Prospects of low temperature co-fired ceramic (LTCC) based microfluidic systems for point-of-care biosensing and environmental sensing

Low temperature co-fired ceramic (LTCC) based microfluidic devices are being developed for point-of-care biomedical and environmental sensing to enable personalized health care. This article reviews the prospects of LTCC technology for microfluidic device development and its advantages and limitations in processing capabilities compared to silicon, glass and polymer processing. The current state of the art in LTCC-based processing techniques for fabrication of microfluidic components such as microchannels, chambers, microelectrodes and valves is presented. LTCC-based biosensing applications are discussed under the classification of (a) microreactors, (b) whole cell-based and (c) protein biosensors. Biocompatibility of LTCC pertaining to the development of biosensors and whole cell sensors is also discussed. Other significant applications of LTCC microfluidic systems for detection of environmental contaminants and toxins are also presented. Technological constraints and advantages of LTCC-based microfluidic system are elucidated in the conclusion. The LTCC-based microfluidic devices provide a viable platform for the development of point-of-care diagnostic systems for biosensing and environmental sensing applications.     

Stability of spore-based biosensing systems under extreme conditions

The full exploitation of bacterial whole-cell biosensing systems in field applications requires the survival of bacterial cells and long-term preservation of their sensing ability during transportation and on-site storage of such analytical systems. Specifically, there is a need for rapid, simple and inexpensive biosensing systems for monitoring human health and the environment in remote areas as well as developing countries, which often suffer from harsh atmospheric conditions and inadequate commercial distribution and storage facilities. Our laboratory has previously reported the successful use of bacterial spores as vehicles for the long-term preservation and storage of whole-cell biosensing systems at room temperature. In the present research, we have accomplished a year-long study to investigate the effect of extreme climatic conditions on the stability of spores-based whole-cell biosensing systems. The spores were stored in laboratory conditions that simulated those found in real harsh environments, including, extreme temperatures and humidity levels, and desiccation. This study was crucial in determining the germination ability and analytical performance of the spore-based sensing systems upon storage in such conditions in order to support their effective use in the field, in extreme environments. Our results proved that the intrinsic resistance of spores to harsh environmental conditions helped maintain the integrity of the encapsulated sensor bacteria. The revived active cells actually retained their analytical performance during the course of the 12-month storage study. We envision that spore-based sensing systems could pave the way to the use of whole-cell biosensors in field applications and in areas where they have not been employed so far.     

Microfluidic-based biosensor: signal enhancement by gold nanoparticle

Biosensor is an analytical device to detect the biomolecules assisted by the transducer and physicochemical detector. A good biosensor is expecting to be with low cost, easy to perform and identify the results without prior experience. In addition, a good biosensor has two main key characteristics such as sensitivity and specificity; these are mainly determined by the affinity of biomolecules with the assistance of sensing system. Microfluidic-based lab-on-chip is one of the fast growing technologies in the field of biosensor bring the positive characteristics with a fast delivery set-up. On the other hand, gold nanoparticle (GNP) is the powerful tool to enhance the biomolecular detection with higher sensitivity and it has been proved for the effective applications with different sensors. In this review, we discussed the applications of microfluidic-based delivery and GNP for biosensing with the new level of developments, which elevate a step ahead.     

A simple and direct biomolecule detection scheme based on a microwave resonator

Although several successful biosensors exist, they often require complex fabrication sequence or time-consuming sensing processes such as an off-site verification of a sensing result. At the same time, the biosensors generally focus on high sensitivity. This paper reports a cost-competitive biosensor that is capable of simple and direct detection of biomolecules without any off-site verification. The biosensor is realized with a microwave passive with a simple structure, a coplanar waveguide (CPW)-to-slotline ring resonator (CSRR) that resonant frequency is 3.375 GHz. The CSRR biosensor was then modified for higher sensitivity by increasing the effective sensing area. Two kinds of the CSRR biosensor were realized using micromachining technology. After simple fabrication, the biosensors were electrically characterized by measuring the resonant frequency shift as the biotin and streptavidin attached on the CSRR biosensor. The biotin and streptavidin induce a resonant frequency decrease of 65 and 10 MHz for the original CSRR biosensor, and 79 and 18 MHz for the modified CSRR biosensor, respectively. Based on the measurement of the resonant frequency shift, the relative permittivity of the biomolecules was calculated by numerical simulation, and was found to be 9800 for biotin and 500 for streptavidin.     

