Research directions
Engineering vital functions
We treat vital functions as engineering tasks: define the required outcome and compare ways to deliver it through drugs, cells, organoids and artificial systems.
Three functions as engineering tasks
Define the required outcome for each function, then choose how to deliver it. The implementation may be a substance, a group of cells, an organoid, a device or a combination. A function can be distributed across several components and relocated within the body.
These new examples apply Mikhail Batin’s X/S/E/A/R/N framework, retaining all six category names. The example wording and engineering options are editorial contributions.
Delivering oxygen to tissues
Cells need oxygen in proportion to their activity. Oxygenating blood, carrying oxygen and moving blood form a shared task that can be distributed between biological and technical components.
- Oxygenate the blood
- Deliver blood to tissues
- Match delivery to consumption
The function in six categories
- X Component
- A gas-exchange surface, an oxygen carrier, a pump and a vascular network. An artificial oxygenator and mechanical pump can perform part of the work.
- S System
- The system delivering oxygen to tissues.
- E Component effect
- Oxygenates blood and moves it to tissues, where oxygen is released.
- A System capacity
- The capacity to supply tissues with oxygen as their needs change.
- R Functional result
- Oxygen delivery matches consumption in each tissue, including during exertion.
- N Basis of functional status
- This outcome sustains energy production and cell viability.
Implementation options
Gas exchange can be assigned to a membrane oxygenator, blood movement supported by a pump, and flow control linked to measurements of tissue demand. Components may sit inside or outside the body. Each design must be tested across the full chain of oxygen delivery to cells.
In use today
Extracorporeal membrane oxygenation (ECMO) oxygenates blood outside the body. In a configuration supporting circulation, it also temporarily takes over the pumping work of the heart.
This is currently temporary support. Continuous autonomous oxygen delivery requires solutions for microcirculation, blood compatibility and adaptation to demand.
Source · NHLBIThe next engineering task
Build a system that supplies tissues with oxygen over long periods, at rest and during exertion. Assess delivery across tissues, energy requirements, blood damage and operating reliability. Replacing this function removes the corresponding demands on heart and lung performance; their other functions must be considered separately.
Regulating glucose through insulin delivery
The required action of insulin can be supplied by administering the hormone. Glucose sensing, dose calculation and insulin delivery can be distributed across a sensor, software and a pump, or performed by living cells.
- Measure glucose
- Determine insulin requirements
- Deliver the required hormone dose
The function in six categories
- X Component
- In a technical implementation: a glucose sensor, control software, an insulin supply and a pump. In a cellular implementation: insulin-producing cells or islet organoids.
- S System
- The system regulating glucose metabolism.
- E Component effect
- Adjusts insulin delivery according to the state of the organism.
- A System capacity
- The capacity to coordinate nutrient use and storage with intake and expenditure.
- R Functional result
- Glucose remains within the target range during meals, fasting and exercise.
- N Basis of functional status
- This outcome supports energy metabolism and protects tissues from dangerous glucose fluctuations.
Implementation options
Options include administering insulin, automated hormone delivery, and transplanting cells or organoids. Placing beta cells in an arm can be considered as an engineering option: the cells need nourishment, glucose responsiveness, access to the circulation for insulin delivery and immune protection. The location of the function becomes a design parameter.
In use today
Insulin therapy already replaces insufficient hormone production. Automated delivery systems combine a glucose sensor, dose-calculation software and a pump. Sensing, control and delivery are thus performed by separate components.
These systems require maintenance and human input, including around meals. Transplanting cells into an arm is presented here as a design option; the performance and safety of a specific implementation require testing.
Source · NIDDKThe next engineering task
Compare implementations by time in the target glucose range, dangerous highs and lows, response speed and everyday burden. For a cellular solution, also test sustained secretion and the ability to maintain or replace the graft.
Removing metabolic waste and excess water
The body needs to remove particular substances and water at the required rate while retaining useful blood components. This task can be divided into operations, with an implementation selected for each.
- Transfer waste substances across a membrane
- Remove excess water
- Maintain the internal environment
The function in six categories
- X Component
- In a technical implementation: a dialysis membrane, blood circuit, dialysis fluid and control system. In a prospective biohybrid implementation, living cells may perform some selective transport.
- S System
- The system maintaining the composition and volume of the internal environment.
- E Component effect
- Removes metabolic waste and excess water, and regulates dissolved substance transfer.
- A System capacity
- The capacity to match substance and water removal to intake and production.
- R Functional result
- Body fluid composition and volume remain within ranges compatible with normal tissue function.
- N Basis of functional status
- This outcome prevents toxic accumulation and dangerous disturbances of water, electrolyte and acid-base balance.
Implementation options
An external filter can remove substances, while selective transport can be explored in systems containing living cells. Cells and organoids are considered as possible implementations of individual operations. Requirements for each component follow from the blood composition the complete system must maintain.
In use today
Hemodialysis already removes metabolic waste and excess water from blood outside the body and helps maintain mineral balance. It is an established example of assigning part of a vital function to a technical system.
Hemodialysis replaces some kidney functions. Hormonal regulation and other tasks need separate solutions. Systems containing cells and organoids are described here as development directions.
Source · NIDDKThe next engineering task
Maintain the internal environment over long periods as diet and demand change. Compare implementations by the substances removed, retention of useful components, water balance and the time a person spends on treatment.
The outcome sets the requirements
First specify the functional outcome R and its significance N for the organism. Then select a component X and test whether its effect E provides the required capacity A within system S. Compare implementations by outcome quality, operating duration, response to demand and effects on other functions. As functions are replaced, dependence on their original structures may decrease.
The wider strategy
A functional approach breaks life support into specific tasks and selects a suitable implementation for each.
The Death-Fighting Spectrum presentation