Highlights

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Research Highlights

Narrow sample channel injectors

Normal injection modes for chip-based CE systems involve the use of cross, tee or double-tee structures with uniform channel geometries at the injection intersection. Chao-Xuan Zhang and Andreas Manz at Imperial College of Science, Technology and Medicine (UK) have recently reported the use of narrow sample injection channels to address improvements in efficiency, resolution and sensitivity. By reducing the sample channel width down to 5 μm (with a constant separation channel width of 50 μm) the authors demonstrate both resolution and sensitivity improvements through the use of both narrow sample channel (NSC) cross and tee injectors without any leakage control. Additionally, the use of NSC tee injection schemes allows the number of reservoirs in multiplexed systems to be reduced to the theoretical limit of n + 2, where n is the number of parallel CE systems.Analytical Chemistry, 2001, 73, 2657

Time-resolve resonance Raman spectroscopy on chip

The primary driver for downsizing analytical techniques should always involve the idea of improving performance. For example, the miniaturisation of electrophoretic separation methods has primarily occurred due to the significant reductions in analysis times and improvements in separation efficiency. Richard Mathies and Duohai Pan from the University of California, Berkeley, have used this general concept to good effect by utilizing the control aspects of microfluidics to facilitate the spectroscopic analysis of intermediates on a microsecond timescale.

The authors report the use of microfluidic chips for time-resolved resonance Raman studies on the lumirhodopsin (Lumi) and metarhodopsin I (Meta I) photointermediates in the rhodopsin bleaching process. Studies were focused on elucidating the structure of the chromophore in each species and changes in protein-chromophore interaction. Flow of sample through microchannels afforded the facile study of rhodopsin’s microsecond to millisecond photointermediates without the use of excessive pigment by matching the width of the flow channel with the confocal profile of the excitation beam in a micro-probe system. Specifically, two displaced laser beams are used to initiate rhodopsin photochemistry and subsequently measure the Raman spectrum of the intermediate. Through control of both volumetric flow rates and spatial separation of the pump and probe beams time delays ranging from several hundred nanoseconds to several milliseconds can be achieved (see Fig. 1).

The authors use this elegant approach to obtain high quality Raman spectra of the Lumi and Meta I intermediates and further elucidate how hydrogen bonding of the protonated Schiff base changes as the activating protein conformational changes occur.

Fig. 1 Time-resolved resonance Raman microchip apparatus. The two cylindrically focused beams are displaced along the flow direction. The beam separation and flow velocity determine the time delay. (Adapted with permission. Copyright 2001, The American Chemical Society.)

Biochemistry, 2001, 40, 7929

Electromagnetic micromotors

Essential to the successful implementation of multi functional lab-on-a-chip technologies is the development of cost effective miniaturized actuation systems that provide controlled fluid manipulation through microfluidic networks. Mladen Barbic and co-workers at the University of California, San Diego, have addressed this need by creating a simple and inexpensive electromagnetic micromotor. The micromotor consists of two primary parts: microcoils and magnetic microtips as stator actuator elements and magnetic particles as microrotors. The three phase microcoils are remotely located (50 μm from the rotor) and drive rotation of a 40 μm long, 1 μm diameter nickel particle within a fluid environment. The authors demonstrate the basic functioning of the microrotor in glycerol and aqueous media and report maximum rotational speeds of 250 rpm. Although only preliminary results are presented, the authors suggest possible microstirrer, microvalve and microfilter applications.Applied Physics Letters, 2001, 79, 1399

Low temperature chip bonding

To date the vast majority of microchannel chip devices have been fabricated from glass, silicon, quartz or polymeric materials. Glass and quartz have proved particularly attractive substrate materials since they possess excellent optical properties (allowing facile interrogation and detection of sample within the microfluidic environment). Furthermore, bulk and surface micromachining methods are well-established and easily transferable from the semiconductor industries. In practice, a common problem faced by many researchers is efficient bonding of structured substrates to create a sealed fluidic structure. Conventionally, high temperature methods have been used to effect bonding, but these are often inefficient and require multiple bonding attempts to provide the required seal. James Landers and co-workers at the University of Virginia have recently reported a novel method for bonding substrates at room temperature. They exploit a UV curable glue which has low viscosity, high adhesion, good transparency and is non-conducting. Through the use of glue control wells and guide channels the glue is introduced between the two substrates and cured to initiate pre-bonding. The addition and subsequent curing of more glue in the vicinity of the microchannels is then used to fully bond the device. The authors then tested chip fidelity via free-zone and gel electrophoretic separations. Results demonstrate both equivalent performance with respect to conventionally bonded glass CE chips and facile reconditioning of channels.

