Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

Microfluidic laboratories-on-a-chip (LoCs) are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. There are several types of LoCs, each having its advantages and limitations. In this paper we are interested in flow-based LoCs, in which a continuous flow of liquid is manipulated using integrated microvalves. By combining several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. We consider that the architecture of the LoC is given, and we are interested in synthesizing an implementation, consisting of the binding of operations in the application to the functional units of the architecture, the scheduling of operations and the routing and scheduling of the fluid flows, such that the application completion time is minimized. To solve this problem, we propose a list scheduling-based application mapping (LSAM) framework and evaluate it by using real-life as well as synthetic benchmarks. When biochemical applications contain fluids that may adsorb on the substrate on which they are transported, the solution is to use rinsing operations for contamination avoidance. Hence, we also propose a rinsing heuristic, which has been integrated in the LSAM framework

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

Micro- and Nanofluidics for Bionanoparticle Analysis

Bionanoparticles such as microorganisms and exosomes are recoganized as important targets for clinical applications, food safety, and environmental monitoring. Other nanoscale biological particles, includeing liposomes, micelles, and functionalized polymeric particles are widely used in nanomedicines. The recent deveopment of microfluidic and nanofluidic technologies has enabled the separation and anslysis of these species in a lab-on-a-chip platform, while there are still many challenges to address before these analytical tools can be adopted in practice. For example, the complex matrices within which these species reside in create a high background for their detection. Their small dimension and often low concentration demand creative strategies to amplify the sensing signal and enhance the detection speed. This Special Issue aims to recruit recent discoveries and developments of micro- and nanofluidic strategies for the processing and analysis of biological nanoparticles. The collection of papers will hopefully bring out more innovative ideas and fundamental insights to overcome the hurdles faced in the separation and detection of bionanoparticles

Service-oriented design of microfludic devices

Microfluidics is a relatively new and, with an estimation of the market for these devices exceeding $3 billion in 2014, it is considered a profitable domain. Constant development of new technologies and growing demand for more versatile products cause increasing complexity in this area. To address this, the current trends for the domain include automation, standardisation and customisation. At the same time, the society is moving from product types offering to services. Due to the customisation trend this transition appears beneficial for microfluidics. Taking advantage of these opportunities, an investigation of microfluidic design has been undertaken to address the issues at their origins. The literature review showed a lack of a general design methodology applicable for all microfluidic devices, identified existing approaches as technology driven and the domain as unique in terms of design. Also, it highlighted a number of automation and standardisation attempts in the area. In addition, microfluidics shows limited customer and service-orientation. Meanwhile, an investigation of complexity and its implications in microfluidics narrowed the study to sub-section interactions, which allowed standardisation and automation without compromising customisation. In response to these gaps, an aim of the research is to develop a guideline for service- oriented design of microfluidic devices that can deal with sub-section interactions. This research reviews: existing methodologies for design in micro-scale, their applicability to the domain, microfluidic practitioners’ approach to design, state of service-thinking and services in the area and how sub-section interactions are dealt with for these devices. The developed guideline and design enablers present a proposal for a general process for the design of microfluidics. The solution attempts to tackle the issue of sub- section interactions and brings the domain one step towards an ‘experience economy’ by incorporating service-considerations into the design process. The usefulness of this contribution has been confirmed by a variety of methods and numerous sources including experts in the field.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Design of electronic systems for automotive sensor conditioning

This thesis deals with the development of sensor systems for automotive, mainly targeting the exploitation of the new generation of Micro Electro-Mechanical Sensors (MEMS), which achieve a dramatic reduction of area and power consumption but at the same time require more complexity in the sensor conditioning interface. Several issues concerning the development of automotive ASICs are presented, together with an overview of automotive electronics market and its main sensor applications. The state of the art for sensor interfaces design (the generic sensor interface concept), consists in sharing the same electronics among similar sensor applications, thus saving cost and time-to-market but also implementing a sub-optimal system with area and power overheads. A Platform Based Design methodology is proposed to overcome the limitations of generic sensor interfaces, by keeping the platform generality at the highest design layers and pursuing the maximum optimization and performances in the platform customization for a specific sensor. A complete design flow is presented (up to the ASIC implementation for gyro sensor conditioning), together with examples regarding IP development for reuse and low power optimization of third party designs. A further evolution of Platform Based Design has been achieved by means of implementation into silicon of the ISIF (Intelligent Sensor InterFace) platform. ISIF is a highly programmable mixed-signal chip which allows a substantial reduction of design space exploration time, as it can implement in a short time a wide class of sensor conditioning architectures. Thus it lets the designers evaluate directly on silicon the impact of different architectural choices, as well as perform feasibility studies, sensor evaluations and accurate estimation of the resulting dedicated ASIC performances. Several case studies regarding fast prototyping possibilities with ISIF are presented: a magneto-resistive position sensor, a biosensor (which produces pA currents in presence of surface chemical reactions) and two capacitive inertial sensors, a gyro and a low-g YZ accelerometer. The accelerometer interface has also been implemented in miniboards of about 3 cm2 (with ISIF and sensor dies bonded together) and a series of automatic trimming and characterization procedures have been developed in order to evaluate sensor and interface behaviour over the automotive temperature range, providing a valuable feedback for the implementation of a dedicated accelerometer interface