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Numbering up: The use of microreactors for nanomanufacturing
(Nanowerk Spotlight) Microscale reactor technology has tremendous advantage over conventional macro-scale or batch chemical processes, and offers versatility for a wide range of applications including chemical analyses, drug discovery, radiotracer synthesis, and the fabrication of engineered nanomaterials. Attention is currently focused on developing scaleable process regimes, using an approach engineers call 'numbering up'.
Microreactor technology is defined by a series of interconnected, functionally distinct channels formed on a planar surface, utilizing either hydrodynamic or electroosmotic flow (EOF) for pumping, with channel dimensions typically between 10-300 microns.
Because of the radical reduction in size and weight, microreactors exhibit unique advantages, including high surface area to volume ratio, ultra fast mixing, and narrowly distributed residence time. This precise control over key parameters creates a powerful tool; delivering improved selectivity, leading to increased yields and the ability to discriminate reaction enthalpy.
From left. Details of the microfluidic chip cartridge (MCC) and glass chip / O-ring seal arrangement. A photo of the assembled microreactor ready to connect to a power supply. (Source: Jim Clements)
Depending upon the intended application and chemical environment, microreactors can be manufactured in polymer, metal, quartz, silicon, ceramics or glass using a variety of fabrication techniques including photolithography, wet-etching, sand-blasting, micro-injection molding, laser ablation, and hot embossing.
Engineered Nanomaterials
Microreactors have potential for ‘greener’ methods of nanomaterial synthesis. Researchers from the University of Oregon, led by Professor James E. Hutchison, synthesized 1.4 – 1.5 nm gold particles in a microreactor, replacing the highly toxic conventional technique. In an effort to ‘number up’ this process, Hutchison is working with a team including Oregon Nanoscience and Microtechnologies Institute (ONAMI) to construct a reactor with millions of channels.
In a related effort, ONAMI launched an initiative with the Air Force Research Laboratory called SNNI (Safer Nanomaterials and Nanomanufacturing Initiative). SNNI has brought together engineers, biologists, materials scientists, and chemists (including Hutchison) to pioneer and develop new methods of manufacturing engineered nanoparticles.
To achieve this goal, a key mandate for SNNI is to "develop microreactors for efficient, scalable production of structurally-defined, functionalized nanoparticles."
PET Radiosynthesis
Another promising application is in miniaturized radiosynthesis. Positron emission tomography (PET) is a radiotracer imaging technique that provides quantitative information in vivo, used in clinical research and drug discovery. One useful radioisotope is 18F, with a half-life (t ½) of 109.7 minutes. Because syntheses must be conducted within 2-3 half-lives, there is a clear advantage in producing the radiotracer at point-of-use, and any reduction in reaction times could lead to enhanced specific activity, i.e. the PET ligand will have greater sensitivity in vivo.
Microreactors offer additional advantages including more efficient use of hot-cell space for producing multiple tracers, the use of less precursor and the reduced separation challenge to better manage costs.
In a recent cross-border collaboration (which included the U.S. National Institute of Health (NIH), the University of Hull in the U.K., CapiliX BV in The Netherlands, and NanoSciences, Inc.) the electrokinetic properties of [18F]fluoride ion were examined in an effort to develop a process using a glass, EOF-driven microreactor.
The basic micro-reactor design R1, with two flow restrictions to minimize hydrodynamic flow. At 500 V and 10mm height difference between ports 1 and 4, the EOF driven flow is 10x hydrodynamic flow. Channel cross section = 250 x 50 µm2. (Source: Jim Clements)
Utilizing a unique chip-docking design, the results to-date have been extremely promising. Efforts are now underway to design a method to retain the activity while stripping the water off so that the ‘naked’ [18F]fluoride ion can be used for subsequent labelling reactions… all of which can occur within the microreactor.
Summary
Overall, microreactors offer intriguing advantages for researchers and engineers. Higher selectivity, point-of-use or on-demand manufacturing, more efficient use of reagents and precursors, high throughput screening, and a ‘greener’ approach of nanomanufacturing are all key benefits of this emerging technology.
Because microreactor technology impacts such a wide range of scientific, manufacturing and engineering disciplines, one key to its successful adoption and development is through continued education: UC Irvine Extension is providing a forum for career professionals to stay informed of emerging technologies and advancements through its Intensive Seminar Program (ISP), the first of which is scheduled for September 15-16, 2006: "Nanotechnology: Applications and Opportunities".
By James T. Clements, Copyright Nanowerk LLC
Jim Clements is co-founder and Vice President of Business Development at NanoSciences, Inc. in California

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