This PDF file contains the front matter associated with SPIE Proceedings Volume 8548, including the Title Page, Copyright information, Table of Contents, Sponsors, and the Conference Committees listing.

Bio-nanohybrids prepared by assembling natural polymers (polysaccharides, proteins, nucleic acids, etc) to nanosized silicates (nanoclays) and related solids (layered double hydroxides, LDHs) give rise to the so-called bionanocomposites constituting a group of biomaterials with potential applications in medicine. In this way, biopolymers, including chitosan, pectin, alginate, xanthan gum, ι-carrageenan, gelatin, zein, and DNA, as well as phospholipids such as phosphatidylcholine, have been incorporated in layered host matrices by means of ion-exchange mechanisms producing intercalation composites. Also bio-nanohybrids have been prepared by the assembly of diverse bio-polymers with sepiolite, a natural microfibrous magnesium silicate, in this case through interactions affecting the external surface of this silicate. The properties and applications of these resulting biomaterials as active phases of ion-sensors and biosensors, for potential uses as scaffolds for tissue engineering, drug delivery, and gene transfection systems, are introduced and discussed in this work. It is also considered the use of synthetic bionanocomposites as new substrates to immobilize microorganisms, as for instance to bind Influenza virus particles, allowing their application as effective low-cost vaccine adjuvants and carriers.

Iron oxide colloidal nanoparticles (ferrofluids) are investigated for application in the treatment of cystic fibrosis lung infections, the leading cause of mortality in cystic fibrosis patients. We investigate the use of iron oxide nanoparticles to increase the effectiveness of administering antibiotics through aerosol inhalation using two mechanisms: directed particle movement in the presence of an inhomogeneous static external magnetic field and magnetic hyperthermia. Magnetic hyperthermia is an effective method for decreasing the viscosity of the mucus and biofilm, thereby enhancing drug, immune cell, and antibody penetration to the affected area. Iron oxide nanoparticles of various sizes and morphologies were synthesized and tested for specific losses (heating power). Nanoparticles in the superparamagnetic to ferromagnetic size range exhibited excellent heating power. Additionally, iron oxide / zinc selenide core/shell nanoparticles were prepared, in order to enable imaging of the iron oxide nanoparticles. We also report on synthesis and characterization of MnSe/ZnSeS alloyed quantum dots.

Brain tumor, especially glioblastoma multiforme (GBM), is one of the most malignant tumors, which not only demands perplexing treatment approaches but also requires potent and effective treatment modality to deal with recurrence of the tumor. Photodynamic therapy (PDT) is a treatment which has been recommended as a third-level treatment. We are trying to investigate possibility of the PDT as an efficient adjuvant therapeutic modality for the treatment of brain tumor. Inhibition of tumor progression with photosensitizer was verified, in vitro. With micellar nanoscale drug delivery system, localization of the tumor was identified, in vivo, which is able to be referred as photodynamic diagnosis. With consequent results, we are suggesting photodynamic diagnosis and therapy is able to be performed simultaneously with our nanoscale drug delivery system.

In our studies, related to projects developing nanoparticles for sentinel node detection of breast cancer [Nanomagdye FP7, EU project grant agreement nr NMP3-SL-2008-214032 and Nanomatrix INTERREG IV program Upper Rhine Valley A21], we focused on the magnetic iron oxide nanoparticles in 10-40 nm range made by precipitation in aqueous media, on the functionalization by dendrons ensuring the stabilization in aqueous media and on the effect of grafting on the magnetic properties. By combining magnetic measurements, X-ray diffraction and Mössbauer spectrometry, we showed that the nanoparticles can be described by a core-shell model, that is, a magnetite core surrounded by an oxidized layer close to maghemite. The fractional volume of maghemite increases as the particle size decreases so that below 20 nm, the particle is oxidized in the whole volume and the nanoparticles cannot be properly labeled as “magnetite”. The oxide/molecule interactions have a strong effect on the magnetic structure and properties. In case of phosphonate coupling agent, the saturation magnetization is increased and no spin canting is observed due to a covalent bonding.

Semiconductor fluorescent quantum dots (QDs) have just demonstrated their numerous advantages over organic dyes in bioimaging and diagnostics. One of characteristics of QDs is a very large cross section of their twophoton absorption. A common approach to biodetection by means of QDs is to use monoclonal antibodies (mAbs) for targeting. Recently, we have engineered ultrasmall diagnostic nanoprobes (sdAb–QD) based on highly oriented conjugates of QDs with the single-domain antibodies (sdAbs) against cancer biomarkers. With a molecular weight of only 13 kDa (12-fold smaller than full-size mAbs) and extreme stability and capacity to refolding, sdAbs are the smallest functional Ab fragments capable of binding antigens with affinities comparable to those of conventional Abs. Ultrasmall diagnostic sdAb–QD nanoprobes were engineered through oriented conjugation of QDs with sdAbs. This study is the first to demonstrate the possibility of immunohistochemical imaging of colon carcinoma biomarkers with sdAb–QD conjugates by means of two-photon excitation. The optimal excitation conditions for imaging of the markers in clinical samples with sdAb–QD nanoprobes have been determined. The absence of sample autofluorescence significantly improves the sensitivity of biomarker detection with the use of the two-photon excitation diagnostic setup.

