There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Detection of chemical and biological agents plays a fundamental role in biomedical, forensic and environmental sciences1–4 as well as in anti bioterrorism applications.5–7 The development of highly sensitive, cost effective, miniature sensors is therefore in high demand which requires advanced technology coupled with fundamental knowledge in chemistry, biology and material sciences.8–13

In general, sensors feature two functional components: a recognition element to provide selective/specific binding with the target analytes and a transducer component for signaling the binding event. An efficient sensor relies heavily on these two essential components for the recognition process in terms of response time, signal to noise (S/N) ratio, selectivity and limits of detection (LOD).14,15 Therefore, designing sensors with higher efficacy depends on the development of novel materials to improve both the recognition and transduction processes. Nanomaterials feature unique physicochemical properties that can be of great utility in creating new recognition and transduction processes for chemical and biological sensors15–27 as well as improving the S/N ratio by miniaturization of the sensor elements.28

Gold nanoparticles (AuNPs) possess distinct physical and chemical attributes that make them excellent scaffolds for the fabrication of novel chemical and biological sensors (Figure 1).29–36 First, AuNPs can be synthesized in a straightforward manner and can be made highly stable. Second, they possess unique optoelectronic properties. Third, they provide high surface-to-volume ratio with excellent biocompatibility using appropriate ligands.30 Fourth, these properties of AuNPs can be readily tuned varying their size, shape and the surrounding chemical environment. For example, the binding event between recognition element and the analyte can alter physicochemical properties of transducer AuNPs, such as plasmon resonance absorption, conductivity, redox behavior, etc. that in turn can generate a detectable response signal. Finally, AuNPs offer a suitable platform for multi-functionalization with a wide range of organic or biological ligands for the selective binding and detection of small molecules and biological targets.30–32,36 Each of these attributes of AuNPs has allowed researchers to develop novel sensing strategies with improved sensitivity, stability and selectivity. In the last decade of research, the advent of AuNP as a sensory element provided us a broad spectrum of innovative approaches for the detection of metal ions, small molecules, proteins, nucleic acids, malignant cells, etc. in a rapid and efficient manner.37



Figure 1

Physical properties of AuNPs and schematic illustration of an AuNP-based detection system.



In this current review, we have highlighted the several synthetic routes and properties of AuNPs that make them excellent probes for different sensing strategies. Furthermore, we will discuss various sensing strategies and major advances in the last two decades of research utilizing AuNPs in the detection of variety of target analytes including metal ions, organic molecules, proteins, nucleic acids, and microorganisms.

/pdf/gold-nanoparticles-in-chemical-and-biological-sensing-5e2qojkdzn.pdf

Gold nanoparticles in chemical and biological sensing.

基礎講座 電気泳動(Electrophoresis)

This protocol provides an introduction to soft lithography--a collection of techniques based on printing, molding and embossing with an elastomeric stamp. Soft lithography provides access to three-dimensional and curved structures, tolerates a wide variety of materials, generates well-defined and controllable surface chemistries, and is generally compatible with biological applications. It is also low in cost, experimentally convenient and has emerged as a technology useful for a number of applications that include cell biology, microfluidics, lab-on-a-chip, microelectromechanical systems and flexible electronics/photonics. As examples, here we focus on three of the commonly used soft lithographic techniques: (i) microcontact printing of alkanethiols and proteins on gold-coated and glass substrates; (ii) replica molding for fabrication of microfluidic devices in poly(dimethyl siloxane), and of nanostructures in polyurethane or epoxy; and (iii) solvent-assisted micromolding of nanostructures in poly(methyl methacrylate).

/pdf/soft-lithography-for-micro-and-nanoscale-patterning-21e1ngmrqv.pdf

Soft lithography for micro- and nanoscale patterning

A review of the substrates used in microbial fuel cells (MFCs) for sustainable energy production.

In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.

Microfluidic cell culture systems for drug research.