Platelet graphite nanofibers/soft polymer composites for electrochemical sensing and biosensing

The fabrication and attractive sensing and biosensing performance of platelet graphite nanofibers/polysulfone (PGNF/PSf) composite nanomaterials is described. The PGNF/PSf nanocomposites were fabricated by facile phase-inversion method. Their electrochemical performance was compared to the one of carbon nanotubes/PSf and graphite microparticles/PSf composite. It was clearly demonstrated that PGNF/PSf provides superior voltammetric and amperometric performance for sensing and biosensing over those two other sp² carbon materials. This can be attributed to the unparallel amount of electroactive edge sites on PGNF in which electroactivity is not impaired by the polysulfone binder. PGNF/PSf/glucose oxidase nanobiocomposite was prepared and used for proof-of-concept biosensing of glucose.     

基于生物固定基质的电化学生物传感器研究

为了保持生物分子的生物活性并且能够给出检测所需的电化学输出信号,研究者发展了多种具有良好生物相容性的生物固定基质,包括水凝胶,有机-无机复合物衍生的溶胶-凝胶以及脂膜等,并将其引入电化学生物传感器。研究表明,这些生物基质的应用大大提高了电化学生物传感器的性能并拓宽了电化学生物传感器的应用范围。     

电化学生物传感器的研究进展

电化学生物传感器将生物活性识别材料与电化学检测器件有机结合起来,广泛应用于临床医学、药物和食品分析与环境监测等领域。与其他电化学传感器相比,电化学生物传感器具有特异性好、检测灵敏度高和制作简便等优点。文章重点介绍了电化学生物传感器的基本原理、分类、研究进展及其在生物医学领域中的应用,并对电化学生物传感器的发展前景进行展望。     

Nanostructured polyaniline thin films as pH sensing membranes in FET-based devices

Polyaniline (PANI) has become an important conducting polymer for sensing due to its morphological and electrical properties. However, the processing of polyaniline in the form of nanostructured thin films is often limited by the low solubility of the polymer in water. We synthesized nanostructured polyaniline (N-PANI) aimed at improving its solubility to form layer-by-layer (LbL) thin films in conjunction with poly(vinyl sulfonic acid) (PVS) as counter ion. N-PANI was characterized via spectroscopic measurements and SEM images. After assembled as LbL thin films onto gold (Au) substrates, the PVS/N-PANI were employed as separative extended gate pH sensing membrane in FET-based devices presenting pH sensitivity around 58 mV/pH with small voltage drift. The results suggest that N-PANI can be easily processed to form suitable thin films for pH sensing and can be combined with biomolecules to be applied in FET-based biosensors.     

A MEMS nano-extensometer with integrated de-amplification mechanism

Experimental exploration of strained nanostructures, such as nanowires and bio-molecules, is essential for understanding their properties. However, the ability to apply and to quantify nanometer displacements is challenging. We present a novel MEMS nano-extensometer with integrated actuation and compliant de-amplification mechanism allowing the accurate characterization of stretched nanostructures. A feasibility study was followed by fabrication and characterization of the device. The de-amplified displacement was registered via optical microscopy and was processed using an improved digital image correlation algorithm to achieve nanometer measurement accuracy. Using our technique, nanoscale displacement can be determined by means of simple imaging tools. This was demonstrated by stretching suspended single wall carbon nanotubes.     

Carbon nanotube based sensors for the detection of viruses

Carbon nanotube biosensors were assembled using a layer-by-layer (LBL) technique exploiting the chemical functionalization on nanotubes to tailor their interactions with viruses and antiviral antibodies. Gold electrodes were patterned in the form of resistors onto a Si/SiO₂ substrate, followed by stepwise LBL assembly to change the resistivity of the channel. Polyelectrolyte multilayer films were prepared by the sequential electrostatic adsorption of poly(diallyldimethylammonium chloride), poly(styrene sulfonate), and functionalized single-walled carbon nanotubes. Viral antibodies were successfully immobilized between the electrodes and the binding of antibodies to the surface was enhanced by coating with poly(l-lysine). An antigen specific to the immobilized antibody was captured on these devices. The coupled antibody-antigen complex changed the conductance of the device and this change was related to the antigen concentration. The two factors affecting the performance of the device were the number of layers and the channel length between the electrodes. We were able to detect conductance change for a viral antigen with a titer of 10² TCID₅₀/ml (50% tissue culture infective dose).     

