This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using conventional open-channel microsystems made from glass or polymers. In particular, 3D paper-based devices wick fluids and distribute microliter volumes of samples from single inlet points into arrays of detection zones (with numbers up to thousands). This capability makes it possible to carry out a range of new analytical protocols simply and inexpensively (all on a piece of paper) without external pumps. We demonstrate a prototype 3D device that tests 4 different samples for up to 4 different analytes and displays the results of the assays in a side-by-side configuration for easy comparison. Three-dimensional paper-based microfluidic devices are especially appropriate for use in distributed healthcare in the developing world and in environmental monitoring and water analysis.

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Three-dimensional microfluidic devices fabricated in layered paper and tape.

A large part of the excitement behind microfluidics is in its potential for producing practical devices, but surprisingly few lab-on-a-chip based technologies have been successfully introduced into the market. Here, we review current work in commercializing microfluidic technologies, with a focus on point-of-care diagnostics applications. We will also identify challenges to commercialization, including lessons drawn from our experience in Claros Diagnostics. Moving forward, we discuss the need to strike a balance between achieving real-world impact with integrated devices versus design of novel single microfluidic components.

http://mnbs-2014.sciencesconf.org/conference/mnbs-2014/pages/Chin_Lab_Chip_2012_commercialisation_of_PoC.pdf

Commercialization of microfluidic point-of-care diagnostic devices

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

/pdf/point-of-care-diagnostics-status-and-future-5c7xkio6mh.pdf

Point of care diagnostics: Status and future

Biomedical engineers have traditionally developed technologies in response to the needs of the developed world's medical community. As a result, the diagnostic systems on which they have worked have met the requirements of well-funded laboratories in highly regulated and quality-assessed environments. However, such approaches do not address the needs of the majority of the world's people afflicted with infectious diseases, who have, at best, access to poorly resourced health care facilities with almost no supporting clinical laboratory infrastructure. A major challenge for the biomedical engineering community is to develop diagnostic tests to meet the needs of these people, the majority of whom are in the developing world. We here review the context in which the diagnostics must operate, some of the appropriate diagnostic technologies already in distribution, and some emerging technologies that promise to address this challenge. However, there is much room for innovation, adaptation, and cost reduction be...

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.10.061807.160524

Point-of-care diagnostics for global health.

We have developed a novel microfluidic device constructed from poly(dimethylsiloxane) using multilayer soft lithography technology for the analysis of single cells. The microfluidic network enables the passive and gentle separation of a single cell from the bulk cell suspension, and integrated valves and pumps enable the precise delivery of nanoliter volumes of reagents to that cell. Various applications are demonstrated, including cell viability assays, ionophore-mediated intracellular Ca2+ flux measurements, and multistep receptor-mediated Ca2+ measurements. These assays, and others, are achieved with significant improvements in reagent consumption, analysis time, and temporal resolution over macroscale alternatives.

Microfluidic device for single-cell analysis

Microfluidic technologies in clinical diagnostics.

A device for analyzing sample solutions such as whole blood based on coagulation and agglutination which requires no external power source or moving parts to perform the analysis. Single disposable cartridges for performing blood typing assays can be constructed using this technology.

Microfluidic analysis cartridge

An integrated microfluidic design, modeling, and rapid prototyping process is presented. It is based on laser cutting and lamination of individual thin layers of plastic. The process allows the rapid and low-cost manufacturing of both simple and complex 3-dimensional microfluidic flow structures that are routinely designed, fabricated, and tested within the space of 24 hours. It has yielded microfluidic elements and systems, such as mixers, separators, and detectors, as well as complete microfluidic integrated circuits that have been used with complex biological samples such as whole blood. Both “active”, machine-controlled microfluidic disposables as well as “passive”, self-contained cards that do not require any external instrument are presented. Such devices include a disposable hematology analyzer chip, as well as blood separation and analysis tools.

Design and Rapid Prototyping of Thin-Film Laminate-Based Microfluidic Devices

Microfluidic devices and methods for performing a microfluidic process are presented. A microfluidic device conforms with a standard well plate format. The device includes a well plate comprising a plate and an array of wells formed on or in the plate, and a microfluidic structure connecting at least two of the wells. The device can rely exclusively on gravitational and capillary forces that exist in channels within the microfluidic structure when receiving fluid streams. Also disclosed is a microfluidic device having an array of microfluidic structures, each connecting at least two wells of a well plate, and connecting three or more wells in alternative embodiments. With the present invention, a large number of microfluidic processes or reactions can be performed simultaneously.

Well-plate microfluidics

Micronics has developed a wide variety of microfluidic devices and integrated systems for clinical diagnostics and life sciences applications. They fall into two general classes: machine-controlled disposable cartridges, and passive self-contained disposable cards. They include particle separators, flow cytometers, valves, detection channels, mixers, and diluters. Current applications for these devices include a hematology analyzer, stand-alone blood plasma separators, and a variety of chemical and biological assays. In this paper, we will focus on microfluidic structures for chemical and cellular analysis. Experimental data as well as the results of fluid modeling will be shown.

Thomas H. Schulte

Papers

Microfluidic technologies in clinical diagnostics.

Microfluidic analysis cartridge

Design and Rapid Prototyping of Thin-Film Laminate-Based Microfluidic Devices

Well-plate microfluidics

Microfluidic disposables for cellular and chemical detection: CFD model results and fluidic verification experiments