(literally) Rumi Chunara EECS/HST May 1, 2007 1 - - PowerPoint PPT Presentation

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Working at the Interface of Engineering and the Life Sciences…

… (literally)

Rumi Chunara EECS/HST May 1, 2007

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Acknowledgements

• Manalis Lab: Prof. Scott Manalis, all

graduate students, undergrads and post- docs

• Prof. J. Han: graphics

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Engineering

“Engineers like to solve problems. If there are no problems handily available, they will create their own problems.” –Scott Adams “Scientists investigate that which already is; engineers create that which has never been.” –Albert Einstein

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Interfacing with other Fields

Biological systems: networks, systems, feedback pathways Engineering tools: modelling, largescale computational analysis, device design

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Probing Biological Systems

What feature size must we achieve in engineering in order to be able to probe biological systems?

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Biological Sensing

• Fluorescence
• Spectrophotometry
• Gene Chips

There is lots of information in biological pathways – need a plethora of experiments to understand and quantify

Common Laboratory Techniques:

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Our Lab

• Microfabricated devices for molecular

sensing

• Sensing by mass or charge
• Applications: studying properties of

specific cell/molecule types, identification

• f pathogenic cells, specific molecular

markers

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MOSCAP

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Field Effect Sensors

depletion width Si

SiO2

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

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Device Schematic & Readout

electrolyte

current amplifier lock-in amp voltage amp PC n-type

n++ p-type p++

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Fabricated Device

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Charge-based Measurements

time (min)

5 10 15 20 25

surface potential (mV)

• 2

2 4 6 8 10 12

time (min) 5 10 15 20 25 surface potential (mV)

• 16
• 14
• 12
• 10
• 8
• 6
• 4
• 2

2 4

Real-time measurement of Heparin: a heavily charged molecule involved in blood clotting

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Clinical “Bias” Point

Output Potential Vs. Concentration of Heparin (FET sensor) Output Potential Vs. Input Potential (MOSFET)

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Mass sensing

• Mass of items of interest
• Incorporate techniques so that only

measuring items of interest, or enhance mass of items of interest

• Mass is an obvious way to measure.

Not all biological items are charged

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SMR – Detection Principle

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Fabrication

Reactive Ion Etching Buffer Oxide Etching Anodic Bonding Thermal Oxidation

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Transduction of Signal: Readout

Optical Resistive Capacitive

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Transducing the signal

Detection Schemes:

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Applications: Sensing Bacteria

Peak Count (%)

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Applications: Red Blood Cell Weighing

• 10

10 20 30 40 50 60 70 80

• 0.2

0.2 0.4 0.6 0.8 1 1.2 Change in Frequency (Hz) Count

Normalized Human Red Blood Cell Mass Histogram

~125 pg ~100 pg ~150 pg

N=3

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Application: Antibody Detection

Frequency Shift Vs. Molecular Concentration

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Benefits of Portability

Using engineering we can make devices that are sensitive, easy to use, inexpensive and can be used in rural settings.

A health care centre in Laare, Kenya

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Interfacing devices to external world

• Noise
• Small signals
• Keeping actuation/measured signals

separate (coupling)

• Materials compatible with other systems

(oxidation, fluid)

• Cost

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Biosensors: what are they for?

• Diagnostics (inside and outside laboratory)
• Small volumes
• Scalability, making more measurements to

understand biology

• Point of care devices
• Personalized medicine

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Helpful Classes

• Intro. EECS

6.002, 6.003 6.011, 6.012, 6.013 Quantitative Biological Systems 6.021J, 6.023J, 6.561J Lab in Microscale Engineering 6.07J Advanced Device/Electronics 6.777, 6.376

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Groups at MIT and Beyond

Analog Devices, Becton Dickinson and Company, Affymetrix

• S. Manalis (BE/ME)
• J. Voldman (EECS - RLE)
• J. Han (EECS - RLE)
• D. Freeman (EECS)
• M. Schmidt (EECS)
• S. Bhatia (EECS/HST)
• S. Amarasinghe (EECS – CSAIL)
• T. Thorsen (ME)