A Brief Insight on Lab-on-a-Chip (LOC)

What it is, the past, and the future August 13th, 2021

By: Ryan (Yurui) Wang, Dev Purswani

(Intro, Biology, and Focus on Covid-19, Chemistry is done by Ryan, and how is it made, Future advancements is done by Dev)

Introduction
A Lab-on-a-chip is an array of devices with the feature of automating and merging
techniques found in a lab into a system that fits in a chip. These are chips with varying sizes with
goals to achieve automation and high-throughput screening for lab results.1

To begin, the real development of

Lab-on-a-Chips began with the microtechnologies
developed during the American Apollo Program,
where microfabrication technologies were used on
the first Lab-on-a-Chip system, created in 1979 at
Stanford University by S.C. Terry.2 It was used to
analyze gas. The two decades to follow saw the
massive gains in the research for Lab-on-a-chip as
microfluidics and other microelectronic fabrication
technologies were advancing rapidly. In the
mid-1990s, researchers found that the Micro Total
Analysis Systems (µTAS) was able to conduct research for genomic purposes, such as DNA
analysis, still a huge role today for Lab-on-a-Chips. Nowadays, Lab-on-a-chip technology plays
a prodigious role in research.

Applications of Lab-on-a-Chip Technology

Lab-on-a-chip is predominantly used in the research process in the fields of Biology and
Chemistry.

Biology
For the field of biology, applications
include cellular biology, molecular biology,
as well as proteomics3, and has made
significant advances towards global health
research as a whole. Lab-on-a-chip
technology is used for testing, from
pregnancy tests to testing for infectious
1
Volpatti, Lisa R., and Ali K. Yetisen. “Commercialization of Microfluidic Devices.” Trends in Biotechnology, vol. 32, no. 7,
2014, pp. 347–350., doi:10.1016/j.tibtech.2014.04.010.
2
Terry, S.C., et al. “A Gas Chromatographic Air Analyzer Fabricated on a Silicon Wafer.” IEEE Transactions on Electron
Devices, vol. 26, no. 12, 1979, pp. 1880–1886., doi:10.1109/t-ed.1979.19791.
3
Team, Elveflow. “Introduction to Lab-on-a-Chip 2020: Review, History and Future.” Elveflow, Elvesys, 22 Apr. 2021,
www.elveflow.com/microfluidic-reviews/general-microfluidics/introduction-to-lab-on-a-chip-review-history-and-future/.
viruses, and proves to be a cheap and reliable method for third world countries. At the same time,
LOC is used for research processes, including DNA & RNA sequencing, and is done with
extreme precision. LOCs sequences genomes thousands of times faster than traditional methods4,
thus proving effective and efficient.

Special Focus: Covid-19 testing with Lab-on-a-Chip

Amidst the Covid-19 pandemic, fast, and accurate testing are crucial to the successful
containment of the virus. The current method of testing is quite slow and costly. Sample usually
takes time to be sent into labs for further testing, and
patients can expect 1-3 days for testing results to come
back.5 However, researchers across the world are now
attempting to use the Lab-on-a-chip technology to
initiate fast, and cheap testing that would benefit the
world on the containment of the virus.

There are two major methods of testing for

covid, PCR and NAAT. Currently, it has been proven
that the PCR, or polymerase chain reaction test could
be initiated on the Lab-on-a-chip, which provides the possibility of testing for Covid.

The process works like this: The RNA from the original virus is extracted and then
purified and converted to DNA. The DNA, a more stable variant of its genetic sequence. This
ultimately preserves characteristic parts of the coronavirus’ genetics. The DNA is then replicated
millions of times, and then fluorescent dye molecules would now bind the virus DNA, and make
it glow. If the sample contains viral DNA, it would glow up, meaning positivity of the
Coronavirus. If it is covid-negative, it would stay dim.6

The Lab-on-a-chip may provide many advantages to PCR testing. Firstly, it requires low
fluid volumes consumption, and this reduces the use of expensive reagents and less sample fluid
would be used for diagnostics. Secondly, there are shorter mixing times and faster heating times
during the replication and dying stage, thus would prove to be more efficient. Lastly, there are
lower fabrication costs for the Lab-on-a-chip, thus it could be fabricated in mass production.
Thus, the Lab-on-a-chip could be a great way to allow fast, cheap testing for countries with
troubles during the testing stage, and thus could benefit the world’s war against this virus.

4
Team, Elveflow. “Introduction to Lab-on-a-Chip 2020: Review, History and Future.” Elveflow, Elvesys, 22 Apr. 2021,
www.elveflow.com/microfluidic-reviews/general-microfluidics/introduction-to-lab-on-a-chip-review-history-and-future/.
5
Canada, Public Health Agency of. “Government of Canada.” Canada.ca, / Gouvernement Du Canada, 13 July 2021,
www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/symptoms/testing/diagnosing.html#:~:text=r
esults%20are%20generally%20provided%20in,1%20to%203%20days.
6
“How Scientists Test for Covid-19.” Fred Hutch, www.fredhutch.org/en/research/diseases/coronavirus/serology-testing.html.
Chemistry
The first LOCs were used for the
analysis of gases, which fall into the
field of Chemistry.

