This PDF file contains the front matter associated with SPIE Proceedings Volume 8879, including the Title Page, Copyright Information, Table of Contents, and the Conference Committee listing.

Using the measured Raman spectra of triolein and cholesteryl linolenate, the contradiction caused in determining the sequential orders in the two-dimensional correlation spectroscopy was exemplified, in which time-profiles of four marker bands A, B, C, and D were modeled so that A→B→C→D. Here ‘A→B’ is such notation that we read as ‘A is occurred before B’ or ‘A earlier than B’. The two-dimensional correlation method gave the result B→C→D→A which was contradictive to the initial setting. We confirmed that the increments of distance between the peak positions of the Gaussian type time-profiles ƒ and g, through a threshold, gave the unexpected switch in the sequential order. On the complex plane based on the synchronous and asynchronous axes, the vector g is identical to the synchronous axis in direction; the vector ƒ is crossed through the asynchronous axis corresponding to the increments of distance between the peak positions of ƒ and g. By the conventional rule of the correlation method, the vector ƒ just crossing the asynchronous axis is not allowed to be in the second quadrant, but the vector ƒ is transformed to the fourth quadrant with 180 degrees shifted. In the situation, the vector ƒ is located in the later position for the standard vector g, that is, ƒ is occurred ‘after’ g. Based on the revealed mechanism for the contradiction, the time series correlation analysis may be extended in a more versatile manner to allow bio-Raman correlation analysis on diverse dynamics of bio-molecules in living cells.

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.

The EDC-activated protein A has been utilized to directionally immobilize anti-IgG in a miniaturized SPR sensor to enhance IgG detection capability. The SPR sensor chips modified by a self-assembled monolayer (SAM), protein A and the EDC-activated protein A as the linkage layer were compared by the SPR sensor. The SAM was formed on the Au (gold) surface sensor chip by immersing it in the SAM solution. The protein A was formed by injecting their solution to the Au chip. Thirdly, for the EDC-activated protein A, chemical procedure was carried out for the reactable surface of the Au chip. Anti-IgG, bovine serum albumin (BSA) and IgG (50 ng/ml, 100 ng/ml, 150 ng/ml) had been sequently injected into the SPR sensor. In results, the signal of the anti-IgG immobilized by the SAM was the largest increment among three linkage layers. However, the SPR sensor chip modified by EDC-activated protein A showed the highest sensitivity to IgG. From these results, we concluded that the SPR sensor using the EDC-activated protein A can be used to detect biomolecules with trace level concentration for early diagnosis of disease.

Hyper-Rayleigh Scattering (HRS) is a second-order nonlinear optical process in which the scattered light can be detected at the second harmonic wavelength of the input laser beam. Due to its incoherent nature, it can be observed from metal nanoparticles whose size is much smaller than the wavelength. Its sensitive response to the nanoparticle aggregation can be used as a powerful diagnostic tool for the detection of biological target molecules. Many previous bio-sensing applications of HRS have used gold nanoparticles as their sensing platform due to easy synthesis and functionalization of them. Here, we demonstrate that the aggregation of silver nanoparticles induced by poly-L-lysine molecules can generate much higher HRS than that from gold nanoparticle aggregates when using a Ti:Sapphire femtosecond laser. In spite of several drawbacks of silver nanoparticle system regarding the nonlinear response to target concentration and the difficulty of surface functionalization compared to the gold nanoparticle system, much higher HRS from silver nanoparticles can be definitely useful for the sensitive detection of very small amount of target molecules.

We developed a simple method for real-time detection of the neurite outgrowth using microfluidic device. Our microfluidic device contains three compartmentalized channels which are for cell seeding, hydrogel and growth factors. Collagen gel is filled in the middle channel and pheochromocytoma (PC12) cells are seeded in the left channel. To induce differentiation of PC12 cells, 50 ng/ml to1000 ng/ml of nerve growth factor (NGF) is introduced into the right channel. After three days of NGF treatment, PC12 cells begin to extend neurites and formed neurite network from sixth day. Quantification of neurite outgrowth is analyzed by measuring the total area of neurites. On sixth day, the area is doubled compared to the area on third day and increases by 20 times on ninth day.

