Yong-ak Song - Academia.edu (original) (raw)
Papers by Yong-ak Song
2020 IEEE International Symposium on Circuits and Systems (ISCAS), 2020
Microfluidic biochips enable low-cost automation of biochemical protocols with numerous applicati... more Microfluidic biochips enable low-cost automation of biochemical protocols with numerous applications to medical diagnostics, forensics, molecular biology, and drug design. An important component of protocol design is sample preparation, which involves dilution or mixing of two or more fluids in a desired ratio of concentration factors (CF). Existing continuous-flow microfluidic biochips deploy either free-flowing networks where only a single layer of flow-channels is used devoid of any control valves, or valve-based technology where the flow-layer is augmented with a control layer of valves. While the former is easy to fabricate, reliable, and less expensive, they are typically hardwired for specific applications only. The latter class, although programmable, is expensive and prone to various manufacturing and operational defects. In this paper, we present the physical design of a microfluidic network that is free-flowing as well as programmable. The proposed valve-free network rese...
2019 32nd International Conference on VLSI Design and 2019 18th International Conference on Embedded Systems (VLSID), 2019
The fully-programmable-valve-array (FPVA) is a general-purpose programmable flow-based microfluid... more The fully-programmable-valve-array (FPVA) is a general-purpose programmable flow-based microfluidic platform, akin to the VLSI field-programmable gate array (FPGA). FPVAs are dynamically reconfigurable and hence are suitable in a broad spectrum of applications involving immunoassays and cell analysis. Since these applications are safety-critical, addressing security concerns is vital for the success and adoption of FPVAs. This study evaluates the security of FPVA biochips. We show that FPVAs are vulnerable to malicious operations similar to digital and flow-based microfluidic biochips. FPVAs are further prone to new classes of attacks - tunneling and deliberate aging. The study establishes security metrics and describes possible attacks on real-life bioassays.
2020 Design, Automation & Test in Europe Conference & Exhibition (DATE), 2020
Microfluidic technologies find application in various safety-critical fields such as medical diag... more Microfluidic technologies find application in various safety-critical fields such as medical diagnostics, drug research, and cell analysis. Recent work has focused on security threats to microfluidic-based cyberphysical systems and defenses. So far the threat analysis has been limited to the cases of tampering with control software/hardware, which is common to most cyberphysical control systems in general; in a sense, such an approach is not exclusive to microfluidics. In this paper, we present a stealthy attack paradigm that uses characteristics exclusive to the microfluidic devices - a microfluidic trojan. The proposed trojan payload is a valve whose height has been perturbed to vary its pressure response. This trojan can be triggered in multiple ways based on time or specific operations. These triggers can occur naturally in a bioassay or added into the controlling software. We showcase the trojan application in carrying out practical attacks -contamination, parameter-tampering and denial-of-service - on a real-life bioassay implementation. Further, we present guidelines to launch stealthy attacks and to counter them.
IEEE Nanotechnology Magazine, 2020
received the Ph.D. degree in engineering science from the Thayer School of Engineering at Dartmou... more received the Ph.D. degree in engineering science from the Thayer School of Engineering at Dartmouth College in 2015 under the guidance of Dr. B. Pogue exploring the biomedical applications of Cherenkov radiation. After graduation, he joined Dr. J. Liu's research group at the University of Washington as a postdoctoral research associate to work on the development of a miniature dual-axis confocal microscope and investigate the feasibility of performing light-sheet microscopy in biological tissue. His research interests include Monte Carlo methods for modeling radiation and light transport, biomedical optics, molecular imaging, and medical physics.
