Microchip imaging cytometer: making healthcare available, accessible, and affordable

The Microchip Imaging Cytometer (MIC) is a class of integrated point-of-care detection systems based on the combination of optical microscopy and flow cytometry. MIC devices have the attributes of portability, cost-effectiveness, and adaptability while providing quantitative measurements to meet the needs of laboratory testing in a variety of healthcare settings. Based on the use of microfluidic chips, MIC requires less sample and can complete sample preparation automatically. Therefore, they can provide quantitative testing results simply using a finger prick specimen. The decreased reagent consumption and reduced form factor also help improve the accessibility and affordability of healthcare services in remote and resource-limited settings. In this article, we review recent developments of the Microchip Imaging Cytometer from the following aspects: clinical applications, microfluidic chip integration, imaging optics, and image acquisition. Following, we provide an outlook of the field and remark on promising technologies that may enable significant progress in the near future

3D Printed Microfluidic Devices

3D printing has revolutionized the microfabrication prototyping workflow over the past few years. With the recent improvements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols as a promising alternative to the time consuming, costly and sophisticated traditional cleanroom fabrication. Microfluidic devices have enabled a wide range of biochemical and clinical applications, such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. Using 3D printing fabrication technologies, alteration of the design features is significantly easier than traditional fabrication, enabling agile iterative design and facilitating rapid prototyping. This can make microfluidic technology more accessible to researchers in various fields and accelerates innovation in the field of microfluidics. Accordingly, this Special Issue seeks to showcase research papers, short communications, and review articles that focus on novel methodological developments in 3D printing and its use for various biochemical and biomedical applications

Integrated printed microfluidic biosensors

Integrated printed microfluidic biosensors are one of the most recent point-of-care (POC) sensor developments. Fast turnaround time for production and ease of customization, enabled by the integration of recognition elements and transducers, are key for on-site biosensing for both healthcare and industry and for speeding up translation to real-life applications. Here, we provide an overview of recent progress in printed microfluidics, from the 2D to the 4D level, accompanied by novel sensing element integration. We also explore the latest trends in integrated printed microfluidics for healthcare, especially POC diagnostics, and food safety applications

Microfluidics for Biosensing

There are 12 papers published with 8 research articles, 3 review articles and 1 perspective. The topics cover: Biomedical microfluidics Lab-on-a-chip Miniaturized systems for chemistry and life science (MicroTAS) Biosensor development and characteristics Imaging and other detection technologies Imaging and signal processing Point-of-care testing microdevices Food and water quality testing and control We hope this collection could promote the development of microfluidics and point-of-care testing (POCT) devices for biosensing

Wireless colorimetric readout to enable resource-limited point-of-care

Patientennahe Diagnostik in Entwicklungsländer birgt spezielle Herausforderungen, die ihren Erfolg bisher begrenzen. Diese Arbeit widmet sich daher der Entwicklung eines in seiner Herstellung skalierbaren und vielseitig einsetzbaren funkbasierten Auslesegerätes für Laborteststreifen. Durch die Kombination einer wachsenden Auswahl an papierbasierten Teststreifendiagnostiken mit gedruckter Elektronik und unter Berücksichtigung des diagnostischen Alltags im südlichen Afrika wurde ein Gerät entwickelt, das Teststreifen zuverlässig ausliest und die Daten per Funk an eine Datenbank übertragen kann. Die Technik basiert auf RFID-Tags (radio frequency identification devices), welche auf verschiedene flexible Substrate gedruckt wurden, um die technische Umsetzbarkeit und Funktionalität zu evaluieren. Um den Preis für die geplante Anwendung niedrig zu halten, wurden unter anderem Papier und Karton als Substrate genutzt. Das Ergebnis dieser Studie sind passive RFID-Tags auf unterschiedlichen, meist günstigen Substraten, die über eine Distanz von über 75 mm betrieben und ausgelesen werden können. Basierend auf der über RFID bereitgestellten Energie und Datenübertragung wurde eine Ausleseeinheit für Standardpapierstreifentests entwickelt und integriert. Durch das Auslesen verschiedener Teststreifen wurde das Gerät evaluiert und in seiner Aussagekraft mit einer scanner-basierten Aufnahme und anschließender Bildanalyse (ImageJ), einem kommerziellen Auslesegerät sowie einer manuellen Auslesung mit Hilfe von Farbtabellen verglichen. Das Gerät kann die Streifen zuverlässig auslesen und die Daten über die RFID-Schnittstelle übertragen. Die funkbasierte Ausleseeinheit ist mit verschiedenen kommerziellen Teststreifen sowohl im biodiagnostischen (lateral flow tests) wie auch im chemischen Bereich (pH-Wert) kompatibel. Die modulare Lösung erlaubt ein breites Einsatzgebiet und führt dadurch zu reduzierten Trainingszeiten der Anwender und einer zuverlässigen Handhabung. Die vorgestellte Lösung ist äußerst kostengünstig und bedarf keiner Wartung, wodurch sie sich sehr gut für den Einsatz in abgelegenen Feldkrankenhäusern eignet. Es wurde ein skalierbarer Prototyp entwickelt, der auf konventionellen Herstellungsverfahren der Verpackungsindustrie aufbaut. Aktuell handelt es sich noch um einen bogenbasierten Prozess, der sich aber prinzipiell auch auf Rolle-zu-Rolle Maschinen übertragen lässt. Bei der Entwicklung des Geräts spielte die Möglichkeit der lokalen Herstellung in den Einsatzländern eine große Rolle. Diese hätte neben der Generierung von Arbeitsplätzen auch den Vorteil einer einfacheren Verteilung der Geräte in ländliche Regionen, in denen sie den größten Nutzen für die Diagnostik erzielen würden