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.

In this study, a performance of a waveguide coupled bimetallic (WCBiM) chip in a miniaturized surface plasmon resonance (SPR) sensor in a reflectance detection mode was investigated by comparison with a conventional gold (Au) chip. The WCBiM chip makes sharper slope in the SPR curve than conventional Au chip. The detection abilities of both sensor chips were tested by monitoring an interaction between streptavidin and biotin (very low molecular weight). Firstly, an incident light was fixed at an angle which was steepest slope in the scanned the SPR curve; then, the output signal was measured at fixed angle. The streptavidin diluted to 50 μg/ml in the phosphate buffered saline (PBS) was injected into a fluidic module of the SPR sensor. Next, the biotin diluted to 50 ng/ml, 100 ng/ml, 150 ng/ml and 200 ng/ml in the PBS were injected into the sensor. In results, the reflectance increments of the lowest concentration of the biotin (50 ng/ml) using the WCBiM chip and Au chip were 0.11 % and 0.04 %, respectively. Experimental results showed that detection ability of the WCBiM chip was about three times larger than that of conventional Au chip. In conclusion, the miniaturized SPR sensor in the reflectance detection mode using the WCBiM chip was expected to detect the biomolecules at trace level concentration or low molecular weight with high resolution.

This study demonstrates the high sensitivity of high Q polymeric planar waveguide refractive index sensors used on the evanescent field. A Fabry-Perot Bragg gratings cavity was fabricated with a cavity size of 5 mm and 7 mm, respectively. The spectra of light reflected from fabricated Bragg gratings, which were butt-joined, were measured and compared with different indices of surrounding media. It was confirmed the FP Bragg gratings cavity is more sensitive than the single Bragg grating. The sensor developed in this study shows much promise in the application of biomedical diagnostics such as a bio-sensor and/or environmental monitoring systems.

In this paper we present a low-loss hydrogenated amorphous silicon microdisk resonator which is employed for evanescent field refractive index sensing. The resonances of the whispering gallery modes have extinction ratios of <25dB and Q-factors up to 15000 when covered with aqueous solutions. The sensitivity of the microdisk sensor was experimentally determined to be 460nm/RIU for the qTM-mode with different concentrations of NaCl dispersed in deionized water. From the measurements the resonators intrinsic limit of detection was calculated to be LOD=3.3x10^-4 and the minimum detectable amount of NaCl diluted in DI-water was determined to be 0.0375%. The early results prove that photonic microdisk resonators that are fabricated with low-loss hydrogenated amorphous silicon material can be applied in a variety of different areas for label-free lab-on-chip sensing, including chemical, medical and bio-sensing applications.

Expiratory breath contains various VOCs(Volatile Organic Compounds) produced from the human. When a certain disease exists, the exhalation has specific VOCs which may be generated from diseases. Many researchers have been actively working to find different types of biomarkers which are characteristic for particular diseases. Research regarding the identification of specific diseases from exhalation is still in progress. The aim of this research is to implement early detection of lung disease such as lung cancer and COPD(Chronic Obstructive Pulmonary Disease), which was nominated on the 6th of domestic death rate in 2010, based on multi-sensor array system. The system has been used to acquire sampled expiratory gases data and PCA(Principle Component Analysis) technique was applied to analyze signals from multi-sensor array. Throughout the experimental trials, a clearly distinguishable difference between lung disease patients and healthy controls was found from the measurement and analysis of their respective expiratory gases.