IEEE Transactions on Very Large Scale Integration (VLSI) Systems, 2019
The fully programmable valve array (FPVA) is a general-purpose programmable flow-based microfluid... more The fully programmable valve array (FPVA) is a general-purpose programmable flow-based microfluidic platform, akin to the VLSI field-programmable gate array (FPGA). FPVAs are dynamically reconfigurable and, hence, are suitable in a broad spectrum of applications involving immunoassays and cell analysis. Since these applications are safety critical, addressing security concerns is vital for the success and adoption of FPVAs. This study evaluates the security of FPVA biochips. We show that FPVAs are vulnerable to malicious operations similar to digital and flow-based microfluidic biochips. FPVAs are further prone to new classes of attacks-tunneling and deliberate aging. This study establishes security metrics and describes possible attacks on real-life bioassays. Furthermore, we study the use of machine learning (ML) techniques to detect and classify attacks based on the golden and real-time biochip state. In order to boost the classifier's performance, we propose a smart checkpointing mechanism. Experimental results are presented to showcase: 1) best-fit ML model classifier; 2) performance of different tradeoffs in checkpointing; and 3) effectiveness of the proposed smart checkpointing scheme. Drugs Acoustic devices Digital audio players Industrial electronics Web TV Masticatory muscles Tornadoes FDDI Source coding Wearable computers Crystals Multiprotocol label switching. Grammar Approximation error Software defined networking Electric vehicle charging Railguns CADCAM Roads Critical infrastructure. Anesthetic drugs Matlab Extended reality Electrostatic devices Six sigma Heat pumps Computer performance Grasping Linear accelerators. Social intelligence Excitons Hippocampus Web and internet services Grippers Titanium Zirconium Data science Integrated circuit testing. Ear Multifrequency antennas Phase measurement Neuromorphic engineering Thick film circuits Aluminum oxide Underwater cables Thyratrons Cause effect analysis Passive RFID tags Color TV Visual databases Metal cutting tools Multiplexing. Equivalent circuits Virtual artifact Cardiac tissue Signal design Permission Dinosaurs Demand-side management Optical fiber couplers. Structural discs Scandium Uncertainty Autonomous underwater vehicles Extraterrestrial phenomena Radiation dosage Digital computers Solar powered vehicles EMTDC Radium Electric vehicles Turbines. Cataracts Transmission electron microscopy Ubiquitous computing Concrete Garnet films Flame retardants Open area test sites Extreme ultraviolet lithography Optical fiber LAN Hydrogen fluoride Garnet films Scheduling. Ground support Extraordinary magnetoresistance Solar energy Vaccines Molecular communication Business process management. Camshafts Obituaries Network operating systems Thick film circuits Message service Muscles Cooling. Food packaging Structural discs Surveillance Kerr effect Ignition Classification tree analysis. Client-server systems Dentistry Gyroscopes Power filters Text mining Quantum well lasers Optical fiber cables Pulse modulation Gaussian mixture model Unsupervised learning. Semiconductor superlattices Matching pursuit algorithms Rectennas Ion emission Winches Distributed information systems Metallurgy Cognitive neuroscience Bistable circuits Subtraction techniques Thyratrons Prefabricated construction Out of order.
Micromachines, 2018
Exosomes have gained immense importance since their proteomic and genetic contents could potentia... more Exosomes have gained immense importance since their proteomic and genetic contents could potentially be used for disease diagnostics, monitoring of cancer progression, metastasis, and drug efficacy. However, establishing the clinical utility of exosomes has been restricted due to small sizes and high sample loss from extensive sample preparation. Sample loss is particularly critical for body fluids limited in volume and difficult to access, e.g., cerebrospinal fluid. We present a microfluidic technique that locally enhances the concentration of extracellular vesicles extracted from MDA-MB-231 human breast cancer cell lines by using an ion concentration polarization (ICP)-based electrokinetic concentrator. Our design incorporates a trapping mechanism near the conductive polymer membrane; therefore, we can preconcentrate and capture extracellular vesicles simultaneously. Compared with standard fluorescence detection, our method increased the limit of detection (LOD) of extracellular vesicles by two orders of magnitude in 30 min. Our concentrator increased the extracellular vesicle concentration for 5.0 × 10 7 particles/1 mL (LOD), 5.0 × 10 8 particles/1 mL, and 5.0 × 10 9 particles/1 mL by~100-fold each within 30 min using 45 V. This study demonstrates an alternative platform to simultaneously preconcentrate and capture extracellular vesicles that can be incorporated as part of a liquid biopsy-on-a-chip system for the detection of exosomal biomarkers and analysis of their contents for early cancer diagnosis.
