1. Bio – MEMS abbreviated form of Bio – Medical ( or Biological ) Micro Electro Mechanical System. 2. Techniques originally developed in Microelectronic Industries. It considers Lab - on – a – chip (LOC) and Micro Total Analysis System (μTAS). 3. More Focused on ( Made suitable for Biological Application ) 4. Mechanical Parts Microfabrication Techniques Bio – MEMS combines Material Science & Clinical Science Medicines and Surgery Electrical Engineering Optical, Chemical & Biomedical Engineering 5. Applications Includes : a)Geonomics & Proteomics b)Molecular & Point of care Diagnostics c)Tissue Engineering & Implantable Micro Devices

1. Presented By :
2021608030
M.E – Mechatronics Engineering
Department of Production Technology

2.  Introduction
 History
 Approaches
 Bio-MEMS as Miniaturized Biosensors
 Devices
 Application of Bio – MEMS
 Bio-MEMS in Medical Implants and Surgery
 Future Technologies
 Summary
 References
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3.  Bio – MEMS abbreviated form of Bio – Medical ( or Biological ) Micro Electro
Mechanical System.
 Techniques originally developed in Microelectronic Industries. It considers Lab
- on – a – chip (LOC) and Micro Total Analysis System (μTAS).
 More Focused on ( Made suitable for Biological Application )
 Mechanical Parts
 Microfabrication Techniques
 Bio – MEMS combines
 Material Science & Clinical Science
 Medicines and Surgery
 Electrical Engineering
 Optical, Chemical & Biomedical Engineering
 Applications Includes
 Geonomics & Proteomics
 Molecular & Point of care Diagnostics
 Tissue Engineering & Implantable Micro Devices 2

4.  A lab-on-a-chip includes analyses such as
DNA sequencing or biochemical
detection. a miniaturized device that
integrates into a single chip one or
several analyses, which are usually done
in a laboratory.
 A lab-on-a-chip scheme includes
 Blood Sample
 Extraction
 Amplification
 Detection
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5.  Micro Total Analysis Systems (μTAS)
are devices that automate and include all
necessary steps for a chemical analysis of a
sample (e.g. sampling, sample transport,
chemical reactions, detection).
 Micro Total Analysis Systems (μTAS)
Includes :
 Protein Analysis
 DNA Techniques
 Drug Efficiency Studies
 Single Cell Analysis
 Diagnostics and Sensors
(Integration of all the components in one device)
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6.  1990 : HGP (Human Genome Project) started in October created
demand for improvement in DNA sequencing capacity.
 1991 :First Oligonucleotide chip was developed.
 1993 :A Harvard Chemist, George M. Whiteside introduced PDMS – based
microfabrication
 1998 :First solid Micro Needles are developed for drug delivery.
 1998 :Continuous Flow polymerase chain reaction ship was developed.
 1999 :First demonstration of heterogeneous laminar flow for selective
treatment of cells in micro channels.
 Today : Hydrogels and self-assembly are key areas of research in the
improvement of Bio - MEMS
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7.  Materials
 Silicon & Glass
 Conventional micromachining techniques been used in bio mems to make flow channels,
flow sensors, mixers, filters, pumps & valves.
 Due to being once used material, the requirement of high material and processing cost make
silicon based Bio – MEMS less economically attractive.
 Plastic and Polymers
 Using plastic and polymers in Bio – MEMS is attractive because they can be easily
fabricated, low cost & compatible with micromachining and rapid prototyping methods.
 Common polymers are : PMMA, PDMS, OST Emer and SU- 8.
 Biological Materials
 Micro - Scale manipulation and patterning of biological materials used in
development arrays, microarrays, micro fabrication based tissue engineering
and artificial organs.
 Biological Micromachining is used for high throughout single cell analysis and
control integration of cells into multi cellular architectures.
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8.  Paper
 Paper microfluids (Lab-on-paper) is used in microfabrication to manipulate fluid flow for
different applications.
