Yong-Ak Song

Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications

Recently, a new type of electrokinetic concentration devices has been developed in a microfluidic chip format, which allows efficient trapping and concentration of biomolecules by utilizing ion concentration polarization near nanofluidic structures. These devices have drawn much attention not only due to their potential application in biomolecule sensing, but also due to the rich scientific content related to ion concentration polarization, the underlying physical phenomenon for the operation of these electrokinetic concentration devices. This tutorial review provides an introduction to the scientific and engineering advances achieved, in-depth discussion about several interesting applications of these unique concentration devices, and their current limitations and challenges.

Multiplexed Proteomic Sample Preconcentration Device Using Surface-Patterned Ion-Selective Membrane

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 approximately 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 a signal enhancing tool to various detectors such as a mass spectrometer.

Increase of Reaction Rate and Sensitivity of Low-Abundance Enzyme Assay Using Micro/Nanofluidic Preconcentration Chip

We report a novel method of increasing both the reaction rate and the sensitivity of low-abundance enzyme assay using a micro/nanofluidic preconcentration chip. The disposable preconcentration device made out of PDMS with a surface-patterned ion-selective membrane increases local enzyme/substrate concentrations for rapid monitoring of enzyme activity. As a model system, we used trypsin as the enzyme and BODIPY FL casein as the fluorogenic substrate. We demonstrated that the reaction rate of trypsin-BODIPY FL was significantly enhanced by increasing the local concentrations of both trypsin and BODIPY FL casein in the preconcentration chip. The reaction time required to turn over substrates at 1 ng/mL was only approximately 10 min compared to approximately 1 h without preconcentration, which demonstrates a significantly higher reaction rate through the increase of the concentrations of both the enzyme and substrate. Furthermore, trypsin activity can be measured down to a concentration level of 10 pg/mL, which is a approximately 100 fold enhancement in sensitivity compared to the result without the preconcentration step. This micro/nanofluidic preconcentrator chip could be used as a generic micro reaction platform to study any enzyme-substrate systems, or other biochemical reaction systems in low concentration ranges.

Free-Flow Zone Electrophoresis of Peptides and Proteins in PDMS Microchip for Narrow pI Range Sample Prefractionation Coupled with Mass Spectrometry

In this paper, we are evaluating the strategy of sorting peptides/proteins based on the charge to mass without resorting to ampholytes and/or isoelectric focusing, using a single- and two-step free-flow zone electrophoresis. We developed a simple fabrication method to create a salt bridge for free-flow zone electrophoresis in PDMS chips by surface printing a hydrophobic layer on a glass substrate. Since the surface-printed hydrophobic layer prevents plasma bonding between the PDMS chip and the substrate, an electrical junction gap can be created for free-flow zone electrophoresis. With this device, we demonstrated a separation of positive and negative peptides and proteins at a given pH in standard buffer systems and validated the sorting result with LC/MS. Furthermore, we coupled two sorting steps via off-chip titration and isolated peptides within specific pI ranges from sample mixtures, where the pI range was simply set by the pH values of the buffer solutions. This free-flow zone electrophoresis sorting device, with its simplicity of fabrication, and a sorting resolution of 0.5 pH unit, can potentially be a high-throughput sample fractionation tool for targeted proteomics using LC/MS.

Capillary-valve-based fabrication of ion-selective membrane junction for electrokinetic sample preconcentration in PDMS chip.

In this paper, we report a novel method for fabricating ion-selective membranes in poly(dimethylsiloxane) (PDMS)/glass-based microfluidic preconcentrators. Based on the concept of capillary valves, this fabrication method involves filling a lithographically patterned junction between two microchannels with an ion-selective material such as Nafion resin; subsequent curing results in a high aspect-ratio membrane for use in electrokinetic sample preconcentration. To demonstrate the concentration performance of this high-aspect-ratio, ion-selective membrane, we integrated the preconcentrator with a surface-based immunoassay for R-Phycoerythrin (RPE). Using a 1x PBS buffer system, the preconcentrator-enhanced immunoassay showed an approximately 100x improvement in sensitivity within 30 min. This is the first time that an electrokinetic microfluidic preconcentrator based on ion concentration polarization (ICP) has been used in high ionic strength buffer solutions to enhance the sensitivity of a surface-based immunoassay.

Tunable membranes for free-flow zone electrophoresis in PDMS microchip using guided self-assembly of silica microbeads.

