The Experts below are selected from a list of 2295 Experts worldwide ranked by ideXlab platform
Aaron R. Wheeler - One of the best experts on this subject based on the ideXlab platform.
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“Plug-n-Play” Sensing with Digital Microfluidics
2019Co-Authors: Richard P. S. De Campos, Darius G. Rackus, Roger Shih, Chen Zhao, Xinyu Liu, Aaron R. WheelerAbstract:Digital Microfluidics (DMF) is a platform that enables highly reconfigurable and automated fluidic operations using a generic device architecture. A unique hallmark of DMF is its “flexibility”: a generic device design can be used and reused for many different, divergent fluidic operations. The flexibility of DMF is compromised when devices are permanently modified with embedded sensors. Here we introduce a solution to the “flexibility gap” between fluidic operations in Digital Microfluidics and embedded sensors: “plug-n-play DMF” (PnP-DMF). In PnP-DMF, devices are designed to allow for rapid and seamless exchange of sensors depending on the application needs. This paper provides “proof of concept” for PnP-DMF using commercial biosensors for glucose and β-ketone, a custom paper-based electrochemical sensor for lactate, and a generic screen-printed electroanalytical cell. We demonstrate that hot-swapping sensors between experiments allows for convenient implementation of complex processes such as automated analysis of blood samples by standard addition. Finally, we explored the suitability for using PnP sensors in tandem with other sensing modalities, combining biosensor-based electrochemical measurement of glucose with a chemiluminescent magnetic bead-based sandwich immunoassay for insulin. The latter is notable, as it constitutes the first report of an analysis of different analytes in both the supernatant and precipitate from a single sample-aliquot in a microfluidic device. The results presented here highlight the versatility of PnP-DMF, illustrating how it may be useful for a wide range of applications in diagnostics and beyond
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pre concentration by liquid intake by paper p clip a new technique for large volumes and Digital Microfluidics
Lab on a Chip, 2017Co-Authors: Darius G. Rackus, Richard P S De Campos, Calvin Chan, Maria M Karcz, Brendon Seale, Tanya Narahari, Christopher Dixon, Dean M Chamberlain, Aaron R. WheelerAbstract:Microfluidic platforms are an attractive option for incorporating complex fluid handling into low-cost and rapid diagnostic tests. A persistent challenge for Microfluidics, however, is the mismatch in the “world-to-chip” interface – it is challenging to detect analytes present at low concentrations in systems that can only handle small volumes of sample. Here we describe a new technique termed pre-concentration by liquid intake by paper (P-CLIP) that addresses this mismatch, allowing Digital Microfluidics to interface with volumes on the order of hundreds of microliters. In P-CLIP, a virtual microchannel is generated to pass a large volume through the device; analytes captured on magnetic particles can be isolated and then resuspended into smaller volumes for further processing and analysis. We characterize this method and demonstrate its utility with an immunoassay for Plasmodium falciparum lactate dehydrogenase, a malaria biomarker, and propose that the P-CLIP strategy may be useful for a wide range of applications that are currently limited by low-abundance analytes.
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dropbot an open source Digital microfluidic control system with precise control of electrostatic driving force and instantaneous drop velocity measurement
Applied Physics Letters, 2013Co-Authors: Ryan Fobel, Christian Fobel, Aaron R. WheelerAbstract:We introduce DropBot: an open-source instrument for Digital Microfluidics (http://Microfluidics.utoronto.ca/dropbot). DropBot features two key functionalities for Digital Microfluidics: (1) real-time monitoring of instantaneous drop velocity (which we propose is a proxy for resistive forces), and (2) application of constant electrostatic driving forces through compensation for amplifier-loading and device capacitance. We anticipate that this system will enhance insight into failure modes and lead to new strategies for improved device reliability, and will be useful for the growing number of users who are adopting Digital Microfluidics for automated, miniaturized laboratory operation.
