Principles of nanobiosensors


Introduction to a new course on Principles of Nanobiosensors by Prof. Alam

https://www.youtube.com/watch?v=VkibrZEDG8k


1. Introduction and background

Biotechnology and bio-sensing are often mentioned as the next frontier of electronics that could rival semiconductor industry’s broad and revolutionary impact on society. Since any disease is a signature of either a genetic defect or broken signaling pathways that occur far in advance of any overt signature detected by classical sensors, one of the grand challenges of modern bio-sensing is to find cost-effective, reliable, fast methods for gene sequencing (as an ultimate “Finger-print” of one’s biological make-up and possibly early intervention for genetic anomaly) and the detection/identification of the irreducible and emergent protein network for application in proteomics and system biology.

Modern bio-sensors based on nanoscale electrical devices promise highly sensitive detection of bio-molecules unmatched by existing classical techniques. The emergence of nanometer-scale fabrication techniques has enabled a dramatic reduction in device dimensions so that the bulk conduction mechanisms can now be controlled by surface properties, with a corresponding dramatic increase in the sensitivity of nano-scale bio-chemical sensors. Here, we provide a geometro-physical description of nanoscale biosensors in terms of geometry of diffusion, electrolyte screening, and excluded interaction of molecules on sensor surface.

1.1 Some general books and articles

    • Random Walks in Biology, H. C. Berg, Princeton, NJ: Princeton Univ. Press, 1993. Talk1 Talk2
    • http://www.ibiology.org/ibioseminars/biophysics-chemical-biology/howard-berg-part-1.html
    • Life in Moving Fluids: A Physical Biology of Flow, Steven Vogel, Princeton Univ. Press, 1994.
    • A Physicist Looks at Biology, Max Delburck, 1966.
    • Genome: The autobiography of a species in 23 chapters, Matt Ridley, Perennial, 1999.
    • The 1000 dollar genome: Kevin Davies, Free Press, 2010.
    • The Emperor of All Maladies, A Biography of Cancer, Siddhartha Mukherjee, Scribner, 2011.
    • Chemistry: The Central Science, 9th Edition, Prentice Hall
    • The ABC's (and XYZ's) of Peptide Sequencing, H. Steen and M. Mann, Nature, p. 699 2004.
    • Mathematical Model in Biology, Edelstein and Keshet, SIAM Classics.
    • For very basics of biochemistry and biology, see http://www.ibiology.org/
    • Physics of nervous sytems Link . Anatomy Crash Course Youtube AP lectures

1.2 My course on electronic biosensors integrates most of the concepts discussed below

    1. Nanostructured Electronic Devices: Percolation and Reliability http://nanohub.org/resources/7168
    2. Series on Electronics from Bottom Up: http://www.worldscibooks.com/series/lnlns_series.shtml
    3. A Special Section on Nanobiosensors: http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=7244280
    4. A terrific set of video tutorials are available at http://www.sumanasinc.com/webcontent/animations/molecularbiology.html


2 Response Time


2.1 Response in Classical Sensors

    1. Diffusion limited settling time in classical sensors (APL 2006, PRL 2007, M. J. Eddowes, Biosensors, 3,1,1987)
    2. Flow enhanced settling time (NL 2005, NBT 2008, Making it Stick, Nature Biotechnology, 26(4), 417, 2008.
    3. Noise and fluctuation in biosensing (APL 2009)
    4. Stability of biosensors in fluidic enviroment (APL 2010).
    5. Response of microarrays ( Real-time DNA Microarray Analysis,” Nucleic Acids Research, doi:10.1093/nar/gkp675, 1-12,2009).

Geometry of Diffusion and Limits of Nanobiosensing, 2006. A Presentation at nanohub.org

BioSensorLab: An open access tool to evaluate and predict the performance parameters of nanoscale biosensors

http://www.falstad.com/gas/ ... Select Brownian motion to see how the biomolecules diffuse in the presence of random scattering


2.2 Diffusion in Complex Media

    1. Fractal Sensors ( PRL 2007, Fractal 2010)
    2. Diffusion in Complex Environment
    3. Response time vs. Narrow escape time vs. first passage time (Redner, A Guide to First Passage Time, Cambridge)
    4. A broad review of diffusion of molecules in biological systems: D. Holcman and Z. Schuss "Time Scale of Diffusion in Molecular and Cellular Systems", J. of Math Phys. 2014. PDF


2.3 Beating the Diffusion Limit


    1. Setting time in a biobarcode sensors (Analyst 2010)
    2. Ion torrent and making the box smaller (Ion Torrent)
    3. Beating diffusion by evaporation (Analysis of droplet evaporation, Langmuir, 21, 11053, 2005). A glossary of definitions are available at http://www.ramehart.com/glossary.htm
    4. Searching in multiple dimensions (How Proteins search for their specific sites on DNA, Biomedical Journal, 90, 2731,2006.)
    5. Beating the diffusion limit by a superhydrophobic droplet. Experiment Theory


Droplet logic, Advanced Materials, 2012. PDF

Droplet physics: http://nyti.ms/1Z7MGY4


3 Sensitivity


3.1 Screening and Sensitivity

      1. Sensitivity in screening limited enviroment (NL 2008, Debye Screening in Single Molecule CNT, Nano Letters, 2011)
      2. Design consideration of nanobiosensors (TED 2007)
      3. Faradic vs. Nonfaradic electrodes, (Contacting vs. Insulated Gate Electrodes, Analytical Chemistry, 83, 9546, 2011.
      4. Highly sensitive MoS2 sensors, Accepted in Nature Scientific Reports, 2014.
      5. The challenge of Graphene Biosensors (Janata, http://ssl.ecsdl.org/content/1/6/M29.full.pdf+html)

Dried samples retain the memory of charged state (Enzyme memory). H. P. Yennawar, JACS, 1995.

