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.

Circulating tumor cells (CTCs) are indicators for cancer diagnosis and prognosis. In this work, a new integrated microfluidic system capable of un-biased and sensitive “negative” enrichment of CTCs was developed. By using anti-human CD45 coated magnetic beads, leukocytes were removed by external magnetic force, leaving behind an enriched target cell population. The results demonstrated that the developed chip was capable of performing CTC negative enrichment with comparable performance as the conventional benchtop method while offering significant advantages in rapid incubation and potential for automation, suggesting the developed chip is promising for standardized CTC isolation platform.

/pdf/an-integrated-microfluidic-platform-for-negative-selection-3162bvta2k.pdf

An integrated microfluidic platform for negative selection and enrichment of circulating tumor cells

Recently, micro ribonucleic acids (miRNAs) extracted from extracellular vesicles (EVs) have been recognized as promising biomarkers for early detection of cardiovascular diseases (CVDs). However, the detection and quantification of miRNAs by using the existing methods are relatively labor-intensive and time-consuming. In this work, an integrated microfluidic system equipped with highly sensitive field-effect transistors which is capable of performing EVs extraction, EVs lysis, target miRNAs extraction and miRNAs detection was reported. The entire detection process could be automated within three hours on a single chip and the detection limit of miRNAs was observed to be in a femtomolar range, which meets the requirement of physiological concentrations. This integrated microfluidic system has great potential to be a tool for early detection of CVDs.

Detection of micro ribonucleic acids from extracted extracellular vesicles for cardiovascular diseases by using an integrated microfluidic system

Breast cancer is one of the most important cancers among women worldwide. Since breast cancer is prone to metastasis and recurrence, mortality is relatively high if not diagnosed early. Therefore, it is important to develop a device that can quickly and accurately diagnose breast cancer. Recently, microRNAs such as microRNA-195 and microRNA-126 have been reported to act as biomarkers for breast cancer diagnosis. Therefore, this study reported an integrated microfluidic system capable of extracting microRNAs by microfluidic techniques, detecting and quantifying microRNAs by using complementary-metal-oxide-semiconductor (CMOS) capacitive biosensors for rapid and accurate diagnosis of breast cancer. Monolithic sensor with integrated-circuits reduces parasitic effects and submicron interdigitated microelectrodes as sensing interfaces significantly improves sensitivity. microRNA-195 detection for concentrations ranging from 1 fM to 10 pM could be successfully obtained, allowing detection in physiological conditions for cancer patients in the near future.

2 x 3 Arrayed CMOS Capacitive Biosensors for Detection of microRNAs on a Microfluidic System

Mitochondria DNA (mtDNA) plays an important role in both aging-associated degenerative diseases and cancers. In this study, a new microfluidic system integrating functional components including a mtDNA extraction module, a polymerase chain reaction (PCR) module and a micro-capillary electrophoresis (MCE) module has been developed. A new approach to vertically integrate these three modules has been reported. A cell lysis device, pneumatic micropumps, and an active micromixer were first used for fast extraction of mtDNA from cells. Then, the PCR and the MCE modules were used for nucleic acid amplification and separation of mtDNA. Experimental data showed that the deletion of mtDNA can be automatically detected with this approach.

A new microfluid system for mitochondrial DNA extraction and analysis

this study presents a simple microfluidic device which can perform sample pretreatment automatically for rapid bacteria detection. Herein, a new approach to rapidly isolate bacteria incorporated with vancomycin-conjugated magnetic beads by using a new membrane-type microfluidic component with a floating block was proposed and its performance was tested and verified. The experimental results showed the proposed device can automatically isolate methicillin-resistant Staphylococcus aureus from 4 µL of samples within 90 seconds including bacteria isolation and washing processes. Not only does the new membrane-type microfluidic device perform rigid mixing, but it is also capable of uniform sample transportation. Furthermore, it has been successfully demonstrated that it could isolate bacteria in an automated format. With its great mixing efficiency and robust performance, the proposed device might be a promising approach for bacteria diagnosis.

Gwo-Bin Lee

Papers

An integrated microfluidic platform for negative selection and enrichment of circulating tumor cells

Detection of micro ribonucleic acids from extracted extracellular vesicles for cardiovascular diseases by using an integrated microfluidic system

2 x 3 Arrayed CMOS Capacitive Biosensors for Detection of microRNAs on a Microfluidic System

A new microfluid system for mitochondrial DNA extraction and analysis

A new membrane-type microfluidic device for rapid bacteria isolation