 Paper Microfluids is used in the most notable being the commercialized pregnancy test.
 Advantages includes Low cost, Bio degradability & natural wicking action.
 Techniques for the Micro – patterning includes photo lithography, laser cutting, ink jet
printing, plasma treatment and wax patterning
 Electro-Kinetics
 It is exploited for separating mixtures of molecules and cells using electrical fields in
electrophoresis.
 Electrophoresis has been used to fractionate small ions, charged organic molecules,
proteins and DNA.
An Experimental Example
of
Electrophoresis
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9.  Microfluidics
 It is a system that manipulate small amounts of fluids on micro fabricated substrates.
 Approaches configures several advantages :
 Flow in microchannels is laminar, which allow selective treatment of cells.
 Can be fabricated on the cellular scale or smaller, which allows investigation of cellular
phenomena.
 Integration of micro electronics, micro mechanics and micro optics allows automated device
control which reduces errors and operational costs.
 Relatively economical due to batch fabrication.
 Consumes much smaller amount of reagents.
 Appropriate packing needed.
When Multiple channels are added in the same
microchannel, they flow in separate flow lanes
(no mixing) due to laminar flow characteristics
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10.  Biosensors are devices that consist of a biological recognition system, called the bioreceptor and
a transducer.
 The interaction of the analyte with the bioreceptor causes an effect that the transducer can
convert into a measurement, such as an electrical signal.
 The most common bioreceptors used in biosensing are based on the antibody-antigen
interactions, nucleic acid interactions, enzymatic interactions, cellular interactions and
interactions using biometric materials.
 Common transducer techniques include mechanical detection, electrical detection and optical
detection
 Biosensor is an analytical device, used for the detection of an analyte, that combines a
biological component with a physicochemical detector.
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11.  Micromechanical Sensors
 Detection is achieved through micro and nano scale cantilevers for stress and mass sensing.
 In stress sensing, the biochemical reaction is performed on one side of the cantilever to cause
a change in surface free energy.
 When biochemical reaction captured in the cantilever, the mass and resonant frequency of the
cantilever changes.
 Advantages of using cantilever sensor is that there is no need for an optically detectable label
on the bioreceptors.
 Electrical and Electrochemical Sensors
 The detection is easily adapted for portability and miniaturization especially in comparison to
optical detection.
 In amperometric biosensors, an enzyme- catalyzed redox reaction causes a redox electron
current that is measured by a working electrode.
 Amperometric biosensors used in detection of glucose, galactose, lactose, urea & cholesterol. It
also used in gas detection and DNA Hybridization.
 Conductive measurements are simple & easy to use ( due to no need for a specific reference
electrods and have been used to detect biochemicals, toxins and nucleic acids).
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12.  Optical Sensors
 A challenge in optical detection is the need for integrating detectors and photodiodes in a
miniaturized portable format on the bio-MEMS.
 Optical detection consists of fluorescence-based techniques, chemiluminescence-based
techniques and surface plasmon resonance (SPR).
 FBOT use makers that emit light at specific wave lengths and the presence of
enhancement/ reductions in optical signal indicates a reaction has occurred.
 SPR is the resonant oscillation of conduction electrons at the interface between a negative
and positive permittivity material stimulated by indicated light.It is fundamental principle
behind colour-based biosensor applications and different lab-on-a-chip sensors
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13.  In general, the use of micro and nano-scale detection technologies is justified by :
 Reducing the sensor elements to the scale of the target species and hence providing a
higher sensitivity single entity/molecules.
 Reduced reagent volumes and associated costs.
 Reduced time to result due to small volumes resulting in higher effective
concentrations.
 Amenability of portability and miniaturization of the entire system.
 Point-of-care diagnostics.
 Multi-agent detection capability.
 Potential for use in vitro as well as in vivo.
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14.  Through the use of MEMS technology and micro fabrication
techniques, drug delivery research has been able to make a
significant departure from traditional methods.
