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Bioelectronics and Biological Sensory Systems

About this course

Bioelectronics is a new, rapidly developing applied area connecting condensed matter physics, organic chemistry, biophysics, and medical engineering. Its main task is to create methods and devices that effectively exchange information between tissues and cells of living organisms and electronic circuits. Since such an exchange almost always involves the use of electrical or optical signals, the basis of our course is to get acquainted with the advanced concepts of the mechanisms of charge and energy transfer in bioorganic systems and with experimental methods for their determination using specific examples from the course authors' work and scientific articles of other teams.

The main drivers of applied bioelectronics are medical companies that develop so-called electroceuticals - drugs and devices that replace classical organic drugs with artificial stimulators of nervous activity, which leads to a long-term therapeutic effect. Also of great importance for bioelectronics is the request to create neural interfaces aimed at prosthetics for patients’ lost senses and motor skills and the creation of exoskeletons. In this regard, the focus of the course is on the problems of fabricating reliable non-damaging contacts between organic and inorganic materials. The latter leads to the need to touch upon the topic of the so-called green lithography within the course, the purpose of which is to maximize the introduction into practice of low-energy consumer electronics, which accounts for the lion's share of electronic waste on the planet, methods that allow the use of biodegradable and biocompatible materials. In the same context, we consider the principles of operation of (bio)organic transistors and ways to improve their efficiency.

An area relatively close to bioelectronics is industrial bioelectrosynthesis, the purpose of which is the design of microorganisms and biocenoses capable of synthesizing the chemical compounds required by the economy from simple low-molecular precursors and electricity “from the socket.” The success of both directions fundamentally depends on our ability to control the processes of charge and energy transfer both within living systems and during their interaction with an inorganic substrate.

The second part of the course is devoted to the mechanisms of biological sensory systems. Particular attention is paid to the physical principles of their functioning, implementing practical solutions for processing the raw signal and isolating its significant part directly in the sense organ. Within the course framework, questions about the post-processing of signals from sensory systems in the brain are practically not discussed. However, within the framework of two lectures, on organic neuromorphic systems and excitable environments, the topics of alternative computing environments are discussed.

Since the course is read for senior physics students, it is assumed that the mathematical apparatus is used relatively actively as well as essential information from the general physics course.

Lecture I

Course Introduction

The main problems and definitions. Wearable and implantable electronics, green electronics, electroceuticals, electrosynthesis of useful substances and materials by industrial microorganisms. Simple bioelectronic devices. Neurointerfaces and the evolution of prosthetic systems. USA FDA website with information on certification of new electroceuticals for the last month – a brief review of actual cases.

References and links:
  1. Medical devices approved through the CDRH FDA Premarket Approval process (PMA) in 2022
  2. M. Irimia-Vladu, “Green” electronics: biodegradable and biocompatible materials and devices for sustainable future. Chemical Society Reviews, Chem. Soc. Rev., 2014, V. 43, P. 588-610

Lecture II

Excitable Media and Ion Channels

The universal concept of an excitable medium. Autowave processes in chemistry (Belousov-Zhabotinsky reaction) and biology. Biological excitable media: cardiac and neural tussiues. Transmembrane ion potentials in biology. Ion channels and ion pumps. Refractory period. The patch clamp technique. Artificial control of ionic transmembrane currents: optogenetics, magnetothermal effect, ultrasound, etc.

References and links:

Lecture III

Electron Conductivity in Condensed Matter Physics

Review of the mechanisms of electron conductivity in condensed matter physics: Drude model, Drude-Sommerfeld model, nearly free electron model, Bloch’s theorem, tight binding model, LCAO model, various options for hopping and tunneling. Phenomenological equation of Jonscher. Percolation theory. Examples. Using electronic conductivity models to describe ionic conductivity. Examples.

References, www-links and further reading:
  1. V.F. Gantmakher, Electrons and Disorder in Solids, Oxford University Press, 2005
  2. N.W. Ashcroft, N.D. Mermin, Solid state physics, Saunders College Publishing, 1976 (Chapters 1-3, 8-10)
  3. A.K. Jonscher, The ‘universal’ dielectric response. Nature, 1977, V. 267, P. 673–679
  4. TU Delft | Open Solid State Notes
  5. Percolation Theory by Raymond Wieser on YouTube
  6. J. Feder, Fractals, Springer, Boston, MA, 1988
  7. M. Pollak, B.I. Shklovskii, Hopping transport in solids, Elsevier Science Pub. Co., 1991

Lecture IV

Types of Charge Carriers and the Effects of Water

Types of charge carriers. The problem of determining the nature of a charge carrier in a condensed state and methods for its solution. Importance of the large temperature range measurements. Effect of water on conductivity in bioorganics. Review of the main methods: Hall effect; impedance spectroscopy; PdH – based proton-conductive contacts; assistance from proton NMR and neutron scattering techniques; thermal electromotive force; electrochemical transistors.