Scientific reports, Jan 17, 2018
We report an integrated system for accelerating assays with concentrators in a standard 12-well p... more We report an integrated system for accelerating assays with concentrators in a standard 12-well plate (ISAAC-12) and demonstrate its versatility for rapid detection of matrix metalloproteinase (MMP)-9 expression in the cell culture supernatant of breast cancer cell line MDA-MB-231 by accelerating the enzymatic reaction and end-point signal intensity via electrokinetic preconcentration. Using direct printing of a conductive ion-permselective polymer on a polydimethylsiloxane (PDMS) channel, the new microfluidic concentrator chip can be built without modifying the underlying substrate. Through this decoupling fabrication strategy, our microfluidic concentrator chip can easily be integrated with a standard multiwell plate, the de facto laboratory standard platform for high-throughput assays, simply by reversible bonding on the bottom of each well. It increases the reaction rate of enzymatic assays by concentrating the enzyme and the reaction product inside each well simultaneously for ...
Lab on a chip, Jan 13, 2018
In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs... more In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs from a mixed age nematode population, which can subsequently be cultured to a desired developmental stage. For the sorting of a mixture containing three different developmental stages, eggs, L1 and L4, we utilized a microfluidic spiral chip with a trapezoidal channel to obtain a sorting efficiency of above 97% and a sample purity (SP) of above 80% for eggs at different flow rates up to 10 mL min. The result demonstrated a cost-effective, simple, and highly efficient method for synchronizing C. elegans at a high throughput (∼4200 organisms per min at 6 mL min), while eliminating challenges such as clogging and non-reusability of membrane-based filtration. Due to its simplicity, our method can be easily adopted in the C. elegans research community.
SLAS TECHNOLOGY: Translating Life Sciences Innovation, 2016
Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabdit... more Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for hi...
Volume 1: Micro/Nanofluidics and Lab-on-a-Chip; Nanofluids; Micro/Nanoscale Interfacial Transport Phenomena; Micro/Nanoscale Boiling and Condensation Heat Transfer; Micro/Nanoscale Thermal Radiation; Micro/Nanoscale Energy Devices and Systems, 2016
Morpholinos (MOs) are synthetic nucleic acids analogues with a non-charged backbone of morpholine... more Morpholinos (MOs) are synthetic nucleic acids analogues with a non-charged backbone of morpholine rings. To enhance the MO-DNA hybridization assay speed, we propose the integration of a MO microarray with an ion concentration polarization (ICP) based microfluidic concentrator. The ICP concentrator collects target biomolecules from a ∼μL fluidic DNA sample and concentrates them electrokinetically into a ∼nL plug located in the vicinity of the MO probes. ICP preconcentration not only reduces the analyte diffusion length but also increases the binding reaction rate, and as a result, ICP-enhanced MO microarrays allow much faster hybridization than standard diffusion-limited MO microarrays.
Analytical Chemistry, 2016
Supporting information provides: a video showing the automatic PEDOT:PSS printing process on PDMS... more Supporting information provides: a video showing the automatic PEDOT:PSS printing process on PDMS channel, 3D confocal videos of the DNA plug during concentration experiments, confocal data of the vertical concentration profile of the plug in microfluidic concentrators with PEDOT:PSS at the top and bottom of the microchannel, estimation of the pH shift during ET concentration a 5-channel simultaneous DNA concentration video, and a measurement of the channel-tochannel and device-to-device variation.
