Error recovery in digital microfluidics for personalized medicine
09 Mar 2015-pp 247-252
TL;DR: An illustrative survey on recently proposed techniques for error recovery in digital-microfluidic biochips is presented and the parameters of the error-recovery design space are shown and evaluated for these schemes.
Abstract: Due to its emergence as an efficient platform for point-of-care clinical diagnostics, design optimization of digital-microfluidic biochips (DMFBs) has received considerable attention in recent years. In particular, error recoverability is of key interest in medical applications due to the need for system reliability. Errors are likely during droplet manipulation due to defects, chip degradation, and the lack of precision inherent in biochemical experiments. We present an illustrative survey on recently proposed techniques for error recovery. The parameters of the error-recovery design space are shown and evaluated for these schemes. Next, we make use of these evaluations to describe how they can guide error recovery in DMFBs. Finally, an experimental case study is presented to demonstrate how an error-recovery scheme can be applied to real-life biochips.
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TL;DR: Although IoT eHealth has vastly expanded the possibilities to fulfill a number of existing healthcare needs, many challenges must still be addressed in order to develop consistent, suitable, safe, flexible, and power-efficient systems that are suitable fit for medical needs.
Abstract: The interaction between technology and healthcare has a long history. However, recent years have witnessed the rapid growth and adoption of the Internet of Things (IoT) paradigm, the advent of miniature wearable biosensors, and research advances in big data techniques for effective manipulation of large, multiscale, multimodal, distributed, and heterogeneous data sets. These advances have generated new opportunities for personalized precision eHealth and mHealth services. IoT heralds a paradigm shift in the healthcare horizon by providing many advantages, including availability and accessibility, ability to personalize and tailor content, and cost-effective delivery. Although IoT eHealth has vastly expanded the possibilities to fulfill a number of existing healthcare needs, many challenges must still be addressed in order to develop consistent, suitable, safe, flexible, and power-efficient systems that are suitable fit for medical needs. To enable this transformation, it is necessary for a large number of significant technological advancements in the hardware and software communities to come together. This keynote paper addresses all these important aspects of novel IoT technologies for smart healthcare-wearable sensors, body area sensors, advanced pervasive healthcare systems, and big data analytics. It identifies new perspectives and highlights compelling research issues and challenges, such as scalability, interoperability, device-network-human interfaces, and security, with various case studies. In addition, with the help of examples, we show how knowledge from CAD areas, such as large scale analysis and optimization techniques can be applied to the important problems of eHealth.
91 citations
TL;DR: This article considers imprecise droplet mix-split operations and presents a novel roll-forward approach where the erroneous droplets are used in the error-recovery process, instead of being discarded or remixed.
Abstract: Digital (droplet-based) microfluidic technology offers an attractive platform for implementing a wide variety of biochemical laboratory protocols, such as point-of-care diagnosis, DNA analysis, target detection, and drug discovery. A digital microfluidic biochip consists of a patterned array of electrodes on which tiny fluid droplets are manipulated by electrical actuation sequences to perform various fluidic operations, for example, dispense, transport, mix, or split. However, because of the inherent uncertainty of fluidic operations, the outcome of biochemical experiments performed on-chip can be erroneous even if the chip is tested a priori and deemed to be defect-free. In this article, we address an important error recoverability problem in the context of sample preparation. We assume a cyberphysical environment, in which the physical errors, when detected online at selected checkpoints with integrated sensors, can be corrected through recovery techniques. However, almost all prior work on error recoverability used checkpointing-based rollback approach, that is, re-execution of certain portions of the protocol starting from the previous checkpoint. Unfortunately, such techniques are expensive both in terms of assay completion time and reagent cost, and can never ensure full error-recovery in deterministic sense. We consider imprecise droplet mix-split operations and present a novel roll-forward approach where the erroneous droplets, thus produced, are used in the error-recovery process, instead of being discarded or remixed. All erroneous droplets participate in the dilution process and they mutually cancel or reduce the concentration-error when the target droplet is reached. We also present a rigorous analysis that reveals the role of volumetric-error on the concentration of a sample to be prepared, and we describe the layout of a lab-on-chip that can execute the proposed cyberphysical dilution algorithm. Our analysis reveals that fluidic errors caused by unbalanced droplet splitting can be classified as being either critical or non-critical, and only those of the former type require correction to achieve error-free sample dilution. Simulation experiments on various sample preparation test cases demonstrate the effectiveness of the proposed method.
38 citations
Cites background or methods from "Error recovery in digital microflui..."
...Our analysis reveals that fluidic errors caused by unbalanced droplet splitting can be classified as being either critical or non-critical, and only those of the former type require correction to achieve errorfree sample dilution....
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...DOI: http://dx.doi.org/10.1145/2898999...
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...…actuation sequences depending on real-time sensor feedback have been proposed for adaptive biochemical diagnostics or error-recovery [Grissom et al. 2014; Ibrahim and Chakrabarty 2015b; Hu et al. 2013; Luo et al. 2013a; Alistar et al. 2012; Zhao et al. 2010; Luo et al. 2013b; Hsieh et al. 2014]....
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...…even more important in situations that involve mission-critical or life-critical biochemical assays such as pathological diagnostics, DNA analysis, and drug design, where the correctness of assay outcome cannot be compromised [Chakrabarty and Su 2007; Ibrahim and Chakrabarty 2015b; Hu et al. 2013]....
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...…strategy, where, on sensing an error at a checkpoint, the corresponding portion of the protocol is re-executed from the preceding checkpoint [Ibrahim and Chakrabarty 2015b; Hu et al. 2013; Luo et al. 2013a; Alistar et al. 2012; ACM Transactions on Design Automation of Electronic Systems,…...
