Sensors: Biosensors

Sensors, Vol. 12, Pages 1758-1770: Comparison between Conduction and Convection Effects on Self-Heating in Doped Microcantilevers

Mohd Zahid Ansari — Thu, 09 Feb 2012 00:00:00 CET

The present study investigates the effects of thermal conduction and convection on self-heating temperatures and bimetallic deflections produced in doped microcantilever sensors. These cantilevers are commonly used as sensors and actuators in microsystems. The cantilever is a monolith, multi-layer structure with a thin U-shaped element inside. The cantilever substrate is made of silicon and silicon dioxide, respectively, and the element is p-doped silicon. A numerical analysis package (ANSYS) is used to study the effect of cantilever substrate material, element width, applied voltage and the operating environments on cantilever characteristics. The numerical results for temperature are compared against their analytical models. Results indicate the numerical results are accurate within 6% of analytical, and Si/Si cantilevers are more suitable for biosensors and AFM, whereas, Si/SiO2 are for hotplates and actuators applications.

Sensors, Vol. 12, Pages 1657-1687: Noble Metal Nanoparticles for Biosensing Applications

Gonçalo Doria — Tue, 07 Feb 2012 00:00:00 CET

In the last decade the use of nanomaterials has been having a great impact in biosensing. In particular, the unique properties of noble metal nanoparticles have allowed for the development of new biosensing platforms with enhanced capabilities in the specific detection of bioanalytes. Noble metal nanoparticles show unique physicochemical properties (such as ease of functionalization via simple chemistry and high surface-to-volume ratios) that allied with their unique spectral and optical properties have prompted the development of a plethora of biosensing platforms. Additionally, they also provide an additional or enhanced layer of application for commonly used techniques, such as fluorescence, infrared and Raman spectroscopy. Herein we review the use of noble metal nanoparticles for biosensing strategies—from synthesis and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics laboratory.

Sensors, Vol. 12, Pages 1648-1656: Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening

Takuya Chiba — Tue, 07 Feb 2012 00:00:00 CET

Recent drug discovery efforts have utilized high throughput screening (HTS) of large chemical libraries to identify compounds that modify the activity of discrete molecular targets. The molecular target approach to drug screening is widely used in the pharmaceutical and biotechnology industries, because of the amount of knowledge now available regarding protein structure that has been obtained by computer simulation. The molecular target approach requires that the structure of target molecules, and an understanding of their physiological functions, is known. This approach to drug discovery may, however, limit the identification of novel drugs. As an alternative, the phenotypic- or pathway-screening approach to drug discovery is gaining popularity, particularly in the academic sector. This approach not only provides the opportunity to identify promising drug candidates, but also enables novel information regarding biological pathways to be unveiled. Reporter assays are a powerful tool for the phenotypic screening of compound libraries. Of the various reporter genes that can be used in such assays, those encoding secreted proteins enable the screening of hit molecules in both living cells and animals. Cell- and animal-based screens enable simultaneous evaluation of drug metabolism or toxicity with biological activity. Therefore, drug candidates identified in these screens may have increased biological efficacy and a lower risk of side effects in humans. In this article, we review the reporter bioassay systems available for phenotypic drug discovery.

Sensors, Vol. 12, Pages 1544-1571: Pseudomonas fluorescens HK44: Lessons Learned from a Model Whole-Cell Bioreporter with a Broad Application History

Josef Trögl — Mon, 06 Feb 2012 00:00:00 CET

Initially described in 1990, Pseudomonas fluorescens HK44 served as the first whole-cell bioreporter genetically endowed with a bioluminescent (luxCDABE) phenotype directly linked to a catabolic (naphthalene degradative) pathway. HK44 was the first genetically engineered microorganism to be released in the field to monitor bioremediation potential. Subsequent to that release, strain HK44 had been introduced into other solids (soils, sands), liquid (water, wastewater), and volatile environments. In these matrices, it has functioned as one of the best characterized chemically-responsive environmental bioreporters and as a model organism for understanding bacterial colonization and transport, cell immobilization strategies, and the kinetics of cellular bioluminescent emission. This review summarizes the characteristics of P. fluorescens HK44 and the extensive range of its applications with special focus on the monitoring of bioremediation processes and biosensing of environmental pollution.

Sensors, Vol. 12, Pages 1494-1508: Miniaturized Protein Microarray with Internal Calibration as Point-of-Care Device for Diagnosis of Neonatal Sepsis

Patricia Buchegger — Fri, 03 Feb 2012 00:00:00 CET

Neonatal sepsis is still a leading cause of death among newborns. Therefore a protein-microarray for point-of-care testing that simultaneously quantifies the sepsis associated serum proteins IL-6, IL-8, IL-10, TNF alpha, S-100, PCT, E-Selectin, CRP and Neopterin has been developed. The chip works with only a 4 µL patient serum sample and hence minimizes excessive blood withdrawal from newborns. The 4 µL patient samples are diluted with 36 µL assay buffer and distributed to four slides for repetitive measurements. Streptavidin coated magnetic particles that act as distinct stirring detection components are added, not only to stir the sample, but also to detect antibody antigen binding events. We demonstrate that the test is complete within 2.5 h using a single step assay. S-100 conjugated to BSA is spotted in increasing concentrations to create an internal calibration. The presented low volume protein-chip fulfills the requirements of point-of-care testing for accurate and repeatable (CV < 14%) quantification of serum proteins for the diagnosis of neonatal sepsis.

Sensors, Vol. 12, Pages 1455-1467: An Aluminum Microfluidic Chip Fabrication Using a Convenient Micromilling Process for Fluorescent Poly(DL-lactide-co-glycolide) Microparticle Generation

Yung-Sheng Lin — Wed, 01 Feb 2012 00:00:00 CET

This study presents the development of a robust aluminum-based microfluidic chip fabricated by conventional mechanical micromachining (computer numerical control-based micro-milling process). It applied the aluminum-based microfluidic chip to form poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating CdSe/ZnS quantum dots (QDs). A cross-flow design and flow-focusing system were employed to control the oil-in-water (o/w) emulsification to ensure the generation of uniformly-sized droplets. The size of the droplets could be tuned by adjusting the flow rates of the water and oil phases. The proposed microfluidic platform is easy to fabricate, set up, organize as well as program, and is valuable for further applications under harsh reaction conditions (high temperature and/or strong organic solvent systems). The proposed method has the advantages of actively controlling the droplet diameter, with a narrow size distribution, good sphericity, as well as being a simple process with a high throughput. In addition to the fluorescent PLGA microparticles in this study, this approach can also be applied to many applications in the pharmaceutical and biomedical area.

Sensors, Vol. 12, Pages 1383-1397: Multi-Sensor Arrays for Online Monitoring of Cell Dynamics in in vitro Studies with Choroid Plexus Epithelial Cells

Pedro Mestres-Ventura — Wed, 01 Feb 2012 00:00:00 CET

Sensors and multi-sensor arrays are the basis of new technologies for the non-label monitoring of cell activity. In this paper we show that choroid plexus cells can be cultured on silicon chips and that sensors register in real time changes in their activity, constituting an interesting experimental paradigm for cell biology and medical research. To validate the signals recorded (metabolism = peri-cellular acidification, oxygen consumption = respiration; impedance = adhesion, cell shape and motility) we performed experiments with compounds that act in a well-known way on cells, influencing these parameters. Our in vitro model demonstrates the advantages of multi-sensor arrays in assessment and experimental characterization of dynamic cellular events—in this case in choroid plexus functions, however with applicability to other cell types as well.