Biosensors and Bioelectronics, 2015
Electrokinetic methods that conveniently concentrate charged analytes by orders of magnitude are ... more Electrokinetic methods that conveniently concentrate charged analytes by orders of magnitude are highly attractive for nucleic acid assays where they can bypass the complexity and costs of enzyme-based amplification. The present study demonstrates an electrokinetic concentration device incorporating charge-neutral morpholino (MO) probes: as DNA analyte is concentrated in a microfluidic channel using ion concentration polarization (ICP) it is simultaneously hybridized to spots of complementary MO probes immobilized on the channel floor. This approach is uniquely favored by the match between the optimum buffer ionic strength of approximately 10 mM for both MO-DNA surface hybridization and electrokinetic concentration. The simple and easily scalable poly(dimethylsiloxane) (PDMS) microfluidic device was fabricated using soft lithography and contact printing of a conductive polymer, poly(3,4ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) as a cation-selective membrane material. Using the microfluidic concentrator, we could increase the concentration of DNA by three orders of magnitude in less than 5 min at an electric field of 75 V cm À 1. The 1000-fold increase in concentration of DNA led to an increase in the speed of MO-DNA hybridization by two orders of magnitude and enabled a detection sensitivity of $ 1 nM within 15 min of concentration. Using the proposed microfluidic concentrator, we also demonstrated a rapid hybridization with a binary DNA mixture, containing a fully complementary and a non-complementary sequence to mimic molecular backgrounds present in real DNA samples.
Lab on a chip, Jan 7, 2014
In this work we describe a novel and simple self-assembly process of colloidal silica beads to cr... more In this work we describe a novel and simple self-assembly process of colloidal silica beads to create a nanofluidic junction between two microchannels. The nanoporous membrane was used to induce ion concentration polarization inside the microchannel and this electrokinetic preconcentration system allowed rapid concentration of DNA samples by ~1700 times and of protein samples by ~100 times within 5 minutes.
Lab on a Chip, 2010
Capillary-valve-based fabrication of ion-selective membrane junction for electrokinetic sample pr... more Capillary-valve-based fabrication of ion-selective membrane junction for electrokinetic sample preconcentration in PDMS chip The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Liu, Vincent, Yong-Ak Song, and Jongyoon Han. "Capillaryvalve-based Fabrication of Ion-selective Membrane Junction for Electrokinetic Sample Preconcentration in PDMS Chip." Lab on a Chip 10.11 (2010): 1485.
Lab on a Chip, 2008
In this paper, we report a new method of fabricating a high-throughput protein preconcentrator in... more In this paper, we report a new method of fabricating a high-throughput protein preconcentrator in poly(dimethylsiloxane) (PDMS) microfluidic chip format. We print a submicron thick ion-selective membrane on the glass substrate by using standard patterning techniques. By simply plasma-bonding a PDMS microfluidic device on top of the printed glass substrate, we can integrate the ion-selective membrane into the device and rapidly prototype a PDMS preconcentrator without complicated microfabrication and cumbersome integration processes. The PDMS preconcentrator shows a concentration factor as high as ~ 10 4 in 5 min. This printing method even allows fabricating a parallel array of preconcentrators to increase the concentrated sample volume, which can facilitate an integration of our microfluidic preconcentrator chip as signal enhancing tool to various detectors such as mass spectrometer.
Journal of the American Chemical Society, 2011
We introduce an integrated microfluidic device consisting of a biomolecule concentrator and a mic... more We introduce an integrated microfluidic device consisting of a biomolecule concentrator and a microdroplet generator, which enhances the limited sensitivity of low-abundance enzyme assays by concentrating biomolecules before encapsulating them into droplet microreactors. We used this platform to detect ultra low levels of matrix metalloproteinases (MMPs) from diluted cellular supernatant and showed that it significantly (∼10-fold) reduced the time required to complete the assay and the sample volume used.
