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Integrated biosensors with several types of transducers are complex to manufacture. This paper presents the fabrication process for a bimodal biosensor by using silicon microfabrication process. The device is composed of a surface plasmons resonance (SPR) transducer and a microcalorimetric device. The fabrication process has a yield in our academic foundry. The device was functionalized with a simple BSA-biotin adsorption. SPR sensing performance was assessed by neutravidin binding to immobilized biotins.

Nanoscale biosensors are devices designed to detect analytes by combining biological components and physicochemical detectors. A well-known design of these sensors involves the implementation of nanocantilevers. These microscopic diving boards are coated with binding probes that have an affinity for a particular amino acid, enzyme or protein in living organisms. When these probes attract target particles, such as biomolecules, the binding of these particles changes the vibrating frequency of the cantilever. This process is random in nature and produces fluctuations in the frequency and damping of the cantilever. In this paper, we studied the effect of these fluctuations using a stochastically perturbed, classical harmonic oscillator.

MicroRNAs are associated with multiple cellular processes and diseases. Here, we designed a highly sensitive, magnetically retrievable biosensor using magnetic beads (MBs) as a model RNA sensor. The assay utilized two biotinylated probes, which were hybridized to the complementary target miRNA in a sandwich assay format. One of the biotinylated ends of the hybridization complex was immobilized onto the surface of a NeutrAvidin (NAV) coated MB and the other biotinylated end was conjugated to HRP via NAV-biotin interaction. The results were presented by colorimetric absorbance of the resorufin product from amplex red oxidation. We show that by combining the use of MBs as well as bio-specific immobilization, the sensitivity of miRNA detection is down to 100 pM. This model HRP-MBs system can be used for simple, rapid colorimetric quantification of low level DNA/RNA or other small molecules.

In this paper, a new ultra-compact optical biosensor based on photonic crystal (phc) resonant cavity is proposed. This sensor has ability to work in chemical optical processes for the determination and analysis of liquid material. Here, we used an optical filter based on two-dimensional phc resonant cavity on a silicon layer and an active area is created in center of cavity. According to results, with increasing the refractive index of cavity, resonant wavelengths shift so that this phenomenon provides the ability to measure the properties of materials. This novel designed biosensor has more advantage to operate in the biochemical process for example sensing protein and DNA molecule refractive index. This nanoscale biosensor has quality factor higher than 1.5 × 10⁴ and it is suitable to be used in the home healthcare diagnostic applications.

Inflammation is a protective mechanism against invading pathogens and tissue damage. However, the inflammatory process is implicated in a wide range of diseases affecting all organs and body systems. Nitric oxide — a multifunctional signaling molecule that plays a critical role in systemic blood pressure homeostasis, prevention of platelet aggregation, antimicrobial resistance, immunoregulation, tumor suppression and as a neurotransmitter — is used as a surrogate marker for inflammation. However, the most commonly used Griess assay is an indirect and expensive method for the determination of nitric oxide concentration. Hence, single-walled carbon nanotube-based biosensors have been explored as real-time, sensitive, selective and safe methods to determine nitric oxide released during the inflammatory process. In this review, we explore current developments in single-walled carbon nanotube-based biosensors for the detection of nitric oxide in exhaled breath as a direct and noninvasive test for detection of bronchial inflammation.

