NANOROBOTICS

RESPIROCYTES

Smrithi Sasidharan (Btech 3rd Year, ECE)

Varsha Vasudev(BTech 3rd Year, EB )

Amrita School of Engineering Bangalore, Model Engineering College, Kochi

ABSTRACT

Molecules are the universal basic building blocks of all the elements of nature, whether it be living

or non-living. The complex human body with its interdependent physiological subsystems can be

scaled down to a collection of various types of molecules. The accessibility to the molecular and

atomic components of the body can resolve a variety of constraints faced in the medical field and

can provide a tremendous breakthrough for the treatment of a variety of diseases which are

considered incurable in the present scenario. Molecular manufacturing deals with the production of

micron scaled machines or microcontrolled nanorobots composed of nano scale components which

can access each and every molecule in a cell. These nanorobots can be introduced into the human

body orally thus eliminating the need for an invasive technique to access the internal body. One

type of nanorobot which can be used is the respirocytes.The respirocytes are artificial mechanical

red blood cells designed by Robert.A.Fretias. It is a 1000 atm diamondoid pressure vessel designed

to deliver oxygen about 236 times more than the natural blood cells per unit cell volume. These

respirocytes are provided with mechanical, chemical and pressure sensors and are implanted with

an onboard microcomputer. The processor can be remotely controlled by the doctor using acoustic

signals thus directing the respirocyte to the specified location and simultaneously monitoring its

functioning. The respirocytes can be used in a variety of applications like transfusable blood

substitution; partial treatment for anaemia, perinatal/neonatal lung disorders, enhancement of

cardiovascular/neurovascular procedures, tumour therapies and diagnostics, prevention of asphyxia

and artificial breathing. Eventhough the respirocytes have not been practically implemented wide

research is going on for the design of these promising artificial red blood cells. The major problem

in the design of these nanorobots is their manufacturing in the nano scale using materials and

components which are physically and chemically compatible with the human body with minimum

aftereffects. The respirocytes thus give us huge hopes for the elimination of many currently

untreatable diseases with added advantages of precise and effective resolution.

1. INTRODUCTION

Robotics is the branch of engineering science dealing with the design of robot, their manufacture

and applications. This science can be categorised into three fields :

Electronics

Mechanics

Software

Fully autonomous machines started to appear by the start of the twentieth century. The first

digitally operated and programmable robot, Unimate, invented in 1961 was used to lift hot

pieces of metal from a die casting machine. The robots are designed to accomplish relatively

complicated, tedious and dull jobs relative to humans more cheaply, accurately and with utmost

reliability. The basic applications of robots are in manufacturing, assembly and packing,

transport, earth and space exploration, surgery, lab research and safe and mass production of

weaponry.

A. Nanorobotics and Nanomedicine

Nanorobotics is the subbranch of Robotics dealing with machines or robots designed in the

micron scale of .1 -10 micrometers with nano scale assemblies. As no artificial non – biological

nanorobot has been designed till now, it still remains a hypothetical nanotechnology

engineering concept. The terms Nanobots, Nanoids, Nanites and Nanomites are synonyms of

Nanorobots.

Nanomedicine is the application of nanotechnology in medical field.  The approaches to

Nanomedicine range from the medical use of nanomaterials, to nanoelectronic biosensors, and

even possible future applications of molecular nanotechnology.

Molecular technology has clear implications in the medical field. It allows the physicians to

perform precise interventions at the molecular and cellular level. The subassemblies of

nanorobots generally include 100nm manipulator arms, 400nm Gigahertz clock computers, 10

nm sorting rotors for molecule by molecule reagent purification and smooth hard surfaces made

of atomically flawless diamond.

The major use of nanorobots are in:

gerontological applications

pharmaceutical research,

diagnosis of diseases,

mechanical reversal of artherosclerosis,

supplementing the immune system

Rewriting DNA sequences in-vivo

Repair of brain damage

Reversing cellular insults caused by irreversible processes

Cryogenic storage of biological tissues

2. NATURAL GAS TRANSPORT SYSTEM IN THE BODY

Oxygen and carbon dioxide, the by-products of the combustion of foodstuffs are carried between

the lungs and other tissues with the help of the red blood cells. These gases are carried within the

red blood cells.

