This PDF file contains the front matter associated with SPIE Proceedings Volume 7313, including the Title Page, Copyright information, Table of Contents, and the Conference Committee listing.

Overexpression of angiotensin-converting enzyme (ACE) has been associated with the pathophysiology of cardiac and pulmonary fibrosis. Moreover, the prescription of ACE inhibitors, such as lisinopril, has shown a favorable effect on patient outcome for patients with heart failure or systemic hypertension. Thus targeted imaging of the ACE would be of crucial importance for monitoring tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-coated gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. The preparation involved non-modified lisinopril, using its primary amine group as the anchoring function on the gold nanoparticles surface. The stable lisinopril-coated gold nanoparticles obtained were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). Their zeta potential was also measured in order to assess the charge density on the modified gold nanoparticles (GNPs).

Imaging of immune system and tissue response to immunogenic agents can be important to the development of new biomaterials. Additionally, quantitative functional imaging can be useful for testing and evaluation of methods to alter or control the immune system response to implanted materials. In this preliminary study, we employ spectral imaging and fluorescence imaging to measure immune system and tissue response to implanted immunogenic agents. Poly (D,L lactide-co-glycolide) (PLGA) with a 50:50 composition was used to create immunogenic microparticles (MPs). Lipopolysaccharide (LPS) encapsulated in the MPs was used to provoke a tissue immune response in mice and encapsulated fluorescein isothiocyanate (FITC) was used to fluorescently label the MPs for imaging. Control MPs did not contain LPS. The MPs were delivered at 50 particles/μL in a total volume of 20μL by subcutaneous injection in the skin of a nude mouse in a dorsal skin-fold window chamber preparation. Cultured immune cells from a mouse leukemic monocyte macrophage cell line were exogenously labeled with the fluorescent dye DiD in solution at a concentration of 8000cells/μL. Immediately after window chamber surgery and implantation of the MPs, 100μL of the fluorescent macrophage solution was administered via the tail vein. Fluorescence imaging was used to track MPs and macrophages while spectral imaging was used for imaging and measurement of hemoglobin saturation in the tissue microvasculature. Imaging was performed periodically over about three days. The spectral and fluorescence imaging combination enabled detailed observations of the macrophage response and functional effects on the tissue.

An alternative approach for fabricating a protein array at nanoscale (<100 nm) is suggested with a capability of characterization and/or localization of multiple components on a nanoarray. Basically, fluorescent micro- and nanospheres each conjugated with different proteins are size-dependently self-assembled (SDSA) onto these nanometer wells that were created on the polymethyl methacrylate (PMMA) substrate by electron beam lithography (EBL). Particles of different diameters are added serially, and electrostatically attached to the corresponding wells through electrostatic attraction between the carboxylic groups of the spheres and p-doped silicon substrate underneath the PMMA layer. This SDSA was enhanced by wire-guide manipulation of droplets on the surface containing nanometer wells. Target detection utilizes fluorescence resonance energy transfer (FRET) from fluorescent beads to target (mouse immunoglobulin G = mIgG or Octamer-4 = Oct4) and its antibody bound on the beads. The 180 nm blue beads are conjugated with mIgG to capture anti-mIgG-FITC. The 50 nm green and 100 nm yellow-green beads are conjugated with anti-Oct4 to capture Oct4 peptides; where the secondary anti-Oct4 tagged with phycoerythrin via F(ab)2 fragment is then added to function as an indicator of Oct4 detection. These protein-conjugated particles are added serially from the largest to the smallest and the particles are successfully self-assembled to the respective nanometer wells to achieve sizedependent self-assembly. FRET signals are detected through fluorescence and confocal microscopes, and further confirmed by Fluorolog3 spectrofluorometer. Therefore, SDSA is a valuable approach for the fabrication of multiple components array; and FRET is a useful biorecognition technique for the detection of mIgG, Oct4 or other targets of interest.