Micro- and Nano-fabricated membrane sieves have a great potential in molecular separation applications by giving more precise structural and pattern control of shapes. This limitation can be addressed by a class of ultrathin membranes for molecular separations in solutions. Micromachining methods facilitate the accomplishing nanostructures to be used for separation of collections of particles. It makes possible to fabricate nanosieves having a thickness on the order of or even smaller than the diameter of the nanohole [1-2]. However, membrane fragility and complex fabrication have prevented the use of ultrathin membranes for molecular separations [3-4]. Furthermore, it is difficult to control the holes in nanoscale dimensions precisely and uniformly for mass production. Even though there are few reports on the size control of nanopores of the membrane nanosieves, it is necessary to do research on the precise and reliable size control of nanopores for mass production of biosensors or biochips.

Surface plasmon-coupled emission (SPCE) microscopy provides high sensitivity for surface imaging due to the field enhancement effect of surface plasmon resonance. Based on previous theoretical and experimental studies, SPCE microscopy (SPCEM) generates an unusual annular-shape point spread function (PSF). In order to correct the distorted PSF without numerical deconvolution, an experimental method with a spiral phase plate (SPP) has been proposed. However the three-dimensional nature of PSF has not been explored in the past. In this study, we performed a theoretical study to obtain three-dimensional PSF of SPCE microscopy.

Surface-enhanced Raman scattering (SERS) has attracted considerable attention for chemical and biological agent detection through the amplification of electromagnetic fields from localized surface plasmon resonance on a metal nanostructure. The fabrication of metal nanostructure is the key issue for applications of SERS substrate. Particularly, well-ordered noble metal nanodot array can be reproducibly fabricated using anodic aluminum oxide layer with uniform channels of nanometer dimensions. In this study, we report the fabrication of Ag nanodot array on indium-tin-oxide (ITO) glass via the nanoporous alumina mask with through-holes and the utilizing the array as a substrate for SERS application. Ag nanodot array with 55 nm diameter was fabricated in periodic pattern with separation distance of 105 nm as a replica of the alumina mask. Optical property of Methylene Blue adsorption on Ag nanodot array was examined by Raman spectroscopy. These results suggest that Ag nanodot array might be useful as a SERS platform for the future application in sensitive detection of chemical materials.

Protein is a widely used sensing substrate in the biosensing technology. In the study conducted here, we used odorant binding protein, LUSH from Drosophila as a biosensing substrate in a miniaturized surface plasmon resonance (SPR) sensor. LUSH contains the specific alcohols binding sites, which mediates the detection of alcohols and pheromone. We first modified the surface of the gold sensor chip using the self assembled monolayer in the chloroform solution. The saturated concentration was determined prior to the detection of alcohols and pheromone at various concentrations. The results showed that the LUSH was saturated at 1000 μg/ml on the gold sensor chip. The detection response of LUSH was significant at higher concentration of alcohols. LUSH detected ethanol at concentration ≥50%; propanol was detected at ≥25% whereas pheromone was detected at ≥1.25 μg/μl. The results provide some fundamental information on the potential use of LUSH-based SPR as a simple and easy protein-based sensor in the near future.

Distortions caused by the DC-biased laser input can be modeled as DC biased Gaussian noise and removing DC bias is important in the demodulation process of the electrical signal in most optical communications. In this paper, a new performance criterion and a related algorithm for unsupervised equalization are proposed for communication systems in the environment of channel distortions and DC biased Gaussian noise. The proposed criterion utilizes the Euclidean distance between the Dirac-delta function located at zero on the error axis and a probability density function of biased constant modulus errors, where constant modulus error is defined by the difference between the system out and a constant modulus calculated from the transmitted symbol points. From the results obtained from the simulation under channel models with fading and DC bias noise abruptly added to background Gaussian noise, the proposed algorithm converges rapidly even after the interruption of DC bias proving that the proposed criterion can be effectively applied to optical communication systems corrupted by channel distortions and DC bias noise.

