Towards bedside monitoring
at the subcellular level
Bert Mik
Department of Anesthesiology
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the future of Biosensing
Biosensing
Biosensing is the conversion of biological processes
into useful information.
Incorporating “a variety of means, including electrical,
electronic, and photonic devices; biological materials
(e.g., tissue, enzymes, nucleic acids, etc.) and
chemical analysis”
PATIENT MONITORING
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The heart of the hospital
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Bedside monitoring
Heart rate
ECG
Arterial blood pressure
PA/wedge pressure
Central venous pressure
Respiratory rate / etCO2
Arterial oxygen saturation
Body temperature
Bloodgas analysis
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the future of Biosensing
Additional information
 Microbiology
 Virology
 Clinical chemistry
 Laboratory tests
 Organ specific tests
 Imaging
BUT: invasive and / or takes time to get results
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Limitations of monitoring
ONLY:
Conditio sine qua non
No information about:
Microcirculatory function
Tissue oxygenation
Cellular metabolism
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Focus on microcirculation
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Septic Shock
Infection
Sepsis
Septic Shock
30-60% mortality
Blood pressure and cardiac output
Vasodilatation
hemodynamic problems
macrocirculatory failure
Septic cardiac myopathy
hypodynamic
Laser doppler / speckle / MicroScan
microcirculatory
dysfunction
coagulation
hyperdynamic
competitively inhibited
No direct bedside monitoring exists
metabolic problems
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mitochondrial
impairment
reversibly compromised
permanently damaged
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Metabolism
Oxygen
Carbohydrates
CO2
H 2O
+ ENERGY
Energy for life
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Mitochondria
 Energy producing organelles
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 Destination of oxygen
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How to monitor the mitochondria?
?
Pulse oximetry
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O2C/NIRS
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The breakthrough …
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A mitochondrial oxygen sensor
ALA
substrate
PpIX
PO2
DEPENDENT
QUENCHING
Haem
MITOCHONDRIA
cytochrome c
haemoglobin
myoglobin
EG Mik et al., Nature Methods 3: 939-945, 2006
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Induction of protoporphyrin IX
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Thus …
ALA induces PpIX
PpIX localized in the mitochondria
PpIX has oxygen-dependent optical properties
Mitochondrial oxygen sensor
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Basic implementation
Monochromator
Lens
Tissue
PMT
Integrator
Pulsed tunable laser
reset
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Application on tissues
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In vivo rat liver: mitoPO2 vs FiO2
EG Mik et al., Biophys. J. 95: 3977-3990, 2008
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Optical biopsy
Penetration depth ≈ 500 µm
Small tissue volume
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From oxygen to metabolism
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Optical bedside monitoring
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Summary
MACRO
Standard monitoring
MICRO
Microcirculation
NANO
Subcellular / organelle
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Conditio Sine Qua Non
Cellular function
the future of Biosensing