Good afternoon, I am Shantanu Bhattacharya
and I will be your instructor for this course
on the introduction to BioMEMS and Microsystems.
Let me introduce a little bit of, what BioMEMS
really is BioMEMS is also in other words called
bio micro-electromechanical systems. It is
really about things, which I do very useful
and important things that a scale which is
micro or sub macro in the regime. So, I would
like to discuss today a few basic source of
introductory concept, which are important
for understanding this course more properly.
So, let’s go to have a look at what definitional
micro nano-systems can do they are really
system is made up of very small components
micron nanometer in scale they have a relative
high applicability to the field of life sciences
biotechnology and medicine, which as really
started more with you know the advent of things
called lab on chip technology as I will be
describing later throughout the course.
And essentially one of the reasons, why these
components rime so well with life sciences
based detection and diagnostics and biotechnology
and medicine applications is, because they
really size with similarly to some of the
biological entities and as of late the focus
of such micro system research is gradually
shifting to micro fluidic systems.
So, let us understand little more of what
definitionally BioMEMS can be laid out as,
so BioMEMS really is the biological or biomedical
application of MEMS technology. And there
are few more important terms and I would like
to discuss before starting one is Bionanotechnology,
which is the, the Biological applications
of Nanotechnology science and technology at
the scale you known at the scale less than
100 Nano meter is really, what nanotechnology
is and if you combine that to Biological concepts,
then it is also known as Bionanotechnology.
Microfluidics is will be seeing later on throughout
modules is the study of fluid transport at
microscopic length scale and this concept
are really all very integrated important to
understand the utility are the essence of
BioMEMS.
So, let us have a little more diagrammatic
representation on what are the sizes and scales
that I have been talking about. So, if you
really look at this is scale here the scale
here on the left on your left here start from
0.1 Nano meters all the weight about 100 microns.
And let me be a little more specific on, what
100 microns would really look like human hair
diameter typically is that of about 100 micro
meters, so that’s how small it is and 0.1
Nano meter is several 1000 of that dimension
actually.
So, you are dividing that as speeding that
in to almost about 10000 times in order to
achieve something like 0.1 Nano meters. Now,
if you look at some of these entities here
as can be represented on the just very next
to this scale most of the plant and animal
cells and this right here is actually red
blood cell there are millions of such cells
within the human body this is shaped like
something like a button and they rim in the
range of about 100 to 10 microns.
In fact, red blood cell the assume images
of which is represented here is about 20 microns
also. If you go a little bit down this cell
for example, this here is E Coli.. this is
equalize of E Coli. Bacteria most bacteria
cells rim in the range about 1 to 10 microns.
So, they are at least a tenth smaller or at
least a tenth smaller, then million as the
plant and animals cells.
Let us go a little bit down further here this
right here is actually a virus, which is the
essentially nothing but, a cote of a capside
made up proteins an enclosing sum genomic
information. And is the typically the sizes
of this viruses are of the order few 100 Nano
meters. If you go a little bit further down
we have molecules like let say proteins are
DNA and here something very interesting DNA
it is nothing but, it twisted ladder. So,
you take a laded and kind of twisted and one
helical turn of a DNA is something like about
2 to 3 Nano meters about 20, 30 Armstrong
. And, if you go a little bit down further
you have atoms and molecules and this really
is an approach, which is also known as the
bottom up approach are bottom up means of
manufacturing somehow we can illustrated this
as a mother nature’s has been making this
higher form this lower ones which are principally
atoms by using concepts of self-assembly and
energy driven mechanics and so on so forth..
So, if you look at the figures some from the
right here really they are things, which are
actually made using the top down approach,
which means that we have a bigger much bigger
size wafer are plot form. And you are trying
to reduces at through micro machining are
technologies, which we together known as micro
technologies and trying to make smaller and
smaller sizes in the way. So, if you look
at this figure here this illustrates actually
nothing but, a micro cantilever.
So, I call it something like diving board
in a swimming pool as a there is a pool and
there is a kind of you know board, which is
striking out and the only different here is
that board is about nothing but, 200 to 300
Nano meters is thick and the projected about
10 to 50 microns ahead and, so the scale is
simply 2 to 2 very small he go down a bit
further this right here is a very interesting
example It is a poly silicon gate with nitrate
spacing in fact it is the commercially available
device.
So, if you, look at the ITRS road map the
international semiconductor technologies road
map. It mentions that by the year 2004 actually,
which was about 3 to 4 years back the transistors
the minimum features size on a transistor
was close to about 100 Nano meters and it
has even reduce, now further. For such a device
the gate insulator, which is actually something
like you know packing between the it is like
a dielectric material between the metal contact
and the actual device that insulator about
2 to 3 Nano meters.