Haemoglobin combines reversibly with oxygen to form oxyhaemoglobin. 95% of oxygen is carried

within the body in this form. The rest of the oxygen present is transported dissolved in blood. At

normal human body temperature haemoglobin in 1 litre of blood holds 200cm3 of oxygen, which is

87 times more than what the plasma can carry alone which is about 2.3 cm3

Carbon dioxide combines reversibly with amino group of and bicarbonate ions releases hydrogen

ions in t to form carbaminohaemoglobin. 25% of total carbon dioxide within the body is transported

in this form. 10% is dissolved in plasma and the rest 65% is present within the red blood cells

which after hydration is converted to bicarbonate ions.

Creation of carbamino haemoglobin and bicarbonate ions releases hydrogen ions which in the

absence of haemoglobin makes venous blood 800 times more acidic than the arterial blood. But this

does not happen due to the buffering action of haemoglobin and isohydric carriage monitored by it

through the absorption of the excess hydrogen ions mostly within the red blood cells.

The gases are taken and released by haemoglobin according to their local partial pressures.

Haemoglobin’s affinity for oxygen is inversely proportional to its affinity for carbon dioxide. High

level of oxygen in the lungs aids the release of carbon dioxide which is to be expired. High carbon

dioxide level in the other tissues assists the release of oxygen for use by the other tissues.

Tetrameric haemoglobin when freed from the red blood cells loses its effectiveness in three

different ways :

It dissociates to dimmers which are rapidly cleared from circulation by mononuclear

phagocytic system (10-30 mins half life) and by the kidneys (one hour half life).

It binds oxygen more tightly reducing the deliverability of oxygen during tissue hypoxia.

During storage it’s oxidised to useless methaemoglobin due to absence of the protective

enzyme, methemoglobin reductase in the red blood cells.

3. CURRENT BLOOD SUBSTITUTION SYSTEMS

A lot of efforts have thus been put forward to modify haemoglobin to increase its intravascular

dwell time.

3.1 Encapsulation

Haemoglobin is cross-linked internally or externally with a macromolecule, polymerised, modified

by recombinant DNA techniques and microencapsulated. Encapsulation is a very promising

approach as all the vertebrate haemoglobin is contained in cells to maintain its stability, preserve

function and to protect the host from toxicity.

3.2 Fluorocarbon Emissions

Fluorocarbon emulsions provide a simpler approach to oxygen transport and delivery. The

technique relies on physical solubilisation rather than binding of oxygen molecules. Injectable

oxygen carriers which are molecules of eight to ten carbon atoms with a molecular weight of 450-

500 grams are prepared using liquid fluorocarbons. They dissolve about 20-25 more times as much

oxygen as water delivering optimum volume of oxygen to the tissues as delivered by the equivalent

weight of haemoglobin. Mice survive immersion in fluorocarbon through which oxygen is bubbled.

Rats breathing 95% oxygen survived total blood replacement.

Fluorocarbons are insoluble in water. They are administered in the form of emulsions of 0.1 – 0.2

micron sized droplets dispersed in a physiologic solution similar to fat emulsions. After

opsonisation and phagocytosis of emulsion droplets the fluorocarbons are transferred to lipid

carriers in blood and released during passage through pulmonary capillary bed. Thus the

fluorocarbons are not metabolised but excreted unchanged by exhalation as a vapour through lungs

in 4-12 hours.

3.3 Shortcomings

The current blood substitution systems have the following shortcomings:

Too short a survival time in circulation to be useful in treatment of chronic anaemia.

They are not specifically designed to regulate carbon dioxide to participate in acid or base

buffering.

Vaso-constriction

Their use results in reduced tissue oxygenation

Increases the susceptibility to bacterial infection due to blockage of the monocyte-

macrophage system

Nephrotoxicity

Free radical induction

4. DESIGN OF RESPIROCYTES

Nobel physicist Richard.P.Feynman first proposed nanotechnology in the year 1959. A Given a

future to precisely engineer complex, micron scale machines, it is possible to imagine a complete

microscopic chemical factory that avoids the shortcomings of the current blood technology and

simulates most major functions of the natural erythrocyte. Respirocytes are the artificial red blood

cells or erythrocytes designed according to the principles of nanotechnology. They are basically

nanorobots.

4.1. Pressure Vessels

With the goal of oxygen transport from the lungs to other body tissues, the simplest possible design

proposed by Robert.A.Fretias is a microscopic pressure vessel, spherical in shape for maximum

compactness.

Since one of the necessities for a convenient design is durability, the strongest materials like

flawless diamond or sapphire are used and they are constructed with utmost care atom by atom.