In this paper, we evaluate the strategy of using self-assembled microbeads to build a robust and tunable membrane for free-flow zone electrophoresis in a PDMS microfluidic chip. To fabricate a porous membrane as a salt bridge for free-flow zone electrophoresis, we used silica or polystyrene microbeads between 3-6 μm in diameter and packed them inside a microchannel. After complete evaporation, we infiltrated the porous microbead structure with a positively or negatively charged hydrogel to modify its surface charge polarity. Using this device, we demonstrated binary sorting (separation of positive and negative species at a given pH) of peptides and dyes in standard buffer systems without using sheath flows. The sample loss during sorting could be minimized by using ion selectivity of hydrogel-infiltrated microbead membranes. Our fabrication method enables building a robust membrane for pressure-driven free-flow zone electrophoresis with tunable pore size as well as surface charge polarity.

Nanotechnology in plastic surgery.

Background: Nanotechnology has made inroads over time within surgery and medicine. Translational medical devices and therapies based on nanotechnology are being developed and put into practice. In plastic surgery, it is anticipated that this new technology may be instrumental in the future. Microelectromechanical systems are one form of nanotechnology that offers the ability to develop miniaturized implants for use in the treatment of numerous clinical conditions. The authors summarize their published preliminary findings regarding a microelectromechanical systems–based electrochemical stimulation method through modulation of ions around the nerve that is potentially implantable and clinically efficacious, and expand upon current and potential usages of nanotechnology in plastic surgery. Methods: Sciatic nerves (n = 100) of 50 American bullfrogs were placed on a microfabricated planar gold electrode array and stimulated electrically. Using Ca2+-selective membranes, ion concentrations were modulated around the nerve environment in situ. In addition, a comprehensive review of the literature was performed to identify all available data pertaining to the use of nanotechnology in medicine. Results: A 40 percent reduction of the electrical threshold value was observed using the Ca2+ ion–selective membrane. The uses of nanotechnology specifically applicable to plastic surgery are detailed. Conclusions: Nanotechnology may likely lead to advancements in the art and science of plastic surgery. Using microelectromechanical systems nanotechnology, the authors have demonstrated a novel means of modulating the activation of nerve impulses. These findings have potentially significant implications for the design of special nano-enhanced materials that can be used to promote healing, control infection, restore function, and aid nerve regeneration and rehabilitation.

Tunable stiffness scanning microscope probe

Scanning probe microscopy (SPM) has been an important tool to image and manipulate micro/nano scale structures. The measurement is based on the optical detection of a very small deflection of a flexible cantilever while traveling near the sample surface. However, the use of a cantilever with a sharp oxidized conical tip is quite costly, very difficult to scale up and unable to scan variable hardness surfaces, such as cell membranes in vivo. A concept of in-plane probe tip is developed. It has a carbon nanotube tip, built-in actuator and a tip deflection sensor, all assembled in the same plane. Most of all, an in-plane probe design would enable the stiffness of the probe to become tunable by using MEMS clutched springs. This allows a continuous measurement of samples with inhomogeneous surface hardness without changing the probe in the middle of a measurement.

Microfabricated nerve-electrode interfaces in neural prosthetics and neural engineering.

Neural interfaces and implants are finding more clinical applications and there are rapid technological advances for more efficient and safe design, fabrication and materials to establish high-fidelity neural interfaces. In this review paper, we highlight new developments of the microfabricated electrodes and substrates with regard to the design, materials, fabrication and their clinical applications. There is a noticeable trend towards integration of microfluidic modules on a single neural platform. In addition to the microelectrodes for neural recording and stimulation, microfluidic channels are integrated into a nerve–electrode interface to explore the rich neurochemistry present at the neural interface and exploit it for enhanced electrochemical stimulation and recording of the central and peripheral nervous system.

Rapid detection of exosomal microRNA biomarkers by electrokinetic concentration for liquid biopsy on chip

An ion concentration polarization (ICP)-based electrokinetic concentration device is used for accelerating the surface hybridization reaction between exosomal microRNAs (miRNAs) and morpholinos (MOs) as a synthetic oligo capture probe in the nanomolar concentration range in a microfluidic channel. Compared with standard hybridization at the same concentration, the hybridization time of the miRNA target on MO capture probes could be reduced from ∼24 h to 30 min, with an increase in detection speed by 48 times. This ICP-enhanced hybridization method not only significantly decreases the detection time but also makes workflow simple to use, circumventing use of quantitative reverse transcription polymerase chain reaction or other conventional enzyme-based amplification methods that can cause artifacts.