Bacteriorhodopsin (bR) is a unique protein of purple membranes (PMs) of the bacterium Halobacterium salinarum. Tight trimers of this integral photochromic protein form a highly ordered 2D hexagonal crystalline lattice within the PMs. Due to strong excitonic interactions between the bR chromophores (retinals) in the protein trimers, PMs exhibit a strong circular dichroism (CD) activity in the region of the retinal absorption band, which allows monitoring the regularity and stability of the bR trimer organization within the membrane. In this study, the effects of semiconductor quantum dots (QDs) on the bR intramembrane organization and the time course of bR monomerization caused by detergents have been analyzed. The results show that the interaction with QDs does not influence the bR structural organization but considerably accelerates the monomerization of the protein by detergents. These data have been confirmed by the results of atomic force microscopy (AFM) followed by Fourier transform analysis, which have shown that interactions with QDs cause an eightfold acceleration of bR monomerization with Triton. The data show that interactions of nanoparticles with biological membranes may modulate the membrane fluidity and the structural organization and function of integral proteins embedded in these membranes.

Remote point-of-care is expected to revolutionize the modern medical practice, and many efforts have been made for the development of wireless health monitoring systems for continuously detecting the physiological signals of patients. To make the remote point-of-care generally accepted and widely used, it is necessary to develop cost-effective and durable wireless health monitoring systems. Printing technique will be helpful for the fabrication of high-quality and low-cost medical devices and systems because it allows high-resolution and high-speed fabrication, low material consumption and nano-sized patterning on both flexible and rigid substrates. Furthermore, application of thermoelectric generators can replace conventional batteries as the power sources for wireless health monitoring systems because thermoelectric generators can convert the wasted heat or the heat from nature into electricity which is required for the operation of the wireless health monitoring systems. In this research, we propose the concept of printable thermoelectric devices and conductive patterns for the realization of more portable and cost-effective medical devices. To print thermoelectric generators and conductive patterns on substrates, printing inks with special characteristics should be developed. For the development of thermoelectric inks, nano-structured thermoelectric materials are synthesized and characterized; and for the development of conductive inks, two kinds of surface treated carbon nanotubes are used as active materials.

Cellulose-metal oxide nanomaterials were developed the technologies to manipulate self-assembly and multi-functionallity, of new technologies to the point where industry can produce advanced and cost-competitive cellulose and lignocellulose-based materials. The present investigation focused on cellulose–silica and cellulose functionalized 3,4-dihydroxy phenyl alanine(dopamine) silica/gold nanomaterials by in-situ sol-gel process. The tetraethoxysilane (TEOS) and gold precursors such as tetrachloroauricacid (HAuCl₄) and γ- aminopropyltriethoxysilane (γ-APTES) as coupling agent were used for sol-gel crosslinking process. The chemical and morphological properties of cellulose/silica and cellulose /silica-gold nanomaterials via covalent crosslinking hybrids were investigated with FTIR, XRD, SEM and TEM analysis. The results show that cellulose/silica and cellulose functionalized dopamine–silica/gold hybrids form new macromolecular structures in the size of 20 nm.

Implantable glucose sensors can measure real time blood glucose as compared to conventional techniques involving drawing blood samples and in-vitro processing. An implantable sensor requires energy source for operation with wire inout provision for power and sending signals. Implants capable of generation-transmission of sensory signals, with minimal or no power requirement, can solve this problem. An implantable nanosensor design has been presented here, which can passively detect glucose concentration in blood stream and transmit data to a wearable receiver-recorder system or a watch. The glucose sensitive component is a redox pair of electrodes that generates voltage proportional to glucose concentration. The bio-electrode, made of carbon nanotubes-enzyme nanocluster, has been investigated because of the large surface area for taping electrical signals. This glucose sensor can charge a capacitor, which can be a part of a LCR resonance/inductive coupling based radio frequency (RF) sensor telemetry. Such a system can measure change in glucose concentration by the induced frequency shift in the LCR circuit. A simultaneous power transmission and signal transmission can be achieved by employing two separate LCR oscillating loops, one for each operation. The corresponding coupling LCR circuits can be housed in the wearable receiving watch unit. The data logged in this glucose monitoring watch can be instrumental in managing blood glucose as trigger for an insulin dispensing payload worn on person or implanted.

The financial burden of hospital readmissions and treatment of chronic cardiac diseases are global concerns. Point of Care (POC) has been presented as an elegant solution for healthcare cost reduction. However, large scale adoption of POC systems requires an intuitive, unobtrusive and easy to use health monitoring system from patient’s perspective. Healthcare textiles are sensor systems mounted on textile platform that function as wearable unobtrusive health monitoring systems. Although much work has been done in the development and demonstration of textile mounted monitoring systems, material and production costs are still high. Nanomaterials based devices and technology can be employed in these healthcare textiles for improved electrical characteristics of the sensors, lowered cost due to less material consumption and compatibility to varied manufacturing techniques. Carbon nanotube composite ink based printable conductive electrodes is such a textile adaptable nanomaterial technology. Screen printed Nanocomposite electrodes made of carbon nanotubes and an acrylic polymer can be used in undergarments like vests and brassieres, for cardiac biopotential (Electrocardiography, ECG) sensing. A Bluetooth module and a smartphone can then be used to provide cyber-infrastructure connectivity for the healthcare data from these healthcare garments. They can be used to monitor young or elderly recuperating /convalescent patients either in hospital or at home, or they can be used by young athletes to monitor important physiological parameters to better design their training or fitness program. In this study, we evaluate screen printed CNT-acrylic Nanocomposite electrodes for ECG signal quality and any CNT leaching hazard that might lead to skin toxicity.