So, why I am showing you all this is that
if you really compare this features and objects
on a size scale they very well rim with each
other. Like for example, as I told you viruses
about few hundred microns few hundred Nano
meters and you can really with micro and Nano
technologies produce features like a polysilicon
gate, which is of the same range molecules
are even little bit further down and that
rimes very well with this gate insulator.
So, this size compressive kind of allows as
the luxury of bringing these two words close
together. So, that they can be they are accurate
sensing deduction diagnostic so, on, so forth.
So, that is why Bio MEMS
If you look at some of these kind of modules
are you know figures here this represents
the basics schematic of how this MEMS can
be laid out on simple let say to this simple
plot form. So, it is a combination of different
concepts like molecular devices on memoir
you know MEMS and MEMS technologies micro
fluidics systems and then, microelectronic
and you combine everything together to form
something, which you can senses and diagnose
these life size entities very sensitive and
accurately in this area Bio MEMS it is becomes
that if you can develop these kind of approaches
and call them integrated Biochips at the micro
macro Nano scale and this could be very useful
as will see throughout the lecture and letter
how they can various applications of such
architectures of such technologies.
So, one thing very important to mention here
is that, because these life type of entities
tends to be happy with in fluid environments
therefore for their accurate t diagnostics
are deduction it is very important for the
entities to be in actually fluids and we should
prepare fluidics in a manner, which can again
rim very well with their sizes, so that we
can have concepts like you know single cell
by single cells transfer are trying to isolate
the molecules on a plate of surface. So, therefore,
the concept of micro nano fluidic emerges
from there. So, these are really integrated
together and it is very important for understanding
is simple in intuitive engineering design
I would say for doing something with more
precision rapidity accuracy so on so forth..
So, I really put this whole field as it is
as synergistic learning experience between
the areas of micro Nano technology and systems
and Biology Bio medicine. And you know really
these technologies are the systems are Bio
inspired in a sense that there is too inflow
learning between biology and this technique.
And, so if you look at this figure here more
clearly left sides this idea.
So, here if you see the circle in the center
here represents these tow area micro nanotechnology
and systems and biology and bio medicine and
if you see there are these tow arrows and
both sides well they are showing that what
can be learn from, what. So, if you look at
the boxes on the left like diagnostics biochips
quantum dots silicon Nano wires carbon Nano
tubes these are really some of the technologies
that we can applied to biology and Bio medicine
and we can learn from the micro nanotechnology
and systems.
Similarly, you have area like as therapeutics
really target delivery nowadays there is huge
impacted of how microscopic quantities are
mites quantities of tracks can be injected,
how do you do that. So, you have very good
learning experience from micro Nano technology
and systems and try to relies dimensions and
features in a manner that this is doable another
very interesting area is this hybrid bio devices
and nowadays there are this whole initiative
of issue engineering you can develop something
artificial heart or artificial kidney and
artificial liver.
So, essentially is the nothing but, an approach,
we are used tried to utilize some of the learning
experiences from micro nanotechnology and
system and apply directly to make artificial
organs maybe. The boxes here on the right
are actually reveres process of learning;
that means, there are based on concepts where
learning borrowed from biology and Bio medicine
and applied on to micro nanotechnology and
systems. And you can see these some of the
examples as self-assembly are DNA are protein
mediators.
So, I will be describing little bit details
latter what DNA structure looks like are how
it actually self assembles. But, the DNA unique
kind of entity, which is able to you know
it is able to kind of a pack togather in a
certain shape or features or pattern and it
really gives as a lot of inspiration a lot
of learning. So, from the diesel and wiger
with which the two strands of DNA, which are
complementary each other and a self-assemble
and stitch an each other the base pairs we
could have a lot of a learning which we can
apply to really micro and nanotechnology.
So, self-assemble mono layer as matter of
factor another area where you know from just
from basic elemental chemistry we could make
micro Nano patterns are features of this molecule
over the different parts of surface and that
could realize micron Nano domain are micro
Nano features from learning borrowed biology
and Bio medicine. Similarly, another very
fascinating area is molecular electronics
where we talk about single molecule being
able to conduct current between to poles which
are placed one molecule path are may be a
single DNA and there are a lot of interesting
work in this area we says that you know if
you have it is DNA is as a wire which is connecting
between two poles and just simple use it as
a just a .you know the resistive circuit it
just follow the v=yr relationship I own this
case as you know the GC content are the one
side to design content of the DNA is increase
you see that there is change in conductivity
so on so forth. So there is a huge effort
of using the some of the entities to words
transferring charges very sensitively at a
very small scale. And this could be immensely
contribute to the field of micro nano technology.
Similarly human skin its very interesting
example having we called it balance bio inspired
material just think about how important the
human skin is and what kind of properties
does it have it can self-feel it can response
it can do all of you know repairing self-repairing
kind of things automatically. And if you really
what want to replicate something like human
skin that would be a fascinating ease micro
nanotechnology, where probably millions of
sensor are pack on to a surface and each these
sensor has a different job.