In this study, NAC-capped CdTe/CdS/ZnS core/double shell QDs were synthesized in an aqueous medium to investigate their utility in distinguishing normal DNA from mutated DNA extracted from biological samples. Following the interaction between the synthesized QDs with DNA extracted from leukemia cases (represents damaged DNA) and that of healthy donors (represents undamaged DNA), differential fluorescent emission maxima and intensities were observed. It was found that damaged DNA from leukemic cells DNA-QDs conjugates at 585 nm while intact DNA (from healthy subjects) DNA–QDs conjugates at 574 nm. The obtained results from the optical analyses indicate that the prepared QDs could be utilized as probe for detecting disrupted DNA that is associated with a number of diseases including malignancies. Additionally, the manufactured NAC-CdTe core with CdS shell and ZnS shell QDs were further characterized by high-resolution transmission using field emission scanning electron microscopy (FESEM), energy dispersive X-ray fluorescence (EDX), X-ray diffraction (XRD), infrared spectrum (IR), UV-vis absorbance, photoluminescence (PL) and absorbency intensity using the fully automatic ELISA. The XRD results revealed the formation of NAC-CdTe/CdS/ZnS QDs with a grain size of 5.7 nm. While EDX assay emphasizes the compound content of Cd, S, Zn and Te elements. Whereas SEM test’s findings propose the spherical size of NAC- CdTe/CdS/ZnS QDs within the range of 10–40 nm. The demonstrated mono-dispersed lattice structure of NAC-CdTe core with CdS shell and ZnS shell QDs has superior PL emission properties at ${\lambda }_{emi}$ of ${}_{\sim }$600 nm and UV-Vis absorption bands at 350 nm. Overall, this study suggests that the synthesized QDs could be employed in developing optical biosensors for a variety of biomedical applications to improve early detection of diseases marked by damaged DNA profile including cancers.

The sensitive nonenzymatic sensing of glucose has been made feasible for the first time using a nonthermal plasma (NTP)-synthesized ZnO nanostructure. This work presents an interesting and novel method for surface modification. The effects of flow gas of Argon/Oxygen (20, 30 and 40 l/min) on the Zn foil surface and various properties were investigated. Optical emission spectroscopy OES has been used to characterize transmissions for positive and negative systems of Ar/O plasma. X-ray diffraction showed close adjacent tops and the strongest peak at Zn (101). EDX displays the constants (Ok_$\alpha )$, (Znk_$\alpha )$ and (Znk_$\beta )$ and change in (ZnL_$\alpha )$. Photoluminescence (PL) Analysis shows a shift at the vertex toward the left and then toward the right confirming the reaction of all PL spectra within a strong UV emission peak. Raman spectroscopy analysis demonstrates two clear peaks gradually shifting to the right with an increase in the percentage of gas flowing compared to the blank metal, and scanning electron microscopy (FE-SEM) images show changes in the shape of nanoparticles due to increasing gas flow, the surface of zinc metal is affected by cold plasma and forms particles with very small diameters ranging from 10.8nm to 123nm. Also altered the surface morphology where the nano shape changed from flower-like particles to sheets with diameters ranging 282.7–643.5nm and the sheets grew with the increase of gas flow to diameters ranging 132–710nm. ZnO nanostructures are employed as biosensor electrodes (nonenzymatic) glucose as the increase in current is proportional to the flowing gas (2.06E-03mA, 2.09E-03mA and 4.34E-03mA).

Bilirubin is an insoluble yellow pigment produced from heme catabolism and serves as a diagnostic marker of liver and blood disorders. Here, a systematic study of several interactions and arrangements between different forms of natural bilirubin and poly-5, 2${}^{\prime }$-5${}^{\prime }$, 2${}^{\prime \prime }$-terthiophene-3-carboxylic acid/Mn(II)₂ complex, PTTCA–Mn(II)₂, as a biosensor of bilirubin has been investigated extensively. The PTTCA–Mn(II)₂ biosensor detects natural bilirubin through the mediated electron transfer by the Mn${}^{2+}$. Initially, density functional theory (DFT) using B3LYP and different basis sets including 6-31G* and 6-311G** has been employed to calculate the details of electronic structure and electronic energies of natural biliverdin and $\delta$-, $\beta$- and $\gamma$-bilirubin. Next, the interaction of the PTTCA–Mn(II)₂ biosensor, being in three possible spin states, with $\delta$-, $\beta$- and $\gamma$-natural bilirubin with 1:1 and 1:2 stoichiometry using UB3LYP/6-31G* method has been investigated. Natural population analysis (NPA) calculations have been used to derive more suitable interaction sites of bilirubin with Mn${}^{2+}$ ions in PTTCA–Mn(II)₂ biosensor. Investigation of different manganese complexes with bilirubin shows that the most stable complex is high spin state (total electron spin $S=5∕2$) rather than intermediate and low spin states with 1:2 stoichiometry. Also, the temperature effect and interferences from other biological compounds such as ascorbic acid, L-glutamic acid, uric acid, creatine, glucose and dopamine have been investigated. The nature of the interaction between manganese metal cations and natural bilirubin is also discussed employing NPA, molecular orbital (MO) analysis and Bader’s Atoms in Molecule (AIM) theory.

