SEMINAR REPORT

ON
LAB ON A CHIP
BY
PRANJAL GUPTA -170106026
HARSH SARAF-170106015

UNDER THE GUIDANCE OF

Dr. MANOJ KUMAR SHUKLA

DEPARTMENT OF ELECTRONICS ENGINEERING

HBTU,KANPUR
 ACKNOLEDGEMENT
We wish to extend my sincere gratitude to our seminar presentation guide Dr.
Manoj Kumar Shukla, Electronics Engineering Department for his valuable
guidance, encouragement and answering all my queries concerning our seminar
topic.
We would also like to express thanks to Head of Department, Dr. Krishna Raj,
Assistant Professors, and all staff members and friends for all the help and co-
ordination extended in bringing out this presentation successfully. We are
grateful to the authors of the references and other literature referred to in this
project.
 ABSTRACT
Lab-on-a-chip (LOC) devices are being rapidly adopted as sensors and portable analytical
platforms in scientific establishments. Yet this revolutionary technology remains distant from
developing nations, where its benefits can be readily realized. In this report we have tracked
the progress in the field of Lab On A Chip .First we have mentioned about the LOC in
general and then about the backbone of this field which is Microfluidics. Microfluidic
technologies used in lab-on-a-chip devices allow to manufacture millions of microchannels,
each measuring mere micrometres, on a single chip that fits in your hand. We have discussed
the proposed mechanism for the lab on a chip . We have also inculcated the various
manufacturing technologies involved .We have mentioned few advantages as well as the
disadvantages of LOC and also their future scope.
content
Figure List
 INTRODUCTION

A lab-on-a-chip is a miniaturized device that integrates into a single chip one or

several analyses, which are usually done in a laboratory; analyses such as DNA
sequencing or biochemical detection. Research on lab-on-a-chip focuses on
several applications including human diagnostics, DNA analysis and, to a lesser
extent, the synthesis of chemicals. The miniaturization of biochemical
operations normally handled in a laboratory has numerous advantages, such as
cost efficiency, parallelization, ergonomics, diagnostic speed and sensitivity.
The basis of the lab-on-a-chip dream is to integrate onto a single chip thousands
of biochemical operations that could be done by splitting a single drop of blood
collected from the patient in order to get a precise diagnosis of potential
diseases. As we will see, we are currently quite far from this, but current
technologies are already able to do several single tests with specialized lab-on-
a-chip such as HIV or glucose detection , bringing us closer to the realization of
this dream. In the following decades, lab-on-a-chip advancements will change
diagnostic practices.

Figure 1 TRADITIONAL LAB Vs ON CHIP LAB

 TRACKING PROGRESS

The history of lab-on-a-chip is intrinsically linked to microfluidics. And the

history of microfluidics is intrinsically linked to the development of
microtechnology for semiconductors.
To advance the Apollo program, the United States invested billions of dollars to
miniaturize calculators in order to send them into space. In the early 50s,
researchers adapted photographic technologies to create photolithography, in
order to fabricate micro-sized transistors, and thus micro technologies and
microfabrication were born.
Ten years later, in the 60s, researchers used these technologies to fabricate
micromechanical structures called MEMS, enabling the production of
miniaturized accelerometers for use in daily objects such as airbags and
smartphones. Using these fabrication techniques, the first real lab-on-a-chip was
created in 1979 at Stanford University for gas chromatography. However, major
lab-on-a-chip research only began in the late 80s with the development of
microfluidics and the adaptation of microfabrication processes for the
production of polymer chips.
A big boost in research and commercial interest came in the mid-1990s, 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 (Defence
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.
 MICROFLUIDCS CHIPS

