Design and Optimization Methods for Pin-Limited and Cyberphysical Digital Microfluidic Biochips

<p>Microfluidic biochips have now come of age, with applications to biomolecular recognition for high-throughput DNA sequencing, immunoassays, and point-of-care clinical diagnostics. In particular, digital microfluidic biochips, which use electrowetting-on-dielectric to manipulate discrete droplets (or "packets of biochemical payload") of picoliter volumes under clock control, are especially promising. The potential applications of biochips include real-time analysis for biochemical reagents, clinical diagnostics, flash chemistry, and on-chip DNA sequencing. The ease of reconfigurability and software-based control in digital microfluidics has motivated research on various aspects of automated chip design and optimization.</p><p>This thesis research is focused on facilitating advances in on-chip bioassays, enhancing the automated use of digital microfluidic biochips, and developing an "intelligent" microfluidic system that has the capability of making on-line re-synthesis while a bioassay is being executed. This thesis includes the concept of a "cyberphysical microfluidic biochip" based on the digital microfluidics hardware platform and on-chip sensing technique. In such a biochip, the control software, on-chip sensing, and the microfluidic operations are tightly coupled. The status of the droplets is dynamically monitored by on-chip sensors. If an error is detected, the control software performs dynamic re-synthesis procedure and error recovery.</p><p>In order to minimize the size and cost of the system, a hardware-assisted error-recovery method, which relies on an error dictionary for rapid error recovery, is also presented. The error-recovery procedure is controlled by a finite-state-machine implemented on a field-programmable gate array (FPGA) instead of a software running on a separate computer. Each state of the FSM represents a possible error that may occur on the biochip; for each of these errors, the corresponding sequence of error-recovery signals is stored inside the memory of the FPGA before the bioassay is conducted. When an error occurs, the FSM transitions from one state to another, and the corresponding control signals are updated. Therefore, by using inexpensive FPGA, a portable cyberphysical system can be implemented.</p><p>In addition to errors in fluid-handling operations, bioassay outcomes can also be erroneous due the uncertainty in the completion time for fluidic operations. Due to the inherent randomness of biochemical reactions, the time required to complete each step of the bioassay is a random variable. To address this issue, a new "operation-interdependence-aware" synthesis algorithm is proposed in this thesis. The start and stop time of each operation are dynamically determined based on feedback from the on-chip sensors. Unlike previous synthesis algorithms that execute bioassays based on pre-determined start and end times of each operation, the proposed method facilitates "self-adaptive" bioassays on cyberphysical microfluidic biochips.</p><p>Another design problem addressed in this thesis is the development of a layout-design algorithm that can minimize the interference between devices on a biochip. A probabilistic model for the polymerase chain reaction (PCR) has been developed; based on the model, the control software can make on-line decisions regarding the number of thermal cycles that must be performed during PCR. Therefore, PCR can be controlled more precisely using cyberphysical integration.</p><p>To reduce the fabrication cost of biochips, yet maintain application flexibility, the concept of a "general-purpose pin-limited biochip" is proposed. Using a graph model for pin-assignment, we develop the theoretical basis and a heuristic algorithm to generate optimized pin-assignment configurations. The associated scheduling algorithm for on-chip biochemistry synthesis has also been developed. Based on the theoretical framework, a complete design flow for pin-limited cyberphysical microfluidic biochips is presented.</p><p>In summary, this thesis research has led to an algorithmic infrastructure and optimization tools for cyberphysical system design and technology demonstrations. The results of this thesis research are expected to enable the hardware/software co-design of a new class of digital microfluidic biochips with tight coupling between microfluidics, sensors, and control software.</p>Dissertatio

Electronics Thermal Management in Information and Communications Technologies: Challenges and Future Directions

This paper reviews thermal management challenges encountered in a wide range of electronics cooling applications from large-scale (data center and telecommunication) to smallscale systems (personal, portable/wearable, and automotive). This paper identifies drivers for progress and immediate and future challenges based on discussions at the 3rd Workshop on Thermal Management in Telecommunication Systems and Data Centers held in Redwood City, CA, USA, on November 4–5, 2015. Participants in this workshop represented industry and academia, with backgrounds ranging from data center thermal management and energy efficiency to high-performance computing and liquid cooling, thermal management in wearable and mobile devices, and acoustic noise management. By considering a wide range of electronics cooling applications with different lengths and time scales, this paper identifies both common themes and diverging views in the thermal management community

Navigating the lab-on-chip manufacturability roadblock: scalable, low-cost fluorescence detection for lab-on-chip instrumentation with rapid-prototyped microfluidics

Miniaturisation and automation of laboratory testing protocols onto microfluidic chips (lab-on-chip technology) could revolutionise diagnostic testing, though the key challenge of integrating high levels of functionality at a low-cost has so far prevented widespread adoption both in industry and academia. Specifically, implementation of a cost-accessible fluorescence detection has eluded the field and ensured nearly all commercial and academic instruments are too costly for routine applications. The field also faces a manufacturability problem, as it is dominated by expensive and/or low-throughput fabrication approaches. This thesis aims to address core concerns on both the instrument and fluidic chip fronts through the development of a low-cost fluorescence detection module capable of executing standard molecular diagnostics. The detection was inherently designed to interface with a series of rapid-prototyped polymer fluidics that I designed and fabricated with direct-write methods (micromilling and laser ablation) and minimal processing, allowing for quick iterations of fluidic designs while retaining compatibility with high throughput manufacturing procedures such as injection moulding. The result is a sub-$1000 prototype capable of executing gold-standard diagnostic testing at sub-$10 per chip, though the specific protocol development is still on-going. Finally, these components have been designed in a scalable manner such that it is feasible for future manufacturing to be done in a standard CMOS compatible process, a process that also faces manufacturability issues and high development costs that could be avoided by utilising these designs as prototyping testbeds. Thus, this work provides a roadmap from interim low-cost instrumentation and rapid-prototyping methods, through standard high volume polymer processing techniques, to a true single-chip device where the entire instrument may one day be fabricated at high volume in a USB-key sized package