Sensors, Vol. 12, Pages 1035-1041: Post-Synapse Model Cell for Synaptic Glutamate Receptor (GluR)-Based Biosensing: Strategy and Engineering to Maximize Ligand-Gated Ion-Flux Achieving High Signal-to-Noise Ratio

Akito Tateishi — Wed, 18 Jan 2012 00:00:00 CET

Cell-based biosensing is a “smart” way to obtain efficacy-information on the effect of applied chemical on cellular biological cascade. We have proposed an engineered post-synapse model cell-based biosensors to investigate the effects of chemicals on ionotropic glutamate receptor (GluR), which is a focus of attention as a molecular target for clinical neural drug discovery. The engineered model cell has several advantages over native cells, including improved ease of handling and better reproducibility in the application of cell-based biosensors. However, in general, cell-based biosensors often have low signal-to-noise (S/N) ratios due to the low level of cellular responses. In order to obtain a higher S/N ratio in model cells, we have attempted to design a tactic model cell with elevated cellular response. We have revealed that the increase GluR expression level is not directly connected to the amplification of cellular responses because the saturation of surface expression of GluR, leading to a limit on the total ion influx. Furthermore, coexpression of GluR with a voltage-gated potassium channel increased Ca2+ ion influx beyond levels obtained with saturating amounts of GluR alone. The construction of model cells based on strategy of amplifying ion flux per individual receptors can be used to perform smart cell-based biosensing with an improved S/N ratio.

Sensors, Vol. 12, Pages 923-953: Recent Advances in Polymeric Materials Used as Electron Mediators and Immobilizing Matrices in Developing Enzyme Electrodes

Mambo Moyo — Mon, 16 Jan 2012 00:00:00 CET

Different classes of polymeric materials such as nanomaterials, sol-gel materials, conducting polymers, functional polymers and biomaterials have been used in the design of sensors and biosensors. Various methods have been used, for example from direct adsorption, covalent bonding, crossing-linking with glutaraldehyde on composites to mixing the enzymes or use of functionalized beads for the design of sensors and biosensors using these polymeric materials in recent years. It is widely acknowledged that analytical sensing at electrodes modified with polymeric materials results in low detection limits, high sensitivities, lower applied potential, good stability, efficient electron transfer and easier immobilization of enzymes on electrodes such that sensing and biosensing of environmental pollutants is made easier. However, there are a number of challenges to be addressed in order to fulfill the applications of polymeric based polymers such as cost and shortening the long laboratory synthetic pathways involved in sensor preparation. Furthermore, the toxicological effects on flora and fauna of some of these polymeric materials have not been well studied. Given these disadvantages, efforts are now geared towards introducing low cost biomaterials that can serve as alternatives for the development of novel electrochemical sensors and biosensors. This review highlights recent contributions in the development of the electrochemical sensors and biosensors based on different polymeric material. The synergistic action of some of these polymeric materials and nanocomposites imposed when combined on electrode during sensing is discussed.

Sensors, Vol. 12, Pages 784-805: Smart Sensor for Real-Time Quantification of Common Symptoms Present in Unhealthy Plants

Luis M. Contreras-Medina — Wed, 11 Jan 2012 00:00:00 CET

Plant responses to physiological function disorders are called symptoms and they are caused principally by pathogens and nutritional deficiencies. Plant symptoms are commonly used as indicators of the health and nutrition status of plants. Nowadays, the most popular method to quantify plant symptoms is based on visual estimations, consisting on evaluations that raters give based on their observation of plant symptoms; however, this method is inaccurate and imprecise because of its obvious subjectivity. Computational Vision has been employed in plant symptom quantification because of its accuracy and precision. Nevertheless, the systems developed so far lack in-situ, real-time and multi-symptom analysis. There exist methods to obtain information about the health and nutritional status of plants based on reflectance and chlorophyll fluorescence, but they use expensive equipment and are frequently destructive. Therefore, systems able of quantifying plant symptoms overcoming the aforementioned disadvantages that can serve as indicators of health and nutrition in plants are desirable. This paper reports an FPGA-based smart sensor able to perform non-destructive, real-time and in-situ analysis of leaf images to quantify multiple symptoms presented by diseased and malnourished plants; this system can serve as indicator of the health and nutrition in plants. The effectiveness of the proposed smart-sensor was successfully tested by analyzing diseased and malnourished plants.

Sensors, Vol. 12, Pages 732-752: The Evolution of the Bacterial Luciferase Gene Cassette (lux) as a Real-Time Bioreporter

Dan Close — Wed, 11 Jan 2012 00:00:00 CET

The bacterial luciferase gene cassette (lux) is unique among bioluminescent bioreporter systems due to its ability to synthesize and/or scavenge all of the substrate compounds required for its production of light. As a result, the lux system has the unique ability to autonomously produce a luminescent signal, either continuously or in response to the presence of a specific trigger, across a wide array of organismal hosts. While originally employed extensively as a bacterial bioreporter system for the detection of specific chemical signals in environmental samples, the use of lux as a bioreporter technology has continuously expanded over the last 30 years to include expression in eukaryotic cells such as Saccharomyces cerevisiae and even human cell lines as well. Under these conditions, the lux system has been developed for use as a biomedical detection tool for toxicity screening and visualization of tumors in small animal models. As the technologies for lux signal detection continue to improve, it is poised to become one of the first fully implantable detection systems for intra-organismal optical detection through direct marriage to an implantable photon-detecting digital chip. This review presents the basic biochemical background that allows the lux system to continuously autobioluminesce and highlights the important milestones in the use of lux-based bioreporters as they have evolved from chemical detection platforms in prokaryotic bacteria to rodent-based tumorigenesis study targets. In addition, the future of lux imaging using integrated circuit microluminometry to image directly within a living host in real-time will be introduced and its role in the development of dose/response therapeutic systems will be highlighted.

Sensors, Vol. 12, Pages 612-631: Aptamers and Their Biological Applications

Kyung-Mi Song — Mon, 09 Jan 2012 00:00:00 CET

Recently, aptamers have attracted the attention of many scientists, because they not only have all of the advantages of antibodies, but also have unique merits, such as thermal stability, low cost, and unlimited applications. In this review, we present the reasons why aptamers are known as alternatives to antibodies. Furthermore, several types of in vitro selection processes, including nitrocellulose membrane filtration, affinity chromatography, magnetic bead, and capillary electrophoresis-based selection methods, are explained in detail. We also introduce various applications of aptamers for the diagnosis of diseases and detection of small molecules. Numerous analytical techniques, such as electrochemical, colorimetric, optical, and mass-sensitive methods, can be utilized to detect targets, due to convenient modifications and the stability of aptamers. Finally, several medical and analytical applications of aptamers are presented. In summary, aptamers are promising materials for diverse areas, not just as alternatives to antibodies, but as the core components of medical and analytical equipment.