A particularly interesting consequence of the bonding method is the ability to disassemble, clean and reassemble devices that are blocked. Disassembly is effected by simply heating the entire device to temperatures above 500 °C. This fact allied with the ability to efficiently bond dissimilar substrate materials will surely make the general approach extremely attractive for chip fabrication in many research laboratories.

Electrophoresis, 2001, 22, 3924

3-Dimensional microfluidic switches

The development of reliable, low-cost microvalve and microswitch technology is key to the successful creation of highly integrated fluidic circuits. This will be particularly important when processing heterogeneous biological media or ‘real world’ samples that may block or damage conventional valves. George Whitesides and co-workers at Harvard University have recently described controllable laminar flow through a three-dimensional elastomeric microstructure formed by two tangentially connected microchannels (Fig. 2). Flow manipulation is achieved via two basic mechanisms. First, flow across channel intersections is found to be sensitive to the aspect ratio of the channels. If the aspect ratio is high fluid moving along a given channel moves straight through the intersection without extensive fluid exchange. Conversely, if the aspect ratio is low then most of fluid transfers between channels. Since the authors have chosen an elastomeric substrate material, the application external pressure provides a simple way of altering aspect ratios and therefore controlling flow in real time. Secondly, the authors note that the flow direction of an individual stream in a multiphase laminar flow is sensitive to the lateral position of the stream within the channel. This position can be simply controlled by injection of additional streams of fluid into a given channel. Although early in development, elastomeric switches of this kind offer a high degree of operational and configurational flexibility, and through external actuation may allow highly efficient manipulation of complex flow streams.

Fig. 2 Fabrication scheme for tμc. (Adapted with permission. Copyright 2001, The American Chemical Society.)

Analytical Chemistry, 2001, 73, 4682

Monolithic mixers

When performing microfluidic analyses that include chemical or biological reactions a primary issue of concern is the rate and degree to which mixing of reactants can be achieved. Since a lack a turbulence is characteristic of most microfluidic systems, mixing is almost always effected by diffusional processes alone. There have been many different approaches to improving mixing times and efficiencies, with the majority relying on maximizing the contact area between the two phases of interest. This has resulted in the fabrication of many complex microfabricated mixer devices (for example see ‘Picoliter-volume mixer’ in Lab on a Chip, Issue 1, Research Highlights, p. 13N). Jean Fréchet and colleagues in the Department of Chemistry at UC Berkeley have recently proposed an alternative approach to micromixing, through the use of porous polymer monoliths. Using a UV initiated polymerisation process the authors report formation of polymer monoliths in well defined regions of microchannels. The monoliths consist of an array of interconnected microglobules and pores that have a wide variation in their porous properties and morphology. This makes the entire structure highly efficient at promoting lateral mixing. To test this hypothesis the authors used the resulting structures (internal volumes of 45 nL) to mix aqueous solutions at a variety of flow rates. By varying both pore size and pore volume complete mixing could be achieved over a mixing length of approximately 5 mm at flow velocities of 850 μm s⁻¹. The simple structure and low flow resistance of the monoliths, combined with the ability to tune surface properties, will undoubtedly be of great use when designing multifunctional fluidic devices for complex reaction chemistries.Electrophoresis, 2001, 22, 3959

Non-fouling surface coatings

A fundamental consequence of downscaling reaction vessels or separation columns is an increase in the surface-to-volume ratio (S/V). This trend is used to good effect in chip-based capillary electrophoresis, where an increasing S/V provides the dominant route to improved heat dissipation, which in turn improves attainable separation efficiencies. Unfortunately, as vessel size is reduced the surface plays an increasingly dominant role in defining molecular behaviour. Within microfluidic systems interaction of device surfaces with the chemical environment leads to a number of unique problems. This is especially significant when manipulating biological samples. For example, proteins, enzymes and nucleic acids have strong tendencies to interact with and adsorb onto synthetic surfaces. Apart from reducing analyte concentrations, conditioning layers formed at these surfaces will almost certainly lead to non-optimal device functioning. Yael Hanein and co-workers at the University of Washington, Seattle, have addressed this problem by describing photolithographic methods for the patterning of a poly(ethylene glycol) (PEG)-like polymer onto silicon surfaces. The coating has excellent non-fouling properties and good adhesion to many materials including silicon, glass, gold and platinum. The authors report good spatial control over polymeric deposition and demonstrate efficient patterning of proteins and cell-cultures. Furthermore, initial studies demonstrate that metallic elements, such as electrodes, may be efficiently protected from protein and cell adhesion without compromising electrode conductivity. The authors hope to develop the method as a useful tool in engineering surface properties within a wide range of BioMEMS.Sensors & Actuators B, 2001, in the pressAndrew J. de Mello

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