Fabrication of microchannels for use in micro-boiling experiments

Increased power densities in VLSI chips have led to a need to develop cooling methods that can cope with the increased heat produced by such chips. Currently one of the more attractive methods to meet this goal is through the use of two phase flow of a fluid as changing phase of the material allows high heat transfer rates for a low temperature change. To bring this technology to commercialisation a greater understanding of the underlying physics involved at the microscale is required as there is much debate within literature as to what occurs during two phase flow heat transfer at these scales. The work conducted as part of this thesis is a step towards improving the understanding of the mechanisms involved with this process. This thesis describes the fabrication of a novel microchannel structure, which can be used to experimentally characterise two phase heat transfer as it occurs. The final process reported for these microchannels structures provides the basis of a technology for the fabrication of microchannels with increased sensor densities. Two types of microchannel devices have been fabricated for this project. The first device of these was an array of parallel microchannels formed by the reactive ion etching (RIE) of silicon, which was then bonded with Pyrex glass. These microchannels were simple in that sensors were not integrated for local measurement. However the production of these devices incorporated fabrication techniques such as anodic bonding and inductively coupled plasma RIE that were essential to the fabrication of more complex devices. The second device built was a single microchannel that contained an integrated heater and several temperature sensors. The use of wafer bonding enabled the device to take full advantage of both bulk and surface micromachining technology as the placement of the temperature sensors on the channel floor would not be possible with conventional bulk micromachining. The initial microchannel structures demonstrated that wafer bonding could be used to fabricate novel devices, but they highlighted the difficulty of achieving strong anodic bonds due to the presence of dielectric films throughout the fusion bonded wafer stack used in the channel fabrication. To improve the performance of the device the process was optimised through the use of insitu, non-destructive test structures. These structures enabled the uniformity and strength of the bonds to be optimised through visualisation over the whole wafer surface. The integrated sensors enabled temperature measurements to be taken along the channel with a sensitivity 3.60 ΩK-1 while the integrated heater has delivered a controllable and uniform heat flux of 264 kWm-2

Laboratory Directed Research and Development Program FY 2004 Annual Report

The Oak Ridge National Laboratory (ORNL) Laboratory Directed Research and Development (LDRD) Program reports its status to the U.S. Department of Energy (DOE) in March of each year. The program operates under the authority of DOE Order 413.2A, 'Laboratory Directed Research and Development' (January 8, 2001), which establishes DOE's requirements for the program while providing the Laboratory Director broad flexibility for program implementation. LDRD funds are obtained through a charge to all Laboratory programs. This report describes all ORNL LDRD research activities supported during FY 2004 and includes final reports for completed projects and shorter progress reports for projects that were active, but not completed, during this period. The FY 2004 ORNL LDRD Self-Assessment (ORNL/PPA-2005/2) provides financial data about the FY 2004 projects and an internal evaluation of the program's management process. ORNL is a DOE multiprogram science, technology, and energy laboratory with distinctive capabilities in materials science and engineering, neutron science and technology, energy production and end-use technologies, biological and environmental science, and scientific computing. With these capabilities ORNL conducts basic and applied research and development (R&amp;D) to support DOE's overarching national security mission, which encompasses science, energy resources, environmental quality, and national nuclear security. As a national resource, the Laboratory also applies its capabilities and skills to the specific needs of other federal agencies and customers through the DOE Work For Others (WFO) program. Information about the Laboratory and its programs is available on the Internet at &lt;http://www.ornl.gov/&gt;. LDRD is a relatively small but vital DOE program that allows ORNL, as well as other multiprogram DOE laboratories, to select a limited number of R&amp;D projects for the purpose of: (1) maintaining the scientific and technical vitality of the Laboratory; (2) enhancing the Laboratory's ability to address future DOE missions; (3) fostering creativity and stimulating exploration of forefront science and technology; (4) serving as a proving ground for new research; and (5) supporting high-risk, potentially high-value R&amp;D. Through LDRD the Laboratory is able to improve its distinctive capabilities and enhance its ability to conduct cutting-edge R&amp;D for its DOE and WFO sponsors. To meet the LDRD objectives and fulfill the particular needs of the Laboratory, ORNL has established a program with two components: the Director's R&amp;D Fund and the Seed Money Fund. As outlined in Table 1, these two funds are complementary. The Director's R&amp;D Fund develops new capabilities in support of the Laboratory initiatives, while the Seed Money Fund is open to all innovative ideas that have the potential for enhancing the Laboratory's core scientific and technical competencies. Provision for multiple routes of access to ORNL LDRD funds maximizes the likelihood that novel and seminal ideas with scientific and technological merit will be recognized and supported