So, I really call this areas that the inspiration
learning from micro nanotechnology to biology
and bio medicine would be able to develop
novel solutions for some of the frontiers
in materials and information process medicine
biology. And, similarly the learning experience
that we have from biology and bio medicine
would be able to develop some novel solutions
frontiers materials and information process.
So, it is really a synergism, which is exits
between the two areas and therefore, it is
also the best impress to integrate the area
of bio with is micro Nano system and thus
the terminology as we have been describing
like bio memes bio Nano technology etcetera
automatically self immerge, because of this
mechanisms.
Let see, what can these kind of micro systems
really do in biology and this is a slide which
I really keep on illustrating time and again.
It gives in a sense of what kind of applications
are really available and some of them mind
you work really commercially available applications
as well be illustrating. So, this here as
you see is nothing but, and neuro probe it
is develop by doctor wise is group at the,
university of Michigan Ann arbor. And essentially
if you see this is again a very fine example
of micro nanotechnology where in this particular
features is probably of the size of just of
few microns there are these small, small as
you see here the small wires, which are printer
by just lithographic processes on to such
a probe and this prop is use for electrical
monitoring the electrical activate of brain
cells or brain tissues .
Now, the why micro technologies required in
that is that is you think out neurosurgeon
who is actually just operating on some bodies
you know the cranium portion and he wants
to inject big tool we can just to electrical
response monitor it is not a very feasible
option you know the patient would suffer a
lot of pain there would be general, general
tendency of the unnecessary damage, which
may of have along consequence in terms of
the patient’s post-surgical health. And
lot of other issues are considered.
Now, if instead of that replace of whole electrical
sensing tap its very small micro needle, which
can just go in to a very small area of the
cranium and do the same job as a big tip would
be doing that kips really the utility are
a sense of such a technology. This again is
a very fine example it is basically very long
cylindrical like probe neuroprobe developed
at stem probe and essentially use for giving
deep electrical stimulation specially patient
suffering from Parkinson’s disease.
This area again as a very fashioning area
and I call it probably the future in the area
of bio memes bio technology this is essentially
a set of neuron cells, which are growing on
an array of mass fate you can see these here
are the cells they are growing on set of mass
transistors this area as also known as by
the by nanobiology. Now, think about that
the signaling between these cells and I would
going to be little bit details biology later
as we go along these area. Essentially this
cells grow in a very unique manner with there
is a lot of signaling path way between the
two, which would certified are which signified
the behavior of such cells.
So, if we can study uniquely on a single cell
bases what are those signaling path ways is
terms of may be exchange of iron or chemicals
between the these two cell this of humans
utility to in general you know understanding
life process as such. So, there is huge initiated,
now how to study these cells on single cell
bases and trying to illustrate what kind of
chemical reactions on the surface of within
the cells as going on and what kind of communications
is going on between such cells which would
relate to their behavior in general. Again
this a very good example that you know I almost
always keep on mentioning this micro needle
and this comes for very common life experience.
So, the needle of the mosquito is essentially
when a mosquito bites you, you do not really
feel the pain, what happens is that as the
needles goes into your skin the needle of
mosquito go into a skin there is a post injection
swelling, which comes up, that swelling is
not, because of any you know pain effects
or any effects, because of the needle picking
in that essentially, because when the mosquito
actually tries to drop blood it release some
enzymes, which kind of tries to blood sample
and it becomes very easy for to draw a blood
sample in this manner.
But, again the fact that when the needle goes
in to the skin it hardly makes in a difference
to do this can you do not feel any pain. And
the reason why pain is really felt in the
human skin it is because that there are if
you look at the skin really beyond you know
about, let say 100 microns of layer of dead
cells, which we also know epithelium they
starts set of set of receptors called pain
receptors which are nerve ending essentially
and the mosquito needle is.
So, thin that goes into the 100 microns and
goes very close to that region of pain receptors,
but it is hardly able to deflect or damage
some of these receptors. So, there is no pain
sensation and mosquito does his job it goes
into another vasculature pick the blood samples.
And then, you know it kind of feeds itself
on that bases. So, the same principal has
been used using this borrow in this inspiration
from micro nano from the biology and bio medicine
to make what you called micro needles.
This write here a illustration what a micro
needle really means if you look at this needle
it is something close in the dimension to
that, that of mosquito and there is a in fact
commercial company called kumetrix which cells
1000 of needles on something like a patch
which you really wind around the patients
hands and it can do things like you know parallel
processing including monitoring of analyze
inside the blood sample drawing of sample
from time to time extra.
So, it is fascinating example of what micro
Nano technology can do by replicating biology
or getting bio inspire and do something use
full and important. This again is a very interesting
and fascinating example of what we called
bio chip or lab on chip and I am going to
come to it this in just about a minute in
more details about for what bio chips really
are. So, essentially these are you know protocols,
where whatever is possible with in a laboratory
is all miniaturize down to a single chip scale.
