Sample Preparation and Diagnostic Methods for a Variety of Settings: A Comprehensive Review

Sample preparation is an essential step for nearly every type of biochemical analysis in use today. Among the most important of these analyses is the diagnosis of diseases, since their treatment may rely greatly on time and, in the case of infectious diseases, containing their spread within a population to prevent outbreaks. To address this, many different methods have been developed for use in the wide variety of settings for which they are needed. In this work, we have reviewed the literature and report on a broad range of methods that have been developed in recent years and their applications to point-of-care (POC), high-throughput screening, and low-resource and traditional clinical settings for diagnosis, including some of those that were developed in response to the coronavirus disease 2019 (COVID-19) pandemic. In addition to covering alternative approaches and improvements to traditional sample preparation techniques such as extractions and separations, techniques that have been developed with focuses on integration with smart devices, laboratory automation, and biosensors are also discussed.     

Distance versus Capillary Flow Dynamics-Based Detection Methods on a Microfluidic Paper-Based Analytical Device (μPAD)

In recent years, there has been high interest in paper-based microfluidic sensors or microfluidic paper-based analytical devices (μPADs) towards low-cost, portable, and easy-to-use sensing for chemical and biological targets. μPAD allows spontaneous liquid flow without any external or internal pumping, as well as an innate filtration capability. Although both optical (colorimetric and fluorescent) and electrochemical detection have been demonstrated on μPADs, several limitations still remain, such as the need for additional equipment, vulnerability to ambient lighting perturbation, and inferior sensitivity. Herein, alternative detection methods on μPADs are reviewed to resolve these issues, including relatively well studied distance-based measurements and the newer capillary flow dynamics-based method. Detection principles, assay performance, strengths, and weaknesses are explained for these methods, along with their potential future applications towards point-of-care medical diagnostics and other field-based applications.     

Switchable Hydrophobic Valve for Controlled Microfluidic Processing

A simple microfluidic valve, without any moving parts, is presented that can control solution flow on demand in microchannels of many different materials using a low‐power electric signal. Many independently operating valves can easily be integrated into complex microfluidic systems. The valve consists of a self‐assembled monolayer (SAM) formed on a platinum electrode that is incorporated directly in the microchannel. The normally‐on valve stops the solution flow due to a hydrophobic SAM on the electrode surface. The solution is allowed to pass the valve by applying a potential to the electrode, which removes the SAM due to reductive desorption. The valve operation is highly stable and has switching times of the order of 1 s. The valve is ideal for controlled solution manipulation in integrated micro‐analytical systems and autonomous microfluidic systems.     

生物传感器在POCT中的应用研究

即时检测（POCT）是在病人旁边或现场进行的检测,因其简单、快速、便携且不受场所限制已成为目前体外分子诊断技术发展的一支风向标。而生物传感器以其快速、灵敏、高效、便携及易于自动化、微型化等优点在发展现场即时检测技术中具有非常大的潜力。近年来,随着生物传感技术、互联网技术的发展及各种新技术、新方法的兴起和融合,POCT技术和方法得到了实质性发展。本文简要介绍了生物传感器的分类和生物传感器在POCT中的应用现状,综述了近年来各类生物传感器在面向POCT检测应用的研究进展。生物传感器根据类型主要分为基于微流控芯片的生物传感器、基于纸的生物传感器、基于纳米材料的生物传感器、基于手机检测平台的生物传感器及集成的生物传感器等,并对这些传感器平台在POCT检测方面的应用做了阐述,最后对生物传感器在POCT应用中存在的问题进行了讨论,并对其发展趋势及前景做了展望。     

Towards an Integrated Chemical Circuit

Everything on a chip : Recent developments in microfluidics enable the combination of droplet microfluidics with continuous‐flow systems (see picture). This is a promising step towards the development of integrated, complex synthesis and analysis laboratories on chips. For example, a building‐block principle could be used to integrate a multistep reaction with purification and analysis.

     

Quantitative Online Detection of Low‐Concentrated Drugs via a SERS Microfluidic System

Herein, quantitative online monitoring of concentration fluctuations of different interesting drugs, namely, the phenothiazine promethazine as well as the anti‐cancer agent mitoxantrone via surface enhanced Raman scattering assay based on a microfluidic device is demonstrated. With the applied liquid/liquid two‐phase‐segmented flow system we succeed in preventing the adhesion of nanoparticle aggregates to the channel walls which is necessary for a quantitative analysis. Even after repeated cycles no carry‐over due to sedimentation of colloid particles is observed. To the best of our knowledge these are the first measurements applying a combination of a microfluidic device with SERS detection for quantitative online monitoring of fluctuations in drug concentrations over hours without use of aggressive chemicals for rinsing the chip surfaces prior to each measurement.     