Journal of Materials Processing Technology, 2006
Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have been impo... more Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have been impossible to manufacture using conventional techniques. However, the surface finish and accuracy of SFF parts remain lower than those of parts that have been machined in conventional methods such as milling. A process combination of additive and subtractive techniques is currently being developed by our
International Journal of Machine Tools and Manufacture, 2005
Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have thus far ... more Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have thus far proved difficult to manufacture using conventional machining. However, the surface finish and accuracy of SFF parts are lower than those of conventionally machined parts. A process combination of additive and subtractive techniques is currently being developed in order to overcome this problem. A novel
2020 IEEE International Symposium on Circuits and Systems (ISCAS), 2020
Microfluidic biochips enable low-cost automation of biochemical protocols with numerous applicati... more Microfluidic biochips enable low-cost automation of biochemical protocols with numerous applications to medical diagnostics, forensics, molecular biology, and drug design. An important component of protocol design is sample preparation, which involves dilution or mixing of two or more fluids in a desired ratio of concentration factors (CF). Existing continuous-flow microfluidic biochips deploy either free-flowing networks where only a single layer of flow-channels is used devoid of any control valves, or valve-based technology where the flow-layer is augmented with a control layer of valves. While the former is easy to fabricate, reliable, and less expensive, they are typically hardwired for specific applications only. The latter class, although programmable, is expensive and prone to various manufacturing and operational defects. In this paper, we present the physical design of a microfluidic network that is free-flowing as well as programmable. The proposed valve-free network rese...
2019 32nd International Conference on VLSI Design and 2019 18th International Conference on Embedded Systems (VLSID), 2019
The fully-programmable-valve-array (FPVA) is a general-purpose programmable flow-based microfluid... more The fully-programmable-valve-array (FPVA) is a general-purpose programmable flow-based microfluidic platform, akin to the VLSI field-programmable gate array (FPGA). FPVAs are dynamically reconfigurable and hence are suitable in a broad spectrum of applications involving immunoassays and cell analysis. Since these applications are safety-critical, addressing security concerns is vital for the success and adoption of FPVAs. This study evaluates the security of FPVA biochips. We show that FPVAs are vulnerable to malicious operations similar to digital and flow-based microfluidic biochips. FPVAs are further prone to new classes of attacks - tunneling and deliberate aging. The study establishes security metrics and describes possible attacks on real-life bioassays.
2020 Design, Automation & Test in Europe Conference & Exhibition (DATE), 2020
Microfluidic technologies find application in various safety-critical fields such as medical diag... more Microfluidic technologies find application in various safety-critical fields such as medical diagnostics, drug research, and cell analysis. Recent work has focused on security threats to microfluidic-based cyberphysical systems and defenses. So far the threat analysis has been limited to the cases of tampering with control software/hardware, which is common to most cyberphysical control systems in general; in a sense, such an approach is not exclusive to microfluidics. In this paper, we present a stealthy attack paradigm that uses characteristics exclusive to the microfluidic devices - a microfluidic trojan. The proposed trojan payload is a valve whose height has been perturbed to vary its pressure response. This trojan can be triggered in multiple ways based on time or specific operations. These triggers can occur naturally in a bioassay or added into the controlling software. We showcase the trojan application in carrying out practical attacks -contamination, parameter-tampering and denial-of-service - on a real-life bioassay implementation. Further, we present guidelines to launch stealthy attacks and to counter them.
IEEE Nanotechnology Magazine, 2020
received the Ph.D. degree in engineering science from the Thayer School of Engineering at Dartmou... more received the Ph.D. degree in engineering science from the Thayer School of Engineering at Dartmouth College in 2015 under the guidance of Dr. B. Pogue exploring the biomedical applications of Cherenkov radiation. After graduation, he joined Dr. J. Liu's research group at the University of Washington as a postdoctoral research associate to work on the development of a miniature dual-axis confocal microscope and investigate the feasibility of performing light-sheet microscopy in biological tissue. His research interests include Monte Carlo methods for modeling radiation and light transport, biomedical optics, molecular imaging, and medical physics.