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dried blood spot analysis by Digital Microfluidics coupled to nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2012Co-Authors: Steve C C Shih, Hao Yang, Mais J Jebrail, Ryan Fobel, Nathan Mcintosh, Osama Y Aldirbashi, Pranesh Chakraborty, Aaron R. WheelerAbstract:Dried blood spot (DBS) samples on filter paper are surging in popularity as a sampling and storage vehicle for a wide range of clinical and pharmaceutical applications. For example, a DBS sample is collected from every baby born in the province of Ontario, Canada, for quantification of approximately one hundred analytes that are used to screen for 28 conditions, including succinylacetone (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional methods used to evaluate DBS samples for newborn screening and other applications are tedious and slow, with limited options for automated analysis. In response to this challenge, we have developed a method to couple Digital Microfluidics (DMF) to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification in DBS samples. The new system is formed by sandwiching a pulled glass capillary emitter between the two DMF substrates such that the capillary emitter is immobilized without external seals or gaskets. Moreover, we introduce a new feedback control system that enables high-fidelity droplet manipulation across DBS samples without manual intervention. The system was validated by application to on-chip extraction, derivatization, and analysis of SA and other analytes from DBS samples, with comparable performance to gold-standard methods. We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications.
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a new angle on pluronic additives advancing droplets and understanding in Digital Microfluidics
Langmuir, 2011Co-Authors: Sam H. Au, Paresh Kumar, Aaron R. WheelerAbstract:Biofouling in microfluidic devices limits the type of samples which can be handled and the duration for which samples can be manipulated. Despite the cost of disposing fouled devices, relatively few strategies have been developed to tackle this problem. Here, we have analyzed a series of eight amphiphilic droplet additives, Pluronic coblock polymers of poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO), as a solution to biofouling in Digital Microfluidics using serum-containing cell culture media as a model fluid. Our analysis shows that species with longer PPO chains are superior for enabling droplet motion and reducing biofouling. Two of the tested species, L92 and P105, were found to lengthen device lifetimes by 2–3 times relative to additives used previously when used at optimal concentrations. Pluronics with low PEO content such as L92 were found to be cytotoxic to an immortalized mammalian cell line, and therefore we recommend that Pluronic additives with greater or equal to 50% PEO composit...
Krishnendu Chakrabarty - One of the best experts on this subject based on the ideXlab platform.
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Digital Microfluidics: Connecting Biochemistry to Electronic System Design
2020Co-Authors: Krishnendu ChakrabartyAbstract:ABSTRACT Microfluidics-based biochips are revolutionizing highthroughput sequencing, parallel immunoassays, blood chemistry for clinical diagnostics, DNA sequencing, and environmental sensing. The complexity of microfluidic devices, also referred to as lab-on-a-chip, is expected to become significant in the near future due to the need for multiple and concurrent biochemical assays on multifunctional and reconfigurable platforms. This paper provides an overview of droplet-based "Digital" microfluidic biochips. It presents early work on top-down system-level computer-aided design (CAD) tools for the synthesis, testing and reconfiguration of microfluidic biochips. These CAD techniques allow the biochip to concentrate on the development of the nano-and microscale bioassays, leaving assay optimization and implementation details to design automation tools
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Biochip Synthesis and Dynamic Error Recovery for Sample Preparation Using Digital Microfluidics
IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 2014Co-Authors: Yi-ling Hsieh, Tsung-yi Ho, Krishnendu ChakrabartyAbstract:Recent advances in Digital microfluidic biochips have led to a promising future for miniaturized laboratories, with the associated advantages of high sensitivity and reconfigurability. Since sample preparation plays an important front-end role in assays and laboratories in biochemical applications, and most of the analysis time is associated with sample collection, transportation, and preparation, it is important to minimize the time required for this key step in bioassays. Moreover, it is also critical to ensure the correctness of intermediate steps and recover from errors efficiently during sample preparation. We describe an optimization algorithm and the associated chip design method for sample preparation, including architectural synthesis and layout synthesis. We also present the first dynamic error recovery procedure for use during sample preparation. The proposed algorithm is evaluated on both real-life biochemical applications and synthetic test cases to demonstrate its effectiveness and efficiency. Compared to prior work, the proposed algorithm can achieve up to 50% reduction in sample preparation time, and the optimized chip layout can achieve over 40% reduction in sample preparation time.
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design of cyberphysical Digital microfluidic biochips under completion time uncertainties in fluidic operations
Design Automation Conference, 2013Co-Authors: Yan Luo, Krishnendu ChakrabartyAbstract:Cyberphysical Digital Microfluidics enables the integration of fluid-handling operations, reaction-outcome detection, and software-based control in a biochip. However, synthesis algorithms and biochip design methods proposed in the literature are oblivious to completion-time uncertainties in fluidic operations, and they do not meet the requirements of cyberphysical integration in Digital Microfluidics. We present an operation-interdependency-aware synthesis method that uses frequency scaling and is responsive to uncertainties that are inherent in the completion times of fluidic operations such as mixing and thermal cycling. Using this design approach, we can carry out dynamic on-line decision making for the execution of fluidic operations in response to detector feedback. We use three common laboratorial protocols to demonstrate that, compared to uncertainty-oblivious biochip design, the proposed dynamic decision making approach is more effective in satisfying realistic physical constraints. As a result, it decreases the likelihood of erroneous reaction outcomes, and it leads to reduced time-to-results, less repetition of reaction steps, and less wastage of precious samples and reagents.
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fault detection real time error recovery and experimental demonstration for Digital microfluidic biochips
Design Automation and Test in Europe, 2013Co-Authors: Bangning Hsu, Andrew C. Madison, Krishnendu Chakrabarty, Richard B FairAbstract:Advances in Digital Microfluidics and integrated sensing hold promise for a new generation of droplet-based biochips that can perform multiplexed assays to determine the identity of target molecules. Despite these benefits, defects and erroneous fluidic operations remain a major barrier to the adoption and deployment of these devices. We describe the first integrated demonstration of cyberphysical coupling in Digital Microfluidics, whereby errors in droplet transportation on the Digital microfluidic platform are detected using capacitive sensors, the test outcome is interpreted by control hardware, and software-based error recovery is accomplished using dynamic reconfiguration. The hardware/software interface is realized through seamless interaction between control software, an off-the-shelf microcontroller and a frequency divider implemented on an FPGA. Experimental results are reported for a fabricated silicon device and links to videos are provided for the first-ever experimental demonstration of cyberphysical coupling and dynamic error recovery in Digital microfluidic biochips.
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adaptive cooling of integrated circuits using Digital Microfluidics
2007Co-Authors: P Y Paik, Vamsee K Pamula, Krishnendu ChakrabartyAbstract:Thermal management is critical for integrated circuit (IC) design. With each new IC technology generation, feature sizes decrease, while operating speeds and package densities increase. These factors contribute to elevated die temperatures detrimental to circuit performance and reliability. Furthermore, hot spots due to spatially nonuniform heat flux in ICs can cause physical stress that further reduces reliability. While a number of chip cooling techniques have been proposed in the literature, most are still unable to address the varying thermal profiles of an IC and their capability to remove a large amount of heat is undermined by their lack of reconfigurability of flows. We present an alternative cooling technique based on a recently invented ";Digital microfluidic"; platform. This novel Digital fluid handling platform uses a phenomenon known as electrowetting, and allows for a vast array of discrete droplets of liquid, ranging from microliters to nanoliters, and potentially picoliters, to be independently moved along a substrate. While this technology was originally developed for a biological and chemical lab-on-a-chip, we show how it can be adapted to be used as a fully reconfigurable, adaptive cooling platform.
Richard B Fair - One of the best experts on this subject based on the ideXlab platform.