Immunoassays have become a standard in secretome analysis in clinical and research analysis. In this field there is a need for a high throughput method that uses low sample volumes. Microfluidics and nanofluidics have been developed for this purpose. Our lab has developed a nanofluidic bioarray (NBA) chip with the goal being a high throughput system that assays low sample volumes against multiple probes. A combination of horizontal and vertical channels are produced to create an array antigens on the surface of the NBA chip in one dimension that is probed by flowing in the other dimension antibodies from biological fluids. We have tested the NBA chip by immobilizing streptavidin and then biotinylated peptide to detect the presence of a mouse monoclonal antibody (MAb) that is specific for the peptide. Bound antibody is detected by an AlexaFluor 647 labeled goat (anti-mouse IgG) polyclonal antibody. Using the NBA chip, we have successfully detected peptide binding by small-volume (0.5 μl) samples containing 50 attomoles (100 pM) MAb.

Healthcare textiles are ambient health monitoring systems that can contribute towards medical aid as well as general fitness of the populace. These are textile based products that have sensor systems mounted on them or are electrically functionalized to act as sensors. While embedded sensor chipsets and connection wires have been shown as working prototypes of this concept, there is a need for seamless integration of sensor technologies without hindering the inherent properties of the textile. Screen printing or stamping with electrically conductive inks have been demonstrated as technologies for fabricating electronics on flexible substrates. They are applicable to textile manufacturing as well. Printing technology allows for fabrication of nanocomposite based electronics elements in a bottom-up fashion. This has advantages such as low material consumption, high speed fabrication and low temperature processing. In this research, Multi-Wall Carbon Nanotubes (MWCNTs) and polyaniline nanoparticles (PANP) core shell based nanocomposites were synthesized and formulated into colloidal ink. Printed MWCNTs-PANP traces were electrically characterized and compared with traces made with those made by other composites such as Silver, and Carbon Black. The nanocomposite based inks are compared for proposed applications as sensor systems and conductive tracks on smart textile for pervasive wireless healthcare system that can be mass produced using low cost printing processes.

With the advent of targeted agents, it has become clinically important to distinguish histologic types of non-small cell lung cancers (NSCLCs) using biopsy samples. We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may classify histology of NSCLCs. Twentyone pairs of frozen, resected NSCLCs were analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Squamous cell carcinomas and adenocarcinomas, two major histologic types of NSCLC, were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set, suggesting that lipid profiles can classify NSCLCs according to the histologic type. We also found that protein and lipid MALDI MS profiles can classify 30 breast cancers according to the intrinsic subtypes. Immunohistochemistry-defined, luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by cross validation P values < 0.01. Discriminatory proteins and lipids classified tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in 100 random test sets. Potential advantages of this label-free approach may include small tissue requirement, relatively rapid procedure, and low reagent cost. Day-today variation of this technology is also acceptable, with the Pearson correlation of 0.95. Taken together, these results suggest the possible clinical utility of histology-directed, lipid and protein MALDI MS.

The Microinstrumentation Lab group at Simon Fraser University (SFU) develops biomedical nano- and micro-device based microinstrumentation by combining integrated materials and interconnect technologies with a modular systems approach. A major focus of our research is the development and application of disparate materials, including novel nanomaterials developed in our laboratory, to discrete components, combined with integration and interconnection standards that are designed to be generally applicable to multiple systems in our lab. In this overview, we present a sample of these technologies that have been developed by our lab since its inception, and demonstrate use of these technologies in both discrete components and modular systems towards the realization of complex bio-microinstruments for an ever-expanding group of collaborative projects in biology and biomedicine.

The ultrasensitive and selective diagnosis along with efficient therapy in earliest stage of cancer has been enormously highlighted by a better means to treat the cancer. Herein, Gd (III) chelated polyaniline nanoparticles (GPNPs) was synthesized to be served as a highly T₁ enhanced contrast agents and Near-Infrared photothermal therapy probes. In addition, therapeutic antibody was conjugated on the surface of GPNPs for the targeted theragnosis. Fabricated GPNPs significantly reduced the T₁ of water protons with as well as represented photothermal ability. The physicochemical properties and biocompatibilities of GNPSs were fully characterized and GPNPs exhibited excellent tumor targeting ability. Consequently, GPNPs exhibited strong potential for efficient diagnosis of cancer in MR imaging and photothermal ablation of epithelial cancer cells.

The luminescence and magnetic resonance imaging (MRI) and photodynamic therapy (PDT) using lanthanide-doped upconverting nanoparticles (UCNPs) is reported. With the aim to induce a therapeutic effect, a photosensitizer, chlorin e6 (Ce6), was conjugated to UCNPs. Owing to the enhanced permeability and retention effect, UCNPs combined with a photosensitizer, chlorin e6 (UCNP-Ce6) could be readily accumulated at the tumors, which could be clearly observed not only in the upconversion luminescence image but also in the MRI image. Using the energy transfer from UCNPs to Ce6, cytotoxic singlet oxygen could be generated. An in vivo PDT effect by systemic administration of UCNP-Ce6 was demonstrated under 980-nm irradiation. These results indicate that UCNP-Ce6 can be used not only as dual-modal imaging probes for accurate diagnosis but also as photodynamic therapy agent for efficient therapy.

