Transcript of "ETE444-lec7-lab-on-a-chip-microfluidics.pdf"
ETE444 :: Lecture 7
Dr. Mashiur Rahman
Application of Nanotechnology
• Microfluidics and their Applications
– Materials for Microfluidic Devices
– Biochemical Analysis
– Active Microfluidic Devices
• Single electron transistors
Microfluidics and Their Applications
• Microfluidics covers the science of fluidic
behaviors on the micro/nanoscales and the
engineering of design, simulation, and
fabrication of the fluidic devices for the
transport, delivery, and handling of fluids on
the order of microliters or smaller volumes.
– BioMEMS (Biological or Biomedical
– Lab-on-a-chip (μTAS : Micro-Total Analysis
• Inkjet printing
• Blood analysis
• Biochemical detection
• Chemical synthesis
• Drug screening/delivery
• Protein analysis
• DNA sequencing
An inkjet printer is any printer that places
extremely small droplets of ink onto paper to
create an image.
• The dots are extremely small (usually between 50
and 60 microns in diameter), so small that they
are tinier than the diameter of a human hair (70
• The dots are positioned very precisely, with
resolutions of up to 1440x720 dots per inch (dpi).
• The dots can have different colors combined
together to create photo-quality images.
thermal bubble inkjet printer
• Used by manufacturers such as Canon
and Hewlett Packard, this method is
commonly referred to as bubble jet.
• In a thermal inkjet printer, tiny
resistors create heat, and this heat
vaporizes ink to create a bubble. As
the bubble expands, some of the ink
is pushed out of a nozzle onto the
• When the bubble "pops" (collapses), a
vacuum is created. This pulls more ink
into the print head from the cartridge.
A typical bubble jet print head has
300 or 600 tiny nozzles, and all of
them can fire a droplet
simultaneously. Picture: howstuffworks.com
Patented by Epson, this
technology uses piezo crystals. A
crystal is located at the back of
the ink reservoir of each nozzle.
The crystal receives a tiny electric
charge that causes it to vibrate.
When the crystal vibrates inward,
it forces a tiny amount of ink out
of the nozzle. When it vibrates
out, it pulls some more ink into
the reservoir to replace the ink
sprayed out. Picture: howstuffworks.com
• A blood test is a laboratory analysis
performed on a blood sample that is
usually extracted from a vein in the
arm using a needle, or via fingerprick.
• Blood tests are used to determine
physiological and biochemical states,
such as disease, mineral content, drug
effectiveness, and organ function.
Although the term blood test is used,
most routine tests (except for most
haematology) are done on plasma or
serum, instead of blood cells.
• The study of the chemical
substances and vital processes
occurring in living organisms;
• In chemistry, chemical synthesis is purposeful execution of
chemical reactions in order to get a product, or several products.
This happens by physical and chemical manipulations usually
involving one or more reactions. In modern laboratory usage, this
tends to imply that the process is reproducible, reliable, and
established to work in multiple laboratories.
• A chemical synthesis begins by selection of compounds that are
known as reagents or reactants. Various reaction types can be
applied to these to synthesize the product, or an intermediate
product. This requires mixing the compounds in a reaction vessel
such as a chemical reactor or a simple round-bottom flask. Many
reactions require some form of work-up procedure before the final
product is isolated. The amount of product in a chemical synthesis
is the reaction yield.
• Drug delivery is the method or process of administering a pharmaceutical
compound to achieve a therapeutic effect in humans or animals.
• Drug delivery technologies are patent protected formulation technologies
that modify drug release profile, absorption, distribution and elimination
for the benefit of improving product efficacy and safety, as well as patient
convenience and compliance.
• Most common methods of delivery include the preferred non-invasive
peroral (through the mouth), topical (skin), transmucosal (nasal,
buccal/sublingual, vaginal, ocular and rectal) and inhalation routes.
• Current efforts in the area of drug delivery include the development of
targeted delivery in which the drug is only active in the target area of the
body (for example, in cancerous tissues) and sustained release
formulations in which the drug is released over a period of time in a
controlled manner from a formulation. Types of sustained release
formulations include liposomes, drug loaded biodegradable microspheres
and drug polymer conjugates.
• Proteins (also known as polypeptides) are organic
compounds made of amino acids arranged in a linear
chain. The amino acids in a polymer chain are joined
together by the peptide bonds between the carboxyl
and amino groups of adjacent amino acid residues. The
sequence of amino acids in a protein is defined by the
sequence of a gene, which is encoded in the genetic
• The term DNA sequencing refers to methods for determining the order of
the nucleotide bases, adenine, guanine, cytosine, and thymine, in a
molecule of DNA. The first DNA sequences were obtained by academic
researchers, using laborious methods based on 2-dimensional
chromatography in the early 1970s. Following the development of dye-
based sequencing methods with automated analysis, DNA sequencing has
become easier and orders of magnitude faster. Knowledge of DNA
sequences of genes and other parts of the genome of organisms has
become indispensable for basic research studying biological processes, as
well as in applied fields such as diagnostic or forensic research. The advent
of DNA sequencing has significantly accelerated biological research and
discovery. The rapid speed of sequencing attained with modern DNA
sequencing technology has been instrumental in the sequencing of the
human genome, in the Human Genome Project. Related projects, often by
scientific collaboration across continents, have generated the complete
DNA sequences of many animal, plant, and microbial genomes.