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Piezo-driven acoustic streaming in an electrowetting-on-dielectric Digital Microfluidics device
Microfluidics and Nanofluidics, 2017Co-Authors: Andrew C. Madison, Mathew W. Royal, Richard B FairAbstract:We report the integration of a lead zirconate titanate, $$\hbox {Pb[Zr}_{x}\hbox {Ti}_{1-x}\hbox {O}_{3}$$ Pb[Zr x Ti 1 - x O 3 ] (PZT), piezoelectric transducer disk into the top plate of an otherwise conventional electrowetting-on-dielectric (EWD) Digital Microfluidics device to demonstrate on-demand induction of circulating fluid flow within single 200 nL droplets. Microparticle image velocimetry was used to measure in-plane velocity distributions for PZT excitation voltages that ranged from 0 to 50 $$\hbox {V}_{\text {RMS}}$$ V RMS . Intra-droplet streaming velocities in excess of 2.0 $$\hbox {mm}\cdot \hbox {s}^{-1}$$ mm · s - 1 were observed without droplet breakup or damage to the EWD device layer. Additionally, we found median intra-droplet streaming velocity to depend quadratically on PZT excitation voltage up to the stress limit of the interfacial boundary. Our approach offers an alternative device architecture for active micromixing strategies in EWD Digital Microfluidics laboratory-on-chip systems.
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fault detection real time error recovery and experimental demonstration for Digital microfluidic biochips
Design Automation and Test in Europe, 2013Co-Authors: Bangning Hsu, Andrew C. Madison, Krishnendu Chakrabarty, Richard B FairAbstract:Advances in Digital Microfluidics and integrated sensing hold promise for a new generation of droplet-based biochips that can perform multiplexed assays to determine the identity of target molecules. Despite these benefits, defects and erroneous fluidic operations remain a major barrier to the adoption and deployment of these devices. We describe the first integrated demonstration of cyberphysical coupling in Digital Microfluidics, whereby errors in droplet transportation on the Digital microfluidic platform are detected using capacitive sensors, the test outcome is interpreted by control hardware, and software-based error recovery is accomplished using dynamic reconfiguration. The hardware/software interface is realized through seamless interaction between control software, an off-the-shelf microcontroller and a frequency divider implemented on an FPGA. Experimental results are reported for a fabricated silicon device and links to videos are provided for the first-ever experimental demonstration of cyberphysical coupling and dynamic error recovery in Digital microfluidic biochips.
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chemical and biological applications of Digital microfluidic devices
IEEE Design & Test of Computers, 2007Co-Authors: Richard B Fair, Vamsee K Pamula, Andrey Khlystov, Tina D Tailor, V Ivanov, R Evans, P B Griffin, Vijay Srinivasan, Michael G Pollack, Jack ZhouAbstract:Digital-microfluidic lab-on-a chip (LoC) technology offers a platform for developing diagnostic applications with the advantages of portability, sample and reagent volume reduction, faster analysis, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. In addition to diagnostics, Digital Microfluidics is finding use in airborne chemical detection, DNA sequencing by synthesis, and tissue engineering. In this article, we review efforts to develop various LoC applications using electrowetting-based Digital Microfluidics. We describe these applications, their implementation, and associated design issues.
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Microfluidics-Based Biochips: Technology Issues, Implementation Platforms, and Design-Automation Challenges
IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, 2006Co-Authors: F. Su, K. Chakrabarty, Richard B FairAbstract:Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, deoxyribonucleic acid (DNA) sequencing, and other laboratory procedures involving molecular biology. In contrast to continuous-flow systems that rely on permanently etched microchannels, micropumps, and microvalves, Digital Microfluidics offers a scalable system architecture and dynamic reconfigurability; groups of unit cells in a Microfluidics array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This paper presents an overview of an integrated system-level design methodology that attempts to address key issues in the synthesis, testing and reconfiguration of Digital Microfluidics-based biochips. Different actuation mechanisms for Microfluidics-based biochips, and associated design-automation trends and challenges are also discussed. The proposed top-down design-automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures, and it will facilitate the integration of fluidic components with a microelectronic component in next-generation systems-on-chips (SOCs).
Steve C C Shih - One of the best experts on this subject based on the ideXlab platform.