And in terms of handling very small droplets
or micro fluids of micro volume you quickly
and rapidly do whatever laboratory does on
a much bigger scale.
So, this is also known as lab on a chip or
bio chip and lot of research, where in integration
on electronic optics lot of different transition
techniques or taking place into densely integrated
platform also known as bio chip or known as
lab on chip kind of mechanism. This is again
a very fantastic example of what can micro
technology do in biology and these here are
those diving boat kind of swimming fool structure
this are micro cantilevers.
Essentially the scale here if you see is only
250 microns, which means that they are projected
about, let say about three times that size
about 750 microns. But, look at that thickness
really they are about the tenth, which about
lat say about 300 Nano meters are. And interestingly
there are several of these uniquely position
and spaced small, small cantilever devices
available to this edge of this particular,
let say piece material, which can be silicon
and what it did essentially does it is nothing
but, a mass detector. So, if you are able
to somehow you marbleize some cells are some
molecules on the top of this particular structure
of cantilevers due to the weight that is somehow
you marbleize on the top.
There is a deflection in bending and the deflection
and bending you would back calculate by using
the equation called as Stoney’s equation
and I will be doing detail of this little
bit later. The mass of the particular entity;
however, the advantages of small size of the
cantilever the there is solution of to which
you really pick up masses go up o the order
of about femto grams you know Pico to femto
grams and that was give to you a unique of
applications of micro systems in biology.
So, we have been discussing earlier about
micro fluids we have been really learning
it as important, because you talking about
biology entities and typically all biological
entities are happy when they are in fluidic
environments. But, it is very interesting
that you know the behavior of fluid at this
particular scale microns scale really very
very countering to any person, who trained
to microscopic fluid behavior in any engineering
curriculum.
As I earlier indicated that the definition
of micro fluid is really is the transport
of fluid at the microscopic length scale.
And there are some unique properties and changes,
which happen, because of the scale change
while the properties is very, very important
to be mention is of the surface effects become
prominent with high surface area to volume
ratio. And, if you look at, if you just dimensionally
compare surface area to the volume it can
be represented as L square by L cube, which
is about L to the power of minus 1 .
So, if this L is going to the micron level
micrometer level which is nothing about 10
to the power minus 6 meters you can just think
about that the you know the surface area become,
so more most some much more prominent with
respect to the volume it become about 10 to
the power of 6 times more prominent with respect
to the volume. So, you have some forces are
some effects, which are related more towards
the surface they gain much more in prominent
in comparison to the volume force. In case
of fluid volume forces could be something
like you know inertia could be something just
acceleration due do gravity of a small fluid
mass. And these are also packed together is
intertidal effects essentially you know the
pressure driven aspects of flow, which is
consent with the mass of the fluid flow. And
surface area on other hand something, where
there could be forces of surfaces tension,
which is just related to what is the length
you known of interface of fluid with respect
to some other particular boundary or may be
viscous forces, where surface area becomes
more prominent.
So, has surface area related activity are
events become prominent in this case therefore,
you know the viscous forces of surface tension
related forces are much more into question.
And these are critical parameters for designing
such devices over the general macroscopic
idea of designing devices on the bases of
volume based flows. And other very interesting
effects here is, because of the low thermal
mass and high heat transfer we talking about
miniaturize droplet size. In terms few micro
liters of volume and therefore, it is very
easy to probably conclude that it has very
low thermal mass that is number one and essentially,
because of this low thermal mass there would
be high heat transfer they are initiated inside
micro fluid device where in some of the fluids
are tried to make into a thin layer on the
surface. So, if you look that instead of making
that thick layer more volume based your making
more surface base and thinner layer.
How you make that is again what BioMEMS tells
you BioMEMS technology Bio MEMS fabrication
technology tells you. So, essentially you’re
taking the whole fluid surface and therefore,
trying to increase the heat transfer way.
And other very interesting factor is a low
Reynolds’s number Reynolds’s numbers all
we know as the ration of inertial forces.
And essentially you can also represent it
as rho u l by mu as you can see here rho is
the density of the fluid, which is flowing
u is the velocity l is the corresponding length
scale and mu is the essentially the viscosity
of the medium.
So, also you can actually make this in
by rho and make this the dynamic viscosity
of the material. Now, no reynolds number really
is typically asset an domain micro fluids
you know there is lot of changes, because
of this low Reynolds number value number one
change, which happens is we can consider this
as let say a pack of cars. So, you have about
100 of cars, which is moving in a very small
street, which is you know may be peak traffic
hour in our city here and what would happen,
what you think would happen in a such situation
happens. The cars would try to move in aligned
manner in more like steam line fashion without
really much cris-cross.