A recent simulator by the Udine group (ENBios-1D) has been posted at https://nanohub.org/tools/biolab/session?sess=971809

3.2 Calculating Charge of biomolecule

      1. Theory of charges in DNA and Protein (Biophysics -- An Introduction, Cotterill).
      2. Site binding theory of pH sensors (30 years of ISFETOLOGY, Sensors and Actuators B, 88, 1-20, 2008. A general model to describe the electrostatic potential at electrolyte/oxide interface, Colloid and Interface Science, 69, 31-62, 1996
      3. A nice video explaining the practical aspects of a pH sensors is posted at https://www.youtube.com/watch?v=P1wRXTl2L3I


3.3 Beating the Screening Limit

      1. Descreening at high frequencies (Detection beyond Debye screening, Nano Letters, 12, 719, 2012).
      2. Beating the Nernst limit (IEDM 2010, ACS Nano 2012, JAP 2012) (Ning Liu/Qing Yan, APL, 106. 073507, 2015)
      3. Sensitivity of redox enhanced amperometric detection (Arxib 2011)
      4. Flexture-FET Nanobiosensors (Jain, PNAS, 2012)
      5. Review of nano-electromechanical bisoensors (Roukes et al. Science, 2011).


3.4 Linear vs. Nonlinear biosensing in electromechanical system

      1. Reference on Electrochemistry (http://electrochem.cwru.edu/encycl/)
      2. On electrochemical sensors (http://electrochem.cwru.edu/encycl/art-s02-sensor.htm)
      3. A dictionary of terms is useful (http://electrochem.cwru.edu/ed/dict.htm)
      4. A wonderful personal take on the history of electrochemistry is discussed in "A Life in Electrochemistry" by A. Bard Annu. Rev. Anal. Chem. 2014. 7:1–21 (10.1146/annurev-anchem-071213-020227)


4 Selectivity


4.1 Nonselective binding (Energy)

      1. Theory of DNA Binding: Ray and Manning, Langmuir, 10(7), 2460, 1994.
      2. DNA inspired electrostatics, Physics Today, 53(9), 38, 2000. Triple Helix, P.E. Neilson, Scientific American.
      3. Melting Point Calculator: http://protein.bio.puc.cl/cardex/servers/melting/sup_mat/servers_list.html
      4. Designing Aptamers with better selectivity (Applied Physics Reviews, Criaghead) PDF



4.2 Non-selective binding (Space)

      1. Theory of selective absorption (JAP 2010, From Car parking to Protein absorption, Colloid and Surfaces B, 165, 287, 2000).
      2. Background paper on sphere-packing problem (Scientific American 1998).
      3. Kinetics of Irreversible absorption, Langmuir, 16, 5730, 2000. J. M. Evans, Rev. Mod. Phys. 1281, 1993.

4.3 Improved Selectivity -- Filter and Amplify


5 Putting it together


5.1 Physics of Genome Sequencing

      1. Genome sequencing by Illumina
      2. An overview: Breaking the fundamental limits of biosensing
      3. Physics of Genome Sequencing: A Talk at Purdue Physics Department


5.2 Microfluidics (aka the interconnects)

      1. Point-of-care fluidic systems by Theranos: Patent , company
      2. Droplet microfluidics
      3. Review articles on microfludics: PDF-nature, PDF-elveflow, PDF-LOC


5.3 Paper-based Technologies: Biosensors and Electronics

      1. Paper-based energy harvesters (Jun Zhou et al.)
      2. Paper-based sensors (Abren Merkoci et al.)


5.4. Implantable sensors

1. Basics of Hydrogel by P. Gupta and S. Gurg PDF

2. Hydrogel-conductive polymers for neural implants

3. Packmakers, google lens, and brain implants

4. Other resources are available at the Networked Body


5.5 Bacterial resistance

1. New approach to beating the drug resistance

2. Self organization in complex media http://www.bgu.ac.il/~yochelis/arikpub.html


Appendices


A. Sequencing


Review: T.C. Glenn: Field Guide to next-generation DNA sequencers, Molecular Ecology Resources, 11, 759, 2011.


B. Science issues

    • Physics of Interfacial and Confined Water, American Journal of Chemical Physics, 2014. Ed. V. Molinero and B. Kay Link
    • Physics of Undulatory Self propulsion, D. Goldman, Review of Modern Physics, 2014. PDF
    • Semiflexible polymer network, Review of Modern Physics, 2014. PDF
    • Intracellular transport, Review of Modern Physics, 2013. PDF
    • Physics of Adherent cells, Review of Modern Physics, 2013. PDF1 PDF2
    • Antimicrobial Resistance and Food Safety PDF
    • Reducing antibiotic resistance using evolutionary strategies PDF


C. Good books

    • Physical Biochemistry, Kensal
    • Biophysical Chemistry: Part 3; The behavior of biological Macromolecules, Cantor and Schimmel
    • Molecular Driving Forces: Statistical thermodynamics in Chemistry and Biology, Ken Dill and Sarina Bromberg
    • The Machinery of life, David S. Goodsell
    • Life at small scale, D.B. Dusenbery
    • The Molecules of Life, Kuriyan, Konforti, Wemmer