H64BIO Bioelectronic and Biophotonic Interfacing

University of Nottingham H64BIO Bioelectronic and Biophotonic Interfacing Note


Lecture 1

Cell Structure

  • Cell membrane
  • Cytoskeleton
  • Organelles
  • Nucleus
  • Mitochondria
    • Once free-living bacteria
    • Contains its own DNA
    • The cell’s energy source
  •  Endoplasmic Reticulum – molecule processing and packaging
    • Ribosomes – assemble amino acids into proteins
    • Rough ER (with ribosomes) – protein synthesis
    • Smooth ER (no ribosomes) – lipid synthesis
  • Golgi apparatus – protein processing
  • Vesicles –  small transportable compartments

 

  • DNA is a double stranded helix made up of a sequence of bases
  • There are four possible bases (ACGT)
  • A gene is a section of DNA that encodes for one protein
  • Each group of 3 bases form a codon
  • Each codon encodes for an amino acid
  • There are 22 amino acids in total
  • Start and stop codons also exist
  • The sequence of amino acids is the protein

Action potential

  • The stimulus causes sodium channels in the neuron’s membrane to open, allowing the Na+ ions that were outside the membrane to rush into the cell.
  • If the signal is strong enough and the voltage reaches a threshold, it triggers the action potential.
  • The peak voltage of the action potential causes the gated sodium channels to close and potassium channels to open.
  • The neuron becomes hyperpolarized when more potassium ions are on the outside than sodium ions are on the inside.
  • The neuron enters a refractory period, which returns potassium to the inside of the cell and sodium to the outside of the cell.
action potential

Post-synaptic potential

Neuron Structure

Nerve Cell
Nerve Cell

Autonomic Nervous System

  • Sympathetic: Prepares the body for physical activity
  • Parasympathetic: Stimulates involuntary activities

 


Lecture 2

Noise in measurement


Lecture 3: physics

 

Material properties

  • (-ivity) is related to material’s property
  • (-ance) includes the object’s geometry

When an electric field is applied to an atom the electrons will be displaced from their orbit The electron then re-emits its own electric field. Because the electron has mass it has inertia and it takes time to move . This means there is a lag between the applied field and the emitted field. If the E field is oscillating then the field emitted by the electron has a phase lag due to this time lag. The result is the material appears to slow down the propagation of an oscillating EM field. This reduction in speed is described by the refractive index n = sqrt(ε) = c/v.

If the frequency of the applied E field is same as the electrons orbit frequency then resonance occurs The electron will be ejected and the atom will become ionised. At resonance a large amount of energy from the incident EM field is absorbed. The resonance frequency for electrons occurs in the UV

Permittivity

Complex Permittivity Chart
Complex Permittivity Chart
  • Resonance effects – associated with electrons and molecular bonds (UV and IR)

Electronic resonance

  • When an electric field is applied to an atom, electrons will be displaced from their orbit
  •  the electron thenre-emitsitsownelectricfield
  • because the electron has mass this takes time
  • If the E field is oscillating, the field emitted by the electron has a phase lag due to this time lag
  • the result is the material appears to slow down the propagation of an oscillating EM field

Atomic resonance 

  • a similar phenomena occurs with molecular bond
  • the molecule forms a dipole and the bond has resonance frequency
  • the bond can be broken if it is driven at frequency
  • molecular bond resonance frequency occur in IR

 

  • Relaxation effects – associated with molecular dipoles and ionic dipoles (microwave and radiowave)

Molecular relaxation 

  • molecular dipoles rotate to a align with applied electric field
  • as the field changes the molecules become perturbed from an equilibrium state
  • they than ‘relax’ to recover equilibrium
  • this occurs with an exponential distribution
  • This relaxation occurs at microwave frequencies

Ionic Relaxation

  • Occurs with ionic dipoles
  • ions in solution are loosely bound to each other via hydrogen bonded water molecules
  • the applied field will break these bonds and induce non-uniform distribution of these free ions
  • ionic relaxation occurs at radio frequencies and lower

 

  • Conductivity
  • Refractive index

Phenomenological models

Fresnel’s equations

  • Describes the proportion of light power that is reflected and transmitted at a boundary between two materials
  • Distinguish between s-polarised light and p-polarised light

Snell’s law

Beer-Lambert Law

absorption of light as it passes through a material

Debye model

  • assume molecules are free and do not interact with each other

Cole-Cole model

  • adds a correction term, h,
  • determined empirically

Double Debye model

  • Includes a second relaxation term
  • This model is good for frequencies up to 10^12 Hz

Lecture 5: Instrumentation Engineering

Transduction

Noise

  • Pink Noise
    • 1/fnoise(V/Hz)
  • Johnson Noise (Thermal Noise)
    • \( V_{rms} =\sqrt{4 kTRB}\) ,where kB is Boltzmann’s constant [1.4e-23 joules per kelvin] , T is the resistor’s absolute temperature [kelvin] , and R is the resistor value in ohms [Ω].
  • Shot Noise
    • Poisson distribution
  • Excess Noise
    • 1/f noise

Signal to Noise Ratio

Dynamic Range

Sampling

Signal Averaging

Active Filter

  • Butter worth: flattest passband with the slowest rolloff and poor phase characteristics
  • Chebyshev : steeper roll-off and more passband ripple
  • Bessel : maximally flat group/phase delay (maximally linear phase response)

Lecture 6 : Bioelectronics

Nernst Equation

Synaptic Inputs

Action Potentials

Synaptic Release

Cable Theory

  • Ionic current entering the synapses diffuses passively along the dendrites.
  • he dendritic tree can be modelled using cable theory where each segment of dendrite has a longitudinal resistance r_l , and each patch of membrane has a membrane resistance rm and capacitance c_m