We present that the carrier concentration injected from a silicon substrate to a copper phthalocyanine thin film depends on the incidence angle of photoexciting beam. At higher incidence angles of photoexciting beam, the modulation efficiency of terahertz transmission due to TM-polarized excitation is distinctly higher than one due to TE-polarized excitation. We find that this phenomenon is due to the enhancement of carrier injection which is expected when the incident light is more transmitted through the organic thin film.

Automatic determination of the cell shapes of large numbers of melanocytes based on optical images of human skin models have been largely unsuccessful (the complexities introduced by dendrites and the melanin pigmentation over the keratinocytes to give unclear outlines). Here, we present an image enhancement procedure for enhancing the contrast of images with removing the non-uniformity of background. The brightness is normalized also for the non-uniform population density of melanocytes.

Study of biological molecule DNA has contributed to developing many breaking thoughts and wide applications in multidisciplinary fields, such as genomic, medical, sensing and forensic fields. Stretching of DNA molecules is an important supportive tool for AFM or spectroscopic studies of DNA in a single molecular level. In this article, we established a simple method of DNA stretching (to its full length) that occurred on a rotating negatively-charged surface of glass substrate. The isolation of a single DNA molecule was attained by the two competitive forces on DNA molecules, that is, the electrostatic attraction developed between the positively charged YOYO-1 stained DNA and the negatively charged substrate, and the centrifugal force of the rotating substrate, which separates the DNA aggregates into the single molecule. Density of stretched DNA molecules was controlled by selecting the specific parameters such as spinning time and rates, loading volume of DNA-dye complex solution etc. The atomic force microscopy image exhibited a single DNA molecule on the negatively-charged substrate in an isolated state. Further, the photoluminescence spectra of a single DNA molecule stained with YOYO-1 were achieved using the method developed in the present study, which is strongly believed to effectively support the spectroscopic analysis of DNA in a single molecular level.

In this paper, the high thermo-optic coefficient, and enhancing sensitivity with temperature, high birefringence PCF filled in ethanol was manufactured by temperature sensor of filling the air holes with ethanol. The theoretical model of high birefringence PCF has proposed by the plane wave expansion method, at the same time the temperature impacts of the birefringence and beat length in high birefringence PCF which filled with ethanol were numerical analyzed. The birefringence increases as a beat length decreases with a wavelength increases. Especially high birefringence PCF is more sensitive to temperature with the long wavelength, which is a reference significance in useful to design temperature sensors.

Herein, we have developed a label-free and homogeneous fluorescence resonance energy transfer (FRET) immunoassay for the detection of neopterin (NPT), which is an early and valuable biochemical marker of cellular immunity. Owing to intrinsic fluorescence properties of antibody and NPT, anti-NPT antibody (anti-NPT) and analyte played roles as the respective donor and acceptor in the FRET immunoassay. As the concentration of NPT increases, the fluorescence intensity at ~350 nm decreases owing to the formation of increasing amounts of the anti-NPT/NPT complex in which FRET takes place. The assay system was found to display a high specificity and a low detection limit (0.14 ng mL^-1) for NPT. A practical application of the FRET immunoassay system was demonstrated by its use in the detection of NPT in spiked human serum samples. The observations made in these efforts show that the homogeneous FRET immunoassay strategy, which requires a simple sample preparation procedure, serves as a powerful tool for the rapid and sensitive quantitative determination of NPT.

In order to confirm an applying capability of the CLSM, the V₂O₅ nanorods grown by the electron beam irradiation and the thermal oxidation methods were used as nanostructures, and the CLSM was composed in our laboratory. The theoretical resolution of the hand-made CLSM was found to be a 150 nm and evaluated by observing image of an USAF target.The morphologies of the grown V₂O₅ nanorods grown were observed by the CLSM, and the morphologies were compared with those obtained by the SEM. From the comparison with the result by the SEM, the magnification and the resolution of the CLSM were estimated to be approximately 2000 and 500 nm, respectively. On the basis of this result, it was considered that the CLSM can be used to measure the morphology of the nanostructures with a submicro-scale.

