Biotechnology Course: Analysis of Lab-on-a-Chip Technology

This essay provides a detailed overview of lab-on-a-chip (LOC) technology, which integrates laboratory synthesis and chemical analysis onto a handheld device. It discusses the advancements in microfluidics and nanofluidics that have enabled the development of LOC, highlighting its advantages such as reduced sample size, efficient reactions, and portability. The essay covers various aspects of LOC, including its manufacturing methods (soft lithography, micromachining, etc.), essential components (actuators, mixers, sensors), and applications in life sciences (DNA sequencing, protein crystallization). It also addresses the challenges associated with microfluidics, such as small volumes and complex operational control. Furthermore, the essay explores the future of microfluidics, focusing on its potential in DNA/RNA amplification, immunoassays, proteomics, cell biology, and chemistry, while emphasizing its cost-effectiveness, high parallelization, and reduced diagnosis time. Desklib offers this assignment solution and a wealth of other academic resources for students.

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LAB-ON-A-CHIP TECHNOLOGY
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Lab-on-a-chip Technology
Introduction
In the recent past, there have been advancements in molecular biology which has
enabled efficient and rapid analyses for active intervention in the domain of biological research,
management of diseases that are considered to be infectious, bio-defense, and food safety
among others. Additionally, with the introduction of microfluidics and nanotechnologies, new
abilities and capabilities have been enabled. Moreover, instrument sizes that are virtual for
point-of-care (POC) have also been enabled. The other things that have also come along with
the advancement in molecular biology are heightened sensitivity and new functionality. The
cost and time for the diagnostic techniques of conventional molecular have also reduced. This
essay will discuss Lab-on-a-chip, a considered to be a technology that allows operations that
have always required analysis of chemicals and laboratory synthesis to be done within a
handheld or portable device.
Microfluidics dates back to the 1990s during the period of the seminal paper by Andreas
Manz (Manz, 1990). The paper brought about an automated and integrated platform for
undertaking different analysis procedures. Since then, the advancement in microfluidics has
brought us closer to the realisation of the sample-in-answer-out platform vision (Jenkins &
Mansfied, 2013). Microfluidics received a significant boost when soft lithography and PDMS
were introduced at the beginning of the 21st century (Dufft, et al., 1998: Unger, et al., 2000).
These are considered to be rapid, simple, and affordable micro-fabrication techniques that have
made the application of microfluidics possible in many areas like the molecular point of care
(POC) and catalysis. However, diagnostics is still considered to be microfluidics' primary area of
application (Jayamohan, et al., 2015). Moreover, it accounts for the largest share market for
microfluidics.
Lab-on-a-chip Technology
Lab-on-a-chip (LOC) are technologies which permit operations that require a laboratory
synthesis and analysis of chemicals on a very small scale on a handheld device called a chip.
Consequently, there are advantages of using these technologies such as the analysis of samples,
which can be undertaken where the samples were derived. Moreover, since the sample
collected is very small, the interaction and movement of the samples are controlled. Therefore,
the reactions become efficient, and the amount of chemicals used is reduced. One of the
challenges of these technologies is designing the chips on a small scale while still maintaining is
cost-efficiency and as well as functionality. LOC uses other disciplines of technology like
microfluidics and nanofluidics (molecular biology).

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Figure 1 - Schematic of the "Genotyper" device
As earlier explained, microfluidics is the handling and analysing of the flow of minute
quantities of fluid within channels in the micrometre range (David, 2002). On the other hand,
molecular biology is concerned with the movement of single macromolecules in solution.
Additionally, the progress in branches of nanotechnology has facilitated LOC technologies, like
lithography which is used to create nanoscale features on metal and semiconductor surfaces.
Also, nanosensors which are made of carbon nanotubes are able to detect deficient
concentrations thus allowing a high degree of analytical flexibility without having to increase
the size of the device. Life science applications include the sequencing of DNA or RNA,
examination of protein crystallisation to screen for conditions and synthesis of radioactively
labelled compounds. It is mainly for techniques such as positron emission tomography which
has also been investigated and included. Some effects show in microfluidics such as surface
tension to volume ratio, fluidic resistance, diffusion, laminar flow, and surface tension.
There are different methods used for manufacturing microfluidic devices including soft
lithography, micromachining, embossing laser ablation, in situ construction, and injection
moulding. All the mentioned methods have their pros and cons, but the suitable device
fabrication method is dependent on the particular device application. In micromachining, silicon
is usually used. However, the techniques of micromachining are labor intensive, costly, needs
specialised skills equipment and facilities. This technique is appropriate for chemistry
applications that need strong solvents, surfaces that are chemically stable and high
temperatures. Soft lithography is cheaper, faster and preferable for biological applications as
compared to silicon micromachining. It means the moulding of a two-part polymer using
photoresistors or the pattern transfer from micromachined quartz or metal master to a pliable
plastic sheet (David, 2002)
Hot embossing provides cheap devices, but is not preferable for changing designs which
if need be for new channel sixes, a new micromachined master is needed. It is time wasting and
expensive. It is thus an appropriate method for designs that will not require changes. It also
gives more material options. In situ construction uses liquid phase photopolymerizable
materials, laminar flow and lithography to make the devices of microfluidic. The process of
manufacturing is fast, and there is no need for expensive equipment or specialised skills.
Therefore, it is appropriate for researchers who want cheap materials with no cleanroom
facilities, and it also avoids the bonding step. One of the drawbacks of this method is that the

