Microfluidics

Modern analytical chemistry is facing new challenges. One of the urgent targets to cope with the challenges is multiplex analysis requiring as small a sample volume as possible. In this situation, we paid attention to suspension arrays that employ microbeads. Bead-based suspension arrays for common use require enhanced sensitivity and effective prevention of non-specific adsorption, as well as miniaturization of the detection device. We have implemented virus-tethered gold microspheres for multiplex immunoassay applications, employing a DC impedance-based flow cytometer as a detection element. The advantages of virus-tethered gold microspheres, including excellent prevention of non-specific adsorption, are extended to signal enhancement arising from the large quantity of antibody loading on each virion, and to flexible movement of filamentous virus. Individual virus-tethered beads generate their own DC impedance and fluorescence signals, which are simultaneously detected by a chip-based microfluidic flow cytometer. This system successfully realized multiplex immunoassays involving four biomarkers: cardiac troponin I (cTnI), prostate specific antigen (PSA), creatine kinase MB (CK-MB), and myoglobin in undiluted human sera, elevating sensitivity by up to 5.7-fold compared to the beads without virus. Constructive integration between filamentous virus-tethered Au-layered microspheres and use of a microfluidic cytometer suggests a promising strategy for competitive multiplex immunoassay development based on suspension arrays.

RED

의견세 가지 분류 중에서는 Analytical platform에 속한다고 생각합니다. 과거에 RED를 bipolar electrode 센서의 power source로 결합하는 연구를 진행했었고, ionic 소자의 ionic power로 활용가능하다는 연구를 통해 미래의 생체분석장치와의 결합가능성도 보였습니다. 현재는 RED 자체를 분석장치로 활용하는 연구도 하고 있기 때문에 analytical platform 개발에 속한다고 생각합니다.

Reverse electrodialysis (RED) is a energy generating system from the salinity gradient of sea water and river water. We focus on the fact that RED is an ideal power source surrogate to couple with various ionic devices without the need of any metal electrodes. Thus, we developed a miniaturized RED to be used as a power source for a drug delivery system and that of sensors, Conceptual improvement was also made via a precipitation-based approach to enhance its practicality. Now, we are attempting to expand its applications to a wide range of ion-based platforms.

Analytical platform3D Interdigitated array Electrodes(3D IDA)

Sensitivity is significant criteria for biosensors. We devised three-dimensional interdigitated array (3D IDA) platform for amplifying the current signal to enhance the sensitivity of chip-based electrochemical immunosensors. The 3D IDA consists of one pair of IDA which are positioned on the bottom and the ceiling facing each other in a microfluidic channel. Comparing with the case of feedback mode and non-feedback mode, the current signal of feedback mode was ca. 100 times higher than that of non-feedback mode. We also demonstrated the 3D IDA chip that operate as electrochemical immunosensors without reference and counter electrodes, which are essential components to control appllied potential but prevent users from being free to detect targets on-site. Electron transfer mediator is immobilized on the one pair of working electrodes and the electrochemical potential of the electrodes are defined by the formal potential of the mediators in 2-electrode (2E) system. Therefore, the 3D IDA in 2E system constitutes a simple platform for sensitive electrochemical detection and sheds light on miniaturized multiplex immunoassay field.

Iontronics

Iontronics, as the name reminds us of its meaning, mainly deals with electrical signal processing based on ions as signal carriers under aqueous, physiological conditions, and thereby aims to realize a bio-inspired information processing units. For the purpose of a sophisticated control of ions, positively- or negatively charged polyelectrolyte gels are used as a key component in the microfluidic chip. By optimizing the electrochemical circuit design and materials, we demonstrated that systematic combinations of such hydrogels produced the first aqueous microfluidic ion diode, digital logic gates and a polyelectrolytic junction field effect transistor (pJFET). Recently, we have constructed a full ionic circuitry with combination of reverse electrodialysis (RED) as an ionic power source, which is completely composed of non-electronic materials. We envision futuristic ionic devices capable of neurological signal processing functions on biocompatible substrates such as starch paper.