Carbon nanotubes and semiconductor nanowires for active‐matrix backplanes

Abstract— Carbon nanotubes and semiconductor nanowires are a new class of materials currently being studied within the context of molecular electronics. Because of their excellent characteristics, transistors based on carbon nanotubes and semiconductor nanowires could become the workhorse of the post‐CMOS era. Since carbon nanotubes as well as Si or Ge nanowires can be grown at low temperature, using similar CVD‐type processes and on non‐crystalline and non‐refractory substrates, they could (and will) certainly be used in the near future for the fabrication of thin‐film transistors and active‐matrix backplanes. However, the development of these nanomaterials is hampered by the general problems posed by their manipulation, placement, and in‐plane organization. The possible use of CNT random networks (that do not need to be organised) for the fabrication of thin‐film transistors will be reviewed. Then a new way of organizing semiconductor NWs in a thin‐film transistor, based on the use of lateral porous anodic alumina templates, will be presented.     

Optofluidic sensor system with Ge PIN photodetector for CMOS-compatible sensing

Vertical optofluidic biosensors based on refractive index sensing promise highest sensitivities at smallest area footprint. Nevertheless, when it comes to large-scale fabrication and application of such sensors, cheap and robust platforms for sample preparation and supply are needed—not to mention the expected ease of use in application. We present an optofluidic sensor system using a cyclic olefin copolymer microfluidic chip as carrier and feeding supply for a complementary metal–oxide–semiconductor compatibly fabricated Ge PIN photodetector. Whereas typically only passive components of a sensor are located within the microfluidic channel, here the active device is directly exposed to the fluid, enabling top-illumination. The capability for detecting different refractive indices was verified by different fluids with subsequent recording of the optical responsivity. All components excel in their capability to be transferred to large-scale fabrication and further integration of microfluidic and sensing systems. The photodetector itself is intended to serve as a platform for further sophisticated collinear sensing approaches.     

Detection of foodborne pathogens using bioconjugated nanomaterials

This review focuses on applying nanotechnology to foodborne pathogen detection. Because of low infectious doses for most foodborne pathogens, the rapid and sensitive detection methods are essential to ensure the food safety. The advances in the development of nanomaterials have stimulated worldwide research interests in their applications for bioanalysis. The conjugation of biomolecules with nanomaterials is the foundation of nano-biorecognition. A variety of strategies including antibody–antigen, adhesin–receptor, antibiotic, and complementary DNA sequence recognitions have been explored for specific recognition between target bacterial cells and bio-functionalized nanomaterials. The incorporation of these bio-functionalized nanomaterials into current pathogen detection methods has led to rapid and nearly real-time pathogen detection (as short as a few minutes), improved sensitivity (single bacterial cell), and simultaneous detection of multiple micro-organisms from either nutrient broth, liquid or solid food products, or biofilms. The unique properties of nanomaterials in physical strength, chemical reactivity, electrical conductance, magnetism and optical effects make them promising in the development of practical biosensors with emphasis on device portability and simplicity in sample preparation, and the improvement of current pathogen detection methods.     

压电生物传感器响应机制的声阻抗模型理论分析

基于声阻抗概念, 建立起压电传感器响应机制的声阻抗模型, 并引入与传感器负载剪切模量相关的声学校正因子, 以表明传感器响应中的非质量效应. 由此模型在一定近似条件下, 对黏性液体, 气/液相刚性和黏弹性薄膜等不同负载, 分别导出相应的传感器响应方程, 阐明了各种传感器响应机制的物理意义. 另外在实际应用中可能存在摩擦, 非均匀性和界面现象等干扰, 但利用该声阻抗模型可望获取新信息、开拓新的应用.     

Sensing liquid density using resonant flexural plate wave devices with sol–gel PZT thin films

This study presents the design, fabrication and possible applications in liquid density sensing and biosensing of a flexure plate wave (FPW) resonator using sol–gel-derived lead zirconate titanate (PZT) thin films. The resonator has a two-port structure with a reflecting grating on a composite membrane of PZT and SiN_x. The design of the reflecting grating is derived from a SAW resonator model using COM theory to generate a sharp resonant peak. A comparison between the theoretical mass and the viscosity effects reveals the applications and the constraints of the proposed device in liquid sensing. Multiple coatings of sol–gel-derived PZT films are employed because of the cost advantage and the strong electromechanical coupling effect over other piezoelectric films. Issues of fabrication of the proposed material structure are addressed. Theoretical estimates of the mass and the viscosity effects are compared with the experimental values. The resonant frequency relates quite linearly to the density of low-viscosity liquids, revealing the feasibility of the proposed device. An erratum to this article can be found at     