A new silicon-based amperometric microelectrode biosensor produced using bulk micromachining technology is presented here. Bulk micromachining, platinization and polymerization of pyrrole enhance sensitive coefficient, thus helping to miniaturize its dimensions and reduce unit cost. To our knowledge, platinization and polymerization of pyrrole is first used consecutively for microelectrode surface modification. Successful experimental results have been achieved for glucose detection. Compared to conventional amperometric biosensors and amperometric microelectrode biosensors made with surface micromachining technology, it has several advantages, such as smaller sensing surface area (1 mm × 1 mm), lower detection limit (1×10^-4M), larger sensitive coefficient (39.640 nAmM^-1mm^-2), broader linear range (1 × 10^-4-1 × 10^-2M), better replicability (3.2% RSD for five respective detections) and stability (enzyme efficiency remains well above 95% after being stored for a month), easier to be made into arrays and to be integrated with processing circuitry, etc.

An electronic tongue formed by voltammetric sensors and biosensors containing phthalocyanines has been developed and used to analyze grapes of different varieties. The sensors are prepared using the carbon paste technique and have been chemically modified with different metallophthalocyanines. In turn, biosensors consist of carbon paste electrodes modified with phthalocyanines combined with tyrosinase or glucose oxidase. The response of the individual sensors towards model solutions of glucose and catechol have demonstrated that the voltammetric responses depend on the nature of the phthalocyanine, evidencing the important role of the electron mediator in the performance of the sensors. The capability of the system to discriminate grapes according to their sugar and their polyphenolic content has been evidenced using Principal Component Analysis. It has been demonstrated that the proposed array of sensors combines the advantages of classical phthalocyanine based sensors — that provide global information about the sample —, with the specificity of the enzyme substrate reaction typical of biosensors. For this reason, the selectivity of the multisensor system and its capability of discrimination is clearly improved when biosensors containing glucose oxidase or tyrosinase are included in the array.

Voltammetric sensors based on phthalocyanines have been used to detect a variety of compounds. In this paper, the state of the art of sensors prepared using classical techniques will be revised. Then, new strategies to improve the performance of the sensors will be described using as example sensors chemically modified with lutetium bisphthalocyanine (LuPc${}_2)$ dedicated to the detection of phenols of interest in the food industry. Classical LuPc₂ carbon paste electrodes can detect phenols such as catechol, caffeic acid or pyrogallol with limits of detection in the range of 10${}^{-4}$–10${}^{-5}$ M. The performance can be improved by using nanostructured Langmuir–Blodgett (LB) or Layer by Layer (LbL) films. The enhanced surface to volume ratio produce an increase in the sensitivity of the sensors. Limits of detection of 10${}^{-5}$–10${}^{-7}$ M are attained, which are one order of magnitude lower than those obtained using conventional carbon paste electrodes. Moreover, these techniques can be used to co-immobilize two electrocatalytic materials in the same device. The limits of detection obtained in LB sensors combining LuPc₂/AuNPs or LuPc₂/CNT are further improved. Finally, the LB technique has been used to prepare biosensors where a phenol oxydase (such as tyrosinase or lacasse) is immobilized in a biomimetic environment that preserves the enzymatic activity. Moreover, LuPc₂ can be co-immobilized with the enzyme in a lipidic film formed by arachidic acid (AA). LuPc₂ can act as an electron mediator facilitating the electron transfer. These biomimetic sensors formed by LuPc₂/AA/enzyme show Limits of detection of 10${}^{-8}$ M and an enhanced selectivity.