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an integrated droplet Digital microfluidic system for on demand droplet creation mixing incubation and sorting
Lab on a Chip, 2019Co-Authors: Fatemeh Ahmadi, Kenza Samlali, Steve C C ShihAbstract:Droplet Microfluidics is a technique that has the ability to compartmentalize reactions in sub nano- (or pico-) liter volumes that can potentially enable millions of distinct biological assays to be performed on individual cells. In a typical droplet microfluidic system, droplets are manipulated by pressure-based flows. This has limited the fluidic operations that can be performed in these devices. Digital Microfluidics is an alternative microfluidic paradigm with precise control and manipulation over individual droplets. Here, we implement an integrated droplet-Digital microfluidic (which we call 'ID2M') system in which common fluidic operations (i.e. droplet generation, cell encapsulation, droplet merging and mixing, droplet trapping and incubation, and droplet sorting) can be performed. With the addition of electrodes, we have been able to create droplets on-demand, tune their volumes on-demand, and merge and mix several droplets to produce a dilution series. Moreover, this device can trap and incubate droplets for 24 h that can consequently be sorted and analyzed in multiple n-ary channels (as opposed to typical binary channels). The ID2M platform has been validated as a robust on-demand screening system by sorting fluorescein droplets of different concentration with an efficiency of ∼96%. The utility of the new system is further demonstrated by culturing and sorting tolerant yeast mutants and wild-type yeast cells in ionic liquid based on their growth profiles. This new platform for both droplet and Digital Microfluidics has the potential to be used for screening different conditions on-chip and for applications like directed evolution.
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dried blood spot analysis by Digital Microfluidics coupled to nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2012Co-Authors: Steve C C Shih, Hao Yang, Mais J Jebrail, Ryan Fobel, Nathan Mcintosh, Osama Y Aldirbashi, Pranesh Chakraborty, Aaron R. WheelerAbstract:Dried blood spot (DBS) samples on filter paper are surging in popularity as a sampling and storage vehicle for a wide range of clinical and pharmaceutical applications. For example, a DBS sample is collected from every baby born in the province of Ontario, Canada, for quantification of approximately one hundred analytes that are used to screen for 28 conditions, including succinylacetone (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional methods used to evaluate DBS samples for newborn screening and other applications are tedious and slow, with limited options for automated analysis. In response to this challenge, we have developed a method to couple Digital Microfluidics (DMF) to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification in DBS samples. The new system is formed by sandwiching a pulled glass capillary emitter between the two DMF substrates such that the capillary emitter is immobilized without external seals or gaskets. Moreover, we introduce a new feedback control system that enables high-fidelity droplet manipulation across DBS samples without manual intervention. The system was validated by application to on-chip extraction, derivatization, and analysis of SA and other analytes from DBS samples, with comparable performance to gold-standard methods. We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications.
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A feedback control system for high-fidelity Digital Microfluidics
Lab on a chip, 2010Co-Authors: Steve C C Shih, Paresh Kumar, Ryan Fobel, Aaron R. WheelerAbstract:Digital Microfluidics (DMF) is a technique in which discrete droplets are manipulated by applying electrical fields to an array of electrodes. In an ideal DMF system, each application of driving potential would cause a targeted droplet to move onto an energized electrode (i.e., perfect fidelity between driving voltage and actuation); however, in real systems, droplets are sometimes observed to resist movement onto particular electrodes. Here, we implement a sensing and feedback control system in which all droplet movements are monitored, such that when a movement failure is observed, additional driving voltages can be applied until the droplet completes the desired operation. The new system was evaluated for a series of liquids including water, methanol, and cell culture medium containing fetal bovine serum, and feedback control was observed to result in dramatic improvements in droplet actuation fidelity and velocity. The utility of the new system was validated by implementing an enzyme kinetics assay with continuous mixing. The new platform for Digital Microfluidics is simple and inexpensive and thus should be useful for scientists and engineers who are developing automated analysis platforms.
Sung Kwon Cho - One of the best experts on this subject based on the ideXlab platform.