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01 Jan 2015
TL;DR: This chapter describes emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols and shows how recent advances in the integration of sensors into a DMFB can be exploited to provide cyberphysical system adaptation based on feedback-driven control.
Abstract: Due to their emergence as an efficient platform for pointof-care clinical diagnostics, digital-microfluidic biochips (DMFBs) have received considerable attention in recent years. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. In this chapter, we first present an overview of digital-microfluidic biochips. We next describe emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols. The chapter includes solutions for fluidic-operation scheduling, module placement, droplet routing, and pin-constrained chip design. We also show how recent advances in the integration of sensors into a DMFB can be exploited to provide cyberphysical system adaptation based on feedback-driven control.
22 citations
01 Jan 2015
TL;DR: This chapter presents a framework for the verification of safety and timing properties of digital embedded real-time systems, which are modeled in SystemC, using timed automata and the Uppaal model checker.
Abstract: Real-time systems are systems where the correctness does not only depend on their correct functioning but also on meeting realtime constraints. Such systems are often deployed in safety-critical applications, for example in airplanes, trains, or automotive systems. There, a failure may result in enormous costs or even in human injuries or loss of lifes. As a consequence, systematic verification and validation of real-time systems is a crucial issue. The main application area for real-time systems are embedded applications, where the system controls technical processes that also evolve in real-time. Such systems are usually composed of deeply integrated hardware and software components, and they are developed under severe resource limitations and high quality requirements. In connection with the steadily increasing demands on multi-functioning and flexibility, analog control components are more and more replaced by complex digital HW/SW systems. A major challenge is to develop automated quality assurance techniques that can be used for the verification and validation of complex embedded real-time systems that consist of both hardware and software. In this chapter, we give an overview over our research contributions to this topic. In particular, we present our framework for the verification of safety and timing properties of digital embedded real-time systems, which are modeled in SystemC, using timed automata and the Uppaal model checker.
21 citations
24 Oct 2018
TL;DR: This paper introduces BioScript, a domain-specific language for programmable biochemistry which executes on emerging microfluidic platforms and includes novel optimizations that place biochemical operations to execute concurrently on a spatial 2D array platform on the granularity of a control flow graph.
Abstract: This paper introduces BioScript, a domain-specific language (DSL) for programmable biochemistry which executes on emerging microfluidic platforms. The goal of this research is to provide a simple, intuitive, and type-safe DSL that is accessible to life science practitioners. The novel feature of the language is its syntax, which aims to optimize human readability; the technical contributions of the paper include the BioScript type system and relevant portions of its compiler. The type system ensures that certain types of errors, specific to biochemistry, do not occur, including the interaction of chemicals that may be unsafe. The compiler includes novel optimizations that place biochemical operations to execute concurrently on a spatial 2D array platform on the granularity of a control flow graph, as opposed to individual basic blocks. Results are obtained using both a cycle-accurate microfluidic simulator and a software interface to a real-world platform.
19 citations
Cites background or methods from "Error recovery in digital microflui..."
...…2012; Shih et al. 2011; Vo et al. 2017] and online error detection and recovery [Alistar and Pop 2015; Alistar et al. 2016; Hsieh et al. 2014; Ibrahim and Chakrabarty 2015a,b; Ibrahim et al. 2017; Jaress et al. 2015; Li et al. 2017; Luo et al. 2013a,b; Poddar et al. 2016; Zhao et al. 2010];…...
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...…portion of the device unusable; prior work has covered dynamic error recovery in detail [Alistar and Pop 2015; Alistar et al. 2016; Hsieh et al. 2014; Ibrahim and Chakrabarty 2015a,b; Ibrahim et al. 2017; Jaress et al. 2015; Li et al. 2017; Luo et al. 2013a,b; Poddar et al. 2016; Zhao et al. 2010]....
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1,094 citations
"Error recovery in digital microflui..." refers background in this paper
...manipulate droplets of picoliter volumes under program control on a patterned electrode array, is revolutionizing laboratory procedures not only for point-of-care clinical diagnostics [6], but also for many other applications such as environmental monitoring [7] and drug discovery [8]....
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559 citations
"Error recovery in digital microflui..." refers background in this paper
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08 Nov 2004
TL;DR: The disposable plastic biochip incorporating smart passive microfluidics with embedded on-chip power sources and integrated biosensor array for applications in clinical diagnostics and point-of-care testing and a handheld analyzer capable of multiparameter detection of clinically relevant parameters is developed.
Abstract: This paper presents the development of a disposable plastic biochip incorporating smart passive microfluidics with embedded on-chip power sources and integrated biosensor array for applications in clinical diagnostics and point-of-care testing. The fully integrated disposable biochip is capable of precise volume control with smart microfluidic manipulation without costly on-chip microfluidic components. The biochip has a unique power source using on-chip pressurized air reservoirs, for microfluidic manipulation, avoiding the need for complex microfluidic pumps. In addition, the disposable plastic biochip has successfully been tested for the measurements of partial oxygen concentration, glucose, and lactate level in human blood using an integrated biosensor array. This paper presents details of the smart passive microfluidic system, the on-chip power source, and the biosensor array together with a detailed discussion of the plastic micromachining techniques used for chip fabrication. A handheld analyzer capable of multiparameter detection of clinically relevant parameters has also been developed to detect the signals from the cartridge type disposable biochip. The handheld analyzer developed in this work is currently the smallest analyzer capable of multiparameter detection for point-of-care testing.
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488 citations
TL;DR: A framework for envisioning how point-of-care testing can be applied to infectious diseases in low- and middle-income countries is discussed.
Abstract: Madhukar Pai and colleagues discuss a framework for envisioning how point-of-care testing can be applied to infectious diseases in low- and middle-income countries.
466 citations
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