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Journal ArticleDOI

Design of Pin-Constrained General-Purpose Digital Microfluidic Biochips

TL;DR: Compared with previous pin-assignment algorithms, the proposed method can reduce the number of control pins and facilitate the general-purpose use of digital microfluidic biochips for a wider range of applications.
Abstract: Digital microfluidic biochips are being increasingly used for biotechnology applications. The number of control pins used to drive electrodes is a major contributor to the fabrication cost for disposable biochips in a highly cost-sensitive market. Most prior work on pin-constrained biochip design determines the mapping of a small number of control pins to a larger number of electrodes according to the specific schedule of fluid-handling operations and routing paths of droplets. Such designs are, therefore, specific to the bioassay application, hence sacrificing some of the flexibility associated with digital microfluidics. We propose a design method to generate an application-independent pin-assignment configuration with a minimum number of control pins. Layouts of commercial biochips and laboratory prototypes are used as case studies to evaluate the proposed design method for determining a suitable pin-assignment configuration. Compared with previous pin-assignment algorithms, the proposed method can reduce the number of control pins and facilitate the general-purpose use of digital microfluidic biochips for a wider range of applications.
Citations
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Journal ArticleDOI
TL;DR: This technology has emerged as a new tool for many recently used applications in molecular detection, imaging, drug delivery, diagnostics, cell biology and other fields.
Abstract: Droplet-based microfluidics is a colloidal and interfacial system that has rapidly progressed in the past decade because of the advantages of low fabrication costs, small sample volumes, reduced analysis durations, high-throughput analysis with exceptional sensitivity, enhanced operational flexibility, and facile automation. This technology has emerged as a new tool for many recently used applications in molecular detection, imaging, drug delivery, diagnostics, cell biology and other fields. Herein, we review recent applications of droplet microfluidics proposed since 2013.

151 citations

Journal ArticleDOI
TL;DR: A compiler converts an assay, specified using the BioCoder language, into a sequence of electrode activations that execute out the assay on the DMFB; and a printed circuit board layout tool, which includes algorithms to reduce the number of control pins and PCB layers required to drive the chip from an external source.

51 citations


Cites background from "Design of Pin-Constrained General-P..."

  • ...(a) Pin assignment and (b) wire routing solutions for an application-specific DMFB designed for the polymerase chain reaction (PCR) [46,86]....

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  • ...The literature on pin-constrained DMFB design is vast, and includes: (1) pre-computed pin mappings that require specialized scheduling, placement, and routing algorithms [20,25,46]; (2) “pre-synthesis” array partitioning methods that update the pin-map during scheduling, placement, and routing [9,33,40,41,56,84–86]; and (3) “post-synthesis” pin assignment algorithms that derive a pin-map (and, in some cases, a wire routing solution) starting with a fully-compiled assay [34,36,37,76,79,80,86]....

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  • ...Both application-specific [9,33–37,40,41,56,76,79,80,84–86] and general-purpose [20,25,46] pin assignments have been reported in the literature....

    [...]

Journal ArticleDOI
TL;DR: This paper identifies result-manipulation attacks on a DMFB that maliciously alter the assay outcomes and identifies denial-of-service attacks, where the attacker can disrupt the assay operation by tampering either with the droplet-routing algorithm or with the actuation sequence.
Abstract: A digital microfluidic biochip (DMFB) is an emerging technology that enables miniaturized analysis systems for point-of-care clinical diagnostics, DNA sequencing, and environmental monitoring. A DMFB reduces the rate of sample and reagent consumption, and automates the analysis of assays. In this paper, we provide the first assessment of the security vulnerabilities of DMFBs. We identify result-manipulation attacks on a DMFB that maliciously alter the assay outcomes. Two practical result-manipulation attacks are shown on a DMFB platform performing enzymatic glucose assay on serum. In the first attack, the attacker adjusts the concentration of the glucose sample and thereby modifies the final result. In the second attack, the attacker tampers with the calibration curve of the assay operation. We then identify denial-of-service attacks, where the attacker can disrupt the assay operation by tampering either with the droplet-routing algorithm or with the actuation sequence. We demonstrate these attacks using a digital microfluidic synthesis simulator. The results show that the attacks are easy to implement and hard to detect. Therefore, this work highlights the need for effective protections against malicious modifications in DMFBs.

51 citations


Cites background from "Design of Pin-Constrained General-P..."