IEEE Transactions on Very Large Scale Integration (VLSI) Systems, 2019
The fully programmable valve array (FPVA) is a general-purpose programmable flow-based microfluid... more The fully programmable valve array (FPVA) is a general-purpose programmable flow-based microfluidic platform, akin to the VLSI field-programmable gate array (FPGA). FPVAs are dynamically reconfigurable and, hence, are suitable in a broad spectrum of applications involving immunoassays and cell analysis. Since these applications are safety critical, addressing security concerns is vital for the success and adoption of FPVAs. This study evaluates the security of FPVA biochips. We show that FPVAs are vulnerable to malicious operations similar to digital and flow-based microfluidic biochips. FPVAs are further prone to new classes of attacks-tunneling and deliberate aging. This study establishes security metrics and describes possible attacks on real-life bioassays. Furthermore, we study the use of machine learning (ML) techniques to detect and classify attacks based on the golden and real-time biochip state. In order to boost the classifier's performance, we propose a smart checkpointing mechanism. Experimental results are presented to showcase: 1) best-fit ML model classifier; 2) performance of different tradeoffs in checkpointing; and 3) effectiveness of the proposed smart checkpointing scheme. Drugs Acoustic devices Digital audio players Industrial electronics Web TV Masticatory muscles Tornadoes FDDI Source coding Wearable computers Crystals Multiprotocol label switching. Grammar Approximation error Software defined networking Electric vehicle charging Railguns CADCAM Roads Critical infrastructure. Anesthetic drugs Matlab Extended reality Electrostatic devices Six sigma Heat pumps Computer performance Grasping Linear accelerators. Social intelligence Excitons Hippocampus Web and internet services Grippers Titanium Zirconium Data science Integrated circuit testing. Ear Multifrequency antennas Phase measurement Neuromorphic engineering Thick film circuits Aluminum oxide Underwater cables Thyratrons Cause effect analysis Passive RFID tags Color TV Visual databases Metal cutting tools Multiplexing. Equivalent circuits Virtual artifact Cardiac tissue Signal design Permission Dinosaurs Demand-side management Optical fiber couplers. Structural discs Scandium Uncertainty Autonomous underwater vehicles Extraterrestrial phenomena Radiation dosage Digital computers Solar powered vehicles EMTDC Radium Electric vehicles Turbines. Cataracts Transmission electron microscopy Ubiquitous computing Concrete Garnet films Flame retardants Open area test sites Extreme ultraviolet lithography Optical fiber LAN Hydrogen fluoride Garnet films Scheduling. Ground support Extraordinary magnetoresistance Solar energy Vaccines Molecular communication Business process management. Camshafts Obituaries Network operating systems Thick film circuits Message service Muscles Cooling. Food packaging Structural discs Surveillance Kerr effect Ignition Classification tree analysis. Client-server systems Dentistry Gyroscopes Power filters Text mining Quantum well lasers Optical fiber cables Pulse modulation Gaussian mixture model Unsupervised learning. Semiconductor superlattices Matching pursuit algorithms Rectennas Ion emission Winches Distributed information systems Metallurgy Cognitive neuroscience Bistable circuits Subtraction techniques Thyratrons Prefabricated construction Out of order.
Micromachines, 2018
Exosomes have gained immense importance since their proteomic and genetic contents could potentia... more Exosomes have gained immense importance since their proteomic and genetic contents could potentially be used for disease diagnostics, monitoring of cancer progression, metastasis, and drug efficacy. However, establishing the clinical utility of exosomes has been restricted due to small sizes and high sample loss from extensive sample preparation. Sample loss is particularly critical for body fluids limited in volume and difficult to access, e.g., cerebrospinal fluid. We present a microfluidic technique that locally enhances the concentration of extracellular vesicles extracted from MDA-MB-231 human breast cancer cell lines by using an ion concentration polarization (ICP)-based electrokinetic concentrator. Our design incorporates a trapping mechanism near the conductive polymer membrane; therefore, we can preconcentrate and capture extracellular vesicles simultaneously. Compared with standard fluorescence detection, our method increased the limit of detection (LOD) of extracellular vesicles by two orders of magnitude in 30 min. Our concentrator increased the extracellular vesicle concentration for 5.0 × 10 7 particles/1 mL (LOD), 5.0 × 10 8 particles/1 mL, and 5.0 × 10 9 particles/1 mL by~100-fold each within 30 min using 45 V. This study demonstrates an alternative platform to simultaneously preconcentrate and capture extracellular vesicles that can be incorporated as part of a liquid biopsy-on-a-chip system for the detection of exosomal biomarkers and analysis of their contents for early cancer diagnosis.