Lab‐on‐a‐Chip Reactor Imaging with Unprecedented Chemical Resolution by Hadamard‐Encoded Remote Detection NMR

The development of microfluidic processes requires information‐rich detection methods. Here we introduce the concept of remote detection exchange NMR spectroscopy (RD‐EXSY), and show that, along with indirect spatial information extracted from time‐of‐flight data, it provides unique information about the active regions, reaction pathways, and intermediate products in a lab‐on‐a‐chip reactor. Furthermore, we demonstrate that direct spatial resolution can be added to RD‐EXSY efficiently by applying the principles of Hadamard spectroscopy.     

Organs on microfluidic chips: A mini review

Microfluidic technology provides opportunities to create in vitro models with physiological microenvironment for cell study. Introducing the identified key aspects, including tissue-tissue interfaces, spatiotemporal chemical gradients, and dynamic mechanical forces, of living organs into the microfluidic system, “organs-on-chips” display an unprecedented application potential in a lot of biological fields such as fundamental physiological and pathophysiological research, drug efficacy and toxicity testing, and clinical diagnosis. Here, we review the recent development of organs-on-chips and briefly discuss their future challenges.     

Sensitive and Multiplexed On‐chip microRNA Profiling in Oil‐Isolated Hydrogel Chambers

Although microRNAs (miRNAs) have been shown to be excellent indicators of disease state, current profiling platforms are insufficient for clinical translation. Here, we demonstrate a versatile hydrogel‐based microfluidic approach and novel amplification scheme for entirely on‐chip, sensitive, and highly specific miRNA detection without the risk of sequence bias. A simulation‐driven approach is used to engineer the hydrogel geometry and the gel‐reaction environment is chemically optimized for robust detection performance. The assay provides 22.6 fM sensitivity over a three log range, demonstrates multiplexing across at least four targets, and requires just 10.3 ng of total RNA input in a 2 hour and 15 minutes assay.     

Accurate Zygote‐Specific Discrimination of Single‐Nucleotide Polymorphisms Using Microfluidic Electrochemical DNA Melting Curves

We report the first electrochemical system for the detection of single‐nucleotide polymorphisms (SNPs) that can accurately discriminate homozygous and heterozygous genotypes using microfluidics technology. To achieve this, our system performs real‐time melting‐curve analysis of surface‐immobilized hybridization probes. As an example, we used our sensor to analyze two SNPs in the apolipoprotein E (ApoE) gene, where homozygous and heterozygous mutations greatly affect the risk of late‐onset Alzheimer’s disease. Using probes specific for each SNP, we simultaneously acquired melting curves for probe–target duplexes at two different loci and thereby accurately distinguish all six possible ApoE allele combinations. Since the design of our device and probes can be readily adapted for targeting other loci, we believe that our method offers a modular platform for the diagnosis of SNP‐based diseases and personalized medicine.     

Rapid, sensitive, and quantitative detection of pathogenic DNA at the point of care through microfluidic electrochemical quantitative loop-mediated isothermal amplification

Single-step DNA detection: a microfluidic electrochemical loop mediated isothermal amplification platform is reported for rapid, sensitive, and quantitative detection of pathogen genomic DNA at the point of care. DNA amplification was electrochemically monitored in real time within a monolithic microfluidic device, thus enabling the detection of as few as 16 copies of Salmonella genomic DNA through a single-step process in less than an hour.     

微流控芯片细胞实验室

以作者所在课题组近年开展的研究工作为基础,阐述了微流控芯片细胞实验室的平台特征,并从细胞个体、群体和多细胞生命体研究等三个方面概述微流控芯片细胞实验室的应用对象特征,显示其在生物医学领域的应用前景。     

A Review on Microfluidics: An Aid to Assisted Reproductive Technology

Infertility is a state of the male or female reproductive system that is defined as the failure to achieve pregnancy even after 12 or more months of regular unprotected sexual intercourse. Assisted reproductive technology (ART) plays a crucial role in addressing infertility. Various ART are now available for infertile couples. Fertilization in vitro (IVF), intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) are the most common techniques in this regard. Various microfluidic technologies can incorporate various ART procedures such as embryo and gamete (sperm and oocyte) analysis, sorting, manipulation, culture and monitoring. Hence, this review intends to summarize the current knowledge about the application of this approach towards cell biology to enhance ART.     

Electrochemistry on Paper‐based Analytical Devices: A Review

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.