  • ...reconfigurability in DMFBs, it is anticipated that the current use of these devices will shift from an application-specific setting to a general-purpose approach [27], [28]....

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Journal ArticleDOI
TL;DR: This paper demonstrates a scalable single-layer PCB wiring scheme for several FPPC-DMFB variations, and presents efficient algorithms for droplet routing, with and without contamination removal via wash droplets, which offer new insights on the relationship between PCB layer count, pin count, and cost.
Abstract: This paper introduces a field-programmable pin-constrained digital microfluidic biochip (FPPC-DMFB), which offers general-purpose assay execution at a lower cost than general-purpose direct addressing DMFBs and highly optimized application-specific pin-constrained DMFBs. One of the key cost drivers for DMFBs is the number of printed circuit board (PCB) layers, onto which the device is mounted. We demonstrate a scalable single-layer PCB wiring scheme for several FPPC-DMFB variations, for PCB technology with orthogonal routing capacity of at least three; for PCB technology with orthogonal capacity of two, more PCB layers are required, but the FPPC-DMFB retains its cost advantage. These results offer new insights on the relationship between PCB layer count, pin count, and cost. Additionally, to reduce the execution time of assays on the FPPC-DMFB, we present efficient algorithms for droplet routing, with and without contamination removal via wash droplets.

22 citations

Journal ArticleDOI
TL;DR: Improved multiterminal escape routing algorithm for the design of printed circuit boards (PCBs) that control digital microfluidic biochips (DMFBs) can reduce both the number of PCB layers and average wirelength compared to existing DMFB escape routers.
Abstract: This paper introduces a multiterminal escape routing algorithm for the design of printed circuit boards (PCBs) that control digital microfluidic biochips (DMFBs). The new algorithm extends a negotiated congestion-based single-terminal escape router that has been shown to be superior to previous methods. It relaxes the pin assignment to allow pin groups to be broken up when doing so can reduce the number of PCB layers. Experimental results indicate that the improved method can reduce both the number of PCB layers and average wirelength compared to existing DMFB escape routers.

18 citations

References
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Journal ArticleDOI
Richard B. Fair1
TL;DR: To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach.
Abstract: The suitability of electrowetting-on-dielectric (EWD) microfluidics for true lab-on-a-chip applications is discussed. The wide diversity in biomedical applications can be parsed into manageable components and assembled into architecture that requires the advantages of being programmable, reconfigurable, and reusable. This capability opens the possibility of handling all of the protocols that a given laboratory application or a class of applications would require. And, it provides a path toward realizing the true lab-on-a-chip. However, this capability can only be realized with a complete set of elemental fluidic components that support all of the required fluidic operations. Architectural choices are described along with the realization of various biomedical fluidic functions implemented in on-chip electrowetting operations. The current status of this EWD toolkit is discussed. However, the question remains: which applications can be performed on a digital microfluidic platform? And, are there other advantages offered by electrowetting technology, such as the programming of different fluidic functions on a common platform (reconfigurability)? To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach. Diverse applications in biotechnology, for example, will serve as the basis for the requirements for electrowetting devices. These applications drive a set of biomedical fluidic functions required to perform an application, such as cell lysing, molecular separation, or analysis. In turn, each fluidic function encompasses a set of elemental operations, such as transport, mixing, or dispensing. These elemental operations are performed on an elemental set of components, such as electrode arrays, separation columns, or reservoirs. Examples of the incorporation of these principles in complex biomedical applications are described.

1,094 citations

Journal ArticleDOI
TL;DR: The performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples and the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads are demonstrated.
Abstract: Point of care testing is playing an increasingly important role in improving the clinical outcome in health care management. The salient features of a point of care device are rapid results, integrated sample preparation and processing, small sample volumes, portability, multifunctionality and low cost. In this paper, we demonstrate some of these salient features utilizing an electrowetting-based Digital Microfluidic platform. We demonstrate the performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples. Using the same microfluidic cartridge, a 40-cycle real-time polymerase chain reaction was performed within 12 minutes by shuttling a droplet between two thermal zones. We further demonstrate, on the same cartridge, the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads. In addition to rapid results and integrated sample preparation, electrowetting-based digital microfluidic instruments are highly portable because fluid pumping is performed electronically. All the digital microfluidic chips presented here were fabricated on printed circuit boards utilizing mass production techniques that keep the cost of the chip low. Due to the modularity and scalability afforded by digital microfluidics, multifunctional testing capability, such as combinations within and between immunoassays, DNA amplification, and enzymatic assays, can be brought to the point of care at a relatively low cost because a single chip can be configured in software for different assays required along the path of care.