Lecture 7 : Bioelectronics – Electrodes

An electrode acts as a transducer converting between ionic and electronic currents

Resistive electrode 

  • REDOX reaction
  • OIL RIG (Oxidation Is Gain, Reduction is Loss)

Capacitive electrode / polarisable

  • changing the charge distribution within the solution near the electrode.
  • No actual current crosses the electrode-electrolyte interface
  • made from noble metals such as platinum are often highly polarisable
  • Prone to movement artefact

Non-polarisable/ resistive Electrode 

  • allow the current to pass freely across the electrode-electrolyte interface without changing the charge distribution in the electrolytic solution adjacent to the electrode.
  • placed in an electrolyte solution some of the metal atoms will lose electrons and form positive ions which go into solution

Model

Electrode model

Electrode potential

Silver-Chloride electrode

  • Silver-chloride electrodes have characteristics similar to a perfectly non- polarisable electrode
  • Protocol
    • Place silver wire in 0.1M HCl
    • Apply a low current
    • Apply an alternating current to drive chloride ions on/off the silver surface

Lecture 8 : Bioelectronics – BioSignal

EEG: Electroencephalogram 

  • Signal is the summed Post-synaptic potential (PSP)
  • very weak (~100uV) and low bandwidth (~0.5-100 Hz)
    • Filtered by brain structure
    • LPF, spread out
  • Electrodes
    • 3 refs: nose and ears
  • Configurations:
    • Common to ref point
    • averaged reference (of all electrodes)
    • Bipolar config (between neighbouring electrodes)
  • Signals
    • Delta (,4Hz) deep sleep
    • Theta (4-8 Hz), drowsy
    • Alpha (8-13 Hz) awake (eyes closed), need symmetry, 40uV
    • Beta (13-30 Hz) awake, 10 uV
    • Gamma (30-100 Hz)

Each neuron is more likely to fire at a certain phase of the EEG signal -> redundancy of information

ECG: Electrocardiogram 

Typ: 10 electrodes

ECG waveform is comprised of: The P wave, the QRS complex and the T wave.

EOG: Electrooculogram

  • DC voltage, Dipole
  • 10-30 mV

Electroconvulsive Therapy – ECT

  • Current 0.9 A,
  • Stimulation induces a seizure
  • It Is thought to be effective for treating severe depression

Transcranial Direct Current Stimulation

  • non invasive, cheap, easy
  • modulates neural activity
  • Electrodes – sponge pads soaked with saline 5x5cm – 10x10cm

Lecture 9 : Bioelectronics – Recording and Imaging Techniques

Inverse problem

  • ill-posed problem and sensitive to initial condition
  • no unique solution

Lecture 10: Light and Optics

Photons:

a packet of energy, E = h v = h \(\frac{c}{\lambda}\)

Shot noise:

Light

\( E = E_0 e^{i(kr + \omega t } \), where k is spatial frequency and \(\omega \) is angular frequency.

lens equation

\( \frac{1}{f} = \frac{1}{S_1} + \frac{1}{S_2} \)

f < 0, Convex lens ()

f > 0, Concave lens )(

\(S_1\), object is always positive

\(S_2\), image is negative if it is virtual image

Ray tracing

 

Koehler illimination


Lecture 11: Optics (cont.)

Optical Fourier theory

  • Lens transforms between image and spatial frequency, in 3D domain
  • Lens also limits the size of aperture field (physical size)
  • Aperture limits the BW, resolution and acts Low Pass Filter
  • Point Spread Function (PSF)
    • ???
  • Numerical Apature (NA)
    • how much lens collect from a point
    • limit the bandwidth of the imaging
    • \(\sin(\theta)\)

Contrast

  • Intrinsic contrast
  • Phase Contrast
    • phase shift by 90′ degree
  • Fluorescence Contrast Dye

 

Scanning System

 

 


Lecture 12: Advanced imaging techniques

TIRM/TIRF

Surface Plasmon Resonance

Plasmon: Oscillation of elections in conductor surface

  • Oscillation can be driven at resonance frequency
  • Change on surface charge, stiffer resonance, higher resonance frequency
  • Photons in light changes into plasmon
  • can be seen as dip in reflected light
  • the dip is very steep and has high Q
  • tiny change in frequency shift can cause massive response.
  • Plasmon excitation
    • match energy and momentum \(\omega,\k \) and \(\omega_p,\k_p \)
  • only P-polarized light can excite

FLIM – fluorescence lifetime imaging

Lifetime in the excited state is typically 10-7 – 10-9 s

  • Fluorescence follows an exponential decay
  • Lifetime is independent of concentration
  • Fluorescence lifetime is dependent on the local chemical environment

Interferometry

Light is split into two beams, one goes down a reference arm while one reflects off the sample. The beams are then interfered. Contrast results from the differences in optical path length.

Very sensitive technique-stability is difficult, very prone to temperature fluctuations and vibrations

OCT – Optical coherence tomography

An interferometry-based label-free technique

SHG – Second harmonic generation

 


Lecture 13: Light Source and Detect

Arc Lamps

  • xenon results in broadband spectra
  • mercury has high intensity peaks at discrete wavelengths

LEDs

  • Electrons recombine with holes and release photons
  • Narrowest bandwidth (~20-50nm)

Laser

  • Point source
  • coherent – all emitted light has the same frequency and phase
  • Very high power densities possible
  • Tend to be noisy
  • Coherence results in speckle and interference fringes

Detectors