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.

This study reports a new three-dimensional (3-D) micromachined magnetic tweezers, fabricated using MEMS (micro-electro-mechanical systems) technology, for manipulating a single 2-nm diameter DNA molecule The new apparatus uses magnetic forces to exert over 20-pN, with less heating compared to other methods, allowing the extension of the DNA molecule over its whole contour length to investigate its entropic and elastic regions The important elastic modulus of DNA has been explored to be 453 pN at a low ionic strength The force-extension curve for DNA molecules is found to be consistent with theoretical models In addition to a single DNA stretching, this study also successfully demonstrated the stretching of two parallel DNA molecules, which was never reported previously in the literature

3-D Magnetic Tweezers for Investigation of Mechanical Properties of Single DNA Molecules

Cholangiocarcinoma (CCA) is highly metastatic, extremely difficult to diagnose and is consequently characterized by a low 5-year survival rate. Herein we investigated the potential of using exfoliated tumor cells (ETCs) in bile to serve as an early-warning CCA metastasis indicator. ETCs were isolated from bile using a CCA-specific aptamer conjugated to magnetic beads and identified via immunostaining (CK17+CK7+Hoechst+). A conventional protein biomarker, epithelial cell adhesion molecule (EpCAM), was used for comparison. Circulating tumor cell (CTC) isolation in blood was achieved by a microfluidic system from samples from five CCA patients undergoing chemotherapy, and the enumeration results of ETCs and CTCs were compared with diagnoses derived from computed tomography scans. The CCA-specific aptamer-conjugated magnetic beads effectively bound ETCs from bile samples of 40/40 CCA patients (>1 ETC in 3 ml of bile), and the ETC and CTC count data from patients corresponded well with cancer progression and tumor size. ETCs in bile could serve as promising indicators of disease status in early-advanced stage CCA while CTCs in blood could be representative of late-advanced stage CCA. The developed technique could consequently be a powerful tool in CCA diagnostics and prognostics.

Exfoliated tumor cells in bile as a promising indicator of disease status in cholangiocarcinoma

C-reactive protein (CRP) has been used as a common indicator during inflammation process It has been also reported that CRP concentration in serum can be used for risk assessment of cardiovascular diseases In this study, a new microfluidic system for automatic measurement of CRP is developed When compared to our previous work, the new chip can perform the entire measurement process by integrating a new micro-injector with other functional microfluidic devices Experimental data show that the developed system can automate the entire process within 35 minutes with a high sensitivity The development of the new system may provide a promising platform for automatic measurement of the CRP for point-of-care applicationsCopyright © 2009 by ASME

A Magnetic-Bead Based Microfluidic System for Automatic C-Reactive Protein Detection

Early and accurate diagnosis of cancer plays a very important role in cancer treatment. The DNA methylation of tumor suppressor genes has been used as a diagnostic biomarker of early carcinogenesis. The 5-methylcytosine of CpG islands in the promoter region has been demonstrated as an evidence of DNA methylation. In this study, the entire process for performing DNA methylation assay including capturing of target DNA, HpaII and MspI endonuclease digestion and nucleic acid amplification have been realized in an integrated microfluidic system. The limit of detection in the microfluidic system was experimentally found to be 102 cells/reaction. The entire process from sample loading to results observed only takes 3 hrs. Rapid diagnosis of ovarian cancer cells in the integrated microfluidic system has been demonstrated by using cell lines and clinical samples. The developed micro system may be promising for early diagnosis of cancers.

Enzyme digestion-based microfluidic system for DNA methylation assay

In the past decade, microfabrication of miniature fluidic devices has attracted considerable interest and made substantial impact. One of the most promising applications is for biomedical applications, especially for fast diagnosis. A microfluidic system, which integrates sample pretreatment, transportation, reaction, separation, and detection on a small chip, can be realized by combining functional microfluidic components. When compared with their large-scale counterparts, the miniature system may provide advantages including compactness, lower cost, less sample/reagent consumption, automation, and higher sensitivity. In this talk, three microfluidic chips will be reviewed, including (1) an integrated microfluidic chip for fast diagnosis of infectious diseases; (2) an integrated microfluidic chip capable of performing fast detection of generic diseases; (3) an integrated microfluidic system for ELISA detection. It may provide a promising platform for clinical applications.

Gwo-Bin Lee

Papers

3-D Magnetic Tweezers for Investigation of Mechanical Properties of Single DNA Molecules

Exfoliated tumor cells in bile as a promising indicator of disease status in cholangiocarcinoma

A Magnetic-Bead Based Microfluidic System for Automatic C-Reactive Protein Detection

Enzyme digestion-based microfluidic system for DNA methylation assay

Microfluidic systems for fast diagnosis