Lab on a Chip
Lab on a Chip (LOC) is a form of micro-analytic processing referred to as microfluidics - a type of engineered fluid management on a micro scale which promises to improve diagnostics and research. These techniques are also referred to as "miniaturized total analytic systems" or µTAS. These techniques were first developed by the semi-conductor industry and later expanded by the micro-electromechanical systems field. 
Microfluidic assays may ultimately end with a visual end-point. The first visual assays were chemotactic studies, monitoring the migration of macrophages toward a chemoattractant. These were developed by Stephen Boyden and the contraption developed for the analysis was referred to as the Boyden chamber or the Transwell Assay. Further enhancements led to the development of the Zigmond Chamber - a microfluidic device, the Dunn Chamber and the Insall Chamber.
LOC's are mostly manufactured via photolithography. The physical chip devices have been constructed from an array of materials including silicone and glass in "clean room" environments resulting in set of micro-channels etched or molded into a material. Polydimethylsiloxane (PDMS) is currently the material du jour due to a number of compelling factors - it's cheap, it's easy to set-up, it's hydrophillic surfaces are easily "tuned", it's bonding capabilities to dissimilar materials may be achieved reversibly or irreversibly, and lastly it's elasticity, which is important for "valving" and "actuation". While PDMS enjoys many benefits, it has it's drawbacks - including adsorption of solute, leaching of uncrosslinked oligomers, and microevaporation of fluid due the porosity of the matrix. Other materials such as thermoplastics, paper, and wax have situation specific use cases.
Microfluidic flow occurs primarily through electroosmotic flow but also pressure drive flow via micro-pumping mechanisms. LOC's function through the phased introduction of reagents into a matrix of micro-flow channels resulting in a qualitative or quantitative determination.
LOCs often times replicate the same capability as macro-scale assays which may have resulted in their limited use. However, the size and portability of these devices does have compelling advantages and in some instances they are the only possible solution. µTAS systems already in use, such as home use pregnancy tests and/or glucometers, have enjoyed great acceptance and usage by the public. Sackmann et al group these devices into 3 broad categories: diagnostic devices for low resource settings, rapid processing of biofluids for research and clinical applications, and more physiologically relevant in vitro models for drug discovery, diagnostics, and research applications. Examples of which include ELISA-like assays for HIV, purification of neutrophils, and in vitro simulation of organs to wit "organ on a chip" for drug development, respectively.
µTAS systems are also showing promise in non-invasive diagnosis of cancers that are difficult to detect. He et al have shown that microfluidic circuits can effectively isolate exosomes from plasma samples of patients with non-small cell lung cancer (NSCLC). The exosomes are bound by antibody for insulin growth factor receptor (IGF-1R) attached to micro-magnetic spheres allowing for isolation and identification, followed by lysis and determination by immunofluorescence of protein contents. This same process, known as "liquid biopsy", may prove equally as sensitive and specific for other epithelial neoplasms which also produce exosomes with surface IGF-1R, i.e. squamous cell carcinoma, etc., possibly providing a means for early detection of occult neoplasia.
- to reduce the sample volume substantially
- to reduce the cost of reagents and maximize information gleaned from precious samples
- to provide gains in scalability for screening applications and batch sample processing analogous to multi-well plates
- to provide the investigator with substantially more control and predictability of the spatio-temporal dynamics of the cell microenvironment
- they have been shown to be sensitive and specific, but also relatively quick in determination.
- faster analysis
- compact size
- parallelization allowing for high-throughput analysis
- low fabrication cost
- safe platform for chemical, biologic, and radioactive studies
These devices are capable of performing qualitative and quantitative analyses without the need for equipment with a large footprint. More specifically, with further development, microfluidics holds the promise of providing the capability to perform analyses in context-specific settings without the need for large sample volumes nor the wait for determination. Lab on a Chip, as a platform, could become a major component in the further development of wearable devices, coupled to devices for connectivity, capable of communicating with personal health records or in an institutional setting, with electronic healthcare records.
Some of the disadvantages of LOCs are:
- novel technology and therefore not yet fully developed
- physical and chemical effects—like capillary forces, surface roughness, chemical interactions of construction materials on reaction processes—become more dominant on small-scale. This can sometimes make processes in LOCs more complex than in conventional lab equipment
- detection principles may not always scale down in a positive way, leading to low signal to noise ratios
- although the absolute geometric accuracies and precision in micro-fabrication are high, they are often rather poor in a relative way, compared to precision engineering for instance.
There are numerous existing and potential applications for LOC in healthcare informatics as components of clinical integration and innovation. The data from these determinations could be easily incorporated into PHR and EHR databases as highly structured data embedded on the chip. Examples include:
- At home pregnancy tests
- Chemotaxis assays
- Organ on a Chip (liver, kidney, muscle, brain)
- Tumor on a Chip
- Non-invasive cancer screening - "Liquid biopsy"
- Serum chemistry and hematology determinations
- Serum toxicology screening
- Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature. 2014 Mar 13;507(7491):181–9.
- Boyden S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. The Journal of experimental medicine. 1962;115(3):453–66.
- Zigmond S.H. (1977). "Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors". J. of Cell Biology 75 (2): 606–616.
- Zicha D., Dunn G.A., Brown A.F. (1991). "A new direct-viewing chemotaxis chamber.". J Cell Sci 99: 769–75.
- 1. Muinonen-Martin AJ, Knecht DA, Veltman DM, Thomason PA, Kalna G, Insall RH. Measuring chemotaxis using direct visualization microscope chambers. Methods Mol Biol. 2013;1046:307–21.
- Lab-on-a-chip - Wikipedia, the free encyclopedia [Internet]. [cited 2014 Oct 27]. Available from: http://en.wikipedia.org/wiki/Lab-on-a-chip
- Microfluidics and microfluidic devices: a review | Elveflow microfluidic instruments [Internet]. [cited 2014 Oct 27]. Available from: http://www.elveflow.com/microfluidic-reviews-and-tutorials/microfluidics-and-microfluidic-devices-a-review.
- 1. Microfluidic Flow. Fundamentals of Microfluidics and Lab on a Chip for Biological Analysis and Discovery [Internet]. CRC Press; 2010 [cited 2014 Oct 27]. p. 47–86. Available from: http://dx.doi.org/10.1201/b15110-4
- M. He, J. Crow, M Roth, Y. Zeng and A. K. Godwin, Lab Chip, 2014. Manuscript accepted for publication. DOI: 10.1039/C4LC00662C
Submitted by David M. H. Lambert