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antifouling Digital Microfluidics using lubricant infused porous film
Lab on a Chip, 2019Co-Authors: Hongyao Geng, Sung Kwon ChoAbstract:Electrowetting-driven Digital (droplet-based) Microfluidics has a tremendous impact on lab-on-a-chip applications. However, the biofouling problem impedes the real applications of such Digital Microfluidics. Here we report antifouling Digital Microfluidics by introducing lubricant infused porous film to electrowetting (more exactly, electrowetting on dielectric or EWOD). Such film minimizes direct contact between droplets and the solid surface but provides liquid–liquid contact between droplets and the lubricant liquid, which thus prevents unspecific adsorption of biomolecules to the solid surface. We demonstrate the compatibility of the lubricant infused film with EWOD to transport bio droplets. This configuration shows robust and high performance even for long cyclic operations without fouling in a wide range of concentrations of protein solutions. In addition, a variety of conductive droplets, including deionized (DI) water, saline, protein solution, DNA solution, sheep blood, milk, ionic liquid and honey, are examined, similarly showing high performance in cyclic transportations. In addition, using the same electrode patterns used in EWOD, transportations of dielectric (non-conductive) droplets including light crude oil, propylene carbonate and alcohol are also achieved. Such capability of droplet handling without fouling will certainly benefit the practical applications of Digital Microfluidics in droplet handling, sampling, reaction, diagnosis in clinic medicine, biotechnology and chemistry fields.
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Anti-biofouling droplet manipulation by slippery liquid infused porous surface (SLIPS) integrated with electrowetting and liquid-dielectrophoresis
2018 IEEE Micro Electro Mechanical Systems (MEMS), 2018Co-Authors: Hongyao Geng, Sung Kwon ChoAbstract:This paper presents a simple, versatile, and anti-biofouling droplet manipulation on a single substrate using a slippery liquid infused porous surface (SLIPS) integrated with a coplanar electrode array. This platform was confirmed effective for both electrowetting-on-dielectric (EWOD) driving conductive liquids (e.g., water and bovine serum albumin (BSA) protein solution), and liquid-dielectrophoretic (L-DEP) driving dielectric liquids (e.g., propylene carbonate and isopropyl alcohol or IPA) in the open environment. The SLIPS enormously reduces the biological adhesion because of the highly deformable nature of liquid. Biomolecules (e.g., proteins) can move easily on the SLIPS. This property can overcome the burdensome biofouling problem in Digital Microfluidics, as well as other bio-related devices.
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dielectrowetting manipulation for Digital Microfluidics creating transporting splitting and merging of droplets
Lab on a Chip, 2017Co-Authors: Hongyao Geng, Jian Feng, Lisa M Stabryla, Sung Kwon ChoAbstract:Generating, splitting, transporting, and merging droplets are fundamental and critical unit operations for Digital (droplet-based) Microfluidics. State-of-the-art Digital Microfluidics performs such operations commonly using electrowetting-on-dielectric (EWOD) in the typical configuration of two parallel channel plates. This paper presents such operations using dielectrowetting (derived from liquid dielectrophoresis), not EWOD, with an array of interdigitated electrodes. The major and unique feature is that the present droplet manipulations are effective for conductive (water with/without surfactant) and non-conductive (propylene carbonate) fluids. An equally important aspect is that the manipulations are performed in an open space without the covering top plate. This behavior is attributed to the intrinsic nature of dielectrowetting to generate stronger wetting forces than EWOD (with the ability to achieve complete wetting with contact angle = 0° to form a thin film). Using dielectrowetting, micro-droplets of various volumes are created from a large droplet and transported. Splitting a single droplet as well as multiple droplets and merging them are also achieved, even when the droplets are smaller than the electrode pads. The above splitting, transport, and merging operations are effective for propylene carbonate as well as DI water with/without surfactant, though the creating operation is proven only for propylene carbonate at this moment. All the above manipulations are successfully carried out on a single plate, which not only simplifies the structure and operation procedure, but could also eliminate the restriction to the volume of fluid handled.