We present the initial experimental results for manipulating micro-robots featuring permanent magnetic polymer magnets for guided wireless endoscopy applications. The magnetic polymers are fabricated by doping polydimethylsiloxane (PDMS) with permanent isotropic rare earth magnetic powder (MQFP 12-5) with an average particle size of 6 μm. The prepared magnetic nanocomposite polymer (M-NCP) is patterned in the desired shape against a plexiglass mold via soft lithography techniques. It is observed that the fabricated micro-robot magnets have a magnetic field strength of 50 mT and can easily be actuated by applying a field of 8.3 mT (field measured at the capsule’s position) and moved at a rate of 5 inches/second.

Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition, the proposed system provides real time monitoring of physiological signals at remote locations using Wi-Fi.

This paper will cover definition and history of telemedicine, changes in medical paradigm and roll of telemedicine and roll of nano-technology for evolution of telemedicine. Hypothetically, telemedicine is distance communication for medical purpose and modern definition explains telemedicine as ‘a system of health care delivery in which physicians examine distant patients through the use of telecommunications technology. Medical service will change to personalized medicine based on gene information to prevent and manage diseases due to decrease of acute diseases, population aging and increase of prevalence in chronic diseases, which means current medical services based on manualized treatment for diseases will change to personalized medicine based on individual gene information. Also, international healthcare will be activated to provide high quality medical services with low cost using developed transportation. Moreover, hospital centered medical services will change to patients centered medical service due to increase of patient’s rights. Development in sensor technology is required for telemedicine to be applied as basic infrastructure for medical services. Various researches in nano-biosensor field are conducted due to introduction of new technologies. However, most researches are in fundamental levels that requires more researches for stability and clinical usefulness. Nano technology is expected to achieve innovative development and define new criteria for disease prevention and management.

CardioVascular Disease(CVD)s lead the sudden cardiac death due to irregular phenomenon of the cardiac signal by the abnormal case of blood vessel and cardiac structure. For last two decades, cardiac disease research for man is under active discussion. As a result, the death rate by cardiac disease in men has been falling gradually compared with relatively increasing the women death rate due to CVD[2]. The main reason of this phenomenon causes the lack a sense of the seriousness to female CVD and different symptom of female CVD compared with the symptoms of male CVD. Usually, because the women CVD accompanies with ordinary symptoms unrecognizing the heart abnormality signal such as unusual fatigue, sleep disturbances, shortness of breath, anxiety, chest discomfort, and indigestion dyspepsia, most women CVD patients do not realize that these symptoms are related to the CVD symptoms. Therefore, periodic ECG signal observation is required for women cardiac disease patients. ElectroCardioGram(ECG) detection, treadmill test/exercise ECG, nuclear scan, coronary angiography, and intracoronary ultrasound are used to diagnose abnormality of heart. Among the medical checkup methods for CVDs checkup, it is very effective method for the diagnosis of cardiac disease and the early detection of heart abnormality to monitor ECG periodically. This paper suggests the effective ECG monitoring system for woman by attaching the system on woman’s brassiere by using augmented chest lead attachment method. The suggested system in this paper consists of ECG signal transmission system and a server program to display and analyze the transmitted ECG. The ECG signal transmission system consists of three parts such as ECG physical signal detection part with two electrodes made by gold nanowire structure, data acquisition with AD converter, and data transmission part with GPRS(General Packet Radio Service) communication. Usually, to detect human bio signal, Ag/AgCl or gold cup electrodes are used with conductive gel. However, the gel can be dried when taking long time monitoring. The gold nanowire structure electrodes without consideration of uncomfortable usage of gel are attached on beneath the chest position of a brassiere, and the electrodes convert the physical ECG signal to voltage potential signal. The voltage potential ECG signal is converted to digital signal by AD converter included in microprocessor. The converted ECG signal by AD converter is saved on every 1 sec period in the internal RAM in microprocessor. For transmission of the saved data in the internal RAM to a server computer locating at remote area, the system uses the GPRS communication technology, which can develop the wide area network(WAP) without any gateway and repeater. In addition, the transmission system is operated on client mode of GPRS communication. The remote server is installed a program including the functions of displaying and analyzing the transmitted ECG. To display the ECG data, the program is operated with TCP/IP server mode and static IP address, and to analyze the ECG data, the paper suggests motion artifact remove algorithm including adaptive filter with LMS(least mean square), baseline detection algorithm using predictability estimation theory, a filter with moving weighted factor, low pass filter, peak to peak detection, and interpolation.

This paper presents the progress made developments in the area of Smart Garments for chronic disease management over last 10 years. A large number of health monitoring smart garments and wearable sensors have been manufactured to monitor patient’s physiological parameters such as electrocardiogram, blood pressure, body temperature, heart rate, oxygen saturation, while patient is not in hospital. In last few years with the advancement in smartphones and cloud computing it is now possible to send the measure physiological data to any desired location. However there are many challenges in the development of smart garment systems. The two major challenges are development of new lightweight power sources and there is a need for global standardization and a road map for development of smart garments. In this paper we will discuss current state-of-theart smart garments and wearable sensor systems. Also discussed will be the new emerging trends in smart garment research and development.

Microwave/RF energy has been used for wireless power transmission including many therapeutic applications, such as transurethral microwave therapy (TUMT). For safe uses of RF power, it is important to know how to deliver microwave energy on focused area and control the temperature changes not to drastically increase on adjacent areas. Graphical analysis of thermal loading factor is important to understand how to achieve effective transmission of microwave through the tissue. The loss mechanism while transmission often appears as thermal effects due to absorption of microwave, especially for materials such as human skin, muscles, and other organic parts including brain. In this paper, microwave thermal effects are investigated to measure temperatures, penetration depth through animal skins in terms of input power and various frequencies. This result will be compare with the case of human applications.