Emerging applications of aptamers to micro- and nanoscale biosensing

Micro- and nanofabrication has allowed the production of ultra-sensitive, portable, and inexpensive biosensors. These devices generally rely on chemical or biological receptors which recognize a particular compound of interest and relay this recognition event effectively by transduction. Recent advances in RNA and DNA synthesis have enabled the use of aptamers, in vitro generated oligonucleotides, which offer high affinity biomolecular recognition to a theoretically limitless variety of analytes. DNA and RNA aptamers have gained so much attention in the biosensor community, that they have begun competing with more established affinity ligands including enzymes, lectins, and most notably, immunoreceptors such as antibodies. This article reviews the current state-of-the-art of aptasensors, or biosensors that use aptamers as molecular recognition elements, emphasizing the synergy between aptamer-based biosensing and micro- and nanotechnology. Aptasensors developed on micro- and nanoscale platforms based on mass changes, electroanalytical techniques, optical transduction, and purification and separation methods will be covered.     

基于纳米材料的化学与生物传感器研究进展

纳米材料由于其量子尺寸效应和表面效应,可以有效地提高化学或生物传感器的性能.同时,通过对纳米材料的进一步功能化设计与改造,可以研究开发超高灵敏度、超高选择性的新型传感器件.该文主要就金利通课题组近年来基于纳米材料修饰的化学与生物传感器方面的研究工作进行介绍并对该领域的发展作一展望.     

Magnetophoretic mixing for in situ immunochemical binding on magnetic beads in a microfluidic channel

Functionalized magnetic beads offer promising solutions to a host of micro-total analysis systems ranging from immunomagnetic biosensors to cell separators. Immunochemical binding of functional biochemical agents or target biomolecules serves as a key step in such applications. Here we show how magnetophoretic motion of magnetic microspheres in a microchannel is harnessed to promote in situ immunochemical binding of short DNA strands (probe oligonucleotide) on the bead surface via streptavidin–biotin bonds. Using a transverse magnetic field gradient, the particles are transported across a co-flowing analyte stream containing biotinylated probe oligonucleotides that are labeled with a Cy3-fluorophore. Quantification of the resulting biotin–streptavidin promoted binding has been achieved through fluorescence imaging of the magnetophoretically separated magnetic particles in a third stream of phosphate buffered saline. Both the experimental and numerical data indicate that for a given flow rate, the analyte binding per bead depends on the flow fraction of the co-flowing analyte stream through the microchannel, but not on the fluid viscosity. Parametric studies of the effects of fluid viscosity, analyte flow fraction, and total flow rate on the extent of binding and the overall analyte separation rate are also conducted numerically to identify favorable operating regimes of a flow-through immunomagnetic separator for biosensing, cell separation, or high-throughput applications.     

Glycerol biosensor based on glycerol dehydrogenase incorporated into polyaniline modified aluminum electrode using hexacyanoferrate as mediator

Enzyme-modified electrodes were fabricated by the immobilization of glycerol dehyrogenase into the polyaniline film and were used as glycerol biosensors. Two different electrodes were prepared by forming monolayer and bilayer electroactive films on the electrode surface and were compared. Potassium ferrocyanide was used as mediator of the biosensing reaction. The biosensors exhibit amperometric response to the glycerol in the range 5×10⁻⁶ to 2×10⁻³ M with detection limit of 1×10⁻⁶ M. The Michaelis–Menten constants, K_m′, of the electrodes were calculated, their values indicates that the enzyme has not chemically modified with the electrode materials and has its original enzymatic activity. The electrode has a good stability and selectivity due to the enhanced stability of the deposited polyaniline film on Al substrate.     

Low cost chemical sensor device for supersensitive pentaerythritol tetranitrate (PETN) explosives detection based on titanium dioxide nanotubes

Within the last decade there has been a great increase in the need of trace and ultra-trace explosive detection. In this report, we demonstrate a new and versatile type of chemical explosive sensors based on metal oxide nanotubes easily made, even with the need of a low budget. We describe the step-by-step procedure to fabricate a sensing chip device, beginning with the synthesis of the starting materials to the point of supersensitive measurements of PETN explosive. As a result, the whole process actually is one of the most cost-effective methods to produce explosive sensing devices reported until now. The achieved chemical sensor device will be able to detect PETN explosive down to ∼112 ppt.