They have a Young’s modulus of 1012 N/m2 (107 atm) and conservative working stress (~0.2 times

tensile strength) of 1010 N/m2 (100,000 atm).

Considering the simplest design, oxygen release will be continuous throughout the body. A slightly

more sophisticated design constitutes a system responsive to local oxygen partial pressure, with gas

released through one of these methods:

Using a needle valve , controlled by a heme protein that changes conformation in response

to hypoxia

Diffusion via low pressure chamber into a densely packed aggregation of heme-like

molecules trapped in an external fullerene cage porous to environmental gas and water

molecules

Engineering molecular sorting rotors

These proposals have two principal failings:

Once discharged the devices become useless and the discharge time for the presently

designed blood substitutes is very short. In the absence of functioning red blood cells the

oxygen contained in a 1 cm3 injection of 1000 atm microtanks would be exhausted in 2

minutes.

The proposals involve placement of numerous point source oxygen emitters throughout the

capillary bed in conjunction with the existing erythrocyte population. These extra emitters

are equivalent to red blood cells with disabled carbon dioxide transport and acid-buffering

capabilities. Their inclusion in the blood stream leads to increased carbon dioxide acidity

and acidosis especially in patients with respiratory and haemolytic complications.

Neither problem can be overcome by using passive systems alone. A practical and preferable

method to extend the duration is to recharge the microvessels with oxygen gas, preferably via

the lungs since direct regeneration of oxygen from carbon dioxide is energetically prohibitive.

The simplest way to prevent carbon dioxide toxicity is to provide additional tankage for carbon

dioxide transport and become active means for gas loading at the tissues and unloading at the

lungs as physically stored carbon dioxide makes no net addition to blood acidity. But still

respirocytes operating in the absence of red blood cells would generate little carbon dioxide

related acidity. Proper blood pH could probably be maintained by the kidneys alone.

4.2 Molecular Sorting Rotors

Molecular sorting rotors have been proposed for the task of an active method of conveying gas

molecules into, and out of the pressurised microvessels which is the key to the successful

functioning of the respirocyte. Each rotor has binding site "pockets" along the rim exposed

alternately to the blood plasma and interior chamber by the rotation of the disk. Each pocket

selectively binds a specific molecule when exposed to the plasma. Once the binding site rotates to

expose it to the interior chamber, the bound molecules are forcibly ejected by rods thrust outward

by the cam surface. Rotors are fully reversible, so they can be used to load or unload gas storage

tanks, depending upon the direction of rotor rotation.

Figure : Molecular sorting rotor

Typical molecular concentrations in the blood for target molecules of interest (O2, CO2, N2 and

glucose) are ~10-4, which should be sufficient to ensure at least 90% occupancy of rotor binding

sites at the stated rotor speed . Each stage can conservatively provide a concentration factor of

1000, so a multi-stage cascade should ensure storage of virtually pure gases. Since each 12-arm

outbound rotor can contain binding sites for 12 different impurity molecules, the number of

outbound rotors in the entire system can probably be reduced to a small fraction of the number of

inbound rotors.

Figure : Sorting rotor cascade

4.3 Sorting Rotor Binding Sites

Receptors should be should be highly sensitive and they should have binding sites only for specific

molecules. They should have the additional qualities of reliability, high affinity and should survive

long exposures to the aqueous media of blood.

Oxygen transport pigments are a usually coagulated protein that is proteins complexed with another

organic molecule or with one or more metal atoms. The main components of the transport pigments

are the metal atoms like Cu2+ or Fe3+ which constitutes the binding sites to which oxygen can

reversibly attach. Apart from haemoglobin and myoglobin the natural respiratory pigments are

hemocyanin, chlorocruorin, hemerythrin and vanadium chromagen. Artificial reversible oxygen-

binding molecules have also been studied. Some of them are :

Cobalt based porphyrins such as coboglobin and cobaltohistidine

Simple iron-indigo compounds

Iridium complexes

Nonporphyrin lacunar iron complexes

Heme linked oxidase

Implantable blood oxygen sensors like Medtronics haemodynamic monitor are already in clinical

trials. Unlike haemoglobin, the other natural oxygen transport pigments are not susceptible to

carbon monoxide poisoning, neither are the respirocytes.

