Design practices used in the development of microfluidic devices: a services-based view

This paper presents the current state of microfluidic design from a practitioner’s perspective. The capture of microfluidic design practice was facilitated through a combination of industry survey and expert interviews, allowing the authors to draw out models for microfluidic design. Exploration of the current practice of microfluidic design showed that formal design methodologies were not in use. This research has also found that sub-section interactions have been addressed in an inadequate fashion by current design practices. The work presented in this paper outlines the scope for further research in the development of a formal design methodology for microfluidics

ILP-Based Pin-Count Aware Design Methodology for Microfluidic Biochips

Digital microfluidic biochips have emerged as a popular alternative for laboratory experiments. To make the biochip feasible for practical applications, pin-count reduction is a key problem to higher-level integration of reactions on a biochip. Most previous works approach the problem by post-processing the placement and routing solutions to share compatible control signals; however, the quality of such sharing algorithms is inevitably limited by the placement and routing solutions. We present in this paper a comprehensive pin-constrained biochip design flow that addresses the pin-count issue at all design stages. The proposed flow consists of three major stages: (1) pin-count aware stage assignment that partitions the reactions in the given bioassay into execution stages, (2) pin-count aware device assignment that determines a specific device used for each reaction, and (3) guided placement, routing, and pin assignment that utilize the pin-count saving properties from the stage and device assignments to optimize the assay time and pin count. For both the stage and device assignments, exact ILP formulations and effective solution-space reduction schemes are proposed to minimize the assay time and pin count. Experimental results show the efficiency of our algorithms/flow and a 55–57 % pin-count reduction over the state-ofthe-art algorithms/flow

Droplet routing for digital microfluidic biochips based on microelectrode dot array architecture

A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets. The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time

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

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