Chang-Beom Kim

Antibody-based magnetic nanoparticle immunoassay for quantification of Alzheimer’s disease pathogenic factor

Abstract. Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to a decline in cognitive and intellectual abilities and an irreversible mental deterioration. Based on multidisciplinary AD research, the most universally accepted hypotheses on AD pathogenesis are the intracerebral aggregate formation of beta-amyloid (Aβ) peptides. According to medical paradigmatic transition from medical treatment to early diagnostic prevention, scientists have considered physiological body fluid as a biomarker medium, in which the promising AD biomarkers could be verified. Recently, use of saliva has been considered as one of the diagnostic fluids over the past decade with meaningful diagnostic potential. We utilized saliva as a biomarker medium to correlate the salivary Aβ levels to AD pathological aspects, especially to the mild cognitive impairment group among AD patients, and to verify our detecting system to be sensitive enough for an early diagnostic tool. The identification of the salivary AD biomarkers using a facile microarraying method would motivate this study with the assistance of magnetically assembled antibody-conjugated nanoparticles and a photomultiplier tube as an optical detector. This simple magnetoimmunoassay system measures the photointensity generated by fluorescence, enables the quantification of the Aβ peptides from AD salivary samples, and consequently classifies the salivary Aβ levels into AD pathological aspects. This method demonstrates a facile approach enabling it to simply detect salivary Aβ peptides at a concentration as low as ∼20  pg/ml. It is expected that our simple magnetoimmunoassay system may have a potential as a detector for low-level Aβ peptides with weak-fluorescence emission.

Measurement of beta-amyloid peptides in specific cells using a photo thin-film transistor

The existence of beta-amyloid [Aβ] peptides in the brain has been regarded as the most archetypal biomarker of Alzheimers disease [AD]. Recently, an early clinical diagnosis has been considered a great importance in identifying people who are at high risk of AD. However, no microscale electronic sensing devices for the detection of Aβ peptides have been developed yet. In this study, we propose an effective method to evaluate a small quantity of Aβ peptides labeled with fluorescein isothiocyanate [FITC] using a photosensitive field-effect transistor [p-FET] with an on-chip single-layer optical filter. To accurately evaluate the quantity of Aβ peptides within the cells cultured on the p-FET device, we measured the photocurrents which resulted from the FITC-conjugated Aβ peptides expressed from the cells and measured the number of photons of the fluorochrome in the cells using a photomultiplier tube. Thus, we evaluated the correlation between the generated photocurrents and the number of emitted photons. We also evaluated the correlation between the number of emitted photons and the amount of FITC by measuring the FITC volume using AFM. Finally, we estimated the quantity of Aβ peptides of the cells placed on the p-FET sensing area on the basis of the binding ratio between FITC molecules and Aβ peptides.

Fast magnetic field simulation with linear system approach

In this research, we propose a noble methodology for modeling and simulation of the intensity and direction of the magnetic fields generated by coils in a limited 3-dimensional region. This method was strictly based on the Biot-Savarts law determining the magnetic fields induced by currents flowing through the coils. We also used Finite Element Method (FEM), a numerical technique for finding a solution for each subdivision of a whole domain within the regions of interest. Based on the introduction of rotational transform method for an arbitrary axis, this method possesses a strong analysis capability for the magnetic fields in the vicinity of the coil at an arbitrary position in 3-dimensional region. In addition, a linear calculation system adopted in the simulation process was able to carry on high-performance analysis for the magnetic fields generated by even multiple coils. We strongly propose that this noble method would be a powerful simulation tool for the design of a system that can generate magnetic fields within a 3-dim region of interest considering both the intensity and direction.

