Lab-on-a-chip

Source: Wikipedia, the free encyclopedia.
This article is about the technology. For the journal, see Lab on a Chip (journal).

A lab-on-a-chip (LOC) is a device that integrates one or several

microelectromechanical systems (MEMS) devices and sometimes called "micro total analysis systems" (µTAS). LOCs may use microfluidics
, the physics, manipulation and study of minute amounts of fluids. 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.

History

Microelectromechanical systems chip
, sometimes called "lab on a chip"

After the invention of

microelectromechanical systems
(MEMS) era 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 1979 by S.C. Terry at Stanford University.[2][3] However, only at the end of the 1980s and beginning of the 1990s did the LOC research start to seriously grow as a few research groups in Europe developed micropumps, flowsensors and the concepts for integrated fluid treatments for analysis systems.[4]
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 additional cleaning and separation steps.

A big boost in research and commercial interest came in the mid-1990s, when µTAS technologies turned out to provide interesting tooling for

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 systems to aid in the detection of biological and chemical warfare
agents. 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 chemical analysis, environmental monitoring, medical diagnostics and cellomics, but also in synthetic chemistry such as 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 and analysis,[5] and nano-sensors, might become feasible, allowing new ways of interaction with biological species and large molecules. Many books have been written that cover various aspects of these devices, including the fluid transport,[6][7][8] system properties,[9] sensing techniques,[10] and bioanalytical applications.[11][12]

The size of the global lab on chip market was estimated at US$5,698 million in 2021 and is projected to increase to US$14,772 million by 2030, at a CAGR of 11.5% from 2022 to 2030 [13]

Chip materials and fabrication technologies

The basis for most LOC fabrication processes is

injection molding and embossing. The demand for cheap and easy LOC prototyping resulted in a simple methodology for the fabrication of PDMS microfluidic devices: ESCARGOT (Embedded SCAffold RemovinG Open Technology).[15] This technique allows for the creation of microfluidic channels, in a single block of PDMS, via a dissolvable scaffold (made by e.g. 3D printing).[16]
Furthermore, the LOC field more and more exceeds the borders between lithography-based microsystem technology, nanotechnology and precision engineering. Printing is considered as a well-established yet maturing method for rapid prototyping in chip fabrication.[17]

The development of LOC devices using printed circuit board (PCB) substrates is an interesting alternative due to these differentiating characteristics: commercially available substrates with integrated electronics, sensors and actuators; disposable devices at low cost, and very high potential of commercialization. These devices are known as Lab-on-PCBs (LOPs).[18] The following are some of the advantages of PCB technology: a) PCB-based circuit design offers great flexibility and can be tailored to specific demands.[19] b) PCB technology enables the integration of electronic and sensing modules on the same platform, reducing device size while maintaining accuracy of detection. c) The standardized and established PCB manufacturing process allows for cost-effective large-scale production of PCB-based detection devices. d) The growth of flexible PCB technology has driven the development of wearable detection devices. As a result, over the past decade, there have been numerous reports on the application of Lab-on-PCB to various biomedical fields. e) PCBs are compatible with wet deposition methods, to allow for the fabrication of sensors using novel nanomaterials (e.g. graphene).[20]

Advantages

LOCs may provide advantages, which are specific to their application. Typical advantages[10] are:

  • low fluid volumes consumption (less waste, lower reagents costs and less required sample volumes for diagnostics)
  • faster analysis and response times due to short diffusion distances, fast heating, high surface to 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 integration of much 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[21]
  • part quality may be verified automatically[22]
  • safer platform for chemical, radioactive or biological studies because of integration of functionality, smaller fluid volumes and stored energies

Disadvantages

The most prominent disadvantages[23] of labs-on-chip are:

  • The micro-manufacturing process required to make them is complex and labor-intensive, requiring both expensive equipment and specialized personnel.[24] It can be overcome by the recent technology advancement on low-cost 3D printing and laser engraving.
  • The complex fluidic actuation network requires multiple pumps and connectors, where fine control is difficult. It can be overcome by careful simulation, an intrinsic pump, such as air-bag embed chip, or by using a centrifugal force to replace the pumping, i.e. centrifugal micro-fluidic biochip.
  • Most LOCs are novel proof of concept application that are not yet fully developed for widespread use.[25] More validations are needed before practical employment.
  • In the microliter scale that LOCs deal with, surface dependent effects like capillary forces, surface roughness or chemical interactions are more dominant.[25] This can sometimes make replicating lab processes in LOCs quite challenging and 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.