The reference optical path is essential for optical systems which function on the basis of light interference. In the case of frequency domain (FD) fluorescence life-time optrodes, a reference LED is used as a standard for calculating the phase angle. The reference LED is configured so that radiation travels the same length to the detector as that of the fluorescence signal being analyzed. The phase shift, which provides details of fluorescence lifetime, is measured between these two signals - the fluorescence signal and reference LED signal, using a photodetector. We have designed, developed and implemented a FD optrode system without a reference LED. The key requirement of such a system is that phase shifts due to optics at wavelength of fluorescence and electronics have to be calibrated. In the reference-free system, the reference signal comes from the lock-in-amplifier which also drives the excitation LED. The lock-in-amplifier measures the phase shift between the excitation signal and the fluorescence emission signal from the photodetector and is locked at the frequency of modulation of the excitation signal. This insures higher signal to noise ratio and low-noise measurements. The reference-free optrode system removes some constraints on the coupling optics, which help improve the overall performance of the system. After development of electronics, and optimization of coupling optics, the system was calibrated in different oxygen concentration solutions to measure fluorescence intensity and lifetime of the oxygen sensitive dye platinum tetrakis (pentafluorophenyl) porphine (PtTFPP).

A new method of color pixel intensity analysis to obtain an oxygen concentration is presented in this research. Until recently, color charge coupled devices (CCDs) have rarely been used for oxygen imaging in spite of its usefulness for analyzing the spectral content of images. The proposed new method involves extracting the red color element to enhance oxygen-related information and eliminate distorted green color information from the color images of the sensors. A commercial RedEye^TM oxygen sensor patch was used to verify this method. The linearity and sensitivity of oxygen detection based on the red intensity analysis was improved to those of spectrometric measurement and total color intensity analysis. This method also has potential applications in other luminescence sensors and simultaneous structural and functional imaging of biological systems.

Optical sensors are a common tool to measure the dissolved oxygen concentration in environmental, industrial and medical areas. Much effort has been put on developing and using novel optical dyes and materials used as the immobilization matrixes. A poly (ethylene glycol) (PEG)-rich hydrogel was used as a fluorophore matrix. For optical sensor applications, this hydrogel was chemically anchored on negative-tone photopolymer SU-8 surface through a free radical reaction in which 1-hydroxycyclohexyl phenyl ketone (HCPK) served as the surface bound photoinitiator. Dissolved oxygen concentrations were detected based on the fluorescent intensity at emission wavelength of a fluorophore, dichlorotris (1, 10-phenanthroline) ruthenium (II) hydrate 98%, toward dissolved oxygen molecules. The normal characteristics of optical dissolved sensor were measured and recorded. All the results indicate the potential use of patternable polymerized PEGDA membranes, which is chemically anchored to SU-8 surface, as an ideal candidate matrix based on polymeric channel structures

In this work, a novel photopatternable hydrogel-based material for the fluorescent detection of hydrogen peroxide was developed and studied as a possible sensing element in optical biosensors. This composite hydrogel material was developed to maximize analyte transport, be amenable to existing microfabrication techniques, and dovetail with various enzyme immobilization strategies. Nanoparticles loaded with a hydrogen peroxide sensitive europium tetracycline complex (EuTc) were mixed with monomer and crosslinker to form a photopolymerizable precursor. Sensitivity to glucose can be introduced through addition of methacrylated glucose oxidase into the precursor solution, allowing for covalent immobilization of the enzyme. As a result, the material can be integrated directly into optical biosensors for continuous glucose monitoring.

A universal microfluidic platform as a multisensor device for cancer diagnostics, developed within the framework of the EU project SmartHEALTH [1], will be presented. Based on a standardization concept, a microfluidic platform was realized that contains various functional modules in order to allow in its final setup to run a complete diagnostic assay on a chip starting with sample preparation to a final detection via a sensor array. A twofold concept was pursued for the development and standardization: On the one hand, a standard footprint with defined areas for special functional elements was chosen, on the other hand a toolbox-approach [2] was used whereas in a first instance different functional fluidic modules were realized, evaluated and afterwards integrated into the microfluidic multisensor platform. One main characteristic of the platform is that different kind of sensors can be used with the same fluidic chip. For the read-out and fluidic control of the chip, common fluidic interfaces to the instrument were defined. This microfluidic consumable is a hybrid system consisting of a polymer component with an integrated sensor, reagent storage on chip, integrated valves and metering elements.

