7 - Cell Chip Recognition

Goal: using cells as elements for bio-electronic signal transduction to build highly-sensitive sensors

Requirements:

1. cells that respond to compound by changing their properties (e.g. resting membrane potential)

2. Non-invasive measurements for long-term recording by e.g using substrate-embedded recording devices

tiny implant device treating disease by changing electric pulses in nerves to and from specific organs

targeting diseases by neuromodulation without using drugs

1. Peripheral Nerve Interfaces: penetrating electrodes with bioinspired adhesives for stability and minimal tissue damage

2. Stimulation: electrical sinals target peripheral nerves —> influencing adipose tissue processes

3. Feedback loop: Sensor arrays detect biomarkers, refining parameters in closed-loop system

4. Application: potential use in obesity treatment by regulating fat tissues and metabolic pathways

= restore vision for patients with photoreceptor loss (rods, cones)

• light or images captured by external camera and processed in electrical signals

• retinal implant (microelectrode array) tacked to retina, stimulates ganglion cells where photoreceptors are damaged

• send visual information to brain via optic nerve

device, that converts signal from one form of energy to another

in neuroelectronics: translate biological into electrical signals

e.g. translates physiological signals (muscle activity, …) to electrical, measureable outputs (heart rate on EEG, …)

• electrical

• optical/machnical/thermal

• chemical/electrochemical

Galvani: (electricity is biological)

concept of ‘animal electrictiy’, proposing electricity is intrinsic to living tissues

Experiment: frog’s leg twitch when in contact with 2 diffferent metals, suggesting muscles and nerves generate electricity

Volta: (electricity is physical/chemical)

attributed observation to contact between metals

demonstrated, that frog’s leg acted only as conductor and electricity was generated externally

—> invented first battery: voltaic pile

both were partially correct:

• Galvani identified bioelectricity (in nervous and muscular function)

• Volta was right about generation through chemical reactions —> batttery

1. Resting Potential: inside of cell negative

2. Depolarization: voltage-gated sodium channel opens —> Na+ in cell —> cell inside positive

3. Repolarization: Potassium channel open —> K+ exit cell —> restore negative resting potential

4. Hyperpolarization: Excess K+ efflux causes slight overshoot before resting potential

maintains resting potential by actively transporting (using ATP):

• 3 sodium (Na+) ions out of the cell

• 2 potassium (K+) ions into the cell

—> creates gradient where inside is more negative (-70mV), and outside more positive

= explains how membrane voltage (Vm) changes due to flow of ions through channel

gi = conductance of ion channels

Ei = equilibrium potential

—> changes in ion conductance (e.g Na+ and K+) drive depolarization and repolarization during action potential

chemical synapses

use neurotransmitters to transmit signals across synaptic cleft

-> undirectional, slower, allow for signal modulation

electrical synapses

use gap junctions to directly connect cells, allowing ions to flow bidirectional

-> faster, reliable, used for synchronized activity

measures activity of ion channels in a cell, by isolating small patch of membrane

—> detailed study of electrical properties in single cells, like ion currents and membrane potential

• Cell-Attached Recording:

  micropipette forms seal with membrane, without disturbing intracellulare environment

• Whole-Cell Recording:

  strong suction breaks patch, enabling pipette access entire cell

• Inside-Out Patch:

  membrane patch pulled inside pipette, exposing intracellular side —> for testing intracellular channel regulation

• Outside-Out Patch:

  broken membrane reseals on pipette tip, exposing extracellular side —> for testing extracellular ligand effects

modern approach of Patch Clamping

-> multiple cells can be studied simultaneously on chip

• Choice of Material (e.g. Platinum Black, Iridium Oxide, Carbon Nanotube)

• Nanopatterning

• Geometric Design

has layers of aluminium, gold, silicon

1. Anodization of aluminium, creating porous alumina structure

2. Gold is electrochemically deposited into pores, forming nanostructures

3. porous alumina template is dissolved, leaving patterned gold electrode with enhanced surface area

increases surface area of electrodes —> reduces impedance

lower impedance -> improves signal quality, reduce noise

mimic function of organs on microfluidic platforms

Parkinsons Disease (symptoms: rigidity, tremors):

replicate dopaminergic neuron degeneration in substantia nigra

-> study disease progression and testing potential treatments

• temporal resolution - ms range to capure fast dynamics

• localized multichannel recordings - record multiple regions simultaneously

• low noise characteristics - detect < picoAmpere currents

PicoAmp System = 64-channel amplifier with ca. 70 fA rms noise

-> provides precise, localized recordings of neurotransmitter release at single-cell level