Global health

Lab-on-a-chip technology may soon become an important part of efforts to improve

assays
with no laboratory support.

Global challenges

For the chips to be used in areas with limited resources, many challenges must be overcome. In developed nations, the most highly valued traits for diagnostic tools include speed, sensitivity, and specificity; but in countries where the healthcare infrastructure is less well developed, attributes such as ease of use and shelf life must also be considered. The reagents that come with the chip, for example, must be designed so that they remain effective for months even if the chip is not kept in a

recyclability
in mind as they choose what materials and fabrication techniques to use.

Examples of global LOC application

One of the most prominent and well known LOC devices to reach the market is the at home pregnancy test kit, a device that utilizes paper-based microfluidics technology. Another active area of LOC research involves ways to diagnose and manage common

CD4+ T lymphocytes in a person's blood is an accurate way to determine if a person has HIV and to track the progress of an HIV infection [citation needed
]. At the moment, flow cytometry is the gold standard for obtaining CD4 counts, but flow cytometry is a complicated technique that is not available in most developing areas because it requires trained technicians and expensive equipment. Recently such a cytometer was developed for just $5.[30] Another active area of LOC research is for controlled separation and mixing. In such devices it is possible to quickly diagnose and potentially treat diseases. As mentioned above, a big motivation for development of these is that they can potentially be manufactured at very low cost.[21] One more area of research that is being looked into with regards to LOC is with home security. Automated monitoring of volatile organic compounds (VOCs) is a desired functionality for LOC. If this application becomes reliable, these micro-devices could be installed on a global scale and notify homeowners of potentially dangerous compounds.[31]

Plant sciences

Lab-on-a-chip devices could be used to characterize pollen tube guidance in Arabidopsis thaliana. Specifically, plant on a chip is a miniaturized device in which pollen tissues and ovules could be incubated for plant sciences studies.[32]

See also

References

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  2. doi:10.1038/scientificamerican0483-44
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  3. S2CID 21971431
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  4. ^ A.Manz, N.Graber and H.M.Widmer: Miniaturized total Chemical Analysis systems: A Novel Concept for Chemical Sensing, Sensors and Actuators, B 1 (1990) 244–248.
  5. PMID 24185478
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  6. ISBN 978-0-521-11903-0
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  7. ^ Bruus, H. (2007). Theoretical Microfluidics.
  8. Springer Verlag
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  9. ^ Tabeling, P. Introduction to Microfluidic.
  10. ^
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  11. ^ Berthier, J.; Silberzan, P. Microfluidics for Biotechnology.
  12. ^ Gomez, F.A. Biological Applications of Microfluidics.[ISBN missing]
  13. ^ "Acumen Research and Consulting". Retrieved 23 May 2023.
  14. S2CID 225360332
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  15. PMID 27709002
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  16. ^ Vittorio Saggiomo (17 July 2015). "Simple fabrication of complex microfluidic devices (ESCARGOT)". Archived from the original on 2021-12-22 – via YouTube.
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  18. PMID 33578984
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  21. ^
    PMID 24404077
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  23. doi:10.1016/S0924-0136(02)00415-6
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  24. doi:10.1016/j.jmatprotec.2005.06.027
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  25. ^
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  26. S2CID 4429504
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  29. ^ "Global HIV & AIDS statistics — 2019 fact sheet".
  30. ^ Ozcan, Aydogan. "Diagnosis in the palm of your hand". Multimedia::Cytometer. The Daily Bruin. Retrieved 26 January 2015.
  31. doi:10.1038/micronano.2015.39
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  32. S2CID 12989263
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Further reading

Books
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