Microfluidics is both the science which studies the behaviour of fluids through
micro-channels, and the technology of manufacturing microminiaturized
devices containing chambers and tunnels through which fluids flow or are
confined. Microfluidics deal with very small volumes of fluids, down to
femtoliters (fL) which is a quadrillionth of a litre. The key concept related to
microfluidics is to integrate in a simple micro-sized system operations that
commonly solicit a whole laboratory.
A microfluidic chip is a pattern of microchannels, moulded
or engraved. This network of microchannels incorporated
into the microfluidic chip is linked to the macro-
environment by several holes of different dimensions
hollowed out through the chip. It is through these pathways
that fluids are injected into and evacuated from the
microfluidic chip. Fluids are directed, mixed, separated or
manipulated to attain multiplexing, automation, and high-
throughput systems. The microchannels network design Figure 2 MICROFLUIDIC CHIP
must be precisely elaborated to achieve the desired features.
Microfluidics have diverse assets: faster reaction time, enhanced analytical
sensitivity, enhanced temperature control, portability, easier automation and
parallelization, integration of lab routines in one device (lab-on-a-chip). It is
cheap as it does not involve the use of various costly equipment.
Microfluidic devices offer several benefits over conventionally sized systems.
Microfluidics allow the analysis and use of less volume of samples, chemicals
and reagents reducing the global fees of applications. Many operations can be
executed at the same time thanks to their compact size, shortening the time of
experiment. They also offer an excellent data quality and substantial parameter
control which allows process automation while preserving the performances.
They have the capacity to both process and analyse samples with minor sample
handling. The microfluidic chip is elaborated so that the incorporated
automation allows the user to generate multi-step reactions requiring a low level
of expertise and a lot of functionalities.
 LAB ON A CHIP

A lab-on-a-chip (LOC) is a device performing on a miniaturized scale one or

several analyses commonly carried out in a laboratory. It integrates and
automates multiple high-resolution laboratory techniques such as synthesis and
analysis of chemicals or fluid testing into a system that fits on a chip. There are
many advantages to operating at this scale.
Samples analysis can occur on location, where
the samples are generated, rather than being
carried to an extensive laboratory facility. Fluids’
behaviour at this scale makes it easier to control
the movement and interaction of samples,
causing reactions to be much more potent, and
minimizing chemical waste. It also allows
Figure 3 LAB ON A CHIP
reduces exposure to dangerous chemicals.

Lab-on-a-chip devices are a subdivision of Micro-electro-mechanical systems

(MEMS) devices and often indicated by “Micro Total Analysis Systems”
(µTAS). MEMS are information sensors that relay information to a
microcontroller that performs the analysis. These mechanical miniaturized
systems are composed of some substrates (silicon, glass etc.). They make use of
various types of technology. The one encompassing the whole concept is
nanofluidic. Nanofluidic examines the behaviour, manipulation, and control of
fluids that are limited to structures of nanometric (10-9 m) dimensions. Nano
sensors are a primary component of many lab-on-a-chip systems.

Figure 4 PROPOSED LAB ON CHIP

 STAGES OF LAB ON A CHIP

In general, we will require the integration of several steps or operations to

perform Lab On a Chip function. This section will discuss these stages of
operation, including fluidic handling, which assures that the desired fluid arrives
at a specific location at the right time and under the appropriate flow conditions;
molecular recognition, which allows the capture of specific analytes at precise
locations on the chip; transduction of the molecular recognition event into a
measurable signal; sample preparation upstream from analyte capture; and
signal amplification procedures to increase sensitivity. Seamless integration of
the different stages is required to achieve a point-of-care/point-of-use lab-on-
chip device that allows analyte detection at the relevant sensitivity ranges, with
a competitive analysis time and cost.