Breaking the clean room barrier: exploring low-cost alternatives for microfluidic devices

Microfluidics is an interdisciplinary field that encompasses both science and engineering, which aims to design and fabricate devices capable of manipulating extremely low volumes of fluids on a microscale level. The central objective of microfluidics is to provide high precision and accuracy while using minimal reagents and equipment. The benefits of this approach include greater control over experimental conditions, faster analysis, and improved experimental reproducibility. Microfluidic devices, also known as labs-on-a-chip (LOCs), have emerged as potential instruments for optimizing operations and decreasing costs in various of industries, including pharmaceutical, medical, food, and cosmetics. However, the high price of conventional prototypes for LOCs devices, generated in clean room facilities, has increased the demand for inexpensive alternatives. Polymers, paper, and hydrogels are some of the materials that can be utilized to create the inexpensive microfluidic devices covered in this article. In addition, we highlighted different manufacturing techniques, such as soft lithography, laser plotting, and 3D printing, that are suitable for creating LOCs. The selection of materials and fabrication techniques will depend on the specific requirements and applications of each individual LOC. This article aims to provide a comprehensive overview of the numerous alternatives for the development of low-cost LOCs to service industries such as pharmaceuticals, chemicals, food, and biomedicine

Lab-on-PCB Devices

Lab-on-PCB devices can be considered an emerging technology. In fact, most of the contributions have been published during the last 5 years. It is mainly focussed on both biomedical and electronic applications. The book includes an interesting guide for using the different layers of the Printed Circuit Boards for developing new devices; guidelines for fabricating PCB-based electrochemical biosensors, and an overview of fluid manipulation devices fabricated using Printed Circuit Boards. In addition, current PCB-based devices are reported, and studies for several aspects of research and development of lab-on-PCB devices are described