We report the application of Optical Coherence Tomography (OCT) to various types of human cases of otitis media (OM). Whereas conventional diagnostic modalities for OM, including standard and pneumatic otoscopy, are limited to visualizing the surface information of the tympanic membrane (TM), OCT is able to effectively reveal the depth-resolved microstructural below the TM with a very high spatial resolution. With the potential advantage of using OCT for diagnosing different types of OM, we examined in-vivo the use of 840 nm wavelength, and OCT spectral domain OCT (SDOCT) techniques, in several human cases including normal ears, and ears with adhesive and effusion types of OM. Peculiar positions were identified in two-dimensional OCT images of abnormal TMs compared to images of a normal TM. Analysis of A-scan (axial depth-scans) data from these positions could successfully identify unique patterns for different constituents within effusions. These OCT images may not only be used for constructing a database for the diagnosis and classification of OM, but they may also demonstrate the feasibility and advantages for upgrading the current otoscopy techniques.

In this study, we used a Complementary Metal Oxide Semiconductor (CMOS) image sensor with immobilizing antibodies on its surface to detect human cytokines, which are activators that mediate intercellular communication including expression and control of immune responses. The CMOS image sensor has many advantages over the Charge Couple Device, including lower power consumption, operation voltage, and cost. The photodiode, a unit pixel component in the CMOS image sensor, receives light from the detection area and generates digital image data. About a million pixels are embedded, and size of each pixel is 3 x 3 μm. The chemiluminescence reaction produces light from the chemical reaction of luminol and hydrogen peroxide. To detect cytokines, antibodies were immobilized on the surface of the CMOS image sensor, and a sandwich immunoassay using an HRP-labeled antibody was performed. An HRP-catalyzed chemiluminescence reaction was measured by each pixel of the CMOS image sensor. Pixels with stronger signals indicated higher cytokine concentrations; thus, we were able to measure human interleukin-5 (IL-5) at femtomolar concentrations.

Parkinson’s disease (PD) is characterized by progressive dopaminergic cell loss in the substantianigra (SN) and elevated iron levels demonstrated by autopsy and with 7-Tesla magnetic resonance imaging. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells. The cells were exposed to iron by treatment with ferric ammonium citrate (FAC, 100 μM) for up to 6 hours. The hyperspectral fluorescence imaging signal of iron was examined usinga high- resolution dark-field optical microscope system with signal absorption for the visible/ near infrared (VNIR) spectral range. The 6-hour group showed heavy cellular iron deposition compared with the small amount of iron accumulation in the 1-hour group. The cellular iron was dispersed in a small, particulate form, whereas extracellular iron was detected in an aggregated form. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The cellular iron accumulation readily occurred in MPP⁺-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN in PD. This direct iron imaging methodology could be applied to analyze the physiological role of iron in PD, and its application might be expanded to various neurological disorders involving other metals, such as copper, manganese or zinc.

The highly sensitive nanoporous cantilever beam without immobilized receptors was combined with highly selective mid-infrared (IR) spectroscopy for molecular recognition of analytes using characteristic molecular vibrations. Unlike conventional IR spectroscopy, in addition, the detection sensitivity and resolution are drastically enhanced by combining high power tunable quantum cascade laser with a nanoporous cantilever having large surface area, low modulus, and nanowell structures. Further, analytes can be easily loaded on the porous microcantilever without receptor due to nanowells. In addition, orthogonal signals, variations in the mass and IR spectrum, provide more reliable and quantitative results including physical as well as chemical information of samples. We have used this technique to rapidly identify single and double stranded DNA.

The polarization dependence of rotational diffusion of quantum rods was investigated and characterized by analyzing amplitude and characteristic time of the correlation functions. In order to measure the polarization dependence, a polarized fluorescence correlation spectroscopy system was composed based on a microscope. From the results, the rotational diffusion region of Qrod was observed at a time range below 10^-5 s, and the rotational diffusion parameters were extracted by using a rotational diffusion model. The parameters revealed the polarization dependence of rotational diffusion of Qrod in solution. We showed that polarized FCS is quite useful to investigate rotational diffusion of rod-like particles.