Dynamic intracellular analysis has important applications in areas like biomedical research, defense and security and many others. Although, there are several methods for intracellular analysis, surface enhanced Raman scattering (SERS) is becoming a preferred transduction method for such applications, due to its narrow spectral bandwidth, large SERS enhancement factors and high sensitivity. In our laboratory, SERS-based immuno-nanosensors are being developed and optimized for real-time, dynamic, and multiplexed analysis of molecular interaction within individual living cells. These nanosensors are fabricated by drop coating silica nanospheres onto a microscope slide. A film of SERS active metal is deposited on the nanospheres to form metal film over nanospheres (MFON), which are then removed from the slide by mechanical processes. The MFONs are functionalized with antibodies that target specific proteins under investigation. Radiation induced cell perturbation is minimized by the use of a HeNe laser for excitation at 632.8 nm. To improve SERS enhancement, different types of metal deposited substrates have been studied with multilayer- MFON (MULTI-FON) substrates demonstrating ideal enhancement. This paper evaluates the SERS enhancement of MULTI-FONs with self-assembled monolayers (SAMs) spacers sandwiched between layers of the metal film. Monolayers with carboxylic acid tail groups and different chain lengths are used as spacers in order to evaluate the effect of spacer length and chain functionalities on the SERS enhancement. The paper also discusses the effect of solvent used for the monolayer formation on the sensitivity of the SAM MULTI-FON SERS substrates.

The development of monolayer chemistry based on amino acid and short peptides decreases significantly the nonspecific adsorption from biological samples such as serum. Nonspecific adsorption of proteins onto the surface of biosensors currently limits the applicability of many biosensing techniques in real biological samples. In order to minimize this problem, a methodology to immobilize short peptides on surface plasmon resonance (SPR) biosensors was developed using a short chain alkyl thiol monolayer derived with the selected peptides. The chain length of the alkane thiol linking the amino acid to the gold surface influences the physico-chemical properties of the layer and the amount of nonspecifically adsorbed proteins. Varying the composition of the monolayer with peptides formed from the natural amino acids investigates the physico-chemical properties required to minimize nonspecific adsorption of serum. It was observed from monolayers of single amino acids that the composition of the side chain of the amino acid greatly influences the resistance to nonspecific adsorption, with more polar, ionic and small chains resulting in an improved performance in biological samples. Building peptides of different lengths resulted in a further decrease of the amount of nonspecifically bound proteins from serum. Leaving the terminal carboxylic acid end of the peptide unreacted provides an anchoring point for a molecular receptor in the design of a biosensor. Biosensing will be demonstrated with a model system of β-lactamase.

Chemical imaging not only provides structural and spatial information about a sample but also chemical information about the sample. Raman spectroscopy can be a powerful transduction mechanism for chemical imaging due to the narrow vibrational bandwidths and unique spectral fingerprints. Unfortunately, Raman cross-sections are extremely weak (~10^-30 cm^-2), often necessitating long exposure times, making dynamic chemical imaging impractical, particularly for high-resolution images. By utilizing a Raman enhancement technique such as surface enhanced Raman spectroscopy (SERS), the effective scattering cross-sections are increased making practical imaging times feasible. This paper will discuss the fabrication, characterization, and demonstration of a novel SERS substrate and instrumental system for non-scanning SERS chemical imaging with sub-diffraction limited spatial resolution. These substrates are fabricated by chemically etching a polished fiber optic imaging bundle consisting of 30,000, hexagonally packed, 4- micron diameter elements. The chemical etching process creates uniform array of cladding spikes onto which a SERS active metal is vacuum deposited, forming the SERS active surface. By varying the size of the silver islands deposited on the cladding peaks active surface plasmons can be tuned to various excitation frequencies. SERS signals measured both on and off the plasmon absorption band demonstrate that these SERS fiber bundles can be tuned for various excitation frequencies.

