Biostasis Roadmap

A research and technology development roadmap for preservation and recovery of brains (and bodies).
General
Maintaining circulatory system health
1️
?
Anticoagulation protocols
2
$$
Protocol changes based on medical conditions
3
$$
Health monitoring
4
$$
♥️ PRE CARDIAC ARREST
🚑 POST  CARDIAC ARREST STABILIZATION
General
a.
Monitoring
Cardiac arrest notification
1️
$$
b.
Measure of stabilization procedure success
S-MIX value
1️
$$
🧊
Cryopreservation
a.
Acute stabilization protocol
Stabilization medications
1️
$$
Stabilization cooling
2
$$
Field Cardiopulmonary Bypass (CPB)
3
$$
Stabilization Blood Substitution / Transport
4
$$
b.
Abbreviated stabilization (long ischemic time)
Criteria for Abbreviated Protocol vs Acute Protocol
1
$
Medications
2
$
Medication circulation
3
$
Oxygenation after long ischemic time
4
$$
🧪
Chemical Fixation
a.
Stabilization for chemical fixation-based preservation
Medications/Circulation/Cooling/Transport
1️
$$
💧 PRESERVATION COMPOUNDS
General
a.
Interventions and additives to improve perfusion quality
High osmolarity chemicals
1️
$
Blood-brain barrier modifiers (chemical)
2
$
Blood-brain barrier modifiers (ultrasound)
3
$
Blood clot dispersal agents
4
$
🧊
Cryopreservation
a.
Chemical cryoprotectant agents
New cryoprotectants and new mixtures
1️
$$
Lower critical cooling rate
2
$$
Lower critical warming rate
3
$$
Lower toxicity
4
$$
Better perfusability
5
$$
b.
Other additives
Cryoprotective proteins or biologically-insipred agents
1
$$
Oxygenation of perfusate
2
$
🧪
Chemical Fixation
a.
Aldehydes
Aldehyde chemical used
1️
$
Optimize biomolecular preservation
2
$$
Chemicals to accelereate immersion fixation
3
$
b.
Non-aldehyde crosslinkers
Cleavable with contemporary technology
1
$$
c.
Long-term fluid preservatives
Better maintenance of morphology and biomolecules
1
$$
📝 PROCEDURES
General
a.
Surgical & cannulation technique
Transcardiac
1️
$$
Aortic route
2
$$
In situ cardiod roue
3
$$
Cephalon isolated routes
4
$$
Ex situ cerebral vessel cannulation
5
$$
Optimal perfusion pressure curve
6
$
Protocol changes based on patient conditions
7
$$
b.
Preventing air microemboli in brain vessels
Quality of perfusion in realistic cases
1
$
c.
Burr hole creation
Maximize speed while minimizing risk
1
$
d.
Brain extraction
Maximize speed while minimizing trauma
1
$
🧊
Cryopreservation
a.
Rapid cooling techniques
Procedure for fast cooling of large volume
1️
$
b.
Perfusion of cryoprotectants
Improve perfusion procedures
1
$
c.
Persufflation
Persuffation
1
$$
c.
Fracturing
Cryogenic cooling protocols to reduce thermal stress
1
$$
d.
Unprotected cryopreservation
Quantify extent of damage due to ice formation
1
$$
🧪
Chemical Fixation
a.
Immersion fixation
Benchmark existing immersion methods
1️
$
Procedural acceleration of immersion fixation
2
$
b.
Perfusion fixation
Necessity of washout solutions
1
$$
c.
Post-fixation cryoprotectant delivery
Perfusion-based delivery
1
$
Immersion-based delivery
2
$
📏 QUALITY METRICS
General
a.
Microscopic appearance of cells
Light microscopy-level detail metrics
1
$
Ultrastructural-level detail metrics
2
$$
Biomolecular annotation metrics
3
$$
Inferability of structural appearance
4
$$
🧊
Cryopreservation
a.
Intra preservation quality standards
Refractive Index at end of perfusion
1️
$
Dehydration
2
$
b.
Post preservation quality standards
CT-based quality metrics
1
$
c.
Post-devitrification measurements
Post devitrification structural preservation
1
$$
Post devitrification cellular viability
2
$$
Post devitrification neural activity
3
$$
⏳ LONGTERM PRESERVATION
🧊
Cryopreservation
a.
Temperature of storage
Temperature of storage
1️
$
b.
Long-term quality
Establish long term quality metrics
1
$
🧪
Chemical Fixation
a.
Post-fixation cryoprotection and sub-zero storage
Post-fixation cryoprotection and sub-zero storage
1️
$
b.
Long-term fluid preservation
Optimize fluid preservation
1
$$
✅ RESTORATION
General
a.
Repair of general damage
Repair of general damage
1️
$$$$
🧊
Cryopreservation
a.
Rewarming
Dielectric warming
1️
$$$
Nano-rewarming
2
$$$
Ultrasound rewarming
3
$$$
Chemical rewarming
Chemical rewarming
4
$$$
Novel rewarming technology
5
$$$
🧪
Chemical Fixation
a.
Crosslinking reversal
Chemical technology
1️
$$$$
a.
Whole brain emulation
Mapping brains at the connectome level
1️
$$$$
Whole brain emulation of small organisms
2
$$$$