The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

The origins and the future of microfluidics

Self-assembly is the autonomous organization of components into patterns or structures without human intervention. Self-assembling processes are common throughout nature and technology. They involve components from the molecular (crystals) to the planetary (weather systems) scale and many different kinds of interactions. The concept of self-assembly is used increasingly in many disciplines, with a different flavor and emphasis in each.

http://science.sciencemag.org/content/sci/295/5564/2418.full.pdf

Self-assembly at all scales.

Boron-doped silicon nanowires (SiNWs) were used to create highly sensitive, real-time electrically based sensors for biological and chemical species. Amine- and oxide-functionalized SiNWs exhibit pH-dependent conductance that was linear over a large dynamic range and could be understood in terms of the change in surface charge during protonation and deprotonation. Biotin-modified SiNWs were used to detect streptavidin down to at least a picomolar concentration range. In addition, antigen-functionalized SiNWs show reversible antibody binding and concentration-dependent detection in real time. Lastly, detection of the reversible binding of the metabolic indicator Ca2+ was demonstrated. The small size and capability of these semiconductor nanowires for sensitive, label-free, real-time detection of a wide range of chemical and biological species could be exploited in array-based screening and in vivo diagnostics.

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Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species

https://www.cell.com/cell/pdf/S0092-8674(15)00549-8.pdf

Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets

This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.

Fabrication of microfluidic systems in poly(dimethylsiloxane)

The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target protein molecules per bead) with an enzymatic reporter capable of generating a fluorescent product. After isolating the beads in 50-fl reaction chambers designed to hold only a single bead, we used fluorescence imaging to detect single protein molecules. Our single-molecule enzyme-linked immunosorbent assay (digital ELISA) approach detected as few as approximately 10-20 enzyme-labeled complexes in 100 microl of sample (approximately 10(-19) M) and routinely allowed detection of clinically relevant proteins in serum at concentrations (<10(-15) M) much lower than conventional ELISA. Digital ELISA detected prostate-specific antigen (PSA) in sera from patients who had undergone radical prostatectomy at concentrations as low as 14 fg/ml (0.4 fM).

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Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations

This paper describes a microfluidic system in which fluids are pumped by centrifugal force through microscopic channels defined in a plastic disk in order to perform complex analytical processes. The channels are created either by casting poly(dimethylsiloxane) against molds fabricated by photolithography or by conventional machining of poly(methyl methyacrylate). The channels have a wide range of diameters (5 μm−0.5 mm) and depths (16 μm−3 mm). Fluids are loaded into reservoirs near the center of the disk, the disk is rotated on the shaft of a simple motor at 60−3000 rpm, and the fluids are pumped outward by centrifugal force through microfluidic networks. The control of flow in the time domain, i.e., gating, is achieved by the use of passive valves based on capillary forces. Flow rates ranging from 5 nL/s to >0.1 mL/s have been achieved using channels of different dimensions and different rates of rotation. The method of pumping is insensitive to many physicochemical properties of the liquid, such as pH...

Microfabricated Centrifugal Microfluidic Systems: Characterization and Multiple Enzymatic Assays

This paper describes the fabrication of large (up to 45 cm2) arrays of microwells, with volumes as small as ∼3 fL/well and densities as high as 107 wells/cm2. These arrays of microwells are formed by casting an elastomer, poly(dimethylsiloxane) (PDMS), against “masters” prepared by photolithography; arrays of microwells in other polymers can be formed by using a master consisting of posts in PDMS. A straightforward technique, discontinuous dewetting, allows wells to be filled rapidly (typically on the order of 104 wells/s) and uniformly with a wide range of liquids. Several rudimentary strategies for addressing microwells are investigated, including electroosmotic pumping and gaseous diffusion.

David C. Duffy

Papers

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Fabrication of microfluidic systems in poly(dimethylsiloxane)

Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations

Microfabricated Centrifugal Microfluidic Systems: Characterization and Multiple Enzymatic Assays

Fabricating large arrays of microwells with arbitrary dimensions and filling them using discontinuous dewetting