Virtual Electrode

Virtual Electrode

When the semiconductor absorbs photons of high enough energy, electron−hole pairs are created. Among them, the minority carriers migrate to the semiconductor surface and react with the redox species in the solution. Most photoelectrochemistry research has been focused on the production of environmentally friendly fuels taking advantage of the power of semiconductors, to convert solar energy into chemical energy. However, the characteristics of the semiconductor we are interested in is the 'transient' nature of photo-generated excitons. Excitons exclusively exist when and where the light illuminates. Therefore, the photoelectrochemical reactions are also spatiotemporally confined to the illumination. Thus, it is possible to induce a “virtual” electrode on the semiconductor substrate wherever and whenever we want without complicated electrical wiring process or the electrode-positioning procedure. So far, we have showed some applications based on virtual electrode including large scale, maskless metal patterning with amorphous silicon and microscale biomolecule detection with hematite photoanode.

• Maskless Patterning

  

• Biomolecule detection

  

Bio Fuel Cell

Enzymatic biofuel cell is fuel cell that utilizes enzymes as biocatalyst to oxidize its fuel such as glucose and reduce its oxidant to water to harvest energy. At anode, the electrons are separated from the fuel molecules by enzyme and transfer to the anode electrode. At cathode, those electrons transfer to the enzyme and react with the oxidant.

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  Redox polymer

  MET(Mediated electron transfer) system of redox polymer can facilitate electron transfer between the catalyst and the electrode surface. Moreover, electrons generated from several layers of enzymes can be electronically transferred to the electrode.

• Designed by Freepik

  Anode and cathode are packaged in dialysis membranes, respectively. The pore size of dialysis membranes is sufficient for glucose and oxygen to move freely through the membranes. By limiting the environment in which large proteins are exposed directly to the electrode, package prevents contamination of the electrode surface. The packaged BFCs are implanted into an animal, and they generate energy from glucose and oxygen in the body.

Anode와 cathode를 각각 dialysis membrane으로 package한다. dialysis membrane의 pore size는 glucose와 oxygen이 membrane을 통과하여 자유롭게 이동하기에 충분하다. 큰 사이즈의 단백질이 전극에 직접적으로 노출되는 환경을 제한함으로써 package는 전극 표면이 오염되지 않도록 한다. Packaged BFC를 동물 체내에 이식하면 체내에 존재하는 glucose와 oxygen을 연료로 에너지를 생성할 수 있다.

Multi-phase electrochemistry

• Figure 1

  

• Figure 2

  

The Br-/Br2 redox couple in aqueous solution are being studied for redox flow batterys (figure 1). N-methyl-N-ethyl pyrrolidinium bromide (MEPBr) is used in Bromide redox system as bromine-complexing agent, forms an immiscible emulsion to overcome the self-discharge, corrosion and toxicity of Bromine. In recent studies, It is revealed that Bromide is oxidized in not only aqueous solution but also MEPBr2n+1, and there is a large amount of Bromide in the MEPBr2n+1 phase. In addition, We observed that when a single droplet of MEPBr2n+1 collides with electrode, bromide oxidizes immediately and spike-shaped current is occurred using in situ optical and electrochemical tools (figure 2). In the future, we will going to study electrochemistry of single droplet entity and compare the difference from the emulsion which is ensemble of the droplets.

Synaptic Interface

The neurons, a part of our neural system, communicate each other using chemical signal via synapses. We propose an artificial synapse system as a new neural interface, which is composed of a single neuron and a postsynaptic protein-modified ultramicroelectrode. In this system, a presynapse is formed onto a functionalized electrode spontaneously, and exocytotic chemicals are directly released to the electrode. Chemical signals can be converted to electrical information. The artificial synapse is very robust to neural migration and glia penetration, because the induced synapse is firmly bound to the electrode surface by protein-protein interaction.

Solving the mystery of synaptic signaling is highly hindered by structural complexity of synapse. To address this problem, we suggests an ingenious strategy that inducing an postsynapse on an aritifical presynapse. In this system, synapse formation can be spatiotemporally controlled, and chemical release is delicately regulated by electrical potential.

We take the PC-12 cell which is well-known as a neuronal model cell to investigate the cell-to-electrode interface. When a synaptic cell adhesion molecule is expressed on the membrane of PC-12, the cells can be linked to modified electrode with protein-protein interaction. With this model system for artificial synapse, properties of a live cell-electrode interface can be readily studied.

Conventional neuronal culture methods entail cell seeding on two dimensional substrates. Yet, neurons in its native environment form complex three dimensional networks with both cells and the brain extracellular matrix. It has been demonstrated that cells cultured two dimensional substrates differ from those in vivo. To better emulate neurons in vivo, we propose an integrated system of organotypic brain slice and three dimensional extracellular matrix.