Novel measurement of blood velocity profile using translating-stage optical method and theoretical modeling based on non-Newtonian viscosity model

Detailed knowledge of the blood velocity distribution over the cross-sectional area of a microvessel is important for several reasons: (1) Information about the flow field velocity gradients can suggest an adequate description of blood flow. (2) Transport of blood components is determined by the velocity profiles and the concentration of the cells over the cross-sectional area. (3) The velocity profile is required to investigate volume flow rate as well as wall shear rate and shear stress which are important parameters in describing the interaction between blood cells and the vessel wall. The present study shows the accurate measurement of non-Newtonian blood velocity profiles at different shear rates in a microchannel using a novel translating-stage optical method. Newtonian fluid velocity profile has been well known to be a parabola, but blood is a non-Newtonian fluid which has a plug flow region at the centerline due to yield shear stress and has different viscosities depending on shear rates. The experimental results were compared at the same flow conditions with the theoretical flow equations derived from Casson non-Newtonian viscosity model in a rectangular capillary tube. And accurate wall shear rate and shear stress were estimated for different flow rates based on these velocity profiles. Also the velocity profiles were modeled and compared with parabolic profiles, concluding that the wall shear rates were at least 1.46-3.94 times higher than parabolic distribution for the same volume flow rate.

Simple detection method of amyloid-beta peptide using p-FET with optical filtering layer and magnetic particle

This article describes a novel method for detection of amyloid-β (Aβ) peptide that utilizes a photo-sensitive field-effect transistor (p-FET). According to a recent study, Aβ protein is known to play a central role in the pathogenesis of Alzheimer’s disease (AD). Accordingly, we investigated the variation of photo current of the p-FET generated by the magnetic beads conjugated with Aβ peptides which are placed on the p-FET sensing areas. Additionally, in order to amplify the output signal, we used the lock-in amplifier (LIA) and confirmed the generating the photo current by a small incident light power under 100 μW. It means that it is possible to simply detect a certain protein using magnetic beads conjugated with Aβ peptide and fluorescent label located on the p-FET device. Therefore, in this paper, we suggest that our method could detect tiny amounts of Aβ peptide for early diagnosis of AD using the p-FET devices.

The antibody-based magnetic microparticle immunoassay using p-FET sensing platform for Alzheimer's disease pathogenic factor

The importance of early Alzheimer’s disease (AD) detection has been recognized to diagnose people at high risk of AD. The existence of intra/extracellular beta-amyloid (Aβ) of brain neurons has been regarded as the most archetypal hallmark of AD. The existing computed-image-based neuroimaging tools have limitations on accurate quantification of nanoscale Aβ peptides due to optical diffraction during imaging processes. Therefore, we propose a new method that is capable of evaluating a small amount of Aβ peptides by using photo-sensitive field-effect transistor (p-FET) integrated with magnetic force-based microbead collecting platform and selenium(Se) layer (thickness ~700 nm) as an optical filter. This method demonstrates a facile approach for the analysis of Aβ quantification using magnetic force and magnetic silica microparticles (diameter 0.2~0.3 μm). The microbead collecting platform mainly consists of the p-FET sensing array and the magnet (diameter ~1 mm) which are placed beneath each sensing region of the p-FET, which enables the assembly of the Aβ antibody conjugated microbeads, captures the Aβ peptides from samples, measures the photocurrents generated by the Q-dot tagged with Aβ peptides, and consequently results in the effective Aβ quantification.

Estimation of Beta-amyloid Quantity Using Photo-Sensitive Field Effect Transistor Integrated with a Selectively Transmissible Optical Filter

The intra/extracellular beta-amyloid (Aβ) of neuron has been known as the most representative hallmark of Alzheimers disease (AD). Recently, the clinical diagnosis of AD has been significantly issued with early detection of Aβ. For further accurate quantification of Aβ compared to current techniques, we suggest a new technical concept that enables the evaluation of as small as a few femtomolar Aβ peptide by using photo-sensitive field-effect transistor (p-FET) coated with selectively transmissible optical filter for a particular range of wavelengths of excitation beam. The photo-current generated by p-FET with arsenic trisulfide (As2S3) filter is as much apparent as about 76 nA for a small amount of Aβ-conjugated fluorescent particles. This result indicates that even with slightly small amount of Aβ peptides the As2S3 coated p-FET is applicable to recognizing optically tenuous fluorescence.