Sensors, Vol. 12, Pages 347-358: Single-Cell Chemical Lysis on Microfluidic Chips with Arrays of Microwells

Chun-Ping Jen — Fri, 30 Dec 2011 00:00:00 CET

Many conventional biochemical assays are performed using populations of cells to determine their quantitative biomolecular profiles. However, population averages do not reflect actual physiological processes in individual cells, which occur either on short time scales or nonsynchronously. Therefore, accurate analysis at the single-cell level has become a highly attractive tool for investigating cellular content. Microfluidic chips with arrays of microwells were developed for single-cell chemical lysis in the present study. The cellular occupancy in 30-mm-diameter microwells (91.45%) was higher than that in 20-mm-diameter microwells (83.19%) at an injection flow rate of 2.8 mL/min. However, most of the occupied 20-mm-diameter microwells contained individual cells. The results of chemical lysis experiments at the single-cell level indicate that cell membranes were gradually lysed as the lysis buffer was injected; they were fully lysed after 12 s. Single-cell chemical lysis was demonstrated in the proposed microfluidic chip, which is suitable for high-throughput cell lysis.

Sensors, Vol. 12, Pages 297-319: Modulation Techniques for Biomedical Implanted Devices and Their Challenges

Mahammad A. Hannan — Wed, 28 Dec 2011 00:00:00 CET

Implanted medical devices are very important electronic devices because of their usefulness in monitoring and diagnosis, safety and comfort for patients. Since 1950s, remarkable efforts have been undertaken for the development of bio-medical implanted and wireless telemetry bio-devices. Issues such as design of suitable modulation methods, use of power and monitoring devices, transfer energy from external to internal parts with high efficiency and high data rates and low power consumption all play an important role in the development of implantable devices. This paper provides a comprehensive survey on various modulation and demodulation techniques such as amplitude shift keying (ASK), frequency shift keying (FSK) and phase shift keying (PSK) of the existing wireless implanted devices. The details of specifications, including carrier frequency, CMOS size, data rate, power consumption and supply, chip area and application of the various modulation schemes of the implanted devices are investigated and summarized in the tables along with the corresponding key references. Current challenges and problems of the typical modulation applications of these technologies are illustrated with a brief suggestions and discussion for the progress of implanted device research in the future. It is observed that the prime requisites for the good quality of the implanted devices and their reliability are the energy transformation, data rate, CMOS size, power consumption and operation frequency. This review will hopefully lead to increasing efforts towards the development of low powered, high efficient, high data rate and reliable implanted devices.

Sensors, Vol. 11, Pages 11752-11760: Low Cost Sensors Based on SPR in a Plastic Optical Fiber for Biosensor Implementation

Nunzio Cennamo — Fri, 16 Dec 2011 00:00:00 CET

This paper reports the fabrication and testing of two configurations of optical sensor systems based on Surface Plasmon Resonance (SPR) at the interface of a liquid sample and sandwiched structures realized starting from the exposed core of a Plastic Optical Fiber (POF). The proposed geometries have proven to be suitable for measuring the refractive indexes of liquids whose refractive index falls around 1.35. Furthermore, the proposed sensing head, being low cost and relatively easy to realize, may be very attractive for biosensor implementation.

Sensors, Vol. 11, Pages 11679-11691: Amperometric Immunosensor Based on a Protein A/Deposited Gold Nanocrystals Modified Electrode for Carbofuran Detection

Xia Sun — Thu, 15 Dec 2011 00:00:00 CET

In this paper, an amperometric immunosensor modified with protein A/deposited gold nanocrystals (DpAu) was developed for the ultrasensitive detection of carbofuran residues. First, DpAu were electrodeposited onto the Au electrode surface to absorb protein A (PA) and improve the electrode conductivity. Then PA was dropped onto the surface of DpAu film, used for binding antibody Fc fragments. Next, anti-carbofuran monoclonal antibody was immobilized on the PA modified electrode. Finally, bovine serum albumin (BSA) was employed to block the possible remaining active sites avoiding any nonspecific adsorption. The fabrication procedure of the immunosensor was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), respectively. With the excellent electroconductivity of DpAu and the PA’s oriented immobilization of antibodies, a highly efficient immuno-reaction and detection sensitivity could be achieved. The influences of the electrodeposition time of DpAu, pH of the detection solution and incubation time on the current response of the fabricated immunosensor were investigated. Under optimized conditions, the current response was proportional to the concentration of carbofuran which ranged from 1 to 100 ng/mL and 100 ng/mL to 100 μg/mL. The detection limit was 0.1924 ng/mL. The proposed carbofuran immnuosensor exhibited high specificity, reproducibility, stability and regeneration performance, which may open a new door for ultrasensitive detection of carbofuran residues in vegetables and fruits.

Sensors, Vol. 11, Pages 11295-11304: Protein Binding Detection Using On-Chip Silicon Gratings

Anil Kumar Mudraboyina — Mon, 28 Nov 2011 00:00:00 CET

We demonstrate a silicon gratings-based biosensor to detect functionalized protein binding on its surface. The designed silicon gratings have sensitivities up to 197 nm/RIU in detecting refractive index change and 1.61 nm per nanometer of thickness change of bio-material on the surface of silicon gratings. Functionalizing proteins on gratings surface by eliminating unspecific binding makes this device more selective and efficient. Streptavidin at a concentration of 0.016 µmol/mL was functionalized on silicon substrate and biotin of 12 µmol/mL concentration was used as a target molecule in our detection experiments. Normal transmission measurements of gratings are made in air at different stages of immobilization, bare silicon grating, after attaching streptavidin and after trapping biotin. Total shifts in resonant peak wavelength of ~15 nm in normal transmission were observed after immobilizing biotin with ~7 nm of shift in resonant peak wavelength after functionalizing streptavidin to silicon substrate.

Sensors, Vol. 11, Pages 11064-11080: Serological Thymidine Kinase 1 is a Biomarker for Early Detection of Tumours—A Health Screening Study on 35,365 People, Using a Sensitive Chemiluminescent Dot Blot Assay

Zhi Heng Chen — Mon, 28 Nov 2011 00:00:00 CET

Serological thymidine kinase 1 (STK1) is a reliable proliferation marker for prognosis, monitoring tumour therapy, and relapse. Here we investigated the use of STK1 in health screening for early detection of pre-malignant and malignant diseases. The investigation was based on 35,365 participants in four independent health screening studies in China between 2005–2011. All participants were clinically examined. The concentration of STK1 was determined by a sensitive chemiluminescent dot blot ECL assay. The ROCvalue of the STK1 assay was 0.96. At a cut-off STK1 value of 2.0 pM, the likelihood (+) value was 236.5, and the sensitivity and the specificity were 0.78 and 0.99, respectively. The relative number of city-dwelling people with elevated STK1 values (≥2.0 pM) was 0.8% (198/26,484), while the corresponding value for the group of oil-field workers was 5.8% (514/8,355). The latter group expressed significantly higher frequency of refractory anaemia, fatty liver, and obesity, compared to the city dwellers, but no cases of breast hyperplasia or prostate hyperplasia. Furthermore, people working in oil drilling/oil transportation showed higher STK1 values and higher frequency of pre-malignancies and benign diseases than people working in the oil-field administration. In the STK1 elevated group of the city-dwelling people, a statistically significantly higher number of people were found to have malignancies, pre-malignancies of all types, moderate/severe type of hyperplasia of breast or prostate, or refractory anaemia, or to be at high risk for hepatitis B, compared to people with normal STK1 values (< 2.0 pM). No malignancies were found in the normal STK1 group. In the elevated STK1 group 85.4% showed diseases linked to a higher risk for pre-/early cancerous progression, compared to 52.4% of those with normal STK1 values. Among participants with elevated STK1 values, 8.8% developed new malignancies or progress in their pre-malignancies within 5 to 72 months, compared to 0.2% among people with normal STK1 values. People who showed elevated STK1 values were at about three to five times higher risk to develop malignancies compared to a calculated risk based on a cancer incidence rate of 0.2–0.3%. We conclude that serological TK1 protein concentration is a reliable marker for risk assessment of pre/early cancerous progression.