The chip was not called a lab-on-a-chip,

specifically it was an advanced gas
chromatograph(GC)2. This GC has a
powerful chip with a battery-powered
microcomputer hence being called a
lab-on-a-chip. It’s size would make it a
portable monitor for lightweight spacecraft applications. As all other chromatographs this
miniature version has a carrier gas supply,sample injection system,separator column and output
detector as shown in Figure 1. One of the most significant aspects of these GC’s is it’s ability to
detect and differentiate between various gases. With this lab-on-a-chip researchers can control
the sequencing of the GC operation and analyze the detector output signal. A complete gas
analysis system can be conducted in a package smaller than what would be possible using the
traditional way. 7

How is it made?

There are mainly 5 materials used to fabricate a lab-on-a-chip and they can vary due to its
purposes and usages. PDMS(poly-di-methyl-siloxane) is a material that research labs use for
lab-on-a-chip prototyping. It is a transparent and flexible elastomer and is commonly used as it is
easy and cheap to fabricate by casting. LOC’s made by PDMS show severe limitations for
industry production as the material is subject to aging. This is because PDMS absorbs
hydrophobic molecules and it is difficult to integrate the electrode in this chip. Another material
that is used to fabricate LOC’s are

Thermoplastic polymers or PMMA PS for short and these are tricky and more expensive
to produce than PDMS. Thermoplastics are used for fabrication of Loc’s because they are
transparent but also compatible with micrometer-sized lithography and are more chemically inert
than PDMS. Thermoplastic LOC’s are good candidates for the industrialization of chips as it is
possible to integram microelectrodes into them. 8

Glass is another material used to produce LOC’s as it is transparent and chemically inert
with a range of chemical surface treatments and reproducible electrode integration. The

7
Terry, S.C., et al. “A Gas Chromatographic Air Analyzer Fabricated on a Silicon Wafer.” IEEE Transactions on Electron
Devices, vol. 26, no. 12, 1979, pp. 1880–1886., doi:10.1109/t-ed.1979.19791.
8
Team, Elveflow. “Introduction to Lab-on-a-Chip 2020: Review, History and Future.” Elveflow, Elvesys, 22 Apr. 2021,
www.elveflow.com/microfluidic-reviews/general-microfluidics/introduction-to-lab-on-a-chip-review-history-and-future/.
fabrication of glass LOC’s require clean rooms and the knowledge of microfabrication thus
making it hard for all research labs to be able to produce them.

Lastly, Silicon is the main material used for producing LOC’s and the first lab-on-a-chip
was built from this material. Researchers do not use silicon for labs-on-a-chip because silicon is
expensive and the electrical conductivity of silicon makes it hard to use for any lab-on-a-chip
operations requiring high voltage, an example being electrophoresis. Silicon may be a choice for
the industrialization of demanding lab-on-a-chip applications because of the high precision of
silicon microfabrication and the ability to integrate microelectrodes and electronics on the same
chip.

Future Advancements:

The future looks bright in the healthcare industry as there are many applications for
labs-on-a-chip devices. Lab-on-chips are now used as diagnostic chips for Bipolar Disorder,
Cancer and Male Fertility.9 LOC’s are now being used to monitor blood levels of patients with
bipolar disorder. Not only that, the traditional way to determine someone's sperm count has been
completely changed by LOC’s that determine the sperm concentration by using electrical
impedance measurements. These chips can rapidly and accurately count sperm cells and identify
fertile and sub-fertile concentrations allowing the easy indication of male fertility. Also early
diagnosis of intestinal cancer is possible. A disposable LOC inspired nanophill that can detect
intestinal tumours.

9
Cheriyedath, Susha. "Health Applications of Lab-on-a-chip." News-Medical.net. 02 Feb. 2021. Web. 13 Aug. 2021,
https://www.azolifesciences.com/article/Health-Applications-of-Lab-on-a-Chip.aspx
Bibliography

Volpatti, Lisa R., and Ali K. Yetisen. “Commercialization of Microfluidic Devices.” Trends in
Biotechnology, vol. 32, no. 7, 2014, pp. 347–350., doi:10.1016/j.tibtech.2014.04.010.

Terry, S.C., et al. “A Gas Chromatographic Air Analyzer Fabricated on a Silicon Wafer.” IEEE
Transactions on Electron Devices, vol. 26, no. 12, 1979, pp. 1880–1886.,
doi:10.1109/t-ed.1979.19791.

Team, Elveflow. “Introduction to Lab-on-a-Chip 2020: Review, History and Future.” Elveflow,
Elvesys, 22 Apr. 2021,
www.elveflow.com/microfluidic-reviews/general-microfluidics/introduction-to-lab-on-a-chip-rev
iew-history-and-future/.

Canada, Public Health Agency of. “Government of Canada.” Canada.ca, / Gouvernement Du

Canada, 13 July 2021,
www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/symptoms/t
esting/diagnosing.html#:~:text=results%20are%20generally%20provided%20in,1%20to%203%
20days.

“How Scientists Test for Covid-19.” Fred Hutch,

www.fredhutch.org/en/research/diseases/coronavirus/serology-testing.html.

Cheriyedath, Susha. "Health Applications of Lab-on-a-chip." News-Medical.net. 02 Feb. 2021.

Web. 13 Aug. 2021,

https://www.azolifesciences.com/article/Health-Applications-of-Lab-on-a-Chip.aspx

Pictures:

https://agscientific.com/blog/2020/02/advances-in-lab-on-a-chip-technology-ionophores-enzyme
s-in-biosensors/