Many proteins and enzymes like haemoglobin, carbonic anhydrase and ribulose biphosphate

carboxylase have binding sites for carbon dioxide. A wide variety of molecules like deliquescent

crystals, efflorescent minerals, hydrophilic and polar amino acids and numerous enzymes such as

carbonic anhydrase, hydrolases and dehydratases bind water reversibly. Binding sites for glucose

are common in nature. These include the enzyme hexokinase, the glucose transporter molecule and

the glucose binding proteins found in the intestines, liver, kidney and adipose tissue. Implantable

glucose sensors have been developed by Becton, Dickinson Incorporation and by the Japans

University of Osaka. The enzyme nitrogenase is highly labile in the presence of oxygen but

research is concentrated on its highly efficient nitrogen binding sites. Once the required receptor for

the transport of the specific gas is selected they are incorporated into the rotors as precisely shaped

and charged diamondoid surfaces and cavities, atom by atom, using the manufacturing techniques

suggested by Drexler.

4.4 Device Scaling

The upper limit for the physical size of the respirocytes can be easily estimated. It cannot be larger

than the capillaries which have an average diameter of 8 microns. But these capillaries can be as

small as 3.7 microns when the red blood cells have to fold themselves to conveniently pass through

them. Smaller cells face greater danger of environmental insults and they encounter potential

filtration sites throughout the body. For example the fenestrated endothelium of the glomerular

membrane in the kidney filter particles <100 nm from the blood. So these requirements put forward

the need for larger device sizes.

The minimum possible respirocyte diameter is driven by operational requirements and by minimum

component size. The smallest reasonable computer requires 105 nm3, a 58-nm diameter sphere.

Additionally, gas is loaded using molecular sorting rotors mounted on the surface of a spherical

tank. In the baseline design (diameter D = 1 micron), 37.28% of tank surface consists of sorting

rotors and related subsystems. The number of sorting rotors scales with tank volume or R3; tank

surface scales as R2; so the percentage of tank surface in rotors (Rotor/Surface Ratio or RSR) scales

linearly with R (RSR ~ qD, q = 0.3728 fractional surface coverage). RSR ~ 1.00 (100%) coverage

occurs at D = 2.68 microns, the upper limit. Careful review of the baseline design suggests that the

minimum rotor area necessary to achieve all performance specifications while maintaining 10:1

subsystem redundancy is about 17,000 nm2, which implies D = 0.245 micron at RSR = 0.0902

(9.02%). Eliminating all redundancy reduces rotor requirements to 1700 nm2, which implies D =

0.114 micron at RSR = 0.0412 (4.12%). The above considerations suggest a reasonable range for

respirocyte diameter of 0.2-2 microns; the present study assumes a spherical respirocyte diameter of

~1 micron.

4.5 Buoyancy Control Using Water Ballast

Another factor which comes into picture when operating in an aqueous medium is buoyancy which

can be controlled by loading and unloading the water ballast. The smaller the repirocyte, the longer

it settles out of suspension according to the Stokes Law. Even a small difference in density between

individual red blood cells and blood plasma causes the red blood cells to settle out of suspension at

a fast rate depending on haemocrit and degree of red blood cell aggregation. Natural erythrocytes

appear unhandicapped by their faster settling rate, so active ballast management for artificial

respirocytes is probably unnecessary in normal operations. No other solid blood component can

maintain exact neutral buoyancy, hence those other components precipitate outward during gentle

centrifugation and are drawn off and added back to filtered plasma on the other side of the

apparatus. Meanwhile, after a period of centrifugation, the plasma, containing mostly suspended

respirocytes but few other solids, is drawn off through a 1-micron filter, removing the respirocytes.

Filtered plasma is recombined with centrifuged solid components and returned undamaged to the

patient's body. The rate of separation is further enhanced either by commanding respirocytes to

empty all tanks, lowering net density to 66% of blood plasma density, or by commanding

respirocytes to blow a 5-micron O2 gas bubble to which the device may adhere via surface tension,

allowing it to rise at 45 mm/hour under normal gravitational acceleration.

5. BASELINE DESIGN

Many specific design issues must be next confronted like tank configuration, rotor and glucose

engine replacement, subsystem scaling and redundancy level required to produce acceptable system

reliability. The final design represents a compromise among many competing factors.

5.1 Power

Onboard power is provided by a mechanochemical engine that exoenergically combines glucose

and oxygen to generate mechanical energy to drive molecular sorting rotors and other subsystems,

as demonstrated in principle in a variety of biological motor systems. Glucose engine design -

possibly involving a ballistic turbine driven by rotor-combustion ejector operating near 1000 atm is

a critical research issue. Drexler estimates engines can be designed to operate at efficiency greater

than 99%. However, since natural cellular metabolic pathways using the glycolysis and

tricarboxylic acid (TCA) cycles achieve only 68% efficiency, we adopt a more conservative 50%

efficiency for the present study. Sorting rotors absorb glucose directly from the blood and store it in

a fuel tank. Oxygen is tapped from onboard storage.