Sensors, Vol. 11, Pages 11021-11035: System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

Cheng-Hsin Chuang — Wed, 23 Nov 2011 00:00:00 CET

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS).

Sensors, Vol. 11, Pages 10940-10957: Alternative Post-Processing on a CMOS Chip to Fabricate a Planar Microelectrode Array

Francisco López-Huerta — Tue, 22 Nov 2011 00:00:00 CET

We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 µm CMOS standard process and it has 12 pMEA through a 4 ´ 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+-type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications.

Sensors, Vol. 11, Pages 10907-10929: Plasmonic Nanostructures for Nano-Scale Bio-Sensing

Taerin Chung — Mon, 21 Nov 2011 00:00:00 CET

The optical properties of various nanostructures have been widely adopted for biological detection, from DNA sequencing to nano-scale single molecule biological function measurements. In particular, by employing localized surface plasmon resonance (LSPR), we can expect distinguished sensing performance with high sensitivity and resolution. This indicates that nano-scale detections can be realized by using the shift of resonance wavelength of LSPR in response to the refractive index change. In this paper, we overview various plasmonic nanostructures as potential sensing components. The qualitative descriptions of plasmonic nanostructures are supported by the physical phenomena such as plasmonic hybridization and Fano resonance. We present guidelines for designing specific nanostructures with regard to wavelength range and target sensing materials.

Sensors, Vol. 11, Pages 10785-10797: A Nanostructured Piezoelectric Immunosensor for Detection of Human Cardiac Troponin T

Rosana A. S. Fonseca — Wed, 16 Nov 2011 00:00:00 CET

A piezoelectric immunosensor based on gold nanoparticles (AuNPs) co-immobilized on a dithiol-modified surface is proposed for detection of human cardiac troponin T (TnT). Anti-human troponin T (anti-TnT) antibodies were covalently immobilized on the nanostructured electrode surface by thiol-aldehyde linkages. In a homogeneous bulk solution, TnT was captured by anti-TnT immobilized on the QCM electrode. Cyclic voltammetry studies were used to characterize the AuNPs layer on the electrode surface and the anti-TnT immobilization steps. The QCM-flow immunosensor exhibited good reliability, measuring concentrations of TnT from 0.003 to 0.5 ng mL−1 in human serum with high linearity (r = 0.989; p < 0.01). The immunosensor exhibited a 7% coefficient of variation and 0.0015 ng mL−1 limit of detection, indicating a high reproducibility and sensitivity. The proposed QCM nanostructured immunosensor is easy to use and has promising potential in the diagnosis of acute myocardial infarction due to its speed and high sensitivity.

Sensors, Vol. 11, Pages 10187-10196: A Highly Sensitive and Selective Competition Assay for the Detection of Cysteine Using Mercury-Specific DNA, Hg2+ and Sybr Green I

Hui Xu — Wed, 26 Oct 2011 00:00:00 CEST

We here report a rapid, sensitive, selective and label-free fluorescence detection method for cysteine (Cys). The conformation of mercury-specific DNA (MSD) changes from a random coil form to a hairpin structure in the presence of Hg2+ due to the formation of a thymine-Hg2+-thymine (T-Hg2+-T) complex. Cys can selectively coordinate with Hg2+ and extract it from the thymine-Hg2+-thymine complex. The hairpin structure dehybridizes and the fluorescence intensity of Sybr Green I (SG) decreases upon addition of Cys because SG efficiently discriminates mercury-specific DNA and mercury-specific DNA/Hg2+ complex. The detection can be finished within 5 min with high sensitivity and selectivity. In addition, we can obtain variable dynamic ranges for Cys by changing the concentration of MSD/Hg2+.

Sensors, Vol. 11, Pages 10180-10186: Bioinspired Sensor Systems

Manel del Valle — Wed, 26 Oct 2011 00:00:00 CEST

This editorial summarizes and classifies the contributions presented by different authors to the special issue of the journal Sensors dedicated to Bioinspired Sensor Systems. From the coupling of sensor arrays or networks, plus computer processing abilities, new applications to mimic or to complement human senses are arising in the context of ambient intelligence. Principles used, and illustrative study cases have been presented permitting readers to grasp the current status of the field.

Sensors, Vol. 11, Pages 10063-10073: Solid Phase Biosensors for Arsenic or Cadmium Composed of A trans Factor and cis Element Complex

Mohammad Shohel Rana Siddiki — Tue, 25 Oct 2011 00:00:00 CEST

The presence of toxic metals in drinking water has hazardous effects on human health. This study was conducted to develop GFP-based-metal-binding biosensors for on-site assay of toxic metal ions. GFP-tagged ArsR and CadC proteins bound to a cis element, and lost the capability of binding to it in their As- and Cd-binding conformational states, respectively. Water samples containing toxic metals were incubated on a complex of GFP-tagged ArsR or CadC and cis element which was immobilized on a solid surface. Metal concentrations were quantified with fluorescence intensity of the metal-binding states released from the cis element. Fluorescence intensity obtained with the assay significantly increased with increasing concentrations of toxic metals. Detection limits of 1 μg/L for Cd(II) and 5 μg/L for As(III) in purified water and 10 µg/L for Cd(II) and As(III) in tap water and bottled mineral water were achieved by measurement with a battery-powered portable fluorometer after 15-min and 30-min incubation, respectively. A complex of freeze dried GFP-tagged ArsR or CadC binding to cis element was stable at 4 °C and responded to 5 μg/L As(III) or Cd(II). The solid phase biosensors are sensitive, less time-consuming, portable, and could offer a protocol for on-site evaluation of the toxic metals in drinking water.

Sensors, Vol. 11, Pages 10038-10047: Line-Monitoring, Hyperspectral Fluorescence Setup for Simultaneous Multi-Analyte Biosensing

Zhiyi Liu — Tue, 25 Oct 2011 00:00:00 CEST

Conventional fluorescence scanners utilize multiple filters to distinguish different fluorescent labels, and problems arise because of this filter-based mechanism. In this work we propose a line-monitoring, hyperspectral fluorescence technique which is designed and optimized for applications in multi-channel microfluidic systems. In contrast to the filter-based mechanism, which only records fluorescent intensities, the hyperspectral technique records the full spectrum for every point on the sample plane. Multivariate data exploitation is then applied to spectra analysis to determine ratios of different fluorescent labels and eliminate unwanted artifacts. This sensor is designed to monitor multiple fluidic channels simultaneously, providing the potential for multi-analyte biosensing. The detection sensitivity is approximately 0.81 fluors/μm2, and this sensor is proved to act with a good homogeneity. Finally, a model experiment of detecting short oligonucleotides has demonstrated the biomedical application of this hyperspectral fluorescence biosensor.