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dimensions of the device are limited based on the resolution of the mask and polymerisation
effects of the polymer. In micro moulding, the molten plastic is released into the cavity that has
the master which is maintained at a lower temperature to facilitate cooling of the molten
plastic. This method is cheap and is preferred for high volume manufacturing. Its only
disadvantage is material choices and the resolution.
The other way of manufacturing the devices of microfluidic is laser ablation of polymer
surfaces with afterword bonding to create cavities. This process is capable of creating many
more layer channel networks; the only disadvantage being throughput resulting from the
writing nature of the cutting process. The channel network is considered to be the central part
of any microfluidic device, some parts take advantage of the microscale properties to effect the
desired function. First among these parts is the actuator. Actuators have valves that control
fluid flow. There are two types of pipes: passive valves and active valves. Passive valves needs
no energy and can be used to get rid of air, to give a temporary flow stop or to control flow to
one direction. Active valves utilize the external macroscale devices which limit the movement
and produce energy.
Another component that enhances microfluidics is the mixer. Mixing is an essential
process for biological applications. At the microscale, diffusion is not enough but also the
conditions of laminar flow prevent mixing and also diffusion is sometimes not fast especially for
those that require large particles. Also, there are passive mixers that use channel geometry to
fold fluids and by so doing increasing the surface area where diffusion takes place. Examples of
these passive mixers are the vortex mixer, static mixer and the distributive mixer (Yetisen &
Volpatti, 2014). Active mixers, for instance, electrokinetic mixers, utilize external sources to
heighten the interfacial section between fluid streams. The type of mixer to be used is
dependent on the reagent type that requires mixing and the operation of the liquid regime.
Another essential feature of an actuator is the pump which facilitates the flow of the fluids.
Another essential component of the microfluidic devices is the sensor which enables the
capabilities for sensing as well as measuring at the microscale. A simple method of determining
flow rate is to divide the total volume of water collected by the time taken to collect the
samples. It is a suitable method of getting bulk flow rate measurement. The only disadvantage
is that these methods give no spatial information on the flow inside the channel. Due to this
shortcoming, a better way known as fluorescence is used. The fluorescence comes from beads
or chemicals added to the system. This method is primarily used to measure variables like
temperature, flow profiles, cell function, flow velocity, and polymer dynamics. However, its
drawback is that not all chemical, physical, or biological sensors comply with fluorescent tags.
Though the field of microfluidics is relatively new, it has the potential to influence areas
of chemical synthesis, drug discovery, biological analysis and information technology especially
for high throughput applications (Whitesides’, 2006). One of the advantages of LOC technology
is that it is a configurable technology as well as flexible, making it preferable for large-scale
integrations. Even so, a disadvantage of it concerns the material properties of PDMS which are
affected by temperature. the ability to simulate the natural environment of a cell is also
considered to be another advantage of microfluidic cell culture. Additionally, it is able to study
low numbers of cells in a temporal resolution that is high though an automatic on-chip analysis
direct coupling to the analytical chemistry platform. Moreover, microfluidic cell culture is
characterized with low reagent consumption, low risks of contamination, and high throughput