References, www-links and further reading:
  1. M. Amit, S. Roy, Y. Deng, E. Josberger, M. Rolandi, N. Ashkenasy, Measuring Proton Currents of Bioinspired Materials with Metallic Contacts, ACS Appl. Mater. Interfaces, 2018, V. 10, P. 1933
  2. N.W. Ashcroft, N.D. Mermin, Solid state physics, Saunders College Publishing, 1976 (Chapters 1-3, 8-10)
  3. F. Ciucci, Modeling Electrochemical Impedance Spectroscopy, Curr. Opin. Electrochem, 2019, V. 13, P. 132
  4. V.I. Volkov, A.V. Chernyak, I.A. Avilova, N.A. Slesarenko, D.L. Melnikova, V.D. Skirda, Molecular and Ionic Diffusion in Ion Exchange Membranes and Biological Systems (Cells and Proteins) Studied by NMR, Membranes, 2021, V. 11, 6
  5. N.F.Mott, E.A.Davis, Electronic Processes in Non-Crystalline Materials, Oxford University Press, 1971
  6. R. Hempelmann, Quasielastic Neutron Scattering and Solid State Diffusion, Clarendon Press, 2000
  7. E.O. Stejskal, J. E. Tanner, Spin Diffusion Measurements: Spin Echoes in the Presence of a Time‐Dependent Field Gradient, J. Chem. Phys., 1965, V. 42, P. 288
  8. S.J. Blundell, R.D. Renzi, T. Lancaster, F.L. Pratt, Muon Spectroscopy: An Introduction, Oxford University Press, 2022
  9. V. Raicu, Yu. Feldman, Dielcetric Relaxation in Biological Systems, Oxford University Press, 2015.

Lecture V

Protons in Focus

Special case of protons. Why the problem of proton conductivity for bioelectronics is no less topical than the problem of electronic conductivity: the future belongs to proton energy, the largest electrical potentials in biology are produced by protons, the highest speed transistors operate on proton gates. Importance of proton transmembrane potentials for cellular energetics – a brief review of ATP synthase structure. How are proton and electron similar to each other. States of proton in aqueous medium and in bioorganics. Proton delocalization. Anomalous proton mobility. Proton “superconductivity” and “superconductors”. Activation of proton transport on phase borders. Water floating bridges and the possibility of electrohydrodynamic phenomena in biological systems. Isotopic effects and proton/deuteron mobility. Proton wires in proteins.

References and links:
  1. K.-D. Kreuer // Proton Conductivity: Materials and Applications, Chemistry of Materials, 1996, V. 8, P. 610-641
  2. L. Glasser // Proton Conduction and Injection in Solids, Chemical Reviews, 1975, V. 75, P. 21-65
  3. P. Colomban // Proton Conductors and Their Applications: A Tentative Historical Overview of the Early Researches, Solid State Ionics, 2019, V. 334, P. 125-144
  4. K.M. Trent, E.M. Lewandowski, Yu. Chen // Low barrier hydrogen bonds in protein structure and function, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2021, V. 1869, P. 140557
  5. D.I. Kolokolov, M.S. Kazantsev, M.V. Luzgin, H. Jobic, A.G. Stepanov // Characterization and Dynamics of the Different Protonic Species in Hydrated 12-Tungstophosphoric Acid Studied by 2H NMR, The Journal of Physical Chemistry C, 2014, V. 118, P. 30023-30033
  6. A. Migliore, N.F. Polizzi, M.J. Therien, D.N. Beratan // Biochemistry and Theory of Proton-Coupled Electron Transfer, Chemical Reviews, 2014, V. 114, P. 3381-3465
  7. S.B. Rienecker, A.B. Mostert, G, Schenk, G.R. Hanson, P. Meredith // Heavy Water as a Probe of the Free Radical Nature and Electrical Conductivity of Melanin, The Journal of Physical Chemistry B, 2015, V. 119, P. 14994-15000
  8. S. Scheiner, Č. Martin // Relative Stability of Hydrogen and Deuterium Bonds, Journal of the American Chemical Society, 1996, V. 118, P. 1511-1521
  9. Floating water bridge on a homepage of Dr. Elmar Fuchs