Figure 5 SCHEMATIC DIAGRAM OF INTEGRATED LOC

FIRST STAGE- FLUIDIC HANDLING
In an LoC microfluidic network, the flow rates must be controlled in every
location of the network and at every given time of the assay. The first key
choice is whether the fluidic pumping will be achieved using an external pump
or pumped internally by capillarity. The large surface-to-volume ratio of
miniaturized fluidic systems, compared with
their macroscopic counterparts, allows the
efficient design of integrated capillary pumps .
External pumps (such as syringe or peristaltic
pumps) allow a wider range of flow rates,
higher operation times, and no dependence on
the detailed chemical and physical properties
of the inner microchannel surfaces. Capillary
pumps are autonomous and require no
Figure 6 PUMPS AND VALVES
connections to exterior mechanical systems
and hence are particularly suitable for simple inexpensive disposable
miniaturized analytical systems. The second key choice is whether or not
integrated valves should be part of the system. Integrated valves allow active
on-chip flow control, which may be required for complex fluidic handling, but
significantly increases the complexity of the microfluidic device and its control
system.

SECOND STAGE- TARGET CAPTURE

The need for fluidic control is crucial to what is perhaps the key event of the
sensing process: the capture of the target analyte by an immobilized probe. This
capture is based on the principle of molecular recognition–the probe and target
have a set of specific spatial, chemical and physical interactions that should,
under optimized conditions, simultaneously give a high affinity for the specific
probe–target binding, and a high selectivity with respect to other. There are two
main considerations that are necessary to understand the target capture process .
The first is that the target must reach the probe molecule, which occurs most
commonly by diffusion to the channel surface. The second important
consideration is that, once the target molecule has reached the surface, it has to
interact with the probe.
THIRD STAGE-TRANSDUCTION
The capture of the target by an immobilized probe through a molecular
recognition process was discussed. Although central to the biosensing process,
this stage does not complete the assay–one needs now to transduce this
molecular event into a physical signal that can be measured. The selected mode
of transduction is central to the overall design of the integrated LoC system. The
impact of the mode of transduction goes beyond the simple integration of the
transducer into the system. It requires careful co-design with the other stages of
the assay such as the fluidic handling, sample preparation, and, naturally, the
target capture and signal amplification stages.

FOURTH STAGE -AMPLIFICATION

Recently, considerable attention has been devoted to designing processes that
can amplify the signal from each individual molecular recognition event. This
amplification will result in an increase in assay sensitivity. The analysis design
in an integrated LoC system always involves a set of compromises. These
compromises may be ‘external’, such as considerations related to cost or
complexity or ‘internal’, involving intrinsic limitations in the performance of
one or more stages. As in the engineering design of an integrated LoC system,
there are also trade-offs in these amplification strategies. The gain in sensitivity
comes at an increase in the cost of analysis by requiring extra chemicals, and an
increase in time and complexity. Each added step will also increase the chance
of errors and decrease reliability. The inclusion of a signal amplification stage
needs to be carefully pondered within the context of the requirements of the
specific application.
 MANUFACTURING TECHNOLOGIES
Lab-on-a-chip uses the most common microfluidic device manufacturing
technologies, and depending on their applications, various polymers. Such
technologies enable the integration of microchannels with micrometre scale
sizes.
1. PDMS (polydimethylsiloxane)- It is a transparent and flexible
elastomer that is widely used because it is very easy and cheap to
fabricate PDMS labs-on-a-chip by casting. It has the advantage
of, the easy integration of quake microvalves for fast flow switch.
The material is subject to aging, and because PDMS absorbs
hydrophobic molecules, it is hard to integrate electrodes into a
PDMS chip. Figure 7 PDMS

2.Thermo Polymers-Thermoplastic polymers are widely used by

researchers to fabricate labs-on-a-chip. Even if it is a little bit trickier
and more expensive to implement than PDMS, thermoplastics are
good candidates for the fabrication of labs-on-a-chip since they are
transparent, compatible with micrometre-sized lithography and are
more chemically inert than PDMS. Figure 8 Thermo Polymers

3.Glass- Transparent, compatible with micrometre sized machining,

chemically inert, with a wide range of well-known chemical surface
treatments and reproducible electrode integration, glass is a very good
candidate for the industrialization of labs-on-a-chip.

