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Overview of Techniques in Biomedical Engineering

Arunesh Mittal
Introduction
Since the first transistor was created in 1947, Moore's Law, which states that the number of
transistors in an integrated circuit doubles approximately every two years, has generally
held true. This has allowed for us to fit more computing power on smaller devices, in fact,
with simple back of the envelope calculations one can affirm that the computing power of a
modern day smartphone today is on par with that of one of the fastest computers in the
world from 1987. Developments in manufacturing technology have allowed us to create
diminishingly small devices with ever increasing computational power. These advents in
technology have enabled biomedical engineers to develop extremely small instruments for
measurement physiological variables. These advances set the stage for the development of
many small implantable medical devices in use today, such as close loop deep brain
stimulation (DBS) and cardiac pacemakers [1,2] (Fig. 1).

Figure 1: Deep brain stimulation device, schematic for implant placement, cardiac pacemaker, schematic for
implant placement (Top Left, Bottom Left, Top Right, Bottom Right respectively)[4,5]

As computers have evolved so have micro-fabrication techniques and methodologies.


Advances in micro-fabrication techniques have allowed for higher resolution and smaller
micro-fabricated devices; Biological assays that required large volumes of reagents and
samples can now be performed on a chip (Lab on a chip)[3]. Microfluidic devices have made
an impact in many areas of biology and medicine. For example: nucleic acid arrays for
hybridization analyses and microtubule dynamics [6,7] (Fig 2,3).

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Figure 2: Channels containing microfabricated silica pill for nucleic acid purification (filtering) [6]


Figure 3: Positioning of microtubule organizing center (MTOC) in microfabricated chambers [7]


Biomedical Instrumentation
Biomedical instruments usually consist of elements that can broadly be classified into two
categories essential and options. Essential elements are the measurand, primary sensing
element, variable conversion element, signal Processing and output Display. Optional
components include the power Source, control and feedback, data transmission, data
storage, calibration system, radiation, current or other applied energy. The engineered
biomedical instrument usually measures a measurand (Fig. 5). The measurand is the
physiological quantity measured by an instrument [8].

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Figure 5: Component of a biomedical instrumentation system [9]

The sensing element or the sensor can belong to one of the following three broad
categories:

Resistive sensor: a transducer or electromechanical device that converts a mechanical
change such as displacement into a change in electrical signal by changing its resistivity in
some form. Example: Strain Gage.
Capacitive Sensor: a transducer or electromechanical device that converts a mechanical
change such as displacement into a change in electrical signal by changing its capacitance
in some form. Example: Touch Screen.
Inductive Sensor: A transducer or electromechanical device that converts a mechanical
change such as displacement into a change in electrical signal by changing its inductance
in some form. Example: LVDT.
The signal from the sensor is measured using transducer, which is a device that converts a
signal form one form of energy to another form of energy. For example: Thermistors:
Convert heat into change in voltage, Piezoelectric Sensor: Convert change in mechanical
energy to change in electrical Energy and Radiation Sensor: Convert radiation energy into
change in electrical energy [8].

Microfabrication

Microfabrication is a technique used to fabricate Small 3D micrometer scale patterns.
The patters can be created using photolithography on silicon wafers. Photolithography
the transfer of a pattern into a material entails the following steps [9] (Fig. 5):
Thin Film Growth/Deposition micron-scale films grown or deposited on the substrate
Etching creation of features by selectively removing materials in defined patterns
Bonding the bonding of two substrates together

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Figure 5: Schematic outlining the photolithography process [9]


Physiological processes can either be sensed or can act as sensors themselves. Biosensors
such as oxymeters and glucometers are sensors that convert physiological signals into
electrical ones. Microfabricated devices can significantly enhance existing devices and
enable new devices by allowing precise measurements at a micrometer scales. The small
size of microfabricated devices enhances and even enables new applications.
Integration of Instrumentation and Microfabrication
Electrical components have been successfully incorporated in microfabricated systems, for
example, cortical electrode arrays used to record cortical neural activity. The electrode array
consists of sharp silicon needles with integrated electrodes (Figure 6). The electrodes are
fabricated in the process outlined in figure 7. The electrode array is inserted into the cortex
and is used to measure extracellular recordings of action potentials. The integrated circuits
generate stimulus currents, amplify recorded signals, and process the data to reduce the
number of electrical leads needed.


Figure 6: Structure of multichannel silicone recording probe [10]

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Figure 7: Microfabrication sequence for passive multi-electrode probes [10]

Microelectrode technology that combines both microfabrication and instrumentation allows


researchers to measure signals from cortical circuits; this allows researchers to analyze neural
circuits in-vivo. In addition to the example above, several medical devices such as the class of
devices called micro-electric mechanical systems (MEMS), incorporate microfabrication and
instrumentation principles [11]. A current medical device in the research phase that utilizes both
instrumentation and microfabrication is a retinal electrode device developed by the retinal
implant research (RLE) group at MIT (Fig 8).


Figure 8: Retinal implant device integrates micro-fabrication and instrumentation [12]
(Top) First generation retinal implant. (Bottom) Second generation implant

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The RLE group is in the process of developing a retinal prosthesis akin to a cochlear implant but
for vision, to restore partial vision to patients who suffer from diseases such as retinitis
pigmentosa and age-related macular degeneration. The diseases cause loss of the
photoreceptors of the outer retina but spare the inner retinal ganglion nerve cells. A blind
patient can wear a camera mounted on a pair of glasses, which transmits image data to an
implant attached to the eye (Figure 8). The implant electrically stimulates retinal cells via an
array of microelectrodes [12].
Conclusion and other intersections in biomedical disciples:
Biomedical engineering much like many other branches of engineering is extremely
interdisciplinary. New innovations in biomedical engineering draw theoretical and practical
concepts and ideas from a variety of other disciplines, from chemical engineering and electrical
engineering to neuroscience and computer science. Many of the theoretical and practical
underpinnings of the module topics discussed over the course of the BEPI lab can be applied to
novel problems. A tissue culture of myocites can be made to contract using electronic
instrumentation to create a muscular prosthetic, gel compaction can be used to study skeletal
muscle properties and microfabricated devices can be used to create assays for studying cell
adhesion. Many seemingly unrelated concepts can be brought together to improve biomedical
technology and to create novel devices.

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[7] Holy, Timothy E., et al. "Assembly and positioning of microtubule asters in microfabricated chambers."
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[8] Webster, J. G. Medical instrumentation application and design. New York: John Wiley & Sons. (4th
Ed.; 2010).
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Annual review of biomedical engineering 1.1 (1999): 401-425.
[10] Najafi K. 1994. Solid-state microsensors for cortical nerve recordings. IEEE Eng. Med. Biol. Mag. 13(3):37587
[11] Ho, Chih-Ming, and Yu-Chong Tai. "Micro-electro-mechanical-systems (MEMS) and fluid flows."
Annual Review of Fluid Mechanics 30.1 (1998): 579-612.
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