DNA Sequence Trace
• consist of microfluidic platforms or devices for
– Fluidic sampling
• Lab-on-a-chip is becoming a revolutionary tool for
many different applications in chemical and biological
analyses due to its fascinating advantages (fast and low
cost) over conventional chemical or biological
• Furthermore, the simplicity of lab-on-a-chip systems
will enable self-testing capability for patients or health
consumers overcoming space limitation.
• The idea of lab-on-a-chip is basically to reduce
biological or chemical laboratories to a microscale
system, hand-held size or smaller.
• Low cost: Many reagents and chemicals used in biological and
chemical reactions are expensive, so the prospect of using
very small amounts (in micro- to nanoliter range) of reagents
and chemicals for an application is very appealing.
• Requires very small amounts of reagents/chemicals:
– enables rapid mixing and reaction: biochemical reaction is mainly
involved in the diffusion of two chemical or biological reagents
– microscale fluidics reduces diffusion time as it increases reaction
– practical terms, reaction products can be produced in a matter of
seconds/minutes, whereas laboratory scale can take hours, or
• Minimize harmful by-products: since their volume is so small
Casting is a manufacturing process by which a liquid material is usually
poured into a mold, which contains a hollow cavity of the desired shape, and
then allowed to solidify. The solidified part is also known as a casting, which is
ejected or broken out of the mold to complete the process. Casting materials
are usually metals or various cold setting materials that cure after mixing two
or more components together; examples are epoxy, concrete, plaster and
clay. Casting is most often used for making complex shapes that would be
otherwise difficult or uneconomical to make by other methods.
Casting is a 6000 year old process. The oldest surviving casting is a copper
frog from 3200 BC.
Hot embossing is essentially the stamping of a pattern into a polymer softened
by raising the temperature of the polymer just above its glass transition
temperature. The stamp used to define the pattern in the polymer may be made
in a variety of ways including micromachining from silicon, LIGA, and machining
using a CNC tool (for making large features). A wide variety of polymers have
been successfully hot embossed with micron-scale (and below) size features,
including polycarbonate and PMMA. This technique is used primarily for defining
micro-channels and wells for fluidic devices. The benefits of this approach are
the ability to take advantage of the wide range of properties of polymers, as well
as the potential to economically mass produce parts with micron-scale features.
Injection molding (British English: moulding) is a manufacturing process for
producing parts from both thermoplastic and thermosetting plastic materials.
Material is fed into a heated barrel, mixed, and forced into a mold cavity where
it cools and hardens to the configuration of the mold cavity.
After a product is designed, usually by an industrial designer or an engineer,
molds are made by a moldmaker (or toolmaker) from metal, usually either
steel or aluminium, and precision-machined to form the features of the desired
part. Injection molding is widely used for manufacturing a variety of parts, from
the smallest component to entire body panels of cars.
Disposable Smart Lab-on-a-Chip for Blood Analysis
The disposable lab-on-a-chip
cartridge has been fabricated
using plastic micro-injection
molding and plastic-to-plastic
direct bonding techniques.
The biochip cartridge consists
of a fixed volume
microdispenser based on the
system) technique, an air-
bursting, on-chip pressure
source, and electrochemical
• The PCR reaction is a thermal cycling procedure for amplifying a nucleic acid
target. PCR is used to amplify DNA targets and a reverse transcriptase-PCR
(RT-PCR) is used for RNA targets.
• PCR is a three step process in which each step is performed at a different
– 1. In the first step, double-stranded DNA is denatured at a temperature
of approximately 95 °C.
– 2. Next, each of the two single strands of DNA are hybridized (annealed)
to pairs of oligonucleotide primers at approximately 55 °C.
– 3. In the final step, a thermostable magnesium ion-dependent
polymerase derived from Thermophilus aquaticus (Taq polymerase)
synthesizes complementary DNA in the region flanked by the primers
using added deoxynucleotide triphosphates (dNTP) at approximately 72
Schematic of a flow-through-type of PCR microchip. The serpentine reaction microchannel
crosses each of three zones (T1, T2, T3) each of which is set at a different temperature
Microchip PCR Products
• However, despite strong indications that the development
of microchip-based PCR analyzers are nearing completion,
few have been commercialized. One example of a PCR
microchip-based device is the miniature analytical thermal
cycling instrument (MATCHI) system (Smart Cycler see
www.cepheid.com). This is a battery-powered portable,
real-time, integrated analytical system based on PCR
performed in an array of silicon microchambers [52, 59,
61]. The entire system fits inside a briefcase for ease of
transport. Applications identified for this nucleic acid
analysis device include forensic, environmental and
agricultural analyses and detecting biowarfare agents [62,
Optical detection of proteins
Optical detection of proteins and reagent storage and delivery. (i) Schematic representation
of the POCKET immunoassay powered by a 9 V battery. (ii) Actual device. (iii) Apparent silver
absorbance values of anti-HIV-1 antibodies from HIV-positive patients and control patients.
(iv) Schematic representation of reagent-loaded cartridges. (v) Overlay of fluorescence and
brightfield images of the immunoreaction area, with fluorescent signal corresponding to
presence of labeled detection antibodies on antigen stripes. The concentrations indicated
above the picture refer to the concentration of sample tested in each microchannel.
Optical detection of proteins
Immunomagnetic separation and detection of proteins with CMOS Hall sensors. (i)
Schematic representation with inset showing actual chip. (ii) Comparison of the
outputs of CMOS chip and ELISA
detecting nucleic acids
Integrated nanolitre DNA analysis device. (i) Schematic
representation with two liquid samples and electrophoresis gel
present. (ii) Optical micrograph of device.
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