A review of the performances of existing field-effect-transistor (FET) based biosensing devices and reports of fundamental studies of FET structures in a planar geometry identify substantial amplification improvements in eliminating metal intermediaries between the biorecognitive surfaces and the silicon channels, reducing thicknesses of insulating gates and selecting channel apertures that are comparable with achievable thicknesses of depletion layers. Exemplary improvements have been achieved in FET-based silicon nano-wires in which biorecognitive surfaces were attached to the oxidized surfaces that functioned as insulating gates. Fundamental studies in which the silicon dioxide gate was replaced with an organic layer using Si–C chemistry demonstrate the retention of the field-effect characteristics and promise improved performance potential to present FET-based devices. These studies also report electrical field compression of the organic layer and electrical polarisation of the electrolyte that have operational implications for biorecognition. Development of practical robust devices that can exhibit unambiguous recognitive capabilities in diverse biological aquatic environments is dependent on further extensive fundamental studies of organic-silicon interfaces and bio-recognitive processes.

A phenol biosensor based on the skillful immobilization of tyrosinase on zinc oxide (ZnO) nanorods was proposed. The ZnO nanorods fabricated by a simple vapor-phase transport method possess a high aspect ratio, good electron communication, chemical purity, smooth and positive charged surface and are ready for immobilization of biochemicals with low isoelectric point (IEP). Electrochemical measurement and Scanning Electron Microscopic (SEM) analysis showed that the enzyme of tyrosinase with IEP 4.5 can be adsorbed on the surface of ZnO nanorods and kept its bioactivity of the oxidation of phenol to a large extent. This led us to develop phenol biosensor with good stability and reproducibility. The proposed method creates a new way to develop biosensors using nanostructured materials with high IEP.

Carbon nanotube field effect transistor (FET) type biosensors have been widely investigated as one of the promising platforms for highly sensitive personalized disease-monitoring electronic devices. Combined with high level cutting edge information technology (IT) infra systems, carbon nanotube transistor biosensors afford a great opportunity to contribute to human disease care by providing early diagnostic capability. Several key prerequisites that should be clarified for the real application include sensitivity, reliability, reproducibility, and expandability to multiplex detection systems. In this brief review, we introduce the types, fabrication, and detection methods of single-walled carbon nanotube FET (SWNT-FET) devices. As surface functionalization of the devices by which nonspecific bindings (NSBs) are efficiently prohibited is also another important issue regarding reliable biosensors, we discuss several key strategies about surface passivation along with examples of various biomolecules such as proteins, DNA, small molecules, aptamers, viruses, and cancer and neurodegenerative disease markers which have been successfully sensed by SWNT-FET devices. Finally, we discuss proposed detection mechanisms, according to which strategies for fabricating sensor devices having high sensitivity are determined. Two main mechanisms — charge transfer (or electrostatic gate effect) and Schottky barrier effect, depending on the place where biomolecules are adsorbed — will be covered.

One third of the world population is estimated to have Mycobacterium tuberculosis infection. It is urgent to develop a rapid, inexpensive and convenient diagnostic method for detection of tuberculosis. Porous silicon material has taken more and more attention in recent years for biosensing applications and some useful results have been obtained. In this paper, we report the feasibility of applying porous silicon microcavity biosensor in a novel and relatively rapid serodiagnostic approach. Nowadays, most of serodiagnostic tests are based on labeled detection. Applying label-free detection methods can help develop fast and efficient tuberculosis diagnostic tools, which can meet the current demand. In this study, we use this label-free sensing platform (i.e., porous silicon microcavity) to detect the interaction between 16 kDa antigen and anti-16 kDa antibody. Through a series of experiments, we verify the specificity and examine the sensitivity of this new diagnostic technique. The results show that it is feasible to apply porous silicon microcavity in the tests of tuberculosis.