Because, you were packing lots of car together
number one the velocity of the car would also
go down. And then, even if we assume that
the high velocity there is always the tendency
of cars to move one beneath one behind another
there would be hardly any people who would
be trying to acts smart and change their lanes,
because that essentially means collision or
crayons or an accident.
So, therefore, if we just compare similar
analogy in terms of molecules, which we are
compress to the very small street or a very
thin area this molecule also tend moving something
called steam lines wherein they would move
parallel to each other without that many of
them really adventure really going to each
other stand and colliding with each other.
So, therefore, very unfortunate or may be
in some situation fortunate I will be illustration
later these with examples fact is that this
molecules tend to remain in their own path
without really going across parallel tracks
or paths the situation, where is mixing hardly
it becomes almost.
Next to important until and unless as we see
later they are diffuse the forces which the
molecule crisscross on the bases of concentration
radiance between to flows. Just to illustrate
this fact that kind of browed an example from
wide size group here as you see the essentially
this is a simulation, which talks about they
are a set of this 1 2 3 4 5 6 around 6 dies
of different colors, which are flowing, which
are flow in a microscopic dimension.
They go in this manner and there are several
of these track, which are emanating from different
areas and as you see this fluids kind of go
by together there is a unique tendency of
the colors to get separated without getting
mixed. So, this red color which was injected
here as it retreat after a while and this
blue color as treat as while, Similarly, this
drake blue color as treat some while and the
color cell them mix and it is really a real
time simulation and this is what happen in
the micro scale also, where you can see that
the fluids also though flowing parallel hardly
tend to mix because of the low Reynolds number
value. So, just for illustration array in
bio MEMS devices Reynolds numbers in bio MEMS
devices is usually less than 100 are often
or and as most often less than 0.1 are also.
So, let we talk about little bit of sensor,
now because this would be important for understanding
say essentially the purpose of a bio MEMS
devices is to really sense something sense
a detecting something with some degree of
accuracy. So, definitional we look at what
sensors is sensors really is a device that
detects or measure a physical chemical or
biological property or entity and records
are indicates or respond to it. So, essentially
it would use for some kind of measurement
could be a physical property, physical property
could be something like temperature distance
mass of an object the pressure in a particular
channel is are all physical property.
So therefore, sensor can be something which
detects of physical property and those sensor
are known as physical sensors as it illustrate
here. It could detect chemical properties
and chemical substances, where in things like
may be the chemical nature of analytic are
you known the chemical and physical responses
of substance to an environment is recorded.
So, these type of sensors are also known as
chemical sensor.
Then, finally, we have biological sensors
which monitor or measures the chemical substances
using a biological sensing elements. So, essentially
there is always an integration between what
chemistry to offer and what biology has to
do, but the idea is that you classify some
of those chemical sensors or bio sensors if
the detection element is actually, more like
a biological sensing element. So, that was
bio sensors would do.
So, essentially schematically we can really
in a very organize manner represent the sensor
as something, which is going to detect this
analyze or substrate which is present in this
region and for detecting it you have something
called a detection element which can be either
the chemical in nature or biological in nature
and then the detection element has a change
in property. So, it may be a change in chemical
property it may be a change in optical property
and may be change in electrical property.
And essentially this, this element, which
there for the detection proposes has a change
in property in the presence of the analyte
or the substrate of interest.
It generates something called a signal and
the signal can be further transfused by this
particular element here, which is also an
integrate part of the sensor and what does
transaction really mean transaction is essentially
is nothing but, a change of signal from one
form to another. So, if you have a chemical
agent there it is going to change in to a
electrical signal or an optical signal, so
this is called transduction. Transduction
is a change in signal of one kind to another.
So, you have an element here on the bio sensor
as you see here which does this transduction.
So, whatever signal is generated from the
biological detection element of the chemical
detection in the presence of the analyte or
substrate is transuded into a signal some
form and this signal is essentially fade into
a processor, which would be trying to read
analyze interpret the signal and trying to
conclude whether there is an analyte of interest
present or absence are in what quantity is
this analyte of interest are present.
So, to gather this thing is can be define
as an organized this schematic of what a chemical
are a biosensor would do. Let me give an example
the laboratory level litmus paper is something
that probably all of you have used in your
school days. And what essentially happen is
that you if you expose this paper to a variety
of pH; that means, variety of acidic or basic
fluids it is changes it is coloration. So,
there is a change in the absorption wave length
of light, because of, which you can find a
different color appearing based on different
pH. So, there are now, commercial available
litmus papers, where there are range of colorations,
which are illustrate for the even having a
resolution almost 1.0 pH change. So, you can
at all different pH get a different absorption
spectrum on the color. So, this is the finest
example of a sensor are may be something like
a pH indicator electrode, where you deep an
electrode in a material and that electrode
has a change in electrical property, which
is signify what is the hydrogen ion concentration
of a particular medium. So, these are examples
of sensor chemical sensors.