Electrochemical Plug-and-Power e-readers for Point-of-Care Applications

Point-of-Care diagnostic tests enable monitor health conditions and obtain fast results close to the patient, reducing medical costs, and allowing the control of infectious outbreaks. The interest in developing Point-of-Care devices is increasing due to they are suitable for a wide variety of applications. This doctoral thesis focuses on the development of Plug-and-Power electronic readers (e- readers) for electrochemical detections and the demonstration of their possibilities as Point-of-Care diagnostic testing. The solutions proposed in this study make it possible to improve Point-of-Care tests whose premises are laboratory decentralization, personalized medicine, rapid diagnosis, and improvement of patient care. Developed electronic readers can be powered from a conventional system, such as a USB port or a lithium battery, or can be defined as self-powered systems, capable of extracting energy from alternative energy sources, such as fuel cells, defining Plug-and-Power systems. The designed electrochemical detection devices in this thesis are based on low-power consumption electronic instrumentation circuits. These circuits are capable of controlling the sensing element, measuring its response, and representing the result quantitatively. The implemented devices can work with both electrochemical sensors and fuel cells. Furthermore, it is possible to adapt its measurement range, enabling its use in a wide variety of applications. Thanks to their reduced energy consumption, some of these developments can be defined as self-powered platforms able to operate only with the energy extracted from the biological sample, which in turn is monitored. These devices are easy-to-use and plug-and-play, enabling those unskilled individuals to carry out tests after prior training. Moreover, thanks to their user-friendly interface, results are clear and easy to understand. This doctoral dissertation is presented as an article compendium and composed of three publications detailed in chronological order of publication. The first contribution describes an innovative portable Point-of-Care device able to provide a quantitative result of the glucose concentration of a sample. The proposed system combines an e-reader and a disposable device based on two elements: a glucose paper-based power source, and a glucose fuel cell-based sensor. The battery-less e-reader extracts the energy from the disposable unit, acquires the signal, processes it, and shows the glucose concentration on a numerical display. Due to low-power consumption of the e-reader, the whole electronic system can operate only with the energy extracted from the disposable element. Furthermore, the proposed system minimizes the user interaction, which only must deposit the sample on the strip and wait a few seconds to see the test result. The second publication validates the e-reader in other scenarios following two approaches: using fuel cells as a power element, and as a dual powering and sensing element. The device was tested with glucose, urine, methanol, and ethanol fuel cells and electrochemical sensors in order to show the adaptability of this versatile concept to a wide variety of fields beyond clinical diagnostics, such as veterinary or environmental fields. The third study presents a low-cost, miniaturized, and customizable electronic reader for amperometric detections. The USB-powered portable device is composed of a full- custom electronic board for signal acquisition, and software, which controls the systems, represents and saves the results. In this study, the performance of the device was compared against three commercial potentiostats, showing comparable results to those obtained using three commercial systems, which were significantly more expensive. As proof of concept, the system was validated by detecting horseradish peroxidase samples. However, it could be easily extended its scope and measure other types of analytes or biological matrices since it can be easily adapted to detect currents a wide range of currents.Las pruebas de diagnostico Point-of-Care permiten monitorizar las condiciones de salud y obtener resultados rápidos cerca del paciente, reduciendo los costes médicos y permitiendo controlar brotes infecciosos. El interés por desarrollar dispositivos de Point- of-Care está aumentando debido a que son aplicables a una amplia variedad de aplicaciones. Esta tesis doctoral se centra en el desarrollo de lectores electrónicos (e-readers) Plug-and- Power para detecciones electroquímicas y la demostración de sus posibilidades como pruebas de diagnóstico de punto de atención (Point-of-Care). Las soluciones propuestas en este trabajo permiten mejorar las pruebas Point-of-Care, cuyas premisas son la descentralización de laboratorio, la medicina personalizada, el diagnóstico rápido y la mejora de la atención al paciente. Los lectores electrónicos desarrollados pueden ser alimentados desde un sistema convencional, como puede ser un puerto USB o una batería de litio, o definirse como sistemas autoalimentados, capaces de extraen energía de fuentes alternativas de energía, como celdas de combustible (fuel cells), definiendo así sistemas Plug-and-Power. Los dispositivos de detección electroquímica diseñados se basan en circuitos de instrumentación electrónica de bajo consumo. Estos circuitos son capaces controlar el elemento de sensado, medir su respuesta y representar el resultado de forma cuantitativa. Los dispositivos implementados pueden trabajar tanto con sensores electroquímicos como con fuel cells. Además, es posible adaptar su rango de medida, permitiendo su utilización en una amplia variedad de aplicaciones. Gracias a su reducido consumo de energía, algunos de estos desarrollos pueden definirse como plataformas autoalimentadas capaces de operar solo con la energía extraída de la muestra biológica, que a su vez es monitorizada. Estas plataformas electrónicas son fáciles de usar y Plug-and-Play, permitiendo que personas no cualificadas puedan utilizarlas después de un previo entrenamiento. Además, gracias a su interfaz fácil de usar, los resultados son claros y fáciles de interpretar

Fabrication of Microfluidic Devices for Emulsion Formation by Microstereolithography

Droplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited three-dimensional (3D) design flexibility. High-resolution additive manufacturing—and in particular, projection micro-stereolithography (PµSL)—provides a promising path for overcoming these drawbacks. Similar to polydimethylsiloxane-based microfluidics 20 years ago, 3D printing methods, such as PµSL, have provided a path toward a new era of microfluidic device design. PµSL greatly simplifies the device fabrication process, especially the access to truly 3D geometries, is cost-effective, and it enables multimaterial processing. In this review, we discuss both the basics and recent innovations in PµSL; the material basis with emphasis on custom-made photopolymer formulations; multimaterial 3D printing; and, 3D-printed microfluidic devices for emulsion formation as our focus application. Our goal is to support researchers in setting up their own PµSL system to fabricate tailor-made microfluidics

Advances in Microfluidic Technologies for Energy and Environmental Applications

Microfluidics have aroused a new surge of interest in recent years in environmental and energy areas, and inspired novel applications to tackle the worldwide challenges for sustainable development. This book aims to present readers with a valuable compendium of significant advances in applying the multidisciplinary microfluidic technologies to address energy and environmental problems in a plethora of areas such as environmental monitoring and detection, new nanofluid application in traditional mechanical manufacturing processes, development of novel biosensors, and thermal management. This book will provide a new perspective to the understanding of the ever-growing importance of microfluidics