 It can be positioned in the body by implantation or by tradition
pill.
 On promising such devices is a chip that contains micro
reservoirs full of prescribed drug.
 The reservoirs are created on the substrate using micro
fabrication techniques and are filled with the drug.
 The drug contained in the reservoirs are released by a variety
of different techniques.
 The extremely small volumes of the reservoirs means the
concentration of the drug needs to be sufficient to obtain the
desired effect
Fig : Reservoir Chip Schematic
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15.  Transdermal Devices
 As opposed to in VIVO devices, transdermal devices deliver the drug through the skin.
 Most commercially available transdermal devices are passive, meaning the drug is applied
to the skin and is allowed to just soak in.
 Unfortunately, due to the nature of skin, this technique only works on small, lipophilic
molecules. Thus passive thermal devices are minimally invasive, but are often not very
effective.
 To improve the effectiveness of transdermal drug delivery, active devices have been created
that utilize iontophoretic, chemical enhancers and ultrasound. MEMS are also been used in
this respect.
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Fig : The Small Pill

16.  Reservoir Implantation Device
 The implantation devices were found to be the best choice based on the act that they
offer a greater deal of control and are more effective than the transdermal techniques.
Another advantage of this device is its versatility
 The device was chosen over the smart pill because of its design simplicity, which makes
it easier to manufacturer.
 For the most part, the reservoir implantation device can be manufactured using simple
micro fabrication techniques.
 The device can be activated in several different ways. It can be activated by remote
control, giving to the doctor or the patient. It can be activated on a set time basis.
 Some devices are even automatically triggered by sensors built into the device that
detect when the drug needs to be administered.
Fig : a) SEM Picture of a 350 micron high microneedle, with a base of 250 microns, the
flow channel of 70 micron in its widest range b)Schematic Diagram of Iontophoresis
Circuit.
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17.  Genomic and Proteomic Microarrays
 Oligonucleotide Chips
 These are microarrays of oligonucleotides. They can be used for detection of
mutations and expression monitoring and gene discovery and mapping.
 Using gel pads, prefabricated oligonucleotides are attached to patches of
activated polyacrylamide.
 Using microelectrodes, negatively charged DNA molecular probes can be
concentrated on energized for interactions.
 cDNA Microarray
 These are often used for large-scale screening and expression studies. In cDNA
Microarrays, mRNA from cells are collected and converted into cDNA by reverse
transcription.
 For detection, fluorescently-labelled single strand cDNA from cells hybridize to
the molecules on the microarray and a differential comparison between a treated
sample and a untreated sample used for analysis.
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18.  Red dot mean that the corresponding gene was expressed at
the higher level. Green dots mean that the corresponding gene
was expressed at a higher level in the untreated sample.
Yellow dots, as a result of the overlap between red and green
dots.
Fig : Differential comparison
in cDNA microarray
 Peptide and protein Microarrays.
 The motivation for using peptide and protein microarrays is
because mRNA transcripts often correlate poorly with the
actual amount of protein synthesized.
 DNA Microarrays cannot identify post – translational
modification of proteins which directly influences protein
function.
 PCR Chips
 The polymerase chain reaction (PCR) is a fundamental
molecular biology technique that enables the selective
amplification of DNA sequences, which is useful for expanded
use of rare samples.
 E.g. : Stem cells, biopsies, circulating tumour cells
Fig : Circular film based PCR
Microfluidic system
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19.  Point Care Diagnostic Device
 It has been developed to take saliva, blood, or urine samples and in a integrated
approach perform sample preconditioning, sample fraction, sample amplification,
analyte detection, data analysis and result display.
 Types :
 Sample Conditioning
 Sample Fraction
 Bio-MEMS in Tissue Engineering
 Cell culture
 System cell engineering
 Fluid shear stress
 Cell- ECM Interactions
 Cell – Cell Interactions
 Embryoid Body formation and organization
 Assisted Reproductive Technologies
(a) (b)
Fig : a) The lung-on-a-chip device
simulates the contraction of the
diaphragm
b) Murine Embryoid bodies in suspension
culture.