Biomarker-specific photothermal nanoparticles that can efficiently sense the markers, which are overexpressed in distinguished adenocarcinomas, has attracted much interest in an aspect of efficacy increase of cancer treatment. In this study, we demonstrated a promising prospect of smart photothermal therapy agent employing anti-epidermal growth factor receptor aptamer (Apt_EGFR)-conjugated polyethylene glycol (PEG)layted gold nanorods (Apt_EGFR-PGNRs). The cetyltrimethylammonium bromide bilayer on GNRs was replaced with heterobifunctional polyethylene glycol (COOHPEG- SH) not only to serve as a biocompatible stabilizer and but also to conjugate Apt_EGFR. Subsequently, to direct photothermal therapy agent toward epithelial cancer cells, the carboxylated PEGylated GNRs (PGNRs) were further functionalized with Apt_EGFR using carbodiimide chemistry. And then, to assess the potential as biomarker-specific photothermal therapy agent of synthesized Apt_EGFR-PGNRs, the optical properties, biocompatibility, colloidal stability, binding affinity and epicellial cancer cell killing efficacy in vitro/in vivo under NIR laser irradiation were investigated. As a results, Apt_EGFR-PGNRs exhibit excellent tumor targeting ability and feasibility of effective photothermal ablation cancer therapy.

Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer’s nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer’s disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

The objective of our research was to predict cell fates of a multicellular system, accompanied by cellular differentiation. To fulfill this objective, we sought to distinguish the differentiated and undifferentiated cells of filamentous cyanobacteria (Anabaena sp. PCC 7120) using Raman imaging. This technique indicated Raman bands of the cellular system, in which several bands were assigned to vibrations of β-carotene and scytonemin. We applied principal component analysis (PCA) to the Raman spectra to determine the PC1 and PC2 loading plots and their scores. The data points obtained for heterocyst tended to converge along the bottom of the scatterplot whereas those for vegetative cells were more widely distributed in the PC plane. This indicates that the chemical compositions of a heterocyst were relatively stable. As vegetative cells are capable of proliferation or differentiation, they may transit and exist in several states including the pseudo-differentiated state. The results suggest that the chemical compositions of a vegetative cell fluctuated according to its cellular condition. In conclusion, the results of Raman imaging indicate that the diverse states of vegetative cells are localized in a specific state through differentiation.

In order to detect interested matters in fields, various lab-on-a-chips where chemical, physical, or biological sensors are loaded have been developed. eNOSE can be a representative example among them. Because animals can sense 300~1000 different chemicals by olfactory system – smell –, the olfactory system has been spotlighted as new materials in the field of sensing. Those investigations, however, are usually focused on how to detect signals from the olfactory neurons or receptors loaded on chips and enhance sensing efficacy of chips. Therefore, almost of those chips are designed for only one material sensing. Multi-sensing using multi-channels will be needed when the olfactory systems are adopted well on chips. For multiple sensing, we developed an addressable cell array. The chip has 38 cell-chambers arranged in a circle shape and different cell types of thirty eight can be allocated with specific addresses on the chip without any complex valve system. In order to confirm the cell addressing, we loaded EGFP-transfected and empty vector-transfected HEK293a cells into inlets of the cell array in a planned address and those cells were positioned into each chamber by brief aspiration. The arrayed cells were confirmed as a specific pattern through EGFP and nuclei staining. This cell array which can generate address of sensor materials like cells with their own specification is expected to be applied to a platform for a biosensor chip at various sensing fields.