So, let as try to illustrate this simple litmus
paper or pH indicator electrode as a sensor
module. So, you have an analyte which is the
solution in which the pH is to be measured
it can be a basic or acidic pH you have a
detection element an in case of litmus paper
it is the chemical die and in case of pH electrode
this is the set of chemical of course. And
this chemical die what it does it the transduction;
that means, when the expose to an acid or
pH of certain you know kind it is rapidly
changes it is absorbance spectrum. So, therefore,
as you know the absorbance spectrum is change
that is the change in coloration of a particular
material, so it change color.
The change in color because of chemical die
getting expose to a certain level of hydrogen
irons and can calibrate in a manner that if
you have a x concentration you will have a
different color if your y concentration you
will have a different color. And, so there
is certain scale on which is this can be mention
in terms of color scale. So, that is what
the transduction element is and in case of
litmus paper with the human eye which observes
this coloration changes is nothing but, the
signal processor.
So, it is essentially the measuring device,
which tells you that what color corresponds
to what pH looking at a calibrate scale, which
has been done before by somebody and which
is mentioned in all these packs of litmus
papers and you just comparing the color through
your eye to the color that is on the scale
so that is essentially the signal processor.
Similarly, if you look at the pH electrode
the set of chemicals in the pH electrode is
the deduction element and the change in voltage
which is generated by the electrode is essentially
ways and means of chemical to electrical transduction.
So, whatever solutions you are trying to gage
that solution is essentially measure by putting
the electrode inside and there is a change
in voltage or potential because of that. So,
the transduction is from chemical; that means,
generated by hydrogen irons in a particular
solutions of a pH to a voltage, so it is essentially
a potentiometric sensor study in little bit
detail later on..
Then, the signal processor in the devices
really a meter, which can read what is a change
in the voltage. So, that can be electronic
meter which can do that really and therefore,
you can also illustrate the electrode as analyte,
which is the acid or the chemical of whose
pH to be measured set of chemicals inside
the pH electrode as the detection element.
And then, the chemical to voltage change is
a transaction process and the measuring device
as meter, which reads the voltage change,
so, that is how…
. So, as we were talking about sensors let
as actually looking at some the interest sensors
that human body has human nose is the one
of the most important sensor at the human
body has or in fact, our eyes can be illustrate
as a sensor model. So, I would like look little
bit into how human nose functions, because
it is the you known the bio MEMS area and
there is amount of life science aspect in
it one should know really how our body can
be adjust or how can our body can be lead
out in different sense of our body can lead
out sensor.
So, this essentially is what the internal
view of the nasal tract would look like in
a human body and let first illustrate the
functionality aspects. So, what would you
really need the nose for, so there is air,
which has oxygen, which is essentially an
oxygen rich components and we have to take
this in take this air for our survival and
the first thing that this air has to do is
to get pre filter. So, as it enters the nasal
track here there are set of this you see in
this region there are this hair like entities
which are able to kind of pre filter whatever
particulate the air has if for just cleaning
it before entering the human body.
Once the air goes inside it actually touches
the bifurcated blood vessels network in this
region also known as the olfactory mucous
region where there is a membrane which does
two fold objectives one is that it warms up
the air, which you have a taken in and then,
it makes little bit moisten. So, that it adjust
to the internal condition of the lungs, in
to which the air is directly sent in after
passing through it. So, it becomes warm and
become a little moisture, so that is how the
nose operate.
Now, every interesting factor in the nose
is what we know in the sense of smell, how
does really sense of occur look at is nothing
but, the signal transduction process. And
as we know we can really classify something
called smell into different classes like pungent,
sweaty, rotten, sweet, so on, so forth. depending
on whatever the ambient is and really, if
you look at what is going on the smell is
result of thousands of millions of chemical
reactions, which takes the surfaces of very
fine hair like moiety called cilia essentially
in the olfactory cells, which are in this
particular area, so are in this area as a
matter of air.
So, there a fine hair like cilia kind of moiety
of the cell surface, where 1000 of chemical
reaction taking place by the input the air
comes in, which classify the smells as pungent,
sweaty, rotten, sweet so on so forth. So,
essentially the hair like structure 12 percent
volume the whole olfactory membrane, so that
is how small it is and this is the kind of
illustration of this smaller it is the better
it is which is the a driving lesson of micro
Nano technology.
So, just to give you some facts and figure
the tissue in the all factory region has more
than 10 million receptor cells, which have
this hair like moiety and is about 50 microns,
thick in the normal about epithelium layer.
So, the epithelium layer that we have in our
body is about 100 microns, so the total thickness
of this particular you known the olfactory
region about 150 y microns also. And it contain
about 300 distinct genes, which encode the
olfactory region which make up the cilia.
So, the cilia what we talking above 1000 of
chemical reaction are going on are made up
of some protein molecule and they are coded
by about 300 different genes inside this olfactory
cells and it is a self-emerging process. So,
as there is a some transduction of let say
some kind of reaction chemical reaction into
an electronic impulse, which goes through
your bundle of nerves which are connected
add the back end of the olfactory cells like
this you know to your brain. So, essentially
the electronic impulse, which is going because
of this electro chemical process which is
happening on the surface of the cilia..
And those, basically the protein that is changing
it is classification is continuously being
updated or typed by the distinguish gene,
which are available in inside t this cell,
so it is a continuous process. So, there are
new moiety of every time were new reaction
would take place and, because of that new
electrons would generate and the electron
flows the continuous process which goes to
the brain and that classify that based on
that some that to pungent too sweet or rotten
or sweaty kind of sensation, so this are some
category.
So, therefore if I am really like to look
at human sense the human nose as the sensor
model it as containing the biological detection
element, which is working on a sample of interest
here which is nothing but, the air sample
and the biological detection in our cases
olfactory membrane this uniquely made or you
know crafted tissues, which gives you a transduction
from chemical to electrical and the electrical
impulse is taken by nerve inform an electrical
signal all the way to the microprocessor in
our body the signal processor, which is the
brain in this case. So, really human nose
can be categories an artificial sensor..
Let us look at eyes, eyes are typically very
important consequent of the human body, which
takes applied would able take a distinguish
and identify between objects and this is how
it works, so the cornea in the eye as can
be illustrate in this particular figure here
is the equivalent to the lens cover of camera.
So, let us kind of try to analog provide analogy
between the cornea or the lens of the whole
eye structure and mechanical as simple camera
you know an optical device essentially.
So, the lens cover here may be in this region
is equivalent to something, which we called
the cornea and rays, which come and strikes
the cornea kind of get bend through this region
called the pupil region, which is just immediately
behind cornea and focus on into the lens the
eye lens. The eye lens further focus these
rays into the back end of the eye, which is
this particular membrane here, which is also
known as the retina.
So, it is pretty much same as you have these
lens here as you seen the camera you have
a lens cover, which is in the cornea and this
lens is focus the light ray into something
called the film into, which the responses
recorded in terms of an optical signal. So,
the back end of the eye is really a the center
where responses can be converted from optical
into electrical and will learn little bit
how that happens essentially the photoreceptor
nerve cells of the retina changes light rate
into electrical response and send them into
brain through optic nerves and there is a
chemical electro chemical transduction process,
which happens there is compound called retinal,
which changes into it is transform giving
and electron, which goes into the brain and
causes the sensation because of that. So,
the human eye is a fascinating sensor it accommodate
to changing light conditions automatically
there is a contraction and expansion in this
receiving part of the eye due to which the
light can focus on to you know retina for
light emanating from various distances place
close or far away from the eye you have a
different focusing aspect of the length, which
can accurately focus it every time on to the
retina respective of how far or how near in
the object. So, it is essentially again and
interesting sensor model.
So, if you put this whole thing together as
the sensor device. So, the analyte of interest
here really is the light signal, which we
are trying to detected the biological detection
element here of the nerve cell on the retina
as we have been talking about and the transduction
here is a retinol just coming in a little
bit and. So, there is conversion of the light
really passing through this biological detection
element in to an electrical signal, which
goes through these optic eye nerves into the
brain and thus the brain here essentially
is a signal processor. And it detects and
changes according to the responses gets.
So, what happens essentially in the transduction,
let us look at the molecular structure here
called cis retinal is illustrate here the
transduction takes place again through a molecule
called rhodopsin, which is essentially an
opsin protein and covalently linked to this
component called 11 cis isomers of retinal
and whenever light falls on at this retinal
is converted in to transform and this cis
covert into trans retinal form, which slight
change in orientation there is essentially
a the change over a part of a molecule and
what is generate extra electron.
And that electron is what causes sensation,
so the whole retina is split up into millions
of cells each of which is essentially works
in a work center, where there is a change
in these compound retinal from cis to trans
and that generates and impulse or signal which
is also known as light Now this light can
into various intensity it based on how many
electrons are really generated and goes into
the optic nerve. So, human eye again is a
fascinating sensor on which one can really
think of.
So, when we look at the various aspect for
sensor design and I would like to illustrate
this point very well, because again the purpose
of bio MEMS devices is really sensor or diagnosing
some of the things or some of the analyte
of interest So, what are aspects goes into
sensor design there are four different broad
areas in to which categories one are what
is the recognition element really is at a
is at a biological element it is a physical
element, what exactly recognize the analyte
of interest or the object of interest, which
has to be sense, what is the transduction
type, what exactly the transduction type is
the chemical to electrical is at a chemical
to optical is at a electro chemical process.
