抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Dipstick and lateral-flow formats have dominated rapid diagnostics over the last three decades. These formats gained popularity in the consumer markets due to their compactness, portability and facile interpretation without external instrumentation. However, lack of quantitation in measurements has challenged the demand of existing assay formats in consumer markets. Recently, paper-based microfluidics has emerged as a multiplexable point-of-care platform which might transcend the capabilities of existing assays in resource-limited settings. However, paper-based microfluidics can enable fluid handling and quantitative analysis for potential applications in healthcare, veterinary medicine, environmental monitoring and food safety. Currently, in its early development stages, paper-based microfluidics is considered a low-cost, lightweight, and disposable technology. The aim of this review is to discuss: (1) fabrication of paper-based microfluidic devices, (2) functionalisation of microfluidic components to increase the capabilities and the performance, (3) introduction of existing detection techniques to the paper platform and (4) exploration of extracting quantitative readouts via handheld devices and camera phones. Additionally, this review includes challenges to scaling up, commercialisation and regulatory issues. The factors which limit paper-based microfluidic devices to become real world products and future directions are also identified.

Paper-based microfluidic point-of-care diagnostic devices

Recent developments in paper-based microfluidic devices.

A comprehensive review on the development and state of the art of colorimetric and fluorometric sensor arrays is presented Chemical sensing aims to detect subtle changes in the chemical environment by transforming relevant chemical or physical properties of molecular or ionic species (ie, analytes) into an analytically useful output Optical arrays based on chemoresponsive colorants (dyes and nanoporous pigments) probe the chemical reactivity of analytes, rather than their physical properties (eg, mass) The chemical specificity of the olfactory system does not come from specific receptors for specific analytes (eg, the traditional lock-and-key model of substrate-enzyme interactions), but rather olfaction makes use of pattern recognition of the combined response of several hundred olfactory receptors In a similar fashion, arrays of chemoresponsive colorants provide high-dimensional data from the color or fluorescence changes of the dyes in these arrays as they are exposed to analytes This provides chemical sensing with high sensitivity (often down to parts per billion levels), impressive discrimination among very similar analytes, and exquisite fingerprinting of extremely similar mixtures over a wide range of analyte types, in both the gas and liquid phases Design of both sensor arrays and instrumentation for their analysis are discussed In addition, the various chemometric and statistical analyses of high-dimensional data (including hierarchical cluster analysis (HCA), principal component analysis (PCA), linear discriminant analysis (LDA), support vector machines (SVMs), and artificial neural networks (ANNs)) are presented and critiqued in reference to their use in chemical sensing A variety of applications are also discussed, including personal dosimetry of toxic industrial chemical, detection of explosives or accelerants, quality control of foods and beverages, biosensing intracellularly, identification of bacteria and fungi, and detection of cancer and disease biomarkers

The Optoelectronic Nose: Colorimetric and Fluorometric Sensor Arrays.

Multiconfiguration Self-Consistent Field and Multireference Configuration Interaction Methods and Applications

Foodborne pathogens are a major public health threat and financial burden for the food industry, individuals, and society, with an estimated 76 million cases of food-related illness occurring in the United States alone each year. Three of the most important causative bacterial agents of foodborne diseases are pathogenic strains of Escherichia coli, Salmonella spp., and Listeria monocytogenes, due to the severity and frequency of illness and disproportionally high number of fatalities. Their continued persistence in food has dictated the ongoing need for faster, simpler, and less expensive analytical systems capable of live pathogen detection in complex samples. Culture techniques for detection and identification of foodborne pathogens require 5–7 days to complete. Major improvements to molecular detection techniques have been introduced recently, including polymerase chain reaction (PCR). These methods can be tedious; require complex, expensive instrumentation; necessitate highly trained personnel; and ar...

Development of a Paper-Based Analytical Device for Colorimetric Detection of Select Foodborne Pathogens

Even though they were introduced less than a decade ago, electrochemical paper-based devices (ePADs) have attracted widespread attention because of their inherent advantages in many applications. ePADs combine the advantages of microfluidic paper-based devices (low cost, ease of use, equipment free pumping, etc.) for sample handling and processing with the advantages of sensitive and selective detection provided by electrochemistry. As a result, ePADs provide simplicity, portability, reproducibility, low cost and high selectivity and sensitivity for analytical measurements in a variety of applications ranging from clinical diagnostics to environmental sensing. Herein, recent advances in ePAD development and application are reviewed, focusing on electrode fabrication techniques and examples of applications specially focused on environmental monitoring, biological applications and clinical assays. Finally, a summary and prospective directions for ePAD research are also provided.

Electrochemistry on Paper‐based Analytical Devices: A Review

The development of transparency-based electrochemical and paper-based colorimetric analytic detection platforms is presented as complementary methods for food and waterborne bacteria detection from a single assay. Escherichia coli and Enterococcus species, both indicators of fecal contamination, were detected using substrates specific to enzymes produced by each species. β-galactosidase (β-gal) and β-glucuronidase (β-glucur) are both produced by E. coli, while β-glucosidase (β-gluco) is produced by Enterococcus spp. Substrates used produced either p-nitrophenol (PNP), o-nitrophenol (ONP), or p-aminophenol (PAP) as products. Electrochemical detection using stencil-printed carbon electrodes (SPCEs) was found to provide optimal performance on inexpensive and disposable transparency film platforms. Using SPCEs, detection limits for electrochemically active substrates, PNP, ONP, and PAP were determined to be 1.1, 2.8, and 0.5 μM, respectively. A colorimetric paper-based well plate system was developed from a s...

Colorimetric and Electrochemical Bacteria Detection Using Printed Paper- and Transparency-Based Analytic Devices

Self-pumping porous microfluidic devices have attracted significant interest because of their low cost and broad applicability in point-of-care and low resource settings. One limitation of many of the devices is sensitivity and selectivity for detection. Electrochemistry can provide a sensitive, selective detection method while still using low cost, portable instrumentation as typified by handheld glucometers. Here, the development of electrochemical paper-based analytical devices (ePADs) is reviewed. Given the importance of electrode geometry and composition, fabrication methods are reviewed first. This is followed by a review of example applications demonstrated for ePADs. Finally, major accomplishments and future directions are summarized.

Jaclyn A. Adkins

Papers

Recent developments in paper-based microfluidic devices.

Development of a Paper-Based Analytical Device for Colorimetric Detection of Select Foodborne Pathogens

Electrochemistry on Paper‐based Analytical Devices: A Review

Colorimetric and Electrochemical Bacteria Detection Using Printed Paper- and Transparency-Based Analytic Devices

Electrochemical paper‐based microfluidic devices