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Krishnendu Chakrabarty – 1st expert on this subject based on the ideXlab platform

  • Reconfiguration Techniques for Digital Microfluidic Biochips
    , 2020
    Co-Authors: Fei Su, Krishnendu Chakrabarty

    Abstract:

    As digital microfluidic Biochips become widespread in safety-critical biochemical applications, system dependability emerges as a critical performance parameter. The dynamic reconfigurability inherent in digital microfluidic Biochips can be utilized to bypass faulty cells, thereby supporting defect/fault tolerance. In this paper, we propose three different reconfiguration techniques and the corresponding defect/fault tolerance methodologies for digital microfluidic Biochips. The proposed schemes ensure that the bioassays mapped to a droplet-based microfluidic array can still be executed on a defective Biochip. Real-life biochemical assays, namely multiplexed diagnostics on human physiological fluids, are used to evaluate the proposed reconfiguration techniques.

  • Prevention: Tamper-Resistant Pin-Constrained Digital Microfluidic Biochips
    Secure and Trustworthy Cyberphysical Microfluidic Biochips, 2020
    Co-Authors: Jack Tang, Krishnendu Chakrabarty, Mohamed Ibrahim, Ramesh Karri

    Abstract:

    The well-worn maxim that an ounce of prevention is worth a pound of cure certainly applies to the design of secure systems; security breaches are difficult to contain due to the speed, scale, and low-cost of information dissemination on the internet. When security breaches result in physical damage, the lost assets may be difficult or impossible to replace, e.g., DNA samples from a crime scene. This chapter develops techniques for the prevention of actuation tampering attacks on a cyberphysical microfluidic Biochip by leveraging the inherent loss of control freedom from pin-constrained digital microfluidic Biochips.

  • Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test Techniques
    IEEE Transactions on Biomedical Circuits and Systems, 2019
    Co-Authors: Zhanwei Zhong, Krishnendu Chakrabarty, Zipeng Li, Tsung-yi Ho

    Abstract:

    Digital microfluidic Biochips (DMFBs) are being increasingly used for DNA sequencing, point-of-care clinical diagnostics, and immunoassays. DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been proposed, and fundamental droplet manipulations, e.g., droplet mixing and splitting, have also been experimentally demonstrated on MEDA Biochips. There can be thousands of microelectrodes on a single MEDA Biochip, and the fine-grained control of nanoliter volumes of biochemical samples and reagents is also enabled by this technology. MEDA Biochips offer the benefits of real-time sensitivity, lower cost, easy system integration with CMOS modules, and full automation. This review paper first describes recent design tools for high-level synthesis and optimization of map bioassay protocols on a MEDA Biochip. It then presents recent advances in scheduling of fluidic operations, placement of fluidic modules, droplet-size-aware routing, adaptive error recovery, sample preparation, and various testing techniques. With the help of these tools, Biochip users can concentrate on the development of nanoscale bioassays, leaving details of chip optimization and implementation to software tools.

Tsung-yi Ho – 2nd expert on this subject based on the ideXlab platform

  • VOM: Flow-Path Validation and Control-Sequence Optimization for Multilayered Continuous-Flow Microfluidic Biochips
    2019 IEEE ACM International Conference on Computer-Aided Design (ICCAD), 2019
    Co-Authors: Mengchu Li, Tsung-yi Ho, Tsun-ming Tseng, Ulf Schlichtmann

    Abstract:

    Multilayered valve-based continuous-flow microfluidic Biochips are a rapidly developing platform for delicate bio-applications. Due to the high complexity of the Biochip structure and the application protocols, there is an increasing demand for design automation approaches. Current research has enabled automated generation of Biochip physical designs, operation scheduling, and binding protocols, which has demonstrated the potential for better resource utilization and execution time reduction. However, the state-of-the-art high-level synthesis methods are on operation- and device-level. They assume fluid transportation paths to be always available but overlook the physical layout of the control and flow channels. This mismatch leads to a gap in the complete synthesis flow, and can result in performance drop, waste of resources due to redundancy or even infeasible designs. This work proposes to bridge this gap with a simulation-based approach, which takes a Biochip design and a high-level protocol as inputs, and synthesizes channel-level pressurization protocols to support dynamic construction of valid fluid transportation paths. Experimental results show that the proposed method can efficiently validate and optimize the flow paths for feasible designs and protocols, detect redundant resource usage, and locate the conflicts for infeasible designs and protocols. It opens up a new direction to improve the performance and the feasibility of customized Biochip synthesis.

  • Micro-Electrode-Dot-Array Digital Microfluidic Biochips: Technology, Design Automation, and Test Techniques
    IEEE Transactions on Biomedical Circuits and Systems, 2019
    Co-Authors: Zhanwei Zhong, Krishnendu Chakrabarty, Zipeng Li, Tsung-yi Ho

    Abstract:

    Digital microfluidic Biochips (DMFBs) are being increasingly used for DNA sequencing, point-of-care clinical diagnostics, and immunoassays. DMFBs based on a micro-electrode-dot-array (MEDA) architecture have recently been proposed, and fundamental droplet manipulations, e.g., droplet mixing and splitting, have also been experimentally demonstrated on MEDA Biochips. There can be thousands of microelectrodes on a single MEDA Biochip, and the fine-grained control of nanoliter volumes of biochemical samples and reagents is also enabled by this technology. MEDA Biochips offer the benefits of real-time sensitivity, lower cost, easy system integration with CMOS modules, and full automation. This review paper first describes recent design tools for high-level synthesis and optimization of map bioassay protocols on a MEDA Biochip. It then presents recent advances in scheduling of fluidic operations, placement of fluidic modules, droplet-size-aware routing, adaptive error recovery, sample preparation, and various testing techniques. With the help of these tools, Biochip users can concentrate on the development of nanoscale bioassays, leaving details of chip optimization and implementation to software tools.

  • Cloud Columba: Accessible Design Automation Platform for Production and Inspiration: Invited Paper
    2019 IEEE ACM International Conference on Computer-Aided Design (ICCAD), 2019
    Co-Authors: Tsun-ming Tseng, Tsung-yi Ho, Mengchu Li, Yushen Zhang, Ulf Schlichtmann

    Abstract:

    Design automation for continuous-flow microfluidic large-scale integration (mLSI) Biochips has made remarkable progress over the past few years. Nowadays a Biochip containing up to hundreds of components can be automatically synthesized within a few minutes. However, the current advanced design automation tools are mostly developed for research use, which focus essentially on the algorithmic performance but overlook the accessibility. Therefore, we have started the Cloud Columba project since 2017 to provide users from different backgrounds with easy access to the state-of-the-art design automation approaches. Without being limited by the computing power of their end devices, users just need to formulate their design requests in a high abstraction level, based on which the cloud server will automatically synthesize a customized manufacturing-ready Biochip design, which can be viewed and stored using simply a web browser. With the computer-synthesized designs, Cloud Columba supports application developers to explore a wider range of possibilities, and algorithm developers to validate and improve their ideas based on a practical foundation.

Yang Zhao – 3rd expert on this subject based on the ideXlab platform

  • Cross-contamination avoidance for droplet routing in digital microfluidic Biochips
    IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 2012
    Co-Authors: Yang Zhao, Krishnendu Chakrabarty

    Abstract:

    Recent advances in droplet-based digital microfluidics have enabled Biochip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Since cross-contamination between droplets of different biomolecules can lead to erroneous outcomes for bioassays, the avoidance of cross-contamination during droplet routing is a key design challenge for Biochips. We propose a droplet-routing method that avoids cross-contamination in the optimization of droplet flow paths. The proposed approach targets disjoint droplet routes and minimizes the number of cells used for droplet routing. We also minimize the number of wash operations that must be used between successive routing steps that share unit cells in the microfluidic array. Two real-life biochemical applications are used to evaluate the proposed droplet-routing methods.

  • Optimization Techniques for the Synchronization of Concurrent Fluidic Operations in Pin-Constrained Digital Microfluidic Biochips
    IEEE Transactions on Very Large Scale Integration (VLSI) Systems, 2012
    Co-Authors: Yang Zhao, Krishnendu Chakrabarty, Ryan Sturmer, Vamsee K. Pamula

    Abstract:

    The implementation of bioassays in pin-constrained digital microfluidic Biochips may involve pin-actuation conflicts if the concurrently-implemented fluidic operations are not carefully synchronized. We propose a two-phase optimization method to identify and synchronize the fluidic operations that can be executed in parallel. The goal is to implement these fluidic operations without pin-actuation conflict, and minimize the duration of implementing the outcome sequence after synchronization. We also extend the synchronization method with the addition of a small number of control pins, in order to further minimize the completion time while avoiding pin-actuation conflicts. The effectiveness of the proposed synchronization method is demonstrated for a representative 3-plex assay performed on a commercial pin-constrained Biochip and for multiplexed in-vitro diagnostics performed on an experimental pin-constrained Biochip.

  • Cross-Contamination Avoidance for Droplet Routing in Digital Microfluidic Biochips
    IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 2012
    Co-Authors: Yang Zhao, Krishnendu Chakrabarty

    Abstract:

    Recent advances in digital microfluidics have enabled droplet-based Biochip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Since cross-contamination between droplets of different biomolecules can lead to erroneous outcomes for bioassays, the avoidance of cross-contamination during droplet routing is a key design challenge for Biochips. We propose a droplet-routing method that avoids cross-contamination in the optimization of droplet flow paths. The proposed approach targets disjoint droplet routes and synchronizes wash-droplet routing with functional droplet routing, in order to reduce the duration of droplet routing while avoiding the cross-contamination between different droplet routes. In order to avoid cross-contamination between successive routing steps, an optimization technique is used to minimize the number of wash operations that must be used between successive routing steps. Two real-life biochemical applications are used to evaluate the proposed droplet-routing methods.