Nanoconfinement

• Nanoporous Electrode Investigation

  

• Spectroelectrochemistry

  

Nanostructuring materials in the aims to enhance its catalytic activity has long been indispensable in electrocatalyst development. In particular, nanoporous electrodes with numerous pores in the nanoscale, are widely utilized owing to its enlarged surface area as well as activated surface characteristics. In the geometrical point of view, nanocavities of nanoporous electrodes offer unique spatial environment towards reactant molecules, resulting in enhanced interaction between the reactant molecule and the electrode surface. We focus on such electrocatalytic effects stemming from the morphology of nanoporous electrodes, denoted as nanoconfinement effects.

FTEIS

Fourier transform electrochemical impedance spectroscopy (FT-EIS) can be utilized as a powerful tool to a number of applications where the change of components in equivalent circuits should be examined in real-time manner. This technique allows for a very short EIS measurement time by applying a small (5~15 mV) voltage step signal to the system, and thereby calculating impedance values for the frequency range of interest through mathematical signal processing. Among its prospective applications are the fundamental study of electrochemical system, transient electrode process such as etching, electroplating, corrosion, and usages as a novel analytical platform.

Probe Electrochemistry

Probe electrochemistry utilizes a sub-micro level tip, especially at the nano-size level, to conduct the microscopic scale experiment such as surface analysis and single particle analysis on electrochemical condition which go beyond the limitations of conventional macroscopic level experiments. In our lab, we use various types of homemade nano-scale tips in probe instruments, EC-STM and SECM, to investigate the unknown electrochemical behavior in metal-solution interface.

Phage Electrochemistry

Application of Filamentous Bacteriophage& Gold microshell

• Bacteriophage

  Filamentous bacteriophages, such as fd and M13, have nanostructured morphologies with contour length of ≈ 1 μ m and diameter of ≈ 7 nm. The viruses are comprised of five different kinds of structural proteins (pIII, pVI, pVII, pVIII, and pIX) that encase a single-stranded viral DNA. Among them, more than 2700 copies of the major coat protein pVIII serve for the assembly of fi lamentous structure with their ε -amino groups of Lys-8 and α -amino groups of N-termini being exposed, each of which have been successfully modifi ed with macromolecules using chemical conjugation. A minor coat protein pIII, three to five copies per virion, has been dominantly used for the display of peptides and proteins

• Gold microshell

  In biosensor development for immunoassays, preventing non-specific adsorption while providing high antibody loading is of primary importance. Since we had been experiencing a heavy non-specific binding to typical polymer beads when using blood or serum samples, we envisioned that covering the porous and sticky surfaces of the polymer beads with Au and thiol self-assembled monolayers (SAMs) should resolve the adsorption problem. The SAM molecules, if properly chosen, are able to prevent non-specific interactions between Au surface and analytes as well as to provide functional groups for protein conjugation.

Filamentous bacteriophage as a template for OER catalyst

Mass spectrometry on gold microshell

Photoelectrochemical Catalysis

Photoelectrochemical (PEC) solar water splitting is a promising route to sustainably produce hydrogen. In this system, various electrocatalysts, including nickel-molybdate, cobalt phosphate, and nickel-iron (oxy)hydroxide, have been added to semiconductor photoanode surface in order to improve the efficiency of the water electrolysis reaction. Although this approach has shown encouraging results, the reason for this improvement have remained poorly understood. By employing various electrochemical measurements such as impedance spectroscopy and in-situ Raman spectroscopy, we attempt to elucidate electrocatalyst/semiconductor interfaces of photoelectrochemical systems.

SiO2Electrochemistry with an Insulator.

An insulator is a material that does not conduct current. In case of contacting silicon oxide to water, the protons present in the water could introduce into the oxide chain. When a negative potential is applied on the underlying conductive material, it is presumed that the proton in silicon oxide reacts electrochemically to form radical intermediates that transfer electron. At this condition, silicon oxide no longer function as an insulator. We are conducting research to find out what kind of reaction occurs on silicon oxide. By analyzing the oxide with various electrochemical and other analyzing techniques, i.e. voltammetry, electrochemical impedance spectroscopy, product analysis, the origin of electrochemical reaction on the oxide is studied.