Stress can have a significant negative impact on health and stress-induced alterations in sleep are implicated in both human sleep disorders and in psychiatric disorders in which sleep is affected. We have demonstrated that the amygdala, a region critical for regulating emotion, is a key modulator of sleep. Our current research is focused on understanding how the amygdala and stressful emotion affect sleep and on the role sleep plays in recovery from stress. We have implemented animal models to examine the how stress and stress-related memories impact sleep. Experiencing uncontrollable stress and reminders of uncontrollable stress can produce significant reductions in sleep, in particular rapid eye movement sleep. We are using these models to explore the neurobiology linking stress-related emotion and sleep. This research is relevant for sleep disorders such as insomnia and into mental disorders in which sleep is affected such as post-traumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic event.

Ferrimagnetic nanoparticles have been limited in in vivo application because nanoparticles aggregate due to its remanent magnetization. Uniform-sized ferromagnetic iron oxide nanocubes with similar value of bulk saturated magnetization were synthesized. Control of nanocubes’ size minimized their remanence. PEG-phospholipid encapsulation enabled spacing to prevent the aggregation. As a result, water-dispersed single core ferrimagnetic iron oxide nanocubes were successfully prepared and their r₂ relaxivity was 761 s^-1mM^-1. It was very close to theoretical calculated value 800 s^-1mM^-1 in static dephasing regime. in vivo MR images were obtained after intravenous injection of 22 nm nanoparticles to a mouse. The MR signal of tumor site changed significantly. In this research, synthesized ferrimagnetic iron oxide nanocubes showed a superior T2 contrast effect and it would be able to improve the quality of early diagnosis and detection of tumor.

Two kinds of biomimetic systems including engineered organ chip and flexible electronic sensor are presented. First, in vivo, renal tubular epithelial cells are exposed to luminal fluid shear stress (FSS) and a transepithelial osmotic gradient. In this study, we used a simple collecting-duct-on-a-chip to investigate the role of an altered luminal microenvironment in the translocation of aquaporin-2 (AQP2) and the reorganization of actin cytoskeleton (F-actin) in primary cultured inner medullary collecting duct (IMCD) cells of rat kidney. We demonstrate that several factors (i.e., luminal FSS, hormonal stimulation, transepithelial osmotic gradient) collectively exert a profound effect on the AQP2 trafficking in the collecting ducts, which is associated with actin cytoskeletal reorganization. Furthermore, with this kidney-mimicking chip, renal toxicity of cisplatin was tested under static and fluidic conditions, suggesting the physiological relevancy of fluidic environment compared to static culture. Second, we present a simple architecture for a flexible and highly sensitive strain sensor that enables the detection of pressure, shear and torsion. The device is based on two interlocked arrays of high-aspect-ratio Pt-coated polymeric nanofibres that are supported on thin polydimethylsiloxane layers. When different sensing stimuli are applied, the degree of interconnection and the electrical resistance of the sensor changes in a reversible, directional manner with specific, discernible strain-gauge factors. We show that the sensor can be used to monitor signals ranging from human heartbeats to the impact of a bouncing water droplet on a superhydrophobic surface.

Simple esophageal strictures, which are focal, straight, and large in diameter, usually require 1 - 3 dilation sessions to relieve symptoms. However, complex strictures, which are long, tortuous, or associated with a severely compromised luminal diameter, are usually more difficult to treat with conventional bougie or balloon dilation techniques, and often have high recurrence rates. Although the permanent placement of self-expandable metal stents (SEMS) has been used to manage refractory benign esophageal strictures, this procedure is associated with additional problems, such as stricture from tissue hyperplasia, stent migration, and fistula formation. Thus, several new types of stents have been developed, including temporary SEMS, self-expandable plastic stents (SEPS), and biodegradable stents. The use of these new products has produced varied results. Temporary SEMS that have been used to relieve benign esophageal conditions have caused granulation tissue at both ends of the stent because of contact between the mucosa and the exposed metal components of the stent, thus hindering stent removal. We examined the tissue response to two new types of SEMS, a flange-type and a straighttype, each coated with a silicone membrane on the outside of the metal mesh. These two SEMS were evaluated individually and compared with a conventional control stent in animal experiments. Although the newly designed stents resulted in reduced tissue hyperplasia, and were thus more easily separated from the esophageal tissue, some degree of tissue hyperplasia did occur. We suggest that newly designed DES (drug-eluting stents) may provide an alternative tool to manage refractory benign esophageal stricture.

Endoscopic stent insertion is the treatment of choice for patients with malignant biliary obstruction. However, conventional stents enable only mechanical palliation of the obstruction, without any anti-tumor effects. Drugeluting stent (DES), which was first introduced in coronary artery disease, are currently under investigation for sustaining stent patency and prolonging patient survival by inhibiting tumor ingrowth in malignant biliary obstruction. Many factors affecting efficient drug delivery have been studied to determine how drugs with antitumor effects suppress tumor ingrowth, including the specific drugs incorporated, means of incorporating the drugs, mode of drug release, and stent structure. Advances have resulted in the construction of more effective non-vascular DES and ongoing clinical research. Non-vascular DES is expected to play a vital role in prolonging the survival of patients with malignant biliary obstruction.