5.2 Communications

The attending physician can broadcast signals to molecular mechanical systems deployed in the

human body most conveniently using modulated compressive pressure pulses received by

mechanical transducers embedded in the surface of the respirocyte. Converting a pattern of pressure

fluctuations into mechanical motions that can serve as input to a mechanical computer requires

transducers that function as pressure-driven actuators. Internal communications within the

respirocyte may be achieved by impressing modulated low-pressure acoustical spikes on the

hydraulic working fluid of the power distribution system, or via simple mechanical rods and

couplings.

5.3 Sensors

Various sensors are needed to acquire external data essential in regulating gas loading and

unloading operations, tank volume management, and other special protocols.

Figure : Molecular Concentration Sensor

For instance, sorting rotors can be used to construct quantitative concentration sensors for any

molecular species desired. It is also convenient to include internal pressure sensors to monitor O2

and CO2 gas tank loading, (container fullness) sensors for ballast and glucose fuel tanks, and

internal/external temperature sensors to help monitor and regulate total system energy output.

5.4 Onboard Computation

An onboard computer is necessary to provide precise control of respiratory gas loading and

unloading, rotor field and ballast tank management, glucose engine throttling, power distribution,

interpretation of sensor data and commands received from the outside, self-diagnosis and activation

of failsafe shutdown protocols.

5.5 Baseline configuration

The artificial respirocyte is a spherical nanomedical device 1 micron in diameter consisting of 18

billion precisely arranged structural atoms plus 9 billion temporarily resident molecules when fully

loaded. Allocations of device volume and mass were determined by specifying equal O2 and CO2

tank volumes, glucose tank volumes, ballast volume as a variable, and all structural mass as

diamondoid in density.

Figure.4.Glucose Rotor and Tank,engine assembly

Twelve pumping stations are spaced evenly along an equatorial circle. Each station has its own

independent glucose engine, glucose tank, environmental glucose sensors, and glucose sorting

rotors. Each station alone can generate sufficient energy to power the entire respirocyte. Detailed

reliability simulations will be required to determine whether stations should run at

(1) Peak power on a rotating schedule,

(2) Partial power on a continuous basis, or

(3) One at a time until failure, switching to the next backup.

Power is transmitted hydraulically to local station subsystems and also along a dozen independent

interstation trunk lines that allow stations to pass hydraulic power among themselves as required,

permitting load shifting and balancing.

Computer/mass-memory sets are located at the centre of the device allowing maximum shielding

from environmental insults and centralized access to all surface components including

communications links, external sensors, and distributed power supply. Any of the computers at the

core can receive power or communications directly from any of the pumping stations along hard

links in protected utility conduits.

Figure:Pumping station layout

Each pumping station has an array of 3-stage molecular sorting rotor assemblies for pumping O2,

CO2, and H2O into and out of the ambient medium. The number of rotor sorters in each array is

determined both by performance requirements and by the anticipated concentration of each target

molecule in the bloodstream. Any one pumping station, acting alone, can load or discharge any

storage tank in 10 sec whether gas, ballast water, or glucose. Gas pumping rotors are arrayed in a

noncompact geometry to minimize the possibility of local molecule exhaustion during loading.

Each station also includes three glucose engine flues for discharge of CO2 and H2O combustion

waste products, environmental oxygen pressure sensors distributed throughout the O2 sorting rotor

array to provide fine control if unusual concentration gradients are encountered, also similar CO2

pressure sensors on the opposite side, 2 external environment temperature sensors (one on each side

located as far as possible from the glucose engine to ensure true readings), and 2 fluid pressure

transducers for receiving command signals from medical personnel.

Figure:Equatorial Cutaway View of Respirocyte

Figure: Polar Cutaway View of Respirocyte

The equatorial pumping station network occupies 50% of respirocyte surface. On the remaining

surface, a universal "bar code" consisting of concentric circular patterns of shallow rounded ridges

is embossed on each side, centered on the "north pole" and "south pole" of the device. This coding

permits easy product identification by an attending physician with a small blood sample and access

to an electron microscope, and may also allow rapid reading by other more sophisticated medical

nanorobots which might be deployed in the future.