The performance of a nanoscale sensor is not limited by the sensitivity of the sensor itself but rather by the diffusion time required for target molecules to reach to the extremely small sensor surface. In this work, we developed a carbon nanotube device that performed the dual functions of concentrating and detecting microorganisms in a sample solution. The sensor surface area was increased by fabricating a carbon nanotube network device using thermal chemical vapor deposition and standard microfabrication techniques. The target Escherichia coli (E. coli) cells were concentrated at the sensor surface via dielectrophoretic concentration by the carbon nanotube network channels. After 10 min of collection, the chip was washed with ample amounts of a clean buffer solution, and only the E. coli cells that were bound to the antibodies remained on the sensor surface. The binding of E. coli to the CNT network device decreased the conductance, presumably due to an increase in the scattering at the sensor surface. The detection limit and the time required for microorganism detection was greatly improved by combining dielectrophoresis with the carbon nanotube devices.

Immunoglobulin A nephropathy (IgAN) has been recognized as the most prevalent form of glomerulonephritis with various histologic and clinical phenotypes in the world. The Gal-deficient IgA1 with terminally exposed GalNAc residue(s) plays a key role in the pathogenesis of the disease. In this study, a novel colorimetric biosensor based on Helix aspersa agglutinin (HAA) absorbed on polydiacetylene (PCDA) nanovesicles for N-acetylgalactosamine (GalNAC) molecular as core framework of Gal-deficient IgA1 recognition was investigated using the high affinity between lectin HAA and GalNAC. The PCDA nanovesicles were prepared via UV crosslinking. The size, morphology and elastic property of the nanovesicles were tested. The optimal concentration of HAA for the recognition of GalNAC via naked eyes observation was 3 mM and the critical concentration of GalNAC for the sensitive color transition was 2 μg/mL. This novel method has many advantages such as low prices, intuitive, real-time and easy to carry out and great potential in Gal-deficient IgA1 detection.

We report on the sensitive detection of glucose using silicon nanowire array field-effect-transistor (SiNW-FET) upon illumination. The uniformly distributed and size-controlled SiNWs were fabricated by "top-down" approach. The fabricated SiNW-FET device was evaluated for detection of glucose in the range of 100–900 mg/dL. The SiNW-FET shows enhanced sensitivity of 0.988 ± 0.030 nA (mg/dl)^-1 upon illumination at 480 nm light as compared to without illumination as 0.486 ± 0.014 nA (mg/dL)^-1. The presented SiNW-FET device is fast, stable and sensitive to light as well as to bio analyte, and hence can be utilized as sensitive biological sensing platform.

Viability of cancer cell is an important indicator of physiological state and function of cells, which can be effected by the change of pH in the medium solution, due to the increase of carbon oxide and lactic acid caused by respiration. Although many methods have been developed to detect the viability of cells, mostly based on cytochemical staining and polymerase chain reaction (PCR) technology are time consuming. In this paper, an electronic device was made by thermal reduced graphene oxide (RGO) for detection of cancer cell viability in real-time. This electronic device could be used to monitor the metabolic activity and viability of cancer cells based on the change in pH value. As the pH decreases, colon cancer cells loose viability and the current decreases. This RGO device is simple, sensitive and label-free and could serve as a platform for detection of cells and drug testing.

Top-down silicon nanowire (SiNW) fabrication mechanisms for connecting electrodes are widely utilized because they provide good control of the diameter to length ratio. The representative mechanism for the synthesis of SiNWs, a top-down approach, has limitations on the control of their diameter following lithography technologies, requires a long manufacturing process and is not cost-effective. In this study, we have implemented the bottom-up growth of horizontal SiNWs(H-SiNWs) on Si/SiO₂ substrates directly by plasma enhanced chemical vapor deposition (PECVD) under about 400°C. The HAuCl4 solution as a catalyst and SiH₄ gas as a precursor are used for the synthesis of H-SiNWs. After optimization of synthesis conditions, we evaluated the photoelectric properties of the H-SiNWs under illumination with different light intensities. Further, we demonstrated the feasibility of H-SiNW devices for the detection of biotinylated DNA nanostructures and streptavidin interaction.