The shortage of fresh water is one of the acute challenges that the world is facing now and, thus, energy efficient desalination strategies can provide substantial answers for the water-crisis. Current desalination methods utilizing reverse-osmosis and electrodialysis mechanisms required high power consumptions/large-scale infrastructures which do not make them appropriate for disaster-stricken area or underdeveloped countries. In addition, groundwater contamination by heavy metal compounds, such as arsenic, cadmium and lead, poses significant public health challenges, especially in developing countries. Existing water purification strategies for heavy metal removal are not readily applicable due to technological, environmental, and economical barriers. This presentation elucidates a novel desalination/purification process, where a continuous contaminated stream is divided into filtered and concentrated stream by the ion concentration polarization. The key distinct feature is that both salts and larger particles (cells, viruses, and microorganisms) are pushed away from the membrane, in continuous flow operations, eliminating the membrane fouling that plagues the membrane filtration methods. The power consumption is less than 5Wh/L, comparable to any existing systems. The energy and removal efficiency, and low cost manufacturability hold strong promises for portable, self-powered water purification/desalination system that can have significant impacts on water shortage in developing/rural part of the world.

Recently, a bacteria-based drug delivery system has been proposed to achieve effective and localized drug delivery. Researchers have shown that flagellated bacteria have a chemotactic property to tumor cells, and they can be used as an energy source for active drug delivery. Our previous results have reported that a circular droplet made by a biodegradable polymer can be used in this bacteria-based, robotic drug delivery. In this paper, using laminated cubic structures made of several layers of biodegradable polymers for bacteria-based microrobot is proposed. The structures are made by laminating polymer layers and then, micromachining them using a deep X-ray synchrotron radiation into 40 μm x 40 μm x 40 μm cubes. The cubic structure is more beneficial in attaching bacteria in only selective surface directions than a circular structure, and in controlling the volume of drugs to be encapsulated with the outer polymer layer.

Drug-eluting stents (DES) are superior to bare metal stents (BMS) in reducing restenosis rates across a wide range of patients and lesion subsets. This study presented the investigation of one-year clinical follow-up were registered in 52 primary percutaneous coronary intervention sites in Korea, and pre-clinical results of various drug-coated stent fabricating with many other coating approaches on physiological parameters, Based on our clinical study adverse cardiac events were 17.4 % after DES implantation, which was significantly lower compared with 24.9% of BMS implanted patients. As assumption above outcome, it well repays research and development in new DES. Our research group carefully chooses abciximab, alpha-lipoic acid, heparin / dopamine, inhibitors in cell signal cascade were employed as coating drug. These drug candidates were coated on BMS surface by various methods such as TiO2 film deposited by plasma enhanced chemical vapor deposition, ultrasonic sprayer / simple-dip coating, or bio-inspired natural binding technique. In vitro and in vivo results of these new DES fabricated by our research group have showed superior outcomes compare to BMS on physiological parameters such as inflammation score, re-endothelialization, preventing neointema or thrombosis etc. These results are promising safer and more effective to overcome the limitation of DES.

Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

Neurons are the basic units of the brain, and form network by connecting via synapses. So far, there have been limited ways to measure the brain networks. Recently, various imaging modalities are widely used for this purpose. In this paper, brain network mapping using resting state fMRI will be introduced with several applications including neurodegenerative disease such as Alzheimer’s disease, frontotemporal lobar degeneration and Parkinson’s disease. The resting functional connectivity using intrinsic functional connectivity in mouse is useful since we can take advantage of perturbation or stimulation of certain nodes of the network. The study of brain connectivity will open a new era in understanding of brain and diseases thus will be an essential foundation for future research.

Spontaneous neural activities exist early in development and their spatiotemporal patterns play important roles in the development of sensory maps such as maps of retinotopy in the visual system. We summarized different optogenetic tools, including transgenic mouse lines, viral-mediated transfection and electroporation methods to enable the expression of light-gated channelrhodopsin (ChR2) in retinal ganglion cells (RGCs) before the onset of vision. Patch-clamp and extracellular recording experiments verified that activities of ChR2-expressing cells were precisely manipulated by the patterns of optical stimuli. In chronic stimulation experiments, light-emitting diodes controlled the activity patterns of ChR2-expressing RGCs in vivo. Changes in the retinotopic map in Superior Colliculus (SC) were examined by quantifying the relative sizes of fluorescently labeled target zones. Our results revealed that various optogenetic and optical tools can manipulate retinal activities with precise temporal patterns. These techniques can be readily used in studying the development of the central nervous system of neonatal rodents.

Nerve cells (neurons) have been used for a convenient and effective model for basic neurobiology and it has also served as a test bed for the development of neural prosthetic devices. The characterization of neuronal growth in vitro has become an important part of neural tissue engineering. In this talk, I will present recent progresses on the investigation of nano-scale effects on neuronal growth in vitro. Hippocampal neurons from a small brain tissue dissected from E-18 (embryonic stage 18 days) Sprague-Dawley rat were used as a developing neuron model. They were seeded on substrates with carbon nanotube patterned glass substrates, anodized aluminum oxide surfaces with two different pitch sizes (60 nm, 400 nm), and silica nano bead surfaces with five different bead sizes (110, 190, 320, 480, 670 nm). These surfaces uniquely defined nano-scale surfaces with different topographical features. We observed longer neurite outgrowth and faster neuronal development on nano-scale surfaces compared to plain glass surfaces. The results from nano-scale cell culture platforms will be useful to understand nano-environments of the brain during the early neural developments. In addition, the promoted neuronal development could be further applied for neural tissue scaffolds or implantable neural interface systems.