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20.  Implantable Microelectrodes
 The goal of implantable microelectrodes is to interface with thee body’s nervous system
for recording.
 Sending bioelectrical signals to study diseases, improve prostheses and monitor critical
parameters.
 Microfabrication has lead to the development of Michigan probes and the Utah electrode
array, which have increased electrodes per unit volume, while addressing problems of
thick substrates causing damage during implantation and triggering foreign-body
reaction and electrode encapsulation via silicon and metals in electrodes.
 Microtools for surgery
 Bio-MEMs for surgical applications can improve
existing functionality, add new capabilities for
surgeons to develop new techniques and procedures
and improve surgical outcomes by lowering the risk
and providing real-time feedback during the
operations.
 Incorporation of sensors onto surgical tools also
allow tactile feedback for the surgeon. Fig :A Cardiac Balloon Catheter
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21.  Identification of tissue type via strain and density during cutting operations and the blood
diagnostic catheterization to measure the blood flows, pressures, temperatures, oxygen
content and chemical concentrations.
 Drug Delivery
 Microneedles, formulation system and implantable system are Bio-Mems applicable to
drug delivery.
 Microneedles of approximately100um can be penetrate the skin barrier and deliver drugs
to the underlying cells and interstitial fluid with reduced tissue damage, reduced pain and
no bleeding.
 Microneedles can also be integrated with microfluidics for automated drug loading or
multiplexing.
Fig : Transdermal Microneedles patch is less
Invasive compared to conventional drug
Delivery.
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22.  The future of MEMS is the integrity linked to the market trends in general and driven
by the increasing demand to monitor and control our environment and the equipment
and instruments we use in our daily life.
 This demand does, undoubtedly, lead to the need for more sensors in cars, more
sensors in industrial equipment's and installation and more sensors for our ambient
intelligences.
 In order to avoid the need for multitude of wires, such sensors must be self sustaining
and able to communicate wirelessly.
 As a result, not only more sensors are needed, but also small energy generating
modules and wireless transmission components.
 There is a tendency to explore more flexible and more affordable production
technologies. This will be driven by the production research into typical low cost, large
surface area devices like solar cell, displays, wearable electronics and disposable
diagnostics devices.
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23.  MEMS are a class of miniature devices and systems fabricated by micromachining
processes. MEMS devices have critical dimensions in the range of 100nm to 1mm.
 MEMS technology is a precursor to the relatively more popular field of
nanotechnology, which refers to science, engineering and technology below 100nm
down to the atomic scales.
 Occasionally, MEMS devices with dimensions in the millimeter-range are referred
to as meso- scale MEMS devices.
 As drug delivery systems improves, the components of the systems continue to
decrease in size.
 Many of the future and developing technologies are based on the nano – scales.
 These nano- particles are particularly useful when a drug must target certain
areas of the human body.
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24.  Abushagur,.A,.A, Arsad N, Reaz, M.I. & Bakar A. 2014, Advances in Bio-Tactile
sensors for minimally invasive surgery using the fibre bragg grating force sensor
technique : A survey on sensors, Vol. 4, pp. 6633-3335.
 Aguirregabiria, M. Blanco, F. berganzo, J. Ruanao, J. Aranburu, I. Gracia, J &
Mayora K. 2004. novel su8 multilayer technology based on successive c-mos
compatible adhesive bonding and Kapton releasing steps for multilevel
microfluids devices. Special Publication – Royal Society of Chemistry, Vol 297, pp
49-51.
 Cao, C. Britwell, S. W. Hegberg, J. Wolff, A. Murgan, H & bang D, Surface
modification of photoresist su-8 for low autofluorescence and bioanalytical
applications. 15th international conferences on miniaturized systems for chemistry
and life sciences, 2011 . Pp. 1161-1163
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