A novel method for improving the detection limit of normal Raman spectra of chemicals using a micro-Raman system and pico-liters volume is presented. A micro-cavity substrate uses various mechanisms that collectively improve the normal Raman signal from the sample without surface-enhanced Raman scattering (SERS) enhancement. The microcavity substrate enhances the entire Raman spectra of the molecules under investigation and maintains the relative intensity ratios of the various Raman bands. This feature of maintaining the overall integrity of the Raman features during signal enhancement makes the micro-cavity substrate ideal for forensic science applications requiring chemical detection of residual traces and other applications requiring low sample volumes and concentrations. It will be further shown that micro-cavities coated with nano films of gold and silver takes advantage of both SERS and micro-cavity method and significantly improve the detection limits of samples.

Several polymeric membranes were evaluated for their potential to improve the sensitivity and impart chemical selectivity to surface plasmon resonance (SPR)-based sensors. The membranes tested encompass a variety of deposition methods, providing an insight of the contact requirements between polymers and the plasmon supporting metal. Among the membranes evaluated, preliminary results utilizing polyelectrolyte multilayer membranes displayed reliable detection of vapor-phase ammonia at ~40 ppm levels. Chemically synthesized polyaniline also presented encouraging results, responding to ammonia gas at 48 ppm. This is in sharp contrast to the electropolymerized counterpart, which showed minor wavelength shifts even at elevated ammonia levels (4 %). SPR has been adopted by the bioanalytical community to probe biomolecular interactions and obtain information relating to binding kinetics. Similarly, modifying plasmon-supporting surfaces with bioreceptors enables access to biosensing applications. Gas-phase sensing with SPR has largely remained unexplored primarily due to the small changes in refractive index from low molecular weight molecules. Coating SPR sensors with tailored polymers has been discussed as a viable approach to amplifying refractive index changes related to low molecular weight analytes. Ammonia is a low molecular weight analyte that is ubiquitously present in the gas phase. Industrial and medical interest in ammonia at low ppm level yielded numerous scientific contributions describing diverse sensing approaches. Hence, ammonia is a good candidate to provide a baseline for immediate comparison with other approaches for evaluation of the polymers with regards to their susceptibility to undergo changes in dielectric properties and chemical affinity for the analyte.

Fluorescence based biosensors have the ability to provide reliable pathogen detection. However, the performance could be improved by enhancing the effective surface area of the biosensor. We report on a new nanofibrous fluorescencebased biosensor, whereas a sol-gel platform mesh was constructed by utilizing electrospinning techniques. Furthermore, incorporating cetyltrimethylammonium bromide (CTAB) and conducting pore-forming techniques resulted in a high surface area material suitable for biosensor immobilization. The biosensor was designed to detect Helicobacter hepaticus bacterium by sandwiching the pathogen between two antibodies, one labeled with Alexa Fluor 546 fluorescent dye and the other with 20nm Au nanoparticles. In the presence of pathogen, the close proximity of Au nanoparticles quenched the Alexa Fluor fluorescence, suggesting that the electrospun fiber platforms are suitable for sensing H. Hepaticus. Additionally, sol-gel fibers used as biosensor platform have the added benefit of increased immobilization, as fluorescence intensity from immobilized biosensors is 8.5x10⁶ cps higher on fibers than on a flat, non-porous substrate.

Virus antigens of avian influenza subtype H3N2 were detected on two different microfluidic platforms: microchannel and droplet. Latex immunoagglutination assays were performed using 920-nm highly carboxylated polystyrene beads that are conjugated with antibody to avian influenza virus. The bead suspension was merged with the solutions of avian influenza virus antigens in a Y-junction of a microchannel made by polydimethylsiloxane soft lithography. The resulting latex immunoagglutinations were measured with two optical fibers in proximity setup to detect 45° forward light scattering. Alternatively, 10 μL droplets of a bead suspension and an antigen solution were merged on a superhydrophobic surface (water contact angle = 155°), whose movement was guided by a metal wire, and 180° back light scattering is measured with a backscattering optical probe. Detection limits were 0.1 pg mL^-1 for both microchannel with proximity fibers and droplet microfluidics, thanks to the use of micro-positioning stages to help generate reproducible optical signals. Additionally, optical waveguide was tested by constructing optical waveguide channels (filled with mineral oil) within a microfluidic device to detect the same light scattering. Detection limit was 0.1 ng mL^-1 for an optical waveguide device, with a strong potential of improvement in the near future. The use of optical waveguide enabled smaller device setup, easier operation, smaller standard deviations and broader linear range of assay than proximity fiber microchannel and droplet microfluidics. Total assay time was less than 10 min.

A novel surface enhanced Raman scattering (SERS)-based immuno-microwell array has been developed for multiplexed detection of foodborne pathogenic bacteria. The immuno-microwell array was prepared by immobilizing the optical addressable immunomagnetic beads (IMB) into the microwell array on one end of a fiber optic bundle. The IMBs, magnetic beads coated with specific antibody to specific bacteria, were used for immunomagnetic separation (IMS) of corresponding bacteria. The magnetic separation by the homemade magnetic separation system was evaluated in terms of the influences of several important parameters including the beads concentration, the sample volume and the separation time. IMS separation efficiency of the model bacteria E.coli O157:H7 was 63% in 3 minutes. The microwell array was fabricated on hydrofluoric acid etched end of a fiber optic bundle containing 30,000 fiber elements. After being coated with silver, the microwell array was used as a uniform SERS substrate with the relative standard deviation of the SERS enhancement across the microwell array < 2% and the enhancement factor as high as 2.18 x 10⁷. The antibody modified microwell array was prepared for bacteria immobilization into the microwell array, which was characterized by a sandwich immunoassay. To demonstrate the potential of multiplexed SERS detection with the immuno-microwell array, the SERS spectra of different Raman dye labeled magnetic beads as well as mixtures were measured on the mircrowell array. In bead mixture, different beads were identified by the characteristic SERS bands of the corresponding Raman label.

Magnetoelastic sensors exhibit a characteristic resonance frequency upon the application of an alternating magnetic field. In this research, magnetoelastic material was fabricated into micro-sized sensors coated with JRB7 phages to specifically detect Bacillus anthracis spores. Research had shown that the sensor's resonant frequency decreases linearly as its mass increases. As spores are captured, the mass increases. A high mass-sensitivity of up to 7.5 Hz/pg allowed this sensor's use in applications requiring accurate sensing of a very low concentration of B. anthracis spores. A B. anthracis spore weighs about 2 picograms. Two different sizes of sensors, 2000×400 μm and 1000×200 μm, were used in this study. The resonant frequency and the sensitivity of the sensors were found to vary under different magnitudes of DC biasing magnetic field. It was found that both the resonant frequency and the Q-value of the sensed signal increase with an increase of the magnitude of the DC magnetic field until they approach magnetic saturation. As the magnetic field was changed from low to high, it was observed that the signal amplitude increased to a maximum and then decreased to undetectable. Finally, real-time detection of B. anthracis spores is performed under the optimum magnetic field condition.

This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard t-test. These comparison and calculation procedures were carried out for all possible wavelength combinations between 400 nm and 800 nm with 2 nm increments. The positive group consisted of seven pathologically abnormal test sites, and the negative group consisted of 13 normal test sites from non-epileptic tumor patients. A standard t-test showed significant difference between negative correlation time indices from the two groups at the wavelength combinations of 700-760 nm versus 550-580 nm. An empirical discrimination algorithm based on the negative correlation time indices in this range produced 100% sensitivity and 85% specificity. Based on these results time-dependent diffuse reflectance spectroscopy with optimized data analysis methods differentiates epileptic brain tissue from normal brain tissue adequately, therefore can be utilized for surgical guidance, and may enhance the surgical outcome of pediatric epilepsy surgery.