Micro-nano robotic manipulation is one of the promising methods for the treatment of biological cell instead of human handling due to its non-skill dependent, high throughput, and high repeatability. Integration of the microfluidic chip and robotics based on MEMS technology is key challenge for biomedical innovations. In addition to the advantage of environmental control by microfluidic chip, robot enables physical operation to the cell with high throughput. A high power, high precision and high speed microrobot actuated by permanent magnets are introduced and designed for cell handling, cutting, and stimulation in a microfluidic chip.

Magnetic resonance imaging (MRI) and spectroscopy (MRS) is very powerful modality for imaging and localized investigation of biological tissue. Medical MRI measures nuclear magnetization of the water protons, which consists of 70 % of our body. MRI provides superior contrast among different soft tissues to all other existing medical imaging modalities, including ultrasound, X-ray CT, PET, and SPECT. In principle, MRI/S may be an ideal non-invasive tool for drug delivery research. However, because of its low sensitivity, a large dose is required for tracing pharmaceuticals. Therefore, its use for imaging of pharmaceuticals is very limited mostly to molecules that contain a paramagnetic metal ion, such as gadolinium (Gd³⁺) and manganese (Mn²⁺). The paramagnetic metal ion provides a large fluctuating magnetic field at the proton in the water molecule via a coordinate site. The measurement of local drug concentration is the first step for further quantification. Local concentration of the paramagnetic-ion based MRI contrast agent can be indirectly measured via the change in the water signal intensity. ¹⁹F MRI/S of fluorinated complex may be an option for drug delivery and tracing agent, because the fluorinated molecule may be directly detected due to its large magnetic moment (94 % of proton) and 100 % abundance.

Magnetic resonance imaging (MRI) has been widely used as a valuable diagnostic imaging modality that exploits water content and water relaxation properties to provide both structural and functional information with high resolution. Chemical exchange saturation transfer (CEST) in MRI has been recently introduced as a new mechanism of image contrast, wherein exchangeable protons from mobile proteins and peptides are indirectly detected through saturation transfer and are not observable using conventional MRI. It has been demonstrated that CEST MRI can detect important tissue metabolites and byproducts such as glucose, glycogen, and lactate. Additionally, CEST MRI is sensitive to pH or temperature and can calibrate microenvironment dependent on pH or temperature. In this work, we provide an overview on recent trends in CEST MRI, introducing general principles of CEST mechanism, quantitative description of proton transfer process between water pool and exchangeable solute pool in the presence or absence of conventional magnetization transfer effect, and its applications

Propionibacterium acnes (P. acnes), one of the anaerobic bacterium, causes inflammatory acne. To find a novel medication for treating the inflammation caused by P. acnes, we investigated the anti-bacterial and anti-inflammatory activities of several herbal extracts against P. acnes. The aqueous extracts from five dried herbs, Phellodendron amurense Rupr., Paeonia lactiflora Pallas., Houttuynia cordata Thunb., Agrimonia pilosa Ledeb. and Glycyrrhiza uralensis Fisch., were prepared and mixed. In this experiment, 1 mg/ml of the herbal extract mixture caused a decrease in the growth of P. acnes and reduced the production of pro-inflammatory cytokines, TNF-α, IL-8, IL-1β and IL-6, in human monocytic THP-1 cells treated with heat-killed P. acnes. Therefore, this herbal extract mixture may possess both anti-bacterial and anti-inflammatory activities against P. acnes and can be a novel therapeutic agent for treating inflammatory acne.

In clinical and biological fields, circulating tumor cells (CTCs) attracts much attention for the valuable information about cancer progression, cancer status, and prognosis after the treatment with metastatic cancer. Recently, many researchers have studied to count CTCs efficiently. Representative methods of CTC detection are the immune-reaction based method and the morphology-based method. However, the immune-reaction based method is weak due to the imperfect markers, and morphology-based method has a defect because of the unclear criterion. In this paper, we described the CTC detection system based on flow cytometry technique with morphology and immune reaction based methods. The size and the immune-reaction information can be simultaneously obtained from DC impedance based detection and fluorescence detection, respectively. The performance of our system was evaluated with fluorescence beads. To apply the proposed system to biological samples, the human ovarian cancer cell lines (OVCAR-3) suspended in phosphate buffered saline (PBS) were tested. OVCAR-3 cells were stained by fluorescence tagged anti-epithelial cancer adhesion molecule (EpCAM). The portable flow cytometer system could detect the cancer cells with these methods. The proposed system has sufficient potential for point-of-care testing type cancer cell counter and many valuable clinical applications in the near future.

Hybrid organic-inorganic near-infrared responsive magnetic nanoparticles were synthesized for theragnosis combined with localized therapy. In detail, inorganic super-paramagnetic nanoparticles were embedded inside organic polyaniline matrix, which enables localized photothermal therapy upon NIR illumination under intracellular acidic/oxidative condition. In this structure, super-paramagnetic nanoparticle works as MRI contrast agent, that enables the visualization of a tumor and polyaniline works for near-infrared responsive tumor ablation.

Here we introduce a new class of smart imaging probes hybridizing polysorbate 80 coated-magnetic nanoparticles with vascular endothelial growth factor receptor 2 (VEGFR2)-targetable aptamer for specific magnetic resonance (MR) imaging of angiogenesis from glioblastoma.