5.6 Tank Chamber Design

Each storage tank is constructed of diamondoid honeycomb or a geodesic grid skeletal framework

for maximum strength. Thick diamond bulkheads separate internal tankage volumes. Available

structural mass is equivalent to a 10-nm thick (~60 carbon atoms) 2.2 micron x 2.2 micron diamond

sheet. Compartment walls are perforated with sufficient holes of varying sizes to allow gas to flow

easily between them, with larger compartments nearest the rotors graduating to smaller

compartments more distant from the rotors to encourage isobaric entrainment.

The present design includes separate O2 and CO2 chambers. In theory, these gases could be stored

mixed in a single chamber. A single chamber design can effectively double the O2-carrying

capacity of each respirocyte by allowing the entire gas tank volume to be initially charged with

oxygen at 1000 atm. There are four minor drawbacks to this approach:

(1) Respiration is controlled by CO2, not O2, levels, requiring maintenance of sizable CO2

inventories at all times, reducing surplus volume available for O2 storage;

(2) Respirocytes may be deployed to reverse serious tissue CO2 overloading, requiring significant

available storage volume to absorb this gas;

(3) The rate of binding for outbound transport by sorting rotors may be lower for mixed gases,

reducing maximum outgassing rate; and

(4) Inability to emergency vent pure gas.

6. SAFETY FACTORS

Respirocytes should be extremely reliable and usually should have a life of 20 years.

Device overheating: If all the glucose power plants get jammed or refuse to turn off, malfunction

occurs while the respirocyte is in your bloodstream, its temperature won't rise at all. That's because

the 7.3 picowatts of continuous thermal energy the device is generating is easily absorbed by the

huge aqueous heat sink, which has a bountiful heat capacity.

Non combustive device explosion: Each device contains up to 0.24 micron3 of

oxygen and carbon dioxide gas at 1000 tam pressure, representing 24 picojoules of stored

mechanical energy.If the device explodes inside human tissue, the gases may work against the

surrounding fluid forming large bubbles.The only plausible respirocyte explosion scenario is dental

grinding.A patient with an oral lesion could spread respirocyte-impregnated blood over the teeth

can explode thousand of respirocytes at once producing a "fizziness" in the mouth.

Complete structural failure of a respirocyte in vivo is a rare case. A spherical diamondoid shell

should resist accelerations up to 108-1010 g's. Crushing respirocyte-impregnated human tissue in a

hydraulic press is unlikely to destroy any devices, as they will simply slide out of the way.

7. RESPIROCYTE CONTROL PROTOCOLS

Respirocyte behaviour is initially governed by a set of default protocols which can be modified at

any time by the attending physician.Basic protocols will exist for operating molecular sorting rotors

at various speeds and directions in response to sensor data. Gas loading parameters may be

precisely specified in an individualized onboard lookup table provided by the physician for his

patient, as for instance to adjust for declining arterio-venous oxygen gradient at high altitudes.

Respirocytes, like natural haemoglobin, may also participate in the elimination of CO and in NO-

mediated vascular control.

Respirocytes can be programmed with more sophisticated behaviours.

Detection of PCO2 < 0.5 mmHg and PO2 > 150 mmHg, indicating direct exposure to

atmosphere and a high probability that the device has been bled out of the body, should

trigger a prompt gas venting and failsafe device shutdown procedure.

Self-test algorithms monitoring tank filling rates, unaccounted pressure drops (indicating a

leak), clutch responses, etc. may detect significant device malfunction, causing the

respirocyte to place itself in standby mode ready to respond to an acoustic command to

execute the filtration protocol for exfusion.

Out messaging protocols could allow the population of respirocytes to communicate

systemwide status directly with the patient by inducing recognizable physiological cues

(fever, shivering, gasping), or with the physician by generating subtle respiratory patterns

requiring diagnostic equipment to detect, either automatically or in response to an

acoustically-transmitted global inquiry initiated by patient or physician.

8. APPLICATIONS

8.1 Transfusions & Perfusions

Respirocytes may be used as the active oxygen-carrying component of a universally transfusable

blood substitute that is free of disease vectors such as hepatitis, venereal disease, malarial parasites

or AIDS, storable indefinitely and readily available with no need for cross-matching. In current

practice, organs must be transplanted soon after harvest; respirocytes could be used as a long-

duration perfusant to preserve living tissue, especially at low temperature, for grafts (kidney,

marrow, liver and skin) and organ transplantation.

