Biomedical applications of plasmas E. Stoffels, Eindhoven University of Technology The Netherlands. Plasmas in material processing: t hermal vs. non-thermal Plasmas in medicine: service: plasma decontamination “spare parts”: plasma coating of implants healing: plasma surgery
Plasmas in material processing:
thermal vs. non-thermal
Plasmas in medicine:
service: plasma decontamination
“spare parts”: plasma coating of implants
healing: plasma surgery
plasma-tissue interactions on cellular level
A+, B-, e, radicalsWhat is plasma?
Plasmas can perform various surface treatment:
etching - semiconductor elements
deposition - a-Si:H solar cells, hard protective coatings, optically active layers, etc.
cutting, welding, spraying
Refined treatment is possible with non-thermal plasmas (no heat damage to the surface)
Also biological materials can be treated!
Electric gas discharges: electrons/ions are heated
In typical high-frequency plasmas only electrons are heated
No background gas heating when:
electrons/ions in minority
not enough collisions with neutrals
Thermal: gas heating occurs Non-thermal: electrons hot, gas cold
low collision frequency of electrons with gas electrons retain high energy, gas remains cold
(typical situation in vacuum reactors)
short duration of the plasma pulse:
not enough time for gas heating
small size (micro-plasma):
too much energy leaks to outside
What is the maximum length scale (L) of a “cold” plasma?
Electron-induced heating is balanced by thermal conduction losses:
We allow DT to be at most 10 degrees.
For helium under typical conditions L 0.2 mm
(in agreement with observations).
RF applied to a sharp metal pin.
breakdown obtained at ca. 200 V p-p.
plasma operates in helium (most readily), argon, nitrogen, hydrogen, AIR (!)
Temperature measurements using Optical Emission Spectroscopy (N2 bands)
HF plasma pencil (Janca et al. Brno, Czech Republic)
discharge created in a hollow needle/hollow cylinder in argon
various surface treatments
Micro-hollow cathode discharge (Schoenbach, Norfolk, Virginia; Graves, California, Berkeley)
Dielectric barrier discharge DBD (e.g. Kogelschatz, ABB Corp. Research; Chang-Jun Liu, Tianjin, China)
gas conversion (e.g. methane)
Resistive barrier discharge (Laroussi, Old Dominion Univ. Virginia)
radio-frequency (13.56 MHz)
One atmosphere uniform glow discharge plasma OAUGDP (Reece Roth et al. Univ. of Tennessee)
kHz frequency range
operates in air
used for sterilisation
pulsed corona for water cleaning
(V. Veldhuizen, Eindhoven)
single plasma membrane double membrane
Erosion by photodesorption and O radical etching
UV damage to eroded spores
Direct UV absorption and DNA destruction
log(number of survivors)
1 min 10 min 1 min
argon - not very efficient
N2/O2 (air) - efficient, O radicals present
O radicals can also penetrate through the membrane and damage the cell interior
H2O2, CO2- particularly efficient, see Hury et al.
H2 - efficient, reducing agent.
Maybe reducing fatty acids to aldehydes and dissolving the membrane?
In vivo dental cavities using plasma needle
No temperature increase within the tooth
Mineral matrix intact, tissue-saving method
Under investigation: decontamination efficiency, penetration depth, surface activation to enhance adhesion of filling
treatment , gingiva
Coating of artificial implants to increase bio-compatibility
Low-pressure discharges can be used
bone prostheses: diamond-like inert coating on titanium substrate
spraying of hydroxyapatite
micro-patterning of surface to increase cell adhesion
Not always non-thermal plasmas are used, sometimes burning is desired
Techniques already implemented in medicine: electro-surgery and argon plasma coagulation
Spark erosion of atherosclerotic plaque
New trends: minimum invasive, tissue saving methods
Investigation of fine surgery using plasma needle
Electric methods in medicine Alamos)
Electrosurgery: well established technique
High-frequency (350 kHz) cutting and coagulation:
monopolar & bipolar cutting devices
by controlled coagulation
From electricity Alamos)to plasma
First beneficial plasma-tissue interaction
* non contact
* self-limiting desiccation and coagulation (plasma stops when the area is dry)
* no carbonization
* can be applied internally
* good post-operative recovery
Argon plasma coagulation
An APC device in action Alamos)
Example: treatment of hyperplasia of the nasal concha
After APC treatment 10 days later
Plaque is vaporized by electric pulses, 250 kHz, 1200 V, 100 W. Restenosis in rabbits is limited. So far not applied to humans.
A diseased artery Plasma-produced crater
(cross-section): (lipid ablation):
A few words about safety Alamos)
by electric currents
Effects of heat: hyperthermia causes cell death (> 43o C)
(a) Low-power regime: no thermal damage, possibility of refined action.
(b) High-power regime: denaturation of proteins, carbonisation after long exposure.
Possibility of fine surgery must be investigated on cellular level!
Much more complicated structures
More interactions/effects possible
For the sake of plasma surgery, understanding plasma-induced effects on cellular level is necessary
Cell Tracker Green (CTG): stains living cells green
Propidium Iodide (PI): stains dead cells red,
allows to resolve DNA/RNA distribution in the cell
To study long term effects cells are cultured after plasma treatment
Cells are fixed and stained with PI to detect apoptosis
Intact nuclei stained by PI
High precision: influenced cells are strictly localised)
Example of apoptotic cells After plasma treatment
Plasma treated cells: dead cells Alamos)
Even dead cells retain the integrity!
DNA damage and condensation (other than in apoptosis)
Cell detachment Alamos)
Instantaneous effect of plasma treatment
Cells round up and detach from other cells and can be removed
Long term effects Alamos)
Detached cells reattach after ca 1 hour, their viability is demonstrated
cytoskeletonWhat causes cell detachment?
cell adhesion molecules (CAMs) - trans-membrane glycoproteins
Ca2+ dependent adhesion:
Detract Ca and cause
cadherin to disintegrate?
Destroy the cadherin
in vivo tests