Sensors, Vol. 11, Pages 9658-9666: Numerical Optimization of a Microfluidic Assisted Microarray for the Detection of Biochemical Interactions

Emanuele Orabona — Wed, 12 Oct 2011 00:00:00 CEST

Finite element method analysis was applied to the characterization of the biomolecular interactions taking place in a microfluidic assisted microarray. Numerical simulations have been used for the optimization of geometrical and physical parameters of the sensing device. Different configurations have been analyzed and general considerations have been derived. We have shown that a parallel disposition of the sensing area allows the homogeneous formation of the target molecular complex in all the active zones of the microarray. Stationary and time dependent results have also been obtained.

Sensors, Vol. 11, Pages 9613-9627: Cell Docking, Movement and Cell-Cell Interactions of Heterogeneous Cell Suspensions in a Cell Manipulation Microdevice

Fei-Lung Lai — Wed, 12 Oct 2011 00:00:00 CEST

This study demonstrates a novel cell manipulation microdevice for cell docking, culturing, cell-cell contact and interaction by microfluidic manipulation of heterogeneous cell suspensions. Heterogeneous cell suspensions include disparate blood cells of natural killer cells and leukemia cancer cells for immune cell transplantation therapy. However, NK cell alloreactivity from different healthy donors present various recovery response levels. Little is still known about the interactions and cytotoxicity effects between donor NK cells and recipient cancer cells. The cell-based micro device first showed the capability of cell docking, movement, contact and cell-cell interaction with respect to cell cytotoxicity of NK cells against cancer cells. With various flow tests for live cell loading, flow rates of 10 μL/h were chosen for injection in the central and side flows such that both types of suspension cells could be gently docked at the gap structure in a reaction zone. The trapping number of particles and cells was linearly proportional to the gap length. Finally, the cytotoxicity of around 40% was found to be similar in the case of dilute cells and a large cell population. As a result, the cell manipulation microdevice has been validated for live suspensions of natural killer and cancer cells, and exhibited the capability to measure the cytotoxicity of dilute cell suspensions.

Sensors, Vol. 11, Pages 9520-9531: A Label-Free Electrochemical Immunosensor for Carbofuran Detection Based on a Sol-Gel Entrapped Antibody

Xia Sun — Mon, 10 Oct 2011 00:00:00 CEST

In this study, an anti-carbofuran monoclonal antibody (Ab) was immobilized on the surface of a glassy carbon electrode (GCE) using silica sol-gel (SiSG) technology. Thus, a sensitive, label-free electrochemical immunosensor for the direct determination of carbofuran was developed. The electrochemical performance of immunoreaction of antigen with the anti-carbofuran monoclonal antibody was investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), in which phosphate buffer solution containing [Fe(CN)6]3−/4− was used as the base solution for test. Because the complex formed by the immunoreaction hindered the diffusion of [Fe(CN)6]3−/4− on the electrode surface, the redox peak current of the immunosensor in the CV obviously decreased with the increase of the carbofuran concentration. The pH of working solution, the concentration of Ab and the incubation time of carbofuran were studied to ensure the sensitivity and conductivity of the immunosensor. Under the optimal conditions, the linear range of the proposed immunosensor for the determination of carbofuran was from 1 ng/mL to 100 μg/mL and from 50 μg/mL to 200 μg/mL with a detection limit of 0.33 ng/mL (S/N = 3). The proposed immunosensor exhibited good high sensitivity and stability, and it was thus suitable for trace detection of carbofuran pesticide residues.

Sensors, Vol. 11, Pages 9450-9466: Biosensor Applications in the Field of Antibiotic Research—A Review of Recent Developments

Katrin Reder-Christ — Mon, 03 Oct 2011 00:00:00 CEST

Antibacterials are among of the most important medications used in health care. However, their efficacy is increasingly impeded by a tremendous and globally spread bacterial resistance phenomenon. This bacterial resistance is accelerated by inadequate application of antibacterial drugs in humans, the widespread veterinary use of antibacterials, and antibacterial occurrence in the environment and food. Further, there is a lack of development of innovative novel drugs. Therefore, the search for novel antibacterials has to be intensified and the spread of antibacterials in the environment has to be restricted. Due to the fundamental progress in biosensor development and promising applications in the antibiotic field, this review gives for the first time an overview on the use and prospects of biosensor applications in that area. A number of reports have applied biosensors of different design and techniques to search for antibacterials in environmental and foodstuff matrices. These studies are discussed with respect to the analytical values and compared to conventional techniques. Furthermore, biosensor applications to elucidate the mode of action of antimicrobial drugs in vitro have been described. These studies were critically introduced referring to the informational value of those simulations. In summary, biosensors will be illustrated as an innovative and promising, although not yet comprehensively applied, technique in the antibacterial field.

Sensors, Vol. 11, Pages 9442-9449: Self-Assembled Films of Dendrimers and Metallophthalocyanines as FET-Based Glucose Biosensors

Nirton C.S. Vieira — Mon, 03 Oct 2011 00:00:00 CEST

Separative extended gate field effect transistor (SEGFET) type devices have been used as an ion sensor or biosensor as an alternative to traditional ion sensitive field effect transistors (ISFETs) due to their robustness, ease of fabrication, low cost and possibility of FET isolation from the chemical environment. The layer-by-layer technique allows the combination of different materials with suitable properties for enzyme immobilization on simple platforms such as the extended gate of SEGFET devices enabling the fabrication of biosensors. Here, glucose biosensors based on dendrimers and metallophthalocyanines (MPcs) in the form of layer-by-layer (LbL) films, assembled on indium tin oxide (ITO) as separative extended gate material, has been produced. NH3+ groups in the dendrimer allow electrostatic interactions or covalent bonds with the enzyme (glucose oxidase). Relevant parameters such as optimum pH, buffer concentration and presence of serum bovine albumin (BSA) in the immobilization process were analyzed. The relationship between the output voltage and glucose concentration shows that upon detection of a specific analyte, the sub-products of the enzymatic reaction change the pH locally, affecting the output signal of the FET transducer. In addition, dendritic layers offer a nanoporous environment, which may be permeable to H+ ions, improving the sensibility as modified electrodes for glucose biosensing.

Sensors, Vol. 11, Pages 9344-9360: Determination of Ammonium Ion Using a Reagentless Amperometric Biosensor Based on Immobilized Alanine Dehydrogenase

Ling Ling Tan — Thu, 29 Sep 2011 00:00:00 CEST

The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of ammonium ion (NH4+) usually requires the addition of pyruvate substrate and reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the reaction. This addition of reagents is inconvenient when an enzyme biosensor based on AlaDH is used. To resolve the problem, a novel reagentless amperometric biosensor using a stacked methacrylic membrane system coated onto a screen-printed carbon paste electrode (SPE) for NH4+ ion determination is described. A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2-hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH) enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate, NH4+ was consumed in the process and thus the signal from the electrocatalytic oxidation of NADH at an applied potential of +0.55 V was proportional to the NH4+ ion concentration under optimal conditions. The stacked methacrylate membranes responded rapidly and linearly to changes in NH4+ ion concentrations between 10–100 mM, with a detection limit of 0.18 mM NH4+ ion. The reproducibility of the amperometrical NH4+ biosensor yielded low relative standard deviations between 1.4–4.9%. The stacked membrane biosensor has been successfully applied to the determination of NH4+ ion in spiked river water samples without pretreatment. A good correlation was found between the analytical results for NH4+ obtained from the biosensor and the Nessler spectrophotometric method.