Lecture VI

Electron Conductivity in Bioorganics. Marcus Theory

Electron conductivity in biological systems. Chemical viewpoint on hopping: Marcus theory, electron transfer in proteins as a chain of redox-reactions. Long-range electron transfer in biology. Electrogenic bacteria (Shewanella, Geobacter, Desulfobulbus). Why band electronic conduction for aerobic life forms is unlikely. Reactive oxygen species. Efficiency management of ATP synthesis in mitochondria.

References and links:

Lecture VII

Molecular Electronics

“There is plenty of room in the bottom” and Moore’s empirical rule. 1D and 2D molecular electronics. Revolution of conductive polymers. Single-molecule electronics, examples. How to work with single-molecule: the brief review of methods. Conductivity and conductance. Methods of single-molecule electronics as a proxy to the understanding of biomolecules properties. Conjugation with optical methods.

References and links:
  1. From molecular to supramolecular electronics // Nature Reviews Materials, 2021
  2. Large-Area, Ensemble Molecular Electronics: Motivation and Challenges // Chemical Revies, 2017
  3. Amorphous Semiconductor Switching in Melanins // Science, 1974
  4. Mechanically Controlled Break Junctions

Lecture VIII

Lithography and Patterning: Bioorganics

Motivation. The need for consumer low-energy green electronics. Creation of reliable contacts between metals, silicon, and bioorganic matter. Stability of bioorganics under different external conditions. A brief review of bioorganic materials utilized as lithography resists. Perspective methods: ice lithography, photoswitches, magnetic and nanoparticle-based control of resists development.

References and links:
  1. Gentle Patterning Approaches toward Compatibility with Bio-Organic Materials and Their Environmental Aspects // Small, 2022

Lecture IX

Organic Neuromorphous Devices

Neuromorphic system: what is it? Formal functions of nervous systems. Development of memristors. An energy-efficient neuron that acts as an adder and a threshold function. More complex neural network architectures (reservoirs, short-term memory memristors, self-coupled memristors, etc.). Mimicking of natural nervous systems to solve applied problems. Oxide memristors, phase change memristors (PCM), neuromorphic spintronic devices, organic neuromorphic systems and other approaches. Perspectives.

References and links:
  1. Organic electronics for neuromorphic computing // Nature Electronics, 2018
  2. A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing // Nature Materials, 2017
  3. Neuromorphic nanoelectronic materials // Nature Nanotechnology, 2020

Lecture X

Introduction to Natural Sensory Systems

Introduction to natural sensory systems. Again, membranes. Allosteric effect. Receptor molecules. GPCR. Channels and gates. Measument of memrane potentials. Receptor and Generator Potentials. Adaptation. Synaptic transmission.

References and links:
  1. C.U.M. Smith, Biology of Sensory Systems, JONH WILEY & SONS, LTD, 2008 (part I)
  2. G.L. Fain, Sensory Transduction, Oxford University Press, 2nd Edition, 2020 (Chapters 1-4)

Lecture XI

Senses: General Overview

General features of biological sensory systems. Classification of the senses. Modality. Intensity. Adaptation. Receptive Fields. Examples of cerebral analysis of different senses.

References and links:
  1. C.U.M. Smith, Biology of Sensory Systems, JONH WILEY & SONS, LTD, 2008 (part I)
  2. G.L. Fain, Sensory Transduction, Oxford University Press, 2nd Edition, 2020 (Chapters 1-4)

Lecture XII

Chemistry and Physics Behind Biological Senses: Limits and Opportunities

Isomerization of retinal and photochamical aspects of vision. Young's modulus of various different biological structures. Piezo effect in proteins. Decomposition of the sound spectrum. Physical limits to magnetosensitivity. Detection of polarized light.

References and links:
  1. C.U.M. Smith, Biology of Sensory Systems, JONH WILEY & SONS, LTD, 2008 (part I)
  2. G.L. Fain, Sensory Transduction, Oxford University Press, 2nd Edition, 2020 (Chapters 1-4)

Lecture XIII

Prosthetics and the Expansion of the Possibilities of Human Perception

Prosthetics, exoskeletons, neural interfaces, avatars. What already exists. What may be coming soon.