Agglomeration of some proteins may give rise to aggregates that have been identified as the main cause of amyloid diseases. For example, fibrillation of insulin is related to diabetes mellitus. Quantum dots (QDs) are of special interest as tagging agents for diagnostic and therapeutic studies due to their broad absorption spectra, narrow emission spectra, and high photostability. In this study, PEGylated CdSe/ZnS QDs have been shown to induce the formation of amyloid-like fibrils of human insulin under physiological conditions, this process being dependent on the variation of the surface charge of the nanoparticles (NPs) used. Circular dichroism (CD), protein secondary structure analysis, thioflavin T (ThT) fluorescence assay, and the dynamic light scattering (DLS) technique have been used for comparative analysis of different stages of the fibrillation process. In particular, insulin secondary structure remodelling accompanied by a considerable increase in the rate of amyloid fiber formation have been observed after insulin was mixed with PEGylated QDs. Nanoparticles may significantly influence the rate of protein fibrillation and induce new mechanisms of amyloid diseases, as well as offer opportunities for their treatment.

Saccharides have been emerging as promising fuels for future energy industry because they possess high energy density and tremendous amount of them can be obtained from abundant biomass. Direct electrochemical oxidation of saccharides to generate electricity is a potentially competitive approach in terms of the demand for small, handy, and cost-effective electric power sources. To develop efficient sugar fuel cell, it is necessary to understand mechanism of electrooxidation of saccharide at electrode surface. Although glucose oxidation at platinum surface has been well known, fundamental mechanism study on electrooxidation of other sugars is still in its infancy. Based on research of glucose oxidation, we will predict the electrooxidation of other saccharides such as fructose.

This paper reports the synthesis of three types of iron oxide nanotubes, including hematite (α-Fe₂O₃), maghemite (γ-Fe₂O₃) and magnetite (Fe₃O₄), and their applications in neuroscience and drug delivery. Two methods, template-assisted thermal decomposition method and hydrothermal method, were used for synthesizing hematite nanotubes, and maghemite nanotubes were obtained from hematite nanotubes by thermal treatment. Template-assisted filtering method was used for synthesizing magnetite nanotubes from ferrofluid. The crystalline, morphology and magnetic properties of the synthesized iron oxide nanotubes were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and vibrating sample magnetometer (VSM), respectively. The biocompatibility of the synthesized hematite nanotubes was confirmed by the survival and differentiation of PC12 cells in the presence of the hematite nanotubes coupled to nerve growth factor (NGF). The capacity of hematite nanotubes for coupling and leasing NGF was confirmed by cultivating PC12 cells in the presence of NGF-loaded hematite nanotubes. The drug loading and release capabilities of hematite nanotubes were tested by using ibuprofen sodium salt (ISS) as a drug model. Based on the experimental results presented in this paper, it can be concluded that iron oxide nanotubes have good biocompatibility with neurons, could be used in guding neurite growth, and are promising candidates for drug delivery.

The purpose of this study was to develop alendronate (Aln)-eluting Ti substrates to induce osteogenic differentiation of human buccal fat cells (HBFCs). The surface of pristine Ti was modified by dopamine (DOPA) and then heparin was grafted onto the aminated Ti surfaces to achieve the Aln-eluting Ti system. Aln was subsequently immobilized on the surface of heparinized Ti (Hep-Ti). Pristine Ti and surface-modified-Ti were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle. Osteogenic differentiation of HBFCs on the surface of pristine-Ti, Hep-Ti, Aln (1 mg)/Hep-Ti, and Aln (5 mg)/Hep-Ti was demonstrated by alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. Successful immobilization of Aln on Hep-Ti was confirmed by XPS and contact angle. Aln/Hep-Ti showed the sustained release for up to 28 days. Additionally, HBFCs cultured on Aln/Hep-Ti substrates showed significantly induced ALP activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. These results suggest that Aln-eluting Ti substrates have a potential effect on osteogenic differentiation of HBFCs and will be a promising material for bone regeneration.

The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drug delivery systems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg–Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.

We proposed new concepts on the development of intelligent biomedical microrobot using flagellated bacteria Salmonella typhimurium which has various properties such as micro-actuators, micro-sensors, treatment and diagnosis of solid tumors. We fabricated a bacteria-based microrobot using attenuated Salmonella typhimurium for medical applications. In addition, for motility enhancement of microrobots, we regulated the bacteria selective attachment on microbead surfaces using the patterning methods through the submerged property of microbeads on agarose gel. Firstly, we fabricated bacteria-based microrobots using polystyrene (PS) microbeads which are treated with anti-bacterial adherent factors, such as O2 plasma or bovine serum albumin. The selective bacteria-attached PS microbead groups using O2 plasma or BSA are showed higher motility than untreated whole bacteria-attached PS microbead groups. Secondly, we fabricated bacteria-based microrobots using biocompatible materials, poly(ethylene glycol) (PEG). We regulate the bacteria selective attachment on PEG microbead surfaces using bacteria adhesion materials, poly-L-lysine (PLL). Similar with the bacteria-based microrobots using PS microbeads, the selective bacteria-attached PEG microbeads group through the PLL selective coating showed higher motility than PLL-uncoated and whole PLL-coated PEG microbeads groups. Therefore, we expected that the proposed fabrication methods of the bacteria-based microrobots could have the following characteristics such as the high efficiency using flagellated bacteria, the enhanced motility using the bacteria selective patterning, and the potential applicability to human body using the biocompatible materials.