Principles of Electronic Nanobiosensors

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1 Principles of Electronic Nanobiosensors Unit 5: Putting the Pieces Together Lecture 5.4: Concluding Thoughts By Muhammad A. Alam Professor of Electrical and Computer Engineering Purdue University A. Shakouri nanohub-u Fall

2 Outline A summary of what we have learnt in this course History Settling time, Selectivity, Sensitivity Sensors we did not consider Looking ahead Lab on a chip vs. implantable sensors Importance of sensing and actuation Conclusions Geometry is physical, especially at nanoscale Alam, Principles of Nanobiosensors,

3 Why nano-biosensors Protein/Gene network Glucose, DNA, Protein network, virus, bacteria Alam, Principles of Nanobiosensors,

4 A short history of the three sensors Virus/bacteria Protein/DNA PCR ph-meter (potentiometric) Glucose (amperometric) Ion torrent Vacuum tube MOS IC 4 Alam, Principles of Nanobiosensors,

5 Geometry is the key for nanobiosensing Settling time Sensitivity Selectivity Alam, Principles of Nanobiosensors,

6 (A) Settling Time: A Mendeleev Table am fm pm nm mm mm ( ) F ρmin = N0 D t s (3 D ) 2 Alam, Principles of Nanobiosensors,

7 Strategies to Beat the Diffusion Limit τ L D D k T πaη 2 ~ ~ B 6 Fragment the space Reduce the space Generate locally Magnetic Biobarcode Droplet Evaporation Ion Torrent Approach All can achieve sub-fm detection in reasonable time Alam, Principles of Nanobiosensors,

8 (B) Three types of sensors Potentiometric Amperometric Cantilever Fluid Gate Ref. & Aux. Electrode Gate Charge to current Chemical to current Mass to frequency Alam, Principles of Nanobiosensors,

9 Improving the sensitivity limits Potentiometric Amperometric Cantilever Alam, Principles of Nanobiosensors,

10 (C) Selectivity Classified Energetics RSA Noise α+ β α β β β 1 β β β β α 0 = β β β α β 0 α + β β β β α 1 Alam, Principles of Nanobiosensors,

11 Improving Selectivity New DNA Incubation Passivation Noise averaging Alam, Principles of Nanobiosensors,

12 Sensors not discussed: Optical Sensors ELISA SERS Anker et al., Nature Mat., Resonator Vollmer., Nature Methods, 2008 Armani, Science,2008 Settling time, Sensitivity, Selectivity Alam, Principles of Nanobiosensors,

13 Optical Sensors SERS McFarland et al., Nano Lett., λ 2 d () t / l max ( t) mn ( )(1 d after nbefor e e ) where dt ( ) ~ Nt ( ) ~ t t 1/2 (1D) (2D, 3D) Anker et al., Nature Mat., Alam, Principles of Nanobiosensors,

14 Outline A summary of what we learnt in this course History Settling time, Selectivity, Sensitivity Sensors we did not consider Looking ahead Lab on a chip vs. implantable sensors Importance of system level perspective Conclusions Geometry is physical Alam, Principles of Nanobiosensors,

15 Lab on a chip: ph-based genome sequencer Sanger method (1990s) Babbage computer (~1830s) Ion-torrent system (2011) Intel Chip Today Alam, Principles of Nanobiosensors,

16 Promise of nanobiotechnology Lab-on-a-phone (nano+biotechnology) Always on sensor network (nanotechnology + biotechnology + wireless technology) Alam, Principles of Nanobiosensors,

17 Conformal Electronics and Smart Bandages D.-H. Kim et al., Epidermal Electronics, Science, 333, 838, Alam, Principles of Nanobiosensors,

18 Implanted Sensors: Heart D.-H. Kim et al., Materials for multifunctional balloon catheters with capabilities in cardiac electrophysiologial mapping and ablation therapy, Nature Materials, 10, p. 316, Reliability in fluids Energy harvesting Noise immunity Biofouling Alam, Principles of Nanobiosensors,

19 Sensing and actuation Sensor Interpret Actuate Alam, Principles of Nanobiosensors,

20 Sensing and actuation: Optogenetics Photo-sensitive channels Electrodes Interpret Lasers Alam, Principles of Nanobiosensors,

21 Outline A summary of what we learnt in this course History Settling time, Selectivity, Sensitivity Sensors we did not consider Looking ahead Lab on a chip vs. implantable sensors Importance of system level perspective Conclusions Geometry is physical Alam, Principles of Nanobiosensors,

22 A sensor as a biomimetic device Geometry of diffusion Berg, 1963 Alam, Principles of Nanobiosensors,

23 Form Defines Function Everywhere Nature works true to scale, and everything has a proper size accordingly," wrote Thompson. "Cell and tissue, shell and bone, leaf and flower are so many portions of matter, and it is in obedience to the laws of physics that their particles have been moved, moulded and conformed." Life s Other Secret by Ian Stewart Alam, Principles of Nanobiosensors,

24 Performance low medium high Poly-Si Landscape of Electronics Small Medium Large Area Carbon NanoNet OPV supercapacitors Flexible/ wearable electronics Energy Harvesting Biosensors 24

25 Conclusions We discussed the physics of nanbiosensors as a remarkably sensitive analytical tool. This success builds on a century long effort. Many of these sensors will soon be integrated within smartphone platform, with broad technological implications. Nano is different, not because of quantum effects but because of geometry. Biology is biosensing. Lessons learnt in this course is broadly relevant for appreciating many aspects of biophysics. Alam, Principles of Nanobiosensors,

26 Acknowledgement Students Settling Time: Pradeep Nair Beating the diffusion limit: Aida Ebrahimi and Piyush Dak Potentiometric Sensors: Jonghyun Go, Pradeep Nair Cantilever-based Sensors: Ankit Jain Homework and biosensorlab: Xin Jin and Sambit Palit Colleagues Profs. R. Bashir and David Janes Funding National Science Foundation, National Institute of Health, Department of Defense, Network of Computational Nanotechnology Alam, Principles of Nanobiosensors,

27 References Fenno, Lief, Ofer Yizhar, and Karl Deisseroth. "The development and application of optogenetics." Annual review of neuroscience 34 (2011): Stewart, Ian. Life's other secret: The new mathematics of the living world. New York: Wiley, Thompson, Darcy Wentworth. "On growth and form." On growth and form.(1942). Kim, Dae-Hyeong, et al. "Epidermal electronics." Science (2011): Hung, Paul J., et al. "Continuous perfusion microfluidic cell culture array for high throughput cell based assays." Biotechnology and bioengineering 89.1 (2005): 1-8. Alam, Principles of Nanobiosensors,

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