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experimentation (Skarphedinn, 2015). Typical challenges that exist for microfluidics include the
small volumes used which become a problem in subsequent analytical chemistry. Secondly,
there are nonstandard culture protocols. Another challenge posed by microfluidics is the
complex operational control and chip design.
The Future of Microfluidics
It is worth noting that the LOC technology offers detection speed in DNA/RNA
amplification and detection while maintaining the same sensitivity. Initially, the amplification of
DNA with PCR relied on thermal cycles. The reason as to why LOC technology became the
fastest method for performing PCR is clearly elaborated by the ability to undertake thermal
shifts at the microscale. Besides, using LOC to integrate very many DNA probes, it is now
possible to sequence genomes many times faster. Moreover, LOC holds enormous
immunoassays possibilities that can be performed extremely fast as compared to macroscopic
technologies. In the fields of molecular separation, LOC show better results of separation as
compared to conventional systems (Anon, 2015)
Further application is in the field of proteomics. In these LOC gives the chance for
performing protein analysis and at the same time combining all the procedure on the similar
chip that is from extraction from the cell, detachment through electrophoresis, analysis and by
the use of mass spectrometry. All these steps and processes can be done within minutes on a
LOC. Moreover, LOC can also be used for protein crystallization. Another application is in cell
biology. LOC shows that it is possible to control cells at the single cell level and at the same time
deal with many cells in seconds. Using fast optical detectors, it is possible to detect and isolate
a given cell with high throughput. Other applications in cell biology include micro patch clamp,
cytometry of high-speed flow, sorting of cells, and stem cell differentiation control.
The LOC technology is also applicable in chemistry. With regards to chemistry, high
efficiency has been witnessed in certain chemical reactions due to the ability and capability of
performing fast heating and cooling at the microscale. Several advantages accrue from the use
of LOC compared to conventional technologies, for example, it such as it is cheaper. In this,
integration, it allows several tests to be undertaken on the similar chip thereby lowering to a
small amount the cost of every single analysis. Second, is high parallelisation. LOC can allow
very much analysis to be done simultaneously or rather at same instant on a chip. Doctors will
now be able to target specific diseases and illnesses during the time at the time of consultation.
It will allow fast and effective prescription for the best antiviral or antibiotic (Whitesides, 2006).
Additionally, the LOC technology has enabled the integration of many operations within a small
volume. Diagnosis done through LOC technology will not require much handling. The procedure
is simple, and in most cases, will be undertaken on site even by nurses.
Another advantage is the human error reduction: Diagnoses done using LOC will result
to significant reduction in the risk of human error since human handling will be minimized as
compared to the analytical procedures undertaken in the laboratories. Another advantage is
reduced response and diagnosis time; the chemical diffusion, flow switch, and heat distribution
is more rapid and fast at the micrometric scale. It is possible to change the temperature or the
mixing of chemicals by diffusion in seconds (Lochovsky, et al. 2012). Moreover, low volume of
samples is used. Since LOC systems require a small sized sample, thereby the reduction in the
use of expensive chemicals hence reduced cost of analysis. Moreover, it will enable detection of
many illnesses without deducing large quantities of blood from patients. Another advantage is

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sharing the health with everybody. There will be reduced diagnostic costs as well as the costs
associated with training of medical staff. Additionally, the cost of setting up infrastructure will
reduce consequently making medicine more accessible to developing countries at affordable
prices.
The other advantage is monitoring and real-time process control thus increasing
sensitiveness. Through a reactivity that is fast at the microscale, the real time environment of a
chemical reaction can be controlled in the LOC leading to more controlled results. The last
advantage is that LOC is expendable. LOC devices are characterized by low energy consumption,
low price, and automation. It will enable the outdoor use of the LOC devices for monitoring of
water and air without the intervention of humans.
Comparing LOC to classic technologies, the following disadvantages arise: First is
industrialisation-many LOC technologies are not ready for industrialisation. Secondly, for
specific applications; miniaturisation raises the signal or ratio of noise, resulting to LOC
providing poorer outcomes than conventional techniques (Fredrickson and fan, 2004). Thirdly,
LOC needs an external system to work. They require electronics or flow control systems to work
correctly. Therefore, the final cost and size of the entire system is heightened by the external
devices, and limitations can result from flow control equipment, which may affect the
performance of LOC. Last among the drawbacks is the human behaviour element and ethics.
Real-time accessibility and processing of LOC can generate fears of new public diagnosing
possible infections at home if it is not regulated.
In spite of all the pros and cons advanced above, there are several challenges currently
facing LOC technologies. First among these is industrialisation. LOC technologies have not been
industrialised to avail them for commercialisation. It includes the fabrication processes
adaptation, specific surface treatments design, and flow control systems among others (Becker,
2010). The increment in the rate and number of biological operations that can be integtated on
the same chip as well as the rise of parallelization to obtain the detection of the many
pathogens in the similar microfluidic cartridge also brings another challenge. The fundamental
study on certai technologies with a potential impact, for example, interpretation of the
nanopore which requires more research to be done in the future also brings another challenge.
Conclusion
In conclusion, the advancement of Lab-on-a-chip technology is dependent on molecular
biology and microfluidics is the two major scientific disciplines. These two fields are tied
together by nanotechnology, which plays a major role in the advancement of the technology. It
noticeable that there are hurdles associated with the commercialisation of LOC, but viable
examples have started appearing in the market. It is therefore considered to be very important
both in the chemistry Industry and medical word. LOC device with their capabilities and abilities
of performing the full diagnosis at the time of consultation will change the way medicine is
being practiced since people with lower qualifications will make the diagnosis as doctors
concentrate on the treatment. Also, the time period of diagnosis will enhance the survival
chances for emergency services patients and will enable appropriate treatment to be
administered on them in good time. Also, the ability for the diagnosis to be completed at low
cost will enable early detection of illnesses and even early treatment. In the least developed
countries, LOC will enable healthcare professionals to provide diagnostics to a wider population
and to administer the appropriate treatment without the use of costly medications. LOC

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technologies will undoubtedly change the way diagnostics will be done in the near future.
Presently, some of LOC technologies are being used such as in HIV detection or heart attack
diagnosis and also glucose monitoring. Overall, it is expected that LOC technology will save
numerous lives.

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