Electrical stimulation affects cellular behaviors including division, migration and wound healing [1-3]. Cellular injury often occurs due to the imbalance of the endogenous electric field [3]. In order to recover from the injury, wound healing process requires various cellular changes such as regeneration, migration, and the enhancement of cytoskeletal proteins and growth factors. In previous reports, a weak non-contact electric field stimulation (nEFS) accelerates the cell migration as well as cell-to-cell coupling between neuronal cell junction which are accompanied by increasing of cytoskeletal proteins [4, 5]. In this paper, we further investigated the wound healing effect of the nEFS in the neuronal cells (SHSY5Y cells) with live cell optical imaging. Cells were cultured over the optically transparent graphenen EF stimulator. Cellular behavioral changes upon nEFS were recorded with live optical imaging during stimulation of 120 minutes. The ability of wound healing was significantly enhanced with the nEFS. In particular, nEFS significantly shorten the duration of wound healing process. Moreover, after treating cells with cytochalasin D, a block polymerization of the actin filaments, the nEFS significantly enhanced wound healing process of cytochalasin D treated neural cells as compared to the control neural cells. This study suggests that nEFS may provide an effective way to control neural cells repairing process from cellular injury. Further mechanism study about the effect of nEFS on the wound healing may shed new light on cellular behavior.

A kind of novel reflective grating microcantilever based on SOI was designed and fabricated for biosensing. For measuring the extremely low deflections of the microcantilever, a high precision optical readout approach based on diffraction spectrum balancing feedback control was presented. The read out system include a PI M-038 precision motorized rotation stage, a CCD, a 650 nm laser, a fiber, a min fiber GRIN collimator and lens. The practical measurement resolution of the system is up to 1x10^-4 deg, that is to say, for a length of 250um microcantilever, the tip measure resolution is up to 0.043nm.

In this study, we describe the development of cancer biomarker-sensitive nanobiosensor based on localized surface plasmon resonance (LSPR) that enabling recognition for proteolytic activity of membrane type 1 matrix metalloproteinase (MT1-MMP) anchored on invasive cancer cells. First of all, we prepared biomarker-detectable substrate based on gold nanorods (GNRs) using nanoparticle adsorption method. The sensitivity of sensing chip was confirmed using various solvents that having different refractive indexes. Subsequently, MT1-MMP-specific cleavable peptide was conjugated onto surface of GNRs and molecular sensing about proteolytic activity was conducted using MT1-MMP and cell lysates. Collectively, we developed biomarker detectable sensor, which allows for the effective detection of proteolytic activity about MT1-MMP extracted from invasive cancer cells.

We have synthesized ceria nanoparticles by reacting cerium salts and sodium hydroxide without any additive in order to avoid possible cytotoxicity. The synthesized ceria nanoparticles were with cubic structure according to X-ray diffraction and have diameters between 6 and 10 nm analyzed by transmission electron microscopy. Aggregation behaviors of ceria nanoparticles in DI water and cell culture media have been studied by dynamic light scattering. In de-ionized water, ceria nanoparticles formed a stable colloidal solution with hydrodynamic size ~ 70 nm and zeta potential ~ 47 mV. Dispersion of the nanoparticles in serum-free media was found to result in larger aggregates, while the nanoparticles in serumcontaining media form a stable solution, which suggests that proteins in serum and ceria nanoparticles have some interactions. In cellular uptake test, entry of ceria nanoparticles into HeLa cells incubated in serum-containing media at 37 °C for 60 min was observed and without cytotoxicity.

Stem cell therapy is a promising tool for the treatment of diverse conditions including neurodegenerative diseases. To understand transplanted stem cell biology, in vivo imaging is necessary. Nano material has great potential for in vivo imaging and several noninvasive methods are used such as magnetic resonance imaging (MRI), positron emission tomography (PET), Fluorescence imaging (FI) and Near-infrared fluorescence imaging (NIRFI). However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose derived stem cells (hASCs) that labeled with multimodal nano particle, LEO-LIVE^TM-Magnoxide 797 or 675, into the Tg2576 mice, Alzheimer’s disease (AD) mouse model. Sequential in vivo tracking was performed with mice injected with hASCs. We could found fluorescence signals until 10 days after injection.