Sensors, Vol. 11, Pages 9300-9312: A Conductometric Indium Oxide Semiconducting Nanoparticle Enzymatic Biosensor Array

Dongjin Lee — Wed, 28 Sep 2011 00:00:00 CEST

We report a conductometric nanoparticle biosensor array to address the significant variation of electrical property in nanomaterial biosensors due to the random network nature of nanoparticle thin-film. Indium oxide and silica nanoparticles (SNP) are assembled selectively on the multi-site channel area of the resistors using layer-by-layer self-assembly. To demonstrate enzymatic biosensing capability, glucose oxidase is immobilized on the SNP layer for glucose detection. The packaged sensor chip onto a ceramic pin grid array is tested using syringe pump driven feed and multi-channel I–V measurement system. It is successfully demonstrated that glucose is detected in many different sensing sites within a chip, leading to concentration dependent currents. The sensitivity has been found to be dependent on the channel length of the resistor, 4–12 nA/mM for channel lengths of 5–20 µm, while the apparent Michaelis-Menten constant is 20 mM. By using sensor array, analytical data could be obtained with a single step of sample solution feeding. This work sheds light on the applicability of the developed nanoparticle microsensor array to multi-analyte sensors, novel bioassay platforms, and sensing components in a lab-on-a-chip.

Sensors, Vol. 11, Pages 8395-8411: Development of an Integrated Microfluidic Perfusion Cell Culture System for Real-Time Microscopic Observation of Biological Cells

Jr-Lung Lin — Mon, 29 Aug 2011 00:00:00 CEST

This study reports an integrated microfluidic perfusion cell culture system consisting of a microfluidic cell culture chip, and an indium tin oxide (ITO) glass-based microheater chip for micro-scale perfusion cell culture, and its real-time microscopic observation. The system features in maintaining both uniform, and stable chemical or thermal environments, and providing a backflow-free medium pumping, and a precise thermal control functions. In this work, the performance of the medium pumping scheme, and the ITO glass microheater were experimentally evaluated. Results show that the medium delivery mechanism was able to provide pumping rates ranging from 15.4 to 120.0 μL·min−1. In addition, numerical simulation and experimental evaluation were conducted to verify that the ITO glass microheater was capable of providing a spatially uniform thermal environment, and precise temperature control with a mild variation of ±0.3 °C. Furthermore, a perfusion cell culture was successfully demonstrated, showing the cultured cells were kept at high cell viability of 95 ± 2%. In the process, the cultured chondrocytes can be clearly visualized microscopically. As a whole, the proposed cell culture system has paved an alternative route to carry out real-time microscopic observation of biological cells in a simple, user-friendly, and low cost manner.

Sensors, Vol. 11, Pages 8323-8338: A Biosensor for Urea from Succinimide-Modified Acrylic Microspheres Based on Reflectance Transduction

Alizar Ulianas — Fri, 26 Aug 2011 00:00:00 CEST

New acrylic microspheres were synthesised by photopolymerisation where the succinimide functional group was incorporated during the microsphere preparation. An optical biosensor for urea based on reflectance transduction with a large linear response range to urea was successfully developed using this material. The biosensor utilized succinimide-modified acrylic microspheres immobilized with a Nile blue chromoionophore (ETH 5294) for optical detection and urease enzyme was immobilized on the surface of the microspheres via the succinimide groups. No leaching of the enzyme or chromoionophore was observed. Hydrolysis of the urea by urease changes the pH and leads to a color change of the immobilized chromoionophore. When the color change was monitored by reflectance spectrophotometry, the linear response range of the biosensor to urea was from 0.01 to 1,000 mM (R2 = 0.97) with a limit of detection of 9.97 mM. The biosensor response showed good reproducibility (relative standard deviation = 1.43%, n = 5) with no interference by major cations such as Na+, K+, NH4+ and Mg2+. The use of reflectance as a transduction method led to a large linear response range that is better than that of many urea biosensors based on other optical transduction methods.

Sensors, Vol. 11, Pages 8180-8202: LinkMind: Link Optimization in Swarming Mobile Sensor Networks

Trung Dung Ngo — Tue, 23 Aug 2011 00:00:00 CEST

A swarming mobile sensor network is comprised of a swarm of wirelessly connected mobile robots equipped with various sensors. Such a network can be applied in an uncertain environment for services such as cooperative navigation and exploration, object identification and information gathering. One of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm is demonstrated and evaluated in simulation.

Sensors, Vol. 11, Pages 8164-8179: FPGA-Based Multimodal Embedded Sensor System Integrating Low- and Mid-Level Vision

Guillermo Botella — Mon, 22 Aug 2011 00:00:00 CEST

Motion estimation is a low-level vision task that is especially relevant due to its wide range of applications in the real world. Many of the best motion estimation algorithms include some of the features that are found in mammalians, which would demand huge computational resources and therefore are not usually available in real-time. In this paper we present a novel bioinspired sensor based on the synergy between optical flow and orthogonal variant moments. The bioinspired sensor has been designed for Very Large Scale Integration (VLSI) using properties of the mammalian cortical motion pathway. This sensor combines low-level primitives (optical flow and image moments) in order to produce a mid-level vision abstraction layer. The results are described trough experiments showing the validity of the proposed system and an analysis of the computational resources and performance of the applied algorithms.

Sensors, Vol. 11, Pages 8152-8163: An Amperometric Biosensor for Glucose Determination Prepared from Glucose Oxidase Immobilized in Polyaniline-Polyvinylsulfonate Film

Fatma Arslan — Mon, 22 Aug 2011 00:00:00 CEST

In this study, a novel amperometric glucose biosensor with immobilization of glucose oxidase on electrochemically polymerized polyaniline-polyvinylsulphonate (Pani-Pvs) films has been accomplished via the entrapment technique. Electropolymerization of aniline on the Pt surface of the Pt electrode was carried out at constant potential (0.75 V, vs. Ag/AgCl) using an electrochemical cell containing aniline and polyvinylsulphonate. Firstly, the optimum working conditions for preparing polyaniline-polyvinylsulfonate films were investigated. Determination of glucose was carried out by the oxidation of enzymatically produced H2O2 at 0.4 V vs. Ag/AgCl. The effects of pH and temperature were investigated and the optimum pH value was found to be 7.5. The storage stability and operational stability of the enzyme electrode were also studied. The results show that 75% of the response current was retained after 16 activity assays. The prepared glucose biosensor retained 80.6% of initial activity after 40 days when stored in 0.1 M phosphate buffer solution at 4 °C.

