Lab-on-a-chip

Lab-on-a-chip (LOC) is a term for devices that integrate (multiple) laboratory functions on a single chip of only millimeters to a few square centimeters in size and that are capable of handling extremely small fluid volumes down to less than pico liters. Lab-on-a-chip devices are a subset of MEMS devices and often indicated by "Micro Total Analysis Systems" (µTAS) as well. Microfluidics is a broader term that describes also mechanical flow control devices like pumps and valves or sensors like flowmeters and viscometers. However, strictly regarded "Lab-on-a-Chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis. The term "Lab-on-a-Chip" was introduced later on when it turned out that µTAS technologies were more widely applicable than only for analysis purposes.

History

After the discovery of microtechnology (~1958) for realizing integrated semiconductor structures for microelectronic chips, these lithography-based technologies were soon applied in pressure sensor manufacturing (1966) as well. Due to further development of these usually CMOS-compatibility limited processes, a tool box became available to create micrometre or sub-micrometre sized mechanical structures in silicon wafers as well: the Micro Electro Mechanical Systems (MEMS) era (also indicated with Micro System Technology - MST) had started.

Next to pressure sensors, airbag sensors and other mechanically movable structures, fluid handling devices were developed. Examples are: channels (capillary connections), mixers, valves, pumps and dosing devices. The first LOC analysis system was a gas chromatograph, developed in 1975 by S.C. Terry - Stanford University. However, only at the end of the 1980’s, and beginning of the 1990’s, the LOC research started to seriously grow as a few research groups in Europe developed micropumps, flowsensors and the concepts for integrated fluid treatments for analysis systems. These µTAS concepts demonstrated that integration of pre-treatment steps, usually done at lab-scale, could extend the simple sensor functionality towards a complete laboratory analysis, including e.g. additional cleaning and separation steps.

A big boost in research and commercial interest came in the mid 1990’s, when µTAS technologies turned out to provide interesting tooling for genomics applications, like capillary electrophoresis and DNA microarrays. A big boost in research support also came from the military, especially from DARPA (Defense Advanced Research Projects Agency), for their interest in portable bio/chemical warfare agent detection systems. The added value was not only limited to integration of lab processes for analysis but also the characteristic possibilities of individual components and the application to other, non-analysis, lab processes. Hence the term "Lab-on-a-Chip" was introduced.

Although the application of LOCs is still novel and modest, a growing interest of companies and applied research groups is observed in different fields such as analysis (e.g. chemical analysis, environmental monitoring, medical diagnostics and cellomics) but also in synthetic chemistry (e.g. rapid screening and microreactors for pharmaceutics). Besides further application developments, research in LOC systems is expected to extend towards downscaling of fluid handling structures as well, by using nanotechnology. Sub-micrometre and nano-sized channels, DNA labyrinths, single cell detection an analysis and nano-sensors might become feasible that allow new ways of interaction with biological species and large molecules.

Chip materials and fabrication technologies

The basis for most LOC fabrication processes is lithography. Initially most processes were in silicon, as these well-developed technologies were directly derived from semiconductor fabrication. Because of demands for e.g. specific optical characteristics, bio- or chemical compatibility, lower production costs and faster prototyping, new processes have been developed such as glass, ceramics and metal etching, deposition and bonding, PDMS processing (e.g., soft lithography), thick-film- and stereolithography as well as fast replication methods via electroplating, injection molding and embossing. Furthermore the LOC field more and more exceeds the borders between lithography-based microsystem technology, nano technology and precision engineering.

Advantages of LOCs

LOCs may provide advantages, very specifically for their applications. Typical advantages are:

low fluid volumes consumption, because of the low internal chip volumes, which is beneficial for e.g. environmental pollution (less waste), lower costs of expensive reagents and less sample fluid is used for diagnostics
higher analysis and control speed of the chip and better efficiency due to short mixing times (short diffusion distances), fast heating (short distances, high wall surface to fluid volume ratios, small heat capacities)
better process control because of a faster response of the system (e.g. thermal control for exothermic chemical reactions)
compactness of the systems, due to large integration of functionality and small volumes
massive parallelization due to compactness, which allows high-throughput analysis
lower fabrication costs, allowing cost-effective disposable chips, fabricated in mass production
safer platform for chemical, radioactive or biological studies because of large integration of functionality and low stored fluid volumes and energies

Disadvantages of LOCs

novel technology and therefore not fully developed yet
physical effects like capillary forces and chemical effects of channel surfaces become more dominant and make LOC systems behave differently and sometimes more complex than conventional lab equipment
detection principles may not always scale down in a positive way, leading to low signal to noise ratios

External links

Laboratories

Companies

Micronit Microfluidics - Design, development and fabrication of glass microfluidic chips and lab-on-a-chip devices
The Dolomite Centre Ltd - Design led microfluidic technology and applications development and fabrication
miniFAB Pty Ltd - The micro, nano, bio company
Scientific Consultants
Cellix Ltd. - Microfluidics biochips, instrumentation and analysis software for cell based assays.
MicroPlumbers Microsciences LLC - Microdevice R&D consultants: biochemical, immunological, & optical sensors; fluid motion control.

Journals

Conferences

ASME ICNMM The 4th ASME Intl. Conference on Nanochannels, Microchannels and Minichannels - Limerick, Ireland - Jun 19-21, 2006
GRC: MEMS Technology & Biomedical Applications - Gordon Research Conference - New London, CT, USA - Jun 25-30, 2006
IMRET 9 - 9th Intl. Conference on Microreaction Technology - Berlin, Germany - Sep 6-8, 2006
µTAS 2006 - 10th Intl. Conference on Miniaturized Systems for Chemistry and Life Sciences - Tokyo, Japan - Nov 5-9, 2006
NanoTech '06 - 10th European Conference on Micro & Nanoscale Technologies for the Biosciences - Montreux, Switzerland - Nov 14-16, 2006
MSB 2007 - 20th Intl. Symposium on Microscale Bioseparations - Vancouver, Canada - Jan 13-18, 2007
MEMS 2007 - 20th IEEE Intl. Conference on Micro Electro Mechanical Systems - Kobe, Japan - Jan 21-25, 2007
Transducers '07 - 14th Intl. Conference on Solid-State-Sensors, Actuators and Microsystems - Lyon, France - Jun 10-14, 2007
GRC: Physics & Chemistry Of Microfluidics - Gordon Research Conference - Waterville Valley, USA - Jul 15-20, 2007

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