8.2 Treatment of Anaemia

Oxygenating respirocytes offer complete or partial symptomatic treatment for virtually all forms of

anaemia, including acute anaemia caused by a sudden loss of blood after injury or surgical

intervention; secondary anaemia’s caused by bleeding typhoid, duodenal or gastric ulcers; chronic,

gradual, or post-hemorrhagic anaemia’s from bleeding gastric ulcers , excessive menstrual

bleeding, or battle injuries in war zones, hereditary anaemias including haemophilia, leptocytosis

and sicklemia chlorosis and hypochromic anaemia, endocrine deficiency anaemia, pernicious and

other nutritional anaemias; anaemias resulting from infectious diseases including rheumatism,

scarlet fever, tuberculosis, syphilis, chronic renal failure and cancer, or from haemoglobin

poisoning such as by carbon monoxide inhalation.

8.3 Fetal and Child-Related Disorders

Respirocytes may be useful in perinatal medicine, as for example infusions of device suspension to

treat fetal anaemia, neonatal hemolytic disease, or in utero asphyxia from partial detachment of the

placenta or maternal hypoxia, to restore the oxygen-carrying ability of fetal blood. Asphyxia

neonatorum, as from umbilical cord compression during childbirth, may fatally deprive the infant

of oxygen; prenatal respirocyte treatment could be preventative. Many cases of Sudden Infant

Death Syndrome, the leading cause of neonatal death between 1 week and 1 year of age, and

respiratory distress syndrome involve recurrent oxygen deprivation or abnormalities in the

automatic control of breathing, both of which could be delethalized using a therapeutic dose of red

cell devices. Respirocytes could also aid in the treatment of childhood afflictions such as whooping

cough, cystic fibrosis, rheumatic heart disease and rheumatic fever, congenital heart disorders.

8.4 Respiratory Diseases

The devices could provide an effective long-term drug-free symptomatic treatment for asthma, and

could assist in the treatment of hemotoxic (pit viper) and neurotoxic (coral) snake bites; hypoxia,

stress polycythemia and lung disorders resulting from cigarette smoking and alcoholism; neck

goitre and cancer of the lungs, pharynx, or thyroid; pericarditis, coronary thrombosis, hypertension,

and even cardiac neurosis; obesity, quinsy, botulism, diphtheria, tertiary syphilis, amyotrophic

lateral sclerosis, uraemia, coccidioidomycosis (valley fever), and anaphylactic shock; and

Alzheimer's disease where hypoxia is speeding the development of the condition.

8.5 Cardiovascular and Neurovascular Applications

Respirocyte perfusion could be useful in maintaining tissue oxygenation during anaesthesia,

coronary angioplasty, organ transplantation, siamese-twin separation, other aggressive heart and

brain surgical procedures, in postsurgical cardiac function recovery, and in cardiopulmonary bypass

solutions. The device could help prevent gangrene and cyanosis, for example, during treatment of

Raynaud's Disease. Therapeutic respirocyte dosages can delay brain ischemia under conditions of

heart or lung failure, and might be useful in treating senility.

8.6 Tumor Therapy and Diagnostics

Cancer patients are usually anemic. X-rays and many chemotherapeutic agents require oxygen to be

maximally cytoxic, so boosting systemic oxygenation levels into the normal range using

respirocytes might improve prognosis and treatment outcome. Fluorocarbon emulsions have been

used to probe tissue oxygen tension. Respirocytes could be used as reporter devices to map a

patient's whole-body blood pressure or oxygenation profile, storing direct sensor data in each

computer along with positional information recorded from a network of precisely positioned

acoustic transponders, to be later retrieved by device filtration and data reconstruction . A similar

network of acoustic transmitters, making possible respirocyte autotriangulation hence precise

internal positional knowledge, could allow preferential superoxygenation of specific tissues,

enhancing treatment effectiveness.

8.7 Asphyxia

Respirocytes make breathing possible in oxygen-poor environments, or in cases where normal

breathing is physically impossible. Prompt injection with a therapeutic dose, or advance infusion

with an augmentation dose, could greatly reduce the number of choking deaths and the use of

emergency tracheostomies, artificial respiration in first aid, and mechanical ventilators. The device

provides an excellent prophylactic treatment for most forms of asphyxia, including drowning,

strangling, electric shock, nerve-blocking paralytic agents, carbon monoxide poisoning, underwater

rescue operations, smoke inhalation or firefighting activities, anaesthetic/barbiturate overdose and

confinement in airtight spaces. Respirocytes augment the normal physiological responses to

hypoxia, which may be mediated by pulmonary neuroepithelial oxygen sensors in the airway

mucosa of human and animal lungs.