Figure 9 Glass
4. Silicon: The first lab-on-a-chip was made of silicon, and it seems
like a normal choice since microtechnologies are based on the
microfabrication of silicon chips. Nowadays researchers do not often
use silicon for labs-on-a-chip, mainly because silicon is expensive,
not optically transparent (except for IR) and requires a clean room as
well as a strong knowledge of microfabrication. Moreover, the Figure 10 Silicon
electrical conductivity of silicon makes it impossible to use for lab- Chip

on-a-chip operations requiring high voltage.

5.Paper-Lab-on-a-chip devices based on paper technologies
may have strong outcomes for applications requiring ultra-low
costs. Paper labs-on-a-chip may find their market in the future.
Figure 11 Paper
Based
 ADVANTAGES OF LAB ON A CHIP

 Low cost: Micro technologies will decrease the cost of analysis much
like they decreased the cost of computed calculation. Integration will
allow numerous tests to be performed on the same chip, reducing to a
negligible price the cost of each individual analysis.

 Reduction of human error: Since it will strongly reduce human

handling, automatic diagnoses done using lab-on-a-chip will greatly
reduce the risk of human error compared with classical analytical
processes done in laboratories.

 Ease of use and compactness: Lab-on-a-chip allows the integration of a

large number of operations within a small volume. In the end, a chip of
just a few centimetres square coupled with a machine as small as a
computer will allow for analyses comparable to those conducted in full
analytical laboratories.

 Low volume samples: Because lab-on-a-chip systems only require a

small amount of blood for each analysis, this technology will decrease the
cost of analysis by reducing the use of expensive chemicals. Last but not
the least, it will allow to detect of a high number of illnesses without
requiring large quantities of blood from patients

 Real time process control, and monitoring, increase sensitivity:

Thanks to fast reactivity at the microscale, one can control in real time the
environment of a chemical reaction in the lab-on-a-chip, leading to more
controlled results.
 LIMITATIONS OF LAB ON A CHIP

 Industrialization: Most lab-on-a-chip technologies are not yet ready

for industrialization. Regarding its core application, the ultra-
multiplex diagnosis, at this time we are not certain which fabrication
technologies will become the standard.

 Ethics and human behaviour: Without regulations, real-time

processing and the widespread accessibility of labs-on-a-chip may
generate some fears of the untrained public diagnosing potential
infections at home.

 Lab-on-a-chip needs an external system to work: Even if lab-on-a-

chip devices can be small and powerful, they require specific
machinery such as electronics or flow control systems to be able to
work properly. Without a precise system to inject, split and control the
positioning of samples, labs-on-a-chip are useless. External devices
increase the final size and cost of the overall system and some,
particularly flow control equipment, can often pose limitations for lab-
on-a-chip performance.
 CURRENT RESEARCH & FUTURE SCOPE

Much research is being conducted on increasing the ease of use of lab-on-a-chip

like enabling the use of basic lab-on-a-chip functions using a smartphone for
cholesterol testing, anaemia diagnosis, cardiovascular diseases monitoring.
There is also much research being done to improve current technologies for
applications like cell separation, DNA sequencing, and micro reactors.
Today some labs-on-a-chip are already commercialized for targeted applications
such as glucose monitoring or specific pathology detection.
In a near future we can expect that labs-on-a-chip will widely be used in
hospitals everywhere and eventually in the practitioner’s office. Later on, we
can expect that lab-on-a-chip technologies will be able to provide real-time
monitoring of health at home.
It has also proved its potential in the surveillance purposes in the defence
organisations.
In a near future we can expect that labs-on-a-chip will widely be used in
hospitals everywhere and eventually in the practitioner’s office. Later on, we
can expect that lab-on-a-chip technologies will be able to provide real-time
monitoring of health at home. This is why governments and companies are
investing more and more in labs-on-a-chip since it is now clear that these
technologies will change our daily lives.