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.

An integrated microfluidic system for C-reactive protein measurement.

The influenza A virus is a notorious pathogen that causes high morbidity, high mortality, and even severe global pandemics. Early and rapid diagnosis of the virus is therefore crucial in preventing and controlling any influenza outbreaks. Recently, novel nucleic acid-based affinity reagents called aptamers have emerged as promising candidates for diagnostic assays as they offer several advantages over antibodies, including in vitro selection, chemical synthesis, thermal stability and relatively low costs. Aptamers with high sensitivity and specificity are generated via Systematic Evolution of Ligands by Exponential Enrichment (SELEX), a process that is currently time-consuming, as well as labor- and resource-intensive. In this study, an integrated microfluidic system was developed and was successfully applied to screen a specific aptamer for the influenza A/H1N1 (InfA/H1N1) virus in an automated and highly efficient manner. The selected aptamer was implemented in a magnetic-bead assay, which demonstrated specific and sensitive detection of the InfA/H1N1 virus, even in biological samples such as throat swabs. Consequently, this specific aptamer presents a promising affinity reagent for clinical diagnosis of InfA/H1N1. This is the first demonstration of screening influenza virus-specific aptamers using the microfluidic SELEX technology, which may be expanded for the rapid screening of aptamers against other pathogens for future biomedical applications.

Influenza A virus-specific aptamers screened by using an integrated microfluidic system

In this paper we present a novel microfluidic chip capable of continuous multi-sample switching and injection for bio-analytical applications. The innovative device integrates two important microfluidic phenomena, including hydrodynamic focusing and valveless flow switching inside multi-ported microchannels. The multiple samples can be pre-focused to narrow streams and can then be continuously injected into desired outlet ports. In this study, a theoretical model based on the `flow-rate-ratio' method is first proposed to predict the performance of the microfluidic device. Then, a simple but reliable one-mask micromachining process is developed to fabricate the pre-focused M×N flow switch on a quartz substrate. The multi-sample switching and injection is then verified experimentally with the use of microscopic visualization of water sheath flows and dye-containing sample flows. The experimental data indicate that the multi-sample flows can be hydrodynamically pre-focused and then guided into the desired outlet ports precisely based on relative sheath and sample flow rates. The data predicted by the proposed theoretical model are highly consistent with the experimental results. It is also noted that the `pre-focusing' function added prior to multi-sample flow switching is crucial for precise sample injection. The novel microfluidic chip has great potential for high-throughput chemical analysis, cell fusion, fraction collection, fast sample mixing and many other applications in the field of micro-total-analysis systems.

Micromachined pre-focused M×N flow switches for continuous multi-sample injection

This paper presents a new microfluidic system capable of real-time measurement of glucose concentration and automatic insulin injection. The microfluidic system is composed of a microfluidic chip, a measurement and control circuit system, a compressed air source, and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using microfluidic techniques comprising of glucose sensing electrodes, a flow sensor and polydimethylsiloxane (PDMS)-based microfluidic structures such as micropumps, microvalves and microchannels. Commercially available needles are incorporated for continuous glucose monitoring and long-term insulin injection. The microfluidic system performs a variety of processes including blood sample collection, glucose concentration detection and injection of insulin. Compared with separate glucose monitoring and insulin injection platforms, the integrated system has a potential for on-line monitoring of glucose concentration and precise injection of proper doses of insulin. Even though this work is still in a preliminary stage towards practical applications, the developed microfluidic system has shown its potential to become a crucial tool for diabetes patients in the future.

Integrated microfluidic systems for automatic glucose sensing and insulin injection

Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research.

/pdf/stem-cells-in-microfluidics-2j36k7tsb9.pdf

Gwo-Bin Lee

Papers

An integrated microfluidic system for C-reactive protein measurement.

Influenza A virus-specific aptamers screened by using an integrated microfluidic system

Micromachined pre-focused M×N flow switches for continuous multi-sample injection

Integrated microfluidic systems for automatic glucose sensing and insulin injection

Stem cells in microfluidics.