Sensors, Vol. 11, Pages 8018-8027: Detection of Single-Nucleotide Polymorphism on uidA Gene of Escherichia coli by a Multiplexed Electrochemical DNA Biosensor with Oligonucleotide-Incorporated Nonfouling Surface

Gang Liu — Mon, 15 Aug 2011 00:00:00 CEST

We report here a practical application of a multiplexed electrochemical DNA sensor for highly specific single-nucleotide polymorphism (SNP) detection. In this work, a 16-electrode array was applied with an oligonucleotide-incorporated nonfouling surfaces (ONS) on each electrode for the resistance of unspecific absorption. The fully matched target DNA templated the ligation between the capture probe assembled on gold electrodes and the tandem signal probe with a biotin moiety, which could be transduced to peroxidase-based catalyzed amperometric signals. A mutant site (T93G) in uidA gene of E. coli was analyzed in PCR amplicons. 10% percentage of single mismatched mutant gene was detected, which clearly proved the selectivity of the multiplexed electrochemical DNA biosensor when practically applied.

Sensors, Vol. 11, Pages 7851-7864: Design and Control of a Ferromagnetic Coded Micro-Carrier Biochip Sensor for Multiplex Detection of Antibodies

Rong-Seng Chang — Thu, 11 Aug 2011 00:00:00 CEST

This paper describes a method for producing a novel type of ferromagnetic coded micro-carrier. The ferromagnetic coded micro-carriers are about 200 μm in length, 200 μm in width and 50 μm in thickness, and contain eight code elements with two distinguishable codes (hollow and solid), allowing for 28 unique codes. The code shapes include rectangle, circle, etc. Differently shaped coded micro-carriers could carry different antigens for detection of its complementary antibody. These many shapes of coded micro-carriers would be used simultaneously allowing us to make multiple detections for different antibodies at the same time. A molding process is applied for fabrication of the ferromagnetically coded micro-carriers where Fe material (Fe powder mixed with binder) is shaped in many tiny molds to produce the coded shapes used for identification of the bio-molecules. Magnetic force is used to control the movement and location of the ferromagnetic coded micro-carriers to prevent the loss during the hybridization process. The results of image process and analysis system testing are satisfactory. The results of our micro-carrier detection system for two sets of R and B color analysis are proportional to those obtained from ELISA antibody detection.

Sensors, Vol. 11, Pages 7799-7822: A Biomimetic Sensor for the Classification of Honeys of Different Floral Origin and the Detection of Adulteration

Ammar Zakaria — Tue, 09 Aug 2011 00:00:00 CEST

The major compounds in honey are carbohydrates such as monosaccharides and disaccharides. The same compounds are found in cane-sugar concentrates. Unfortunately when sugar concentrate is added to honey, laboratory assessments are found to be ineffective in detecting this adulteration. Unlike tracing heavy metals in honey, sugar adulterated honey is much trickier and harder to detect, and traditionally it has been very challenging to come up with a suitable method to prove the presence of adulterants in honey products. This paper proposes a combination of array sensing and multi-modality sensor fusion that can effectively discriminate the samples not only based on the compounds present in the sample but also mimic the way humans perceive flavours and aromas. Conversely, analytical instruments are based on chemical separations which may alter the properties of the volatiles or flavours of a particular honey. The present work is focused on classifying 18 samples of different honeys, sugar syrups and adulterated samples using data fusion of electronic nose (e-nose) and electronic tongue (e-tongue) measurements. Each group of samples was evaluated separately by the e-nose and e-tongue. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to separately discriminate monofloral honey from sugar syrup, and polyfloral honey from sugar and adulterated samples using the e-nose and e-tongue. The e-nose was observed to give better separation compared to e-tongue assessment, particularly when LDA was applied. However, when all samples were combined in one classification analysis, neither PCA nor LDA were able to discriminate between honeys of different floral origins, sugar syrup and adulterated samples. By applying a sensor fusion technique, the classification for the 18 different samples was improved. Significant improvement was observed using PCA, while LDA not only improved the discrimination but also gave better classification. An improvement in performance was also observed using a Probabilistic Neural Network classifier when the e-nose and e-tongue data were fused.

Sensors, Vol. 11, Pages 7749-7762: A Renewable and Ultrasensitive Electrochemiluminescence Immunosenor Based on Magnetic RuL@SiO2-Au~RuL-Ab2 Sandwich-Type Nano-Immunocomplexes

Ning Gan — Fri, 05 Aug 2011 00:00:00 CEST

An ultrasensitive and renewable electrochemiluminescence (ECL) immunosensor was developed for the detection of tumor markers by combining a newly designed trace tag and streptavidin-coated magnetic particles (SCMPs). The trace tag (RuL@SiO2-Au~RuL-Ab2) was prepared by loading Ru(bpy)32+(RuL)-conjuged secondary antibodies (RuL-Ab2) on RuL@SiO2 (RuL-doped SiO2) doped Au (RuL@SiO2-Au). To fabricate the immunosensor, SCMPs were mixed with biotinylated AFP primary antibody (Biotin-Ab1), AFP, and RuL@SiO2-Au~RuL-Ab2 complexes, then the resulting SCMP/Biotin-Ab1/AFP/RuL@SiO2-Au~RuL-Ab2 (SBAR) sandwich-type immunocomplexes were absorbed on screen printed carbon electrode (SPCE) for detection. The immunocomplexes can be easily washed away from the surface of the SPCE when the magnetic field was removed, which made the immunosensor reusable. The present immunosensor showed a wide linear range of 0.05–100 ng mL–1 for detecting AFP, with a low detection limit of 0.02 ng mL–1 (defined as S/N = 3). The method takes advantage of three properties of the immunosensor: firstly, the RuL@SiO2-Au~RuL-Ab2 composite exhibited dual amplification since SiO2 could load large amount of reporter molecules (RuL) for signal amplification. Gold particles could provide a large active surface to load more reporter molecules (RuL-Ab2). Accordingly, through the ECL response of RuL and tripropylamine (TPA), a strong ECL signal was obtained and an amplification analysis of protein interaction was achieved. Secondly, the sensor is renewable because the sandwich-type immunocomplexes can be readily absorbed or removed on the SPCE’s surface in a magnetic field. Thirdly, the SCMP modified probes can perform the rapid separation and purification of signal antibodies in a magnetic field. Thus, the present immunosensor can simultaneously realize separation, enrichment and determination. It showed potential application for the detection of AFP in human sera.

Sensors, Vol. 11, Pages 7656-7664: Development of a Mass Sensitive Quartz Crystal Microbalance (QCM)-Based DNA Biosensor Using a 50 MHz Electronic Oscillator Circuit

Gonzalo García-Martinez — Wed, 03 Aug 2011 00:00:00 CEST

This work deals with the design of a high sensitivity DNA sequence detector using a 50 MHz quartz crystal microbalance (QCM) electronic oscillator circuit. The oscillator circuitry is based on Miller topology, which is able to work in damping media. Calibration and experimental study of frequency noise are carried out, finding that the designed sensor has a resolution of 7.1 ng/cm2 in dynamic conditions (with circulation of liquid). Then the oscillator is proved as DNA biosensor. Results show that the system is able to detect the presence of complementary target DNAs in a solution with high selectivity and sensitivity. DNA target concentrations higher of 50 ng/mL can be detected.

Sensors, Vol. 11, Pages 7219-7230: Development of Sensor Cells Using NF-κB Pathway Activation for Detection of Nanoparticle-Induced Inflammation

Peng Chen — Mon, 18 Jul 2011 00:00:00 CEST

The increasing use of nanomaterials in consumer and industrial products has aroused concerns regarding their fate in biological systems. An effective detection method to evaluate the safety of bio-nanomaterials is therefore very important. Titanium dioxide (TiO2), which is manufactured worldwide in large quantities for use in a wide range of applications, including pigment and cosmetic manufacturing, was once thought to be an inert material, but recently, more and more studies have indicated that TiO2 nanoparticles (TiO2 NPs) can cause inflammation and be harmful to humans by causing lung and brain problems. In order to evaluate the safety of TiO2 NPs for the environment and for humans, sensor cells for inflammation detection were developed, and these were transfected with the Toll-like receptor 4 (TLR4) gene and Nuclear Factor Kappa B (NF-κB) reporter gene. NF-κB as a primary cause of inflammation has received a lot of attention, and it can be activated by a wide variety of external stimuli. Our data show that TiO2 NPs-induced inflammation can be detected by our sensor cells through NF-κB pathway activation. This may lead to our sensor cells being used for bio-nanomaterial safety evaluation.

Sensors, Vol. 11, Pages 7022-7036: An Asynchronous Multi-Sensor Micro Control Unit for Wireless Body Sensor Networks (WBSNs)

Chiung-An Chen — Wed, 06 Jul 2011 00:00:00 CEST

In this work, an asynchronous multi-sensor micro control unit (MCU) core is proposed for wireless body sensor networks (WBSNs). It consists of asynchronous interfaces, a power management unit, a multi-sensor controller, a data encoder (DE), and an error correct coder (ECC). To improve the system performance and expansion abilities, the asynchronous interface is created for handshaking different clock domains between ADC and RF with MCU. To increase the use time of the WBSN system, a power management technique is developed for reducing power consumption. In addition, the multi-sensor controller is designed for detecting various biomedical signals. To prevent loss error from wireless transmission, use of an error correct coding technique is important in biomedical applications. The data encoder is added for lossless compression of various biomedical signals with a compression ratio of almost three. This design is successfully tested on a FPGA board. The VLSI architecture of this work contains 2.68-K gate counts and consumes power 496-μW at 133-MHz processing rate by using TSMC 0.13-μm CMOS process. Compared with the previous techniques, this work offers higher performance, more functions, and lower hardware cost than other micro controller designs.

Sensors, Vol. 11, Pages 6978-6990: Fabrication of a Micro-Fluid Gathering Tool for the Gastrointestinal Juice Sampling Function of a Versatile Capsular Endoscope

Kyo-in Koo — Mon, 04 Jul 2011 00:00:00 CEST

This paper presents a micro-fluid gathering tool for a versatile capsular endoscope that employs a solid chemical propellant, azobisisobutyronitrile (AIBN). The proposed tool consists of a micro-heater, an AIBN matrix, a Venturi tube, a reservoir, an inlet, and an outlet. The micro-heater heats the AIBN matrix to be decomposed into by-products and nitrogen gas. This nitrogen gas generates negative pressure passing through the Venturi tube. The generated negative pressure inhales a target fluid from around the inlet into the reservoir. All the parts are designed to be embedded inside a cylindrical shape with a diameter of 17 mm and a height of 2.3 mm in order to integrate it into a versatile developmental capsular endoscope without any scaledown. Two sets of the proposed tools are fabricated and tested: one is made of polydimethylsiloxane (PDMS) and the other is made of polymethylmethacrylate (PMMA). In performance comparisons, the PDMS gathering tool can withstand a stronger pulling force, and the PMMA gathering tool requires a less negative pressure for inhaling the same target fluid. Due to the instant and full activation of the thin AIBN matrix, both types of gathering tool show analogous performance in the sample gathering evaluation. The gathered volume is approximately 1.57 μL using approximately 25.4 μL of AIBN compound.

Sensors, Vol. 11, Pages 6719-6727: DNA Strand Patterns on Aluminium Thin Films

Nadia Mahmoudi Khatir — Tue, 28 Jun 2011 00:00:00 CEST

A new patterning method using Deoxyribose Nucleic Acid (DNA) strands capable of producing nanogaps of less than 100 nm is proposed and investigated in this work. DNA strands from Bosenbergia rotunda were used as the fundamental element in patterning DNA on thin films of aluminium (Al) metal without the need for any lithographic techniques. The DNA strands were applied in buffer solutions onto thin films of Al on silicon (Si) and the chemical interactions between the DNA strands and Al creates nanometer scale arbitrary patterning by direct transfer of the DNA strands onto the substrate. This simple and cost-effective method can be utilized in the fabrication of various components in electronic chips for microelectronics and Nano Electronic Mechanical System (NEMS) applications in general.

Sensors, Vol. 11, Pages 6685-6696: Label Free Inhibitor Screening of Hepatitis C Virus (HCV) NS5B Viral Protein Using RNA Oligonucleotide

Changhyun Roh — Mon, 27 Jun 2011 00:00:00 CEST

Globally, over 170 million people (ca. 3% of the World’s population) are infected with the hepatitis C virus (HCV), which can cause serious liver diseases such as chronic hepatitis, evolving into subsequent health problems. Driven by the need to detect the presence of HCV, as an essential factor in diagnostic medicine, the monitoring of viral protein has been of great interest in developing simple and reliable HCV detection methods. Despite considerable advances in viral protein detection as an HCV disease marker, the current enzyme linked immunosorbent assay (ELISA) based detection methods using antibody treatment have several drawbacks. To overcome this bottleneck, an RNA aptamer become to be emerged as an antibody substitute in the application of biosensor for detection of viral protein. In this study, we demonstrated a streptavidin-biotin conjugation method, namely, the RNA aptamer sensor system that can quantify viral protein with detection level of 700 pg mL−1 using a biotinylated RNA oligonucleotide on an Octet optical biosensor. Also, we showed this method can be used to screen inhibitors of viral protein rapidly and simply on a biotinylated RNA oligonucleotide biosensor. Among the inhibitors screened, (−)-Epigallocatechin gallate showed high binding inhibition effect on HCV NS5B viral protein. The proposed method can be considered a real-time monitoring method for inhibitor screening of HCV viral protein and is expected to be applicable to other types of diseases.

Sensors, Vol. 11, Pages 6645-6655: Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin with Current Modulation

Joshua A. Hagen — Mon, 27 Jun 2011 00:00:00 CEST

Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3’ terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels.

Sensors, Vol. 11, Pages 6435-6453: An Electronic Nose for Reliable Measurement and Correct Classification of Beverages

Mazlina Mamat — Fri, 17 Jun 2011 00:00:00 CEST

This paper reports the design of an electronic nose (E-nose) prototype for reliable measurement and correct classification of beverages. The prototype was developed and fabricated in the laboratory using commercially available metal oxide gas sensors and a temperature sensor. The repeatability, reproducibility and discriminative ability of the developed E-nose prototype were tested on odors emanating from different beverages such as blackcurrant juice, mango juice and orange juice, respectively. Repeated measurements of three beverages showed very high correlation (r > 0.97) between the same beverages to verify the repeatability. The prototype also produced highly correlated patterns (r > 0.97) in the measurement of beverages using different sensor batches to verify its reproducibility. The E-nose prototype also possessed good discriminative ability whereby it was able to produce different patterns for different beverages, different milk heat treatments (ultra high temperature, pasteurization) and fresh and spoiled milks. The discriminative ability of the E-nose was evaluated using Principal Component Analysis and a Multi Layer Perception Neural Network, with both methods showing good classification results.