559 citations

Journal ArticleDOI
TL;DR: In this paper, a review of the electrowetting-on-dielectric (EWOD) actuation mechanism is presented, which summarizes the observations, insights, and modeling techniques that have led to the current picture showing how forces act on liquid droplets and how droplets respond in EWOD microfluidic devices.
Abstract: This paper reviews publications that have fortified our understanding of the electrowetting-on-dielectric (EWOD) actuation mechanism. Over the last decade, growing interest in EWOD has led to a wide range of scientific and technological investigations motivated by its applicability in microfluidics, especially for droplet-based optical and lab-on-a-chip systems. At this point in time, we believe that it is helpful to summarize the observations, insights, and modeling techniques that have led to the current picture showing how forces act on liquid droplets and how droplets respond in EWOD microfluidic devices. We discuss the basic physics of EWOD and explain the mechanical response of a droplet using free-body diagrams. It is our hope that this review will inspire new research approaches and help design useful devices.

366 citations

Journal ArticleDOI
TL;DR: A low voltage, two-level-metal, and multi-layer insulator electrowetting-on-dielectric (EWD) platform, which enables the fabrication of smaller and denser electrodes with high interconnect routing flexibility and achieves low dispensing and actuation voltages for scaled devices with 30pl droplets.
Abstract: A low voltage, two-level-metal, and multi-layer insulator electrowetting-on-dielectric (EWD) platform is presented. Dispensing 300pl droplets from 140nl closed on-chip reservoirs was accomplished with as little as 11.4V solely through EWD forces, and the actuation threshold voltage was 7.2V with a 1Hz voltage switching rate between electrodes. EWD devices were fabricated with a multilayer insulator consisting of 135nm sputtered tantalum pentoxide (Ta(2)O(5)) and 180nm parylene C coated with 70nm of CYTOP. Furthermore, the minimum actuation threshold voltage followed a previously published scaling model for the threshold voltage, V(T), which is proportional to (t/e(r))(1/2), where t and e(r) are the insulator thickness and dielectric constant respectively. Device threshold voltages are compared for several insulator thicknesses (200nm, 500nm, and 1µm), different dielectric materials (parylene C and tantalum pentoxide), and homogeneous versus heterogeneous compositions. Additionally, we used a two-level-metal fabrication process, which enables the fabrication of smaller and denser electrodes with high interconnect routing flexibility. We also have achieved low dispensing and actuation voltages for scaled devices with 30pl droplets.

162 citations

Journal ArticleDOI
JinHo Song, R.D. Evans1, Yan-You Lin1, Bang-Ning Hsu1, Richard B. Fair1 
TL;DR: In this article, a hydrodynamic scaling model of droplet actuation in an electrowetting-on-dielectric (EWD) actuator is presented that takes into account the effects of contact angle hysteresis, drag from the filler fluid, and change in the actuation force while a droplet traverses a neighboring electrode.
Abstract: A hydrodynamic scaling model of droplet actuation in an electrowetting-on-dielectric (EWD) actuator is presented that takes into account the effects of contact angle hysteresis, drag from the filler fluid, drag from the solid walls, and change in the actuation force while a droplet traverses a neighboring electrode. Based on this model, the threshold voltage, VT, for droplet actuation is estimated as a function of the filler medium of a scaled device. It is shown that scaling models of droplet splitting and liquid dispensing all show a similar scaling dependence on [t/er(d/L)]1/2, where t is insulator thickness and d/L is the aspect ratio of the device. It is also determined that reliable operation of a EWD actuator is possible as long as the device is operated within the limits of the Lippmann–Young equation. The upper limit on applied voltage, Vsat, corresponds to contact-angle saturation. The minimum 3-electrode splitting voltages as a function of aspect ratio d/L < 1 for an oil medium are less than Vsat. However, for an air medium the minimum voltage for 3-electrode droplet splitting exceeds Vsat for d/L ≥ 0.4. EWD actuators were fabricated to operate with droplets down to 35pl. Reasonable scaling results were achieved.

157 citations