Scientific reports, Jan 17, 2018
We report an integrated system for accelerating assays with concentrators in a standard 12-well p... more We report an integrated system for accelerating assays with concentrators in a standard 12-well plate (ISAAC-12) and demonstrate its versatility for rapid detection of matrix metalloproteinase (MMP)-9 expression in the cell culture supernatant of breast cancer cell line MDA-MB-231 by accelerating the enzymatic reaction and end-point signal intensity via electrokinetic preconcentration. Using direct printing of a conductive ion-permselective polymer on a polydimethylsiloxane (PDMS) channel, the new microfluidic concentrator chip can be built without modifying the underlying substrate. Through this decoupling fabrication strategy, our microfluidic concentrator chip can easily be integrated with a standard multiwell plate, the de facto laboratory standard platform for high-throughput assays, simply by reversible bonding on the bottom of each well. It increases the reaction rate of enzymatic assays by concentrating the enzyme and the reaction product inside each well simultaneously for ...
Lab on a chip, Jan 13, 2018
In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs... more In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs from a mixed age nematode population, which can subsequently be cultured to a desired developmental stage. For the sorting of a mixture containing three different developmental stages, eggs, L1 and L4, we utilized a microfluidic spiral chip with a trapezoidal channel to obtain a sorting efficiency of above 97% and a sample purity (SP) of above 80% for eggs at different flow rates up to 10 mL min. The result demonstrated a cost-effective, simple, and highly efficient method for synchronizing C. elegans at a high throughput (∼4200 organisms per min at 6 mL min), while eliminating challenges such as clogging and non-reusability of membrane-based filtration. Due to its simplicity, our method can be easily adopted in the C. elegans research community.
SLAS TECHNOLOGY: Translating Life Sciences Innovation, 2016
Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabdit... more Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for hi...
Volume 1: Micro/Nanofluidics and Lab-on-a-Chip; Nanofluids; Micro/Nanoscale Interfacial Transport Phenomena; Micro/Nanoscale Boiling and Condensation Heat Transfer; Micro/Nanoscale Thermal Radiation; Micro/Nanoscale Energy Devices and Systems, 2016
Morpholinos (MOs) are synthetic nucleic acids analogues with a non-charged backbone of morpholine... more Morpholinos (MOs) are synthetic nucleic acids analogues with a non-charged backbone of morpholine rings. To enhance the MO-DNA hybridization assay speed, we propose the integration of a MO microarray with an ion concentration polarization (ICP) based microfluidic concentrator. The ICP concentrator collects target biomolecules from a ∼μL fluidic DNA sample and concentrates them electrokinetically into a ∼nL plug located in the vicinity of the MO probes. ICP preconcentration not only reduces the analyte diffusion length but also increases the binding reaction rate, and as a result, ICP-enhanced MO microarrays allow much faster hybridization than standard diffusion-limited MO microarrays.
Analytical Chemistry, 2016
Supporting information provides: a video showing the automatic PEDOT:PSS printing process on PDMS... more Supporting information provides: a video showing the automatic PEDOT:PSS printing process on PDMS channel, 3D confocal videos of the DNA plug during concentration experiments, confocal data of the vertical concentration profile of the plug in microfluidic concentrators with PEDOT:PSS at the top and bottom of the microchannel, estimation of the pH shift during ET concentration a 5-channel simultaneous DNA concentration video, and a measurement of the channel-tochannel and device-to-device variation.