The article aims first to present a new study on the thermal regulatory response of the human skin surface while exposed to a cold environment. Our work has shown that when a cold stress is applied to the left hand, thermal infrared imaging (MWIR spectral band: 3-5 μm) allows a clear observation of a temperature rise on the right hand. Moreover, a frequency analysis was also carried out upon selected vein pixels of the images monitored during the same cold stress experiment. The objective was to identify the specific frequencies that could be linked to some physiological mechanisms of the human body. This kind of study could be very useful for the characterization of possible thermo-physiological pathologies. Besides thermoregulation, we also present in this article some results on the extraction of the hand vein pattern. Firstly, we show some vein extraction results obtained after image processing of the thermal images recorded in the thermal band (MWIR), then we compare this vein pattern to the signature obtained with a camera operating in the NIR spectral band (0.85-1.7 μm). This method could be used as a complementary means for finger print signatures in biometrics.

In this paper we outline the application of a novel electric field sensor technology, developed and patented at the University of Sussex, to the sensing of movement and proximity, using a technique which is generally unaffected by the presence of walls and other structures. This is achieved by monitoring electric field disturbances which occur when a large dielectric object, such as a human or animal body, is moved through the ambient electric field. These sensors detect, passively, changes in spatial potential (electric field) created by a capacitively coupled electric field. To date we have already demonstrated the potential applications of these devices, in principle, across many areas of interest, including body electrophysiology, novel nuclear magnetic resonance (NMR) probes, non destructive testing of composite materials as well as the detection of a heart beat from distances of up to 40 cm. Here we show how, with multiple sensors in a variety of spatial arrangements, it is possible to use simple signal processing and analysis in Labview to detect movement, give an indication of direction and speed as well as track position within an open environment.

Today's state-of-the-art medical vests and shirts for health status monitoring are inflexible and expensive. The high cost and the lack of flexibility and integral-unity of the current vests are prohibiting factors for their use in first responder applications. The vests also lack an in-built intelligence to accurately determine the health status of the person wearing the vest. We present a hardware plus software solution for monitoring the health status of first responders in pressurized and adversarial missions. The technology consists of two main components. The first component is a physiological vest consisting of a suite of physiological sensors interfaced with energy management units designed to prolong the life of the sensors. The sensors communicate wirelessly with a personal server consisting of a Decision Support Software (DSS), which forms the second major component of our technology. The DSS (1) integrates the physiologic sensors readings for global assessment of the individual's health status; (2) recommends medical Alerts and Actions based on the fusion of the sensor readings; and (3) applies cognitive computation to personalize the medical vest to the specific physiologic and motion characteristics of the individual wearing the vest, in the theater of the operation or during exercise.

This paper presents a commercial metal-oxide-semiconductor field-effect transistor (MOSFET)-based biosensor with a gold extended-gate electrode for the electronic detection of C-reactive protein (CRP). From a component point of view, the commercial MOSFET-based biosensor consists of a commercial MOSFET with a socket for connecting the gold electrode which was fixed on a printed circuit board (PCB) and a reaction-vessel module which was assembled with the gold electrode and the Ag/AgCl reference electrode. The gold electrode with only one gold layer was fabricated on a glass substrate simply and it was used as the extended-gate metal to form a self-assembled monolayer (SAM). The binding of the CRP to anti-CRP was detected by measuring the electrical characteristics of the biosensor. Variation of the drain current before and after the interaction of CRP and anti-CRP was about 1.2mA on the measured I_DS-V_DS and real-time characteristics. The concentration of the CRP solution was adjusted to 10μg/ml by dissolving in PBS. The change of surface voltage of the gold extended-gate electrode was about 30mV by I_DS-V_GS characteristic curve of the commercial MOSFET. Therefore, it is confirmed that the detection of CRP is possible by measuring the drain current of the commercial MOSFET. The proposed biosensor might open up a new possibility for FET-based biosensors with lowcost and simple construction. It is expected that the commercial MOSFET-based biosensor with the gold extended-gate electrode could also be used for detecting various biomarkers by modifying the surface of the gold extended-gate electrode.