether this simplified system could also lower the barrier to deployment in a clinical setting. The ability for the fluidic system to handle whole blood was chosen as a deliberately challenging target with great sensitivity to fluid dynamics and large variability in patient samples and environmental factors, requiring large number of replicate devices to determine statistical significance. Here the fabrication technique is applied to enable a study investigating the hemocompatibility of common multilayer control components, paving the way for point of care blood handling devices.&amp;nbsp; It is shown that not only can the technique be used to rapidly develop platforms that can be used with blood, but the same technique can produce even hundreds of replicates required for limited clinical trials, leading the collaborating clinicians to seriously consider these complex microfluidics for future point of care diagnostics. In Summary, it has been demonstrated that access to complex multilayer microfluidic systems without the fabrication overheads generally associated with these systems can allow their application to areas that would otherwise be prohibitively difficult. The fabrication method presented can allow rapid development, and rapid and reliable deployment to various research applications, while allowing the consistency and throughput required enabling large volume fabrication required for clinical investigations.&amp;nbsp; The fact that such a large advancement toward real world application within the scope of a single PhD is possible, supports the hypothesis that lowering the barrier to fabricating complex microfluidic devices has the potential to significantly increase their scope of application

Development of a PDMS Based Micro Total Analysis System for Rapid Biomolecule Detection

The emerging field of micro total analysis system powered by microfluidics is expected to revolutionize miniaturization and automation for point-of-care-testing systems which require quick, efficient and reproducible results. In the present study, a PDMS based micro total analysis system has been developed for rapid, multi-purpose, impedance based detection of biomolecules. The major components of the micro total analysis system include a micropump, micromixer, magnetic separator and interdigitated electrodes for impedance detection. Three designs of pneumatically actuated PDMS based micropumps were fabricated and tested. Based on the performance test results, one of the micropumps was selected for integration. The experimental results of the micropump performance were confirmed by a 2D COMSOL simulation combined with an equivalent circuit analysis of the micropump. Three designs of pneumatically actuated PDMS based active micromixers were fabricated and tested. The micromixer testing involved determination of mixing efficiency based on the streptavidin-biotin conjugation reaction between biotin comjugated fluorescent microbeads and streptavidin conjugated paramagnetic microbeads, followed by fluorescence measurements. Based on the performance test results, one of the micromixers was selected for integration. The selected micropump and micromixer were integrated into a single microfluidic system. The testing of the magnetic separation scheme involved comparison of three permanent magnets and three electromagnets of different sizes and magnetic strengths, for capturing magnetic microbeads at various flow rates. Based on the test results, one of the permanent magnets was selected. The interdigitated electrodes were fabricated on a glass substrate with gold as the electrode material. The selected micropumps, micromixer and interdigitated electrodes were integrated to achieve a fully integrated microfluidic system. The fully integrated microfluidic system was first applied towards biotin conjugated fluorescent microbeads detection based on streptavidin-biotin conjugation reaction which is followed by impedance spectrum measurements. The lower detection limit for biotin conjugated fluorescent microbeads was experimentally determined to be 1.9 x 106 microbeads. The fully integrated microfluidic system was then applied towards immuno microbead based insulin detection. The lower detection limit for insulin was determined to be 10-5M. The total detection time was 20 min. An equivalent circuit analysis was performed to explain the impedance spectrum results