8.8 Underwater Breathing

Respirocytes could serve as an in vivo SCUBA (Self-Contained Underwater Breathing Apparatus)

device. With an augmentation dose or nanolung, the diver holds his breath for 0.2-4 hours, goes

about his business underwater, then surfaces, hyperventilates for 6-12 minutes to recharge, and

returns to work below.

Respirocytes can relieve the most dangerous hazard of deep sea diving - decompression sickness

("the bends") or caisson disease.

8.9 Other Applications

Respirocytes could permit major new sports records to be achieved, because the devices can deliver

oxygen to muscle tissues faster than the lungs can provide, for the duration of the sporting event.

This would be especially useful in running, swimming, and other endurance-oriented events, and in

competitive sports such as basketball, football and soccer where extended periods of sustained

maximum exertion are required.

Artificial blood substitutes may also have wide use in veterinary medicine, especially in cases of

vehicular trauma and renal failure where transfusions are required, and in battlefield applications

demanding blood replacement or personnel performance enhancement.

9. DEVICE TESTING AND FDA APPROVAL

Since the respirocyte depends for its function on mechanical pumping rather than chemical action,

and is not metabolized during the achievement of its purposes, it is clearly a device and not a drug

under the Federal Food, Drug, and Cosmetic Act. Devices are regulated under the provisions of the

Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Medical

Device Amendments of 1992.

In order for the FDA to approve or license any blood substitute, both efficacy and safety must be

established to the satisfaction of the FDA's Office of Device Evaluation using preclinical and

clinical data to support a Premarket Approval Application (PMA). In 1990 the FDA's Centre for

Biologics Evaluation and Research issued points to consider document governing artificial oxygen

carriers. The document does not address devices, but many of its suggestions are relevant. The FDA

recommends first a program of in vitro biologic assays to characterize the product, including tests

for generation of oxygen radicals, activation of triggered enzyme/cell systems such as the

complement/kinin/coagulation cascades, macrophage/neutrophil/platelet activation, and mediator

release such as histamine, thromboxane metabolites, leukotrienes, and interleukins. This should be

followed by animal safety testing to determine effects on microvascular circulation and

endothelium, evaluation of nephrotoxicity, blood chemistry assays and hematologic studies.

Finally, low-dose human studies could begin, with subjects monitored carefully for circulatory,

immune, and other animal-study parameters, as well as for inflammation mediators, specific

interactions with human diseases, and comparison of product safety profile with other approved

artificial oxygen carriers, and with natural red cells. Since the respirocyte is a purely mechanical 1-

micron device, there is no concern with electromagnetic interference. The product liability situation

is such that no physician uses any experimental device unless he or she is certain of its effectiveness

and safety anyone with insufficient data to demonstrate such is subject to lawsuit, and loss of the

right to practice medicine. Clearly a formidable regimen of laboratory, field, and clinical testing lies

ahead before the respirocyte could be deemed ready for routine medical use.

10.CONCLUSION

This paper presents a preliminary design for a simple nanomedical device that functions as an

artificial erythrocyte, duplicating the oxygen and carbon dioxide transport functions of red cells

while largely eliminating the need to manage carbonic acidity because CO2 is carried mechanically,

rather than chemically, in the blood. The baseline respirocyte can deliver 236 times more oxygen to

the tissues per unit volume than natural red cells, and enjoys a similar advantage in carbon dioxide

transport.

The respirocyte is constructed of tough diamondoid material, employs a variety of chemical,

thermal and pressure sensors, has an onboard nanocomputer which enables the device to display

many complex responses and behaviours, can be remotely reprogrammed via external acoustic

signals to modify existing or to install new protocols, and draws power from abundant natural

serum glucose supplies, thus is capable of operating intelligently and virtually indefinitely, unlike

red cells which have a natural lifespan of four months. This device cannot be built today. However,

when future advances in the engineering of molecular machine systems permit its construction, the

artificial respirocyte may find dozens of applications in therapeutic and critical care medicine, and

elsewhere.

REFERENCES

http://www.kurzweilai.net/meme/frame.html?main=/articles/art0468.html

http://www.foresight.org/nanomedicine/Respirocytes.html

www.wikepedia.com