And then, we have very important issues called
method of immobilization, which means that
this recognize element has to be immobilized
on to the sensor surface .So, there are different
ways and means of doing that. So, that is
another aspect when we consider sensor design
and then finally, we are left with the performance
factors of the sensor, where in we gage how
effective the sensor would be is it really
doing is job in the manner that is supposed
are this design is, do far.
So, we will study this aspect one by one and
go a little bit more into recognition elements.
So, what really recognition element are so,
recognition element as I told you before are
elements, which would impart of the selectivity
enabling the sensor to respond selectively
to a particular analyte avoiding the interference
from other substances. So, if there are more
than one analytes in a solution and you want
to investigate a certain analyte over the
other. The recognize element, which would
give this selectivity of measuring, what you
want to measure has supposed to other five
components may be or six components which
are just presented there.
So, therefore, some examples of this recognition
element could be things like let say ion selective
electrode you have a membrane which is selective
for the analyte of interest. So, essentially
there is a membrane which would pick and choose
the particular ion of interest in to picture,
so that is what the recognition element would
be probably in bio sensor these could be biological
moieties like enzymes antibodies, nucleic
acids and receptors etcetera. So, e will be
studying it off and on detail later that,
Let say for a example the glucose bio sensor
the enzyme called gluco oxidase.
In short form we called god, which converts
glucose into gluconic acid in NHO2, if you
have a pH sensor monitor and increase in hydrogen
concentration to keep see in there is keep
increase, because of NHO2 god catalyst into
gluconic acid. So, but recognition element
is that in enzyme and so, there is a very
important aspect, that what that element would,
which can select the specific chemical of
interest over the others. So, therefore, you
know this the recognition element is very
important for any sensor essentially.
So, let be give a illustration of what some
of these element look like this is diagnostic
or detection process known as Elisa which
you also know as enzyme linked immunosorbent
assays. So, let us look at step by step, what
happens in such mechanism such a such a diagnostic
protocol. Here, it is essentially the play
of enzyme it is play of enzyme which causes
a change in color are change in absorption
spectrum of the particular media, which let
us you know whether there is a presence and
absence of the antigen of interest enzyme
or the analyte of interest enzyme the blood
of the particular patient. So, f, you look
at the various steps here, so you take something
called a plate in which antigens and I just
in a minute come to what antigens are HIV
antigens are immobilize you see this particular
you know this moieties which are present here
there are HIV antigens.
So, antigens are set of chemicals which come
as the response of pathetic attack with in
the human body, which are chemicals which
are generated inside the body I nothing these
antigens. Which show are signify the presence
or absence of particular you know taking species,
which may be to healthy over all physiological
set up of particular be. So, there are this
antigen, which is coated on it particular
plated here and we essentially take the serum
patient who is probably we diagnosis for HIV
as positive or negative. And as we know the
first line of defense within the human body
is our human immune system and whenever there
is a some kind of you know antigen attack
first line defense generate chemical are moiety
antibodies, which is try to bind or leave
are some of these attack and they do very
well with antigen and they bond do very well
with antigen.
So, we drop the blood into this particular
coated antigens and assuming that they are
the patient is positive, which is immune response
happen there is tendency of some of anti-bodies
get bonded on to this immobilized antigens
the unbounded wash out later on and so you
have only this bonded on to the antigens the
antigen are immobilized that means they chemically
somehow attached to the surface of interest
in this case which is actually reaped. And
here the antigen was getting bonded and unbounded
typically washed of this surface then want
a then, we secondary anti body which bind
to the primary anti body on particular to
secondary anti body that you have an enzyme
of a certain conjugate on secondary enzyme.
So, essentially to this element as you seeing
by a blue arrow or this blue feature and this
red feature they are conjugate of each other.
So, they are bind together to this secondary
anti body this is primary anti body which
is this immobilized antigen and the secondary
anti body which enzyme, which is actually
conjugate to the antibody Now, this kind of
orientation wash out those and you have bound
specimen here on to the surface of the plate.
And then, you put something called which can
change color on coming in the contact this
enzyme in interest.
So, this is called a chromogen, so in the
case you dropping a material chromogen into
the plane as soon as the chromogen come into
the here the color of the chromogen consider
the change in coloration from blue to green
assuming that there where known antibodies
in the patient serum very beginning here,
so there would be any bound antibodies surface
due to which he enzymes will not bind into
the immobilized antigen, because the secondary
anti body only bind to the primary anti body
the red anti body, so the absence of red would
mean all free they would be washed off and
there would be hardly change color of the
chromogen.
So, if there a change in chromogen it kind
of reflects the concentration secondary anti
body in the patient blood and the sorry the
primary anti body in the patient blood it
also indicate that how badly or how worstly
mean effected or inflected. So, with this
I would like to round of the first lecture
and in the next section we would discuss little
bit detail on how the other aspect on sensor
design in can be you know illustrate or study
in details.
Thank you.
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