Biosensors and Bioelectronics, 2015
Electrokinetic methods that conveniently concentrate charged analytes by orders of magnitude are ... more Electrokinetic methods that conveniently concentrate charged analytes by orders of magnitude are highly attractive for nucleic acid assays where they can bypass the complexity and costs of enzyme-based amplification. The present study demonstrates an electrokinetic concentration device incorporating charge-neutral morpholino (MO) probes: as DNA analyte is concentrated in a microfluidic channel using ion concentration polarization (ICP) it is simultaneously hybridized to spots of complementary MO probes immobilized on the channel floor. This approach is uniquely favored by the match between the optimum buffer ionic strength of approximately 10 mM for both MO-DNA surface hybridization and electrokinetic concentration. The simple and easily scalable poly(dimethylsiloxane) (PDMS) microfluidic device was fabricated using soft lithography and contact printing of a conductive polymer, poly(3,4ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) as a cation-selective membrane material. Using the microfluidic concentrator, we could increase the concentration of DNA by three orders of magnitude in less than 5 min at an electric field of 75 V cm À 1. The 1000-fold increase in concentration of DNA led to an increase in the speed of MO-DNA hybridization by two orders of magnitude and enabled a detection sensitivity of $ 1 nM within 15 min of concentration. Using the proposed microfluidic concentrator, we also demonstrated a rapid hybridization with a binary DNA mixture, containing a fully complementary and a non-complementary sequence to mimic molecular backgrounds present in real DNA samples.
Lab on a chip, Jan 7, 2014
In this work we describe a novel and simple self-assembly process of colloidal silica beads to cr... more In this work we describe a novel and simple self-assembly process of colloidal silica beads to create a nanofluidic junction between two microchannels. The nanoporous membrane was used to induce ion concentration polarization inside the microchannel and this electrokinetic preconcentration system allowed rapid concentration of DNA samples by ~1700 times and of protein samples by ~100 times within 5 minutes.
Lab on a Chip, 2010
Capillary-valve-based fabrication of ion-selective membrane junction for electrokinetic sample pr... more Capillary-valve-based fabrication of ion-selective membrane junction for electrokinetic sample preconcentration in PDMS chip The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Liu, Vincent, Yong-Ak Song, and Jongyoon Han. "Capillaryvalve-based Fabrication of Ion-selective Membrane Junction for Electrokinetic Sample Preconcentration in PDMS Chip." Lab on a Chip 10.11 (2010): 1485.
Lab on a Chip, 2008
In this paper, we report a new method of fabricating a high-throughput protein preconcentrator in... more In this paper, we report a new method of fabricating a high-throughput protein preconcentrator in poly(dimethylsiloxane) (PDMS) microfluidic chip format. We print a submicron thick ion-selective membrane on the glass substrate by using standard patterning techniques. By simply plasma-bonding a PDMS microfluidic device on top of the printed glass substrate, we can integrate the ion-selective membrane into the device and rapidly prototype a PDMS preconcentrator without complicated microfabrication and cumbersome integration processes. The PDMS preconcentrator shows a concentration factor as high as ~ 10 4 in 5 min. This printing method even allows fabricating a parallel array of preconcentrators to increase the concentrated sample volume, which can facilitate an integration of our microfluidic preconcentrator chip as signal enhancing tool to various detectors such as mass spectrometer.
Journal of the American Chemical Society, 2011
We introduce an integrated microfluidic device consisting of a biomolecule concentrator and a mic... more We introduce an integrated microfluidic device consisting of a biomolecule concentrator and a microdroplet generator, which enhances the limited sensitivity of low-abundance enzyme assays by concentrating biomolecules before encapsulating them into droplet microreactors. We used this platform to detect ultra low levels of matrix metalloproteinases (MMPs) from diluted cellular supernatant and showed that it significantly (∼10-fold) reduced the time required to complete the assay and the sample volume used.
Journal of Materials Processing Technology, 2006
Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have been impo... more Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have been impossible to manufacture using conventional techniques. However, the surface finish and accuracy of SFF parts remain lower than those of parts that have been machined in conventional methods such as milling. A process combination of additive and subtractive techniques is currently being developed by our
International Journal of Machine Tools and Manufacture, 2005
Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have thus far ... more Solid Freeform Fabrication (SFF) gives engineers a new freedom to build parts that have thus far proved difficult to manufacture using conventional machining. However, the surface finish and accuracy of SFF parts are lower than those of conventionally machined parts. A process combination of additive and subtractive techniques is currently being developed in order to overcome this problem. A novel