Jungsuk Kim

Blood-based immunoassay of tau proteins for early diagnosis of Alzheimer's disease using surface plasmon resonance fiber sensors

We present the immunoassay of tau proteins (total tau and phosphorylated tau) in human sera using surface plasmon resonance (SPR) fiber sensors. This assay aimed at harvesting the advantages of using both SPR fiber sensors and a blood-based assay to demonstrate label-free point-of-care-testing (POCT) patient-friendly assay in a compact format for the early diagnosis of Alzheimers disease (AD). For conducting the assay, we used human sera of 40 subjects divided into halves, which were grouped into AD patients and control groups according to a number of neuropsychological tests. We found that on an average, the concentrations of both total tau and phosphorylated tau proteins (all known to be higher in cerebrospinal fluid (CSF) and the brain) turned out to be higher in human sera of AD patients than in controls. The limits of detection of total tau and phosphorylated tau proteins were 2.4 pg mL−1 and 1.6 pg mL−1, respectively. In particular, it was found that the AD group exhibited average concentration of total tau proteins 6-fold higher than the control group, while concentration of phosphorylated tau proteins was 3-fold higher than that of the control. We can attribute this inhomogeneity between both types of tau proteins (in terms of increase of control-to-AD in average concentration) to un-phosphorylated tau proteins being more likely to be produced in blood than phosphorylated tau proteins, which possibly is one of the potential key elements playing an important role in AD progress.

Mechanical characterization of HIV-1 with a solid-state nanopore sensor

Enveloped viruses fuse with cells to transfer their genetic materials and infect the host cell. Fusion requires deformation of both viral and cellular membranes. Since the rigidity of viral membrane is a key factor in their infectivity, studying the rigidity of viral particles is of great significance in understating viral infection. In this paper, a nanopore is used as a single molecule sensor to characterize the deformation of pseudo‐type human immunodeficiency virus type 1 at sub‐micron scale. Non‐infective immature viruses were found to be more rigid than infective mature viruses. In addition, the effects of cholesterol and membrane proteins on the mechanical properties of mature viruses were investigated by chemically modifying the membranes. Furthermore, the deformability of single virus particles was analyzed through a recapturing technique, where the same virus was analyzed twice. The findings demonstrate the ability of nanopore resistive pulse sensing to characterize the deformation of a single virus as opposed to average ensemble measurements.

Bias-Voltage Stabilizer for HVHF Amplifiers in VHF Pulse-Echo Measurement Systems

The impact of high-voltage–high-frequency (HVHF) amplifiers on echo-signal quality is greater with very-high-frequency (VHF, ≥100 MHz) ultrasound transducers than with low-frequency (LF, ≤15 MHz) ultrasound transducers. Hence, the bias voltage of an HVHF amplifier must be stabilized to ensure stable echo-signal amplitudes. We propose a bias-voltage stabilizer circuit to maintain stable DC voltages over a wide input range, thus reducing the harmonic-distortion components of the echo signals in VHF pulse-echo measurement systems. To confirm the feasibility of the bias-voltage stabilizer, we measured and compared the deviations in the gain of the HVHF amplifier with and without a bias-voltage stabilizer. Between −13 and 26 dBm, the measured gain deviations of a HVHF amplifier with a bias-voltage stabilizer are less than that of an amplifier without a bias-voltage stabilizer. In order to confirm the feasibility of the bias-voltage stabilizer, we compared the pulse-echo responses of the amplifiers, which are typically used for the evaluation of transducers or electronic components used in pulse-echo measurement systems. From the responses, we observed that the amplitudes of the echo signals of a VHF transducer triggered by the HVHF amplifier with a bias-voltage stabilizer were higher than those of the transducer triggered by the HVHF amplifier alone. The second, third, and fourth harmonic-distortion components of the HVHF amplifier with the bias-voltage stabilizer were also lower than those of the HVHF amplifier alone. Hence, the proposed scheme is a promising method for stabilizing the bias voltage of an HVHF amplifier, and improving the echo-signal quality of VHF transducers.

A Novel Fisheye-Lens-Based Photoacoustic System

This paper presents a novel fisheye-lens-based photoacoustic (PA) system. In conventional PA systems, mechanical motors are utilized to obtain the target information due to the small fields of view of such systems. The use of such motors introduces mechanical noise, which is difficult to remove when processing the echo signals. A fisheye lens system offering a wide field of view would effectively reduce the motor effects (i.e., the noise) and enable the system to have a wide field of view. Therefore, in this work, we propose a novel fisheye lens scheme and describe a PA system based on the developed lens scheme. In addition, to confirm the feasibility of the fisheye-lens-based PA system, we present the typical pulse-echo responses obtained using a 20 MHz single element immersion transducer and the echo signals measured from bull’s eye tissue samples separated by approximately 4, 6, 8, and 10 cm diagonally and 2 cm vertically from the fisheye lens. The experimental results demonstrate that the echo signal amplitudes, their center frequencies, and the −6 dB bandwidths obtained using red, green, and blue lights and a fisheye lens are acceptable when the fisheye lens is separated from a sample both diagonally and vertically. Therefore, fisheye-lens-based PA systems could be a potential method of achieving wide fields of view while reducing the mechanical motor effects.

Sensitivity enhancement of capacitive tumor necrosis factor-α detection by deposition of nanoparticles on interdigitated electrode

An interdigitated electrodes (IDE) modified with gold nanoparticles (AuNPs) was fabricated to enhance the capacitive detection of tumor necrosis factor-α (TNF-α) and compared with a bare IDE. A TNF-α immunosensor was developed by covalently conjugating TNF-α antibodies with 3-mercaptopropionic acid by a carbodiimide/N-hydroxysuccinimide reaction on the AuNP/IDE. After the application of human serum samples containing various concentrations of TNF-α to the sensing electrode, changes in both the impedance spectrum and the electrode interfacial capacitance were measured. The capacitance changes were dependent on the TNF-α concentration in the range of 1 pg ml−1 to 10 ng ml−1, and the device had the calculated detection limit of 0.83 pg ml−1. The developed AuNP/IDE-based immunosensor was successfully used for the capacitive detection of the binding of TNF-α to its antibody, and was found to be feasible for the analysis of TNF-α in human blood serum.

A low-noise and wide-bandwidth transimpedacne amplifier design for bionanopore applications

This paper presents a low-noise and wide-bandwidth transimpedance amplifier for bionanopore applications. Using a capacitive-feedback transimpedance amplifier for a headstage, the input-referred noise is drastically reduced, which enables one to accurately monitor DNA translocation. To achieve a wide bandwidth, an intermediator-and-differentiator structure and a split-resistor technique are proposed in this work.

An integrated potentiostat sensor with digitally-controlled input-parasitic compensation for nanopore applications

This paper presents an integrated low-power and low-noise potentiostat sensor for nanopore sensing. This high-sensitivity sensor consists of four stages: a preamplifier, a difference amplifier, a unity-gain buffer and a capacitive compensation unit. For the preamplifier, a resistive-feedback transimpedance amplifier with 50MΩ is used to detect an ionic current variation and the difference amplifier then provides a programmable voltage gain. The compensation block works to cancel out the input-parasitic capacitance effect, which causes a dead-time during nanopore sensing, as well as estimate it along with the control unit. For high-throughput nanopore sensing, in this work, a potentiostat sensor is designed and simulated in a 0.35μm CMOS process.