Humidity Sensors: A Review

This study reports an integrated microfluidic chip for polymerase chain reaction (PCR) applications utilizing digital microfluidic chip (DMC) technology. Several crucial procedures including sample transportation, mixing, and DNA amplification were performed on the integrated chip using electro-wetting-on-dielectric (EWOD) effect. An innovative concept of hydrophobic/hydrophilic structure has been successfully demonstrated to integrate the DMC chip with the on-chip PCR device. Sample droplets were generated, transported and mixed by the EWOD-actuation. Then the mixture droplets were transported to a PCR chamber by utilizing the hydrophilic/hydrophobic interface to generate required surface tension gradient. A micro temperature sensor and two micro heaters inside the PCR chamber along with a controller were used to form a micro temperature control module, which could perform precise PCR thermal cycling for DNA amplification. In order to demonstrate the performance of the integrated DMC/PCR chips, a detection gene for Dengue II virus was successfully amplified and detected. The new integrated DMC/PCR chips only required an operation voltage of 12V(RMS) at a frequency of 3 KHz for digital microfluidic actuation and 9V(DC) for thermal cycling. When compared to its large-scale counterparts for DNA amplification, the developed system consumed less sample and reagent and could reduce the detection time. The developed chips successfully demonstrated the feasibility of Lab-On-a-Chip (LOC) by utilizing EWOD-based digital microfluidics.

Integrated polymerase chain reaction chips utilizing digital microfluidics

In this paper we describe a new process for fabricating ultra-thick microfluidic devices utilizing SU-8 50 negative photoresist (PR) by standard UV lithography. Instead of using a conventional spin coater, a simple 'constant-volume-injection' method is used to create a thick SU-8 PR film up to 1.5 mm with a single coating. The SU-8 PR is self-planarized during the modified soft-baking process and forms a highly-uniform surface without any edge bead effect, which commonly occurs while using a spin coater. Photomasks can be in close contact with the PR and a better lithographic image can be generated. Experimental data show that the average thickness is 494.32 ± 17.13 μm for a 500 μm thick film (n = 7) and the uniformity is less than 3.1% over a 10 × 10 cm2 area. In this study, the temperatures for the soft-baking process and post-exposure baking are 120 °C and 60 °C, respectively. These proved to be capable of reducing the processing time and of obtaining a better pattern definition of the SU-8 structures. We also report on an innovative photomask design for fabricating ultra-deep trenches, which prevents the structures from cracking and distorting during developing and hard-baking processes. In this paper, two microfluidic structures have been demonstrated using the developed novel methods, including a micronozzle for thruster applications and a microfluidic device with micropost arrays for bioanalytical applications.

https://iopscience.iop.org/article/10.1088/0960-1317/12/5/312/pdf

A new fabrication process for ultra-thick microfluidic microstructures utilizing SU-8 photoresist

Design and fabrication of microfluidic devices on polymethylmethacrylate (PMMA) substrates for analytical chemistry and biomedical-related applications using novel microfabrication methods are described. The image of microstructures is transferred from quartz master templates possessing the inverse image of the devices to plastic plates by using hot embossing methods. The microchannels on quartz master templates are formed by the combination of metal etch mask and wet chemical etching of a photomask blank. The micromachined quartz templates can be used repeatedly to replicate cheap and disposable plastic devices. The reproducibility of the hot embossing method is evaluated using 10 channels on different PMMA plastics. The relative standard deviation of the channel profile on the plastic chips is less than 1%. In this study, the PMMA microfluidic chips have been demonstrated as a microcapillary electrophoresis (μ-CE) device for DNA separation and detection. The capability of the fabricated chip for electrophoretic injection and separation is characterized via the analysis of DNA fragments ∅X-174-RF Hae III digest. Experimental results indicate that all of the 11 DNA fragments of the size marker could be identified in less than 2 min with relative standard deviations less than 0.4 and 8% for migration time and peak area, respectively. Moreover, with the use of a near-infrared (IR) dye, fluorescence signals of the higher molecular weight fragments (>603 bp in length) could be detected at total DNA concentrations as low as 0.1 μg/ml. In addition to DNA fragments ∅X-174-RF Hae III digest, DNA sizing of hepatitis C viral (HCV) amplicon is also achieved using microchip electrophoresis on PMMA substrates.

/pdf/microfabricated-plastic-chips-by-hot-embossing-methods-and-eckvh8uglh.pdf

Gwo-Bin Lee

Papers

Microfluidic cell culture systems for drug research.

Humidity Sensors: A Review

Integrated polymerase chain reaction chips utilizing digital microfluidics

A new fabrication process for ultra-thick microfluidic microstructures utilizing SU-8 photoresist

Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection