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Nanotechnology in Transfusion medicine

Nanotechnology
Technology

development at the atomic, molecular, or macromolecular range of approximately 1-100 nanometers that is able to create structures, devices, and systems that have novel properties.
1 nanometer = 1 x 10-9 m

A nanometer

is a billionth of a meter.

The

emerging field of nanotechnology involves scientists from many different disciplines, including physicists, chemists, engineers, and biologists. are many interesting nanodevices being developed that have a potential to improve cancer detection, diagnosis, and treatment.

There

Applications

of Nanotechnology in Medicine and Health

Diagnostics

Using Sensors and Micro Electro Mechanical Systems (MEMS) & implants

Drug

Delivery Using Nanoparticles and Molecular Carriers on a Chip and Advanced Drug Delivery Systems

Lab

As

diagnostics

Biosensing

Microarrays:

genes and proteins complexes of DNA and peptides

Nanoparticle

Designing Nanodevices for Use in the Body


Nanostructures

can be so small that the body may clear them too rapidly for them to be effective in detection or imaging. nanoparticles may accumulate in vital organs, creating a toxicity problem.
will need to consider these factors as they attempt to create nanodevices the body will accept.

Larger

Scientists

Designing Nanodevices for Use in the Body

Nanodevices Are Small Enough to Enter Cells

Most

animal cells are 10,000 to 20,000 nanometers in diameter.

This

means that nanoscale devices(less than 100 nanometers) can enter cells and the organelles inside them to interact with DNA and proteins.
developed through nanotechnology may be able to detect disease in a very small amount of cells or tissue.

Tools

They may also be able to enter and monitor cells within a living body.

Nanodevices Can Preserve PatientsSamples


Many

nanotechnology tools will make it possible for clinicians to run tests without physically altering the cells or tissue they take from a patient. is important because the samples clinicians use to screen for cancer are often in limited supply.

This

It

is also important because it can capture and preserve cells in their active state. would like to perform tests without altering cells, so the cells can be used again if further tests are needed.

Scientists

Uses for nanotechnology in health


There

are several developments in nanotechnology that can help improve health in developing countries.

Disease diagnosis and screening


Nanolitre

systems (known as lab-on-a-chip): devices that automate a biological process using fluids at the nanolitre scale. dots: Nanosized semiconductors that can be used as biosensors to find disease. Because they fluoresce they can be used to tag diseased cells. nanoparticles: used as nanosensors

Quantum

Magnetic

Nanosensor

arrays: grids of carbon nanotubes

Antibody-dendrimer

conjugates: branched nanomolecules with antibodies on their ends for diagnosis of HIV and cancer nanotubes and flatter, thin wires called nanobelts or nanowires (often made of gold) as nanosensors for disease diagnosis as they bond to biomarkers that indicate cancer such as mutated RNA

Carbon

Nanoparticles

as medical image enhancers: Medical imaging relies on looking for contrasts in the way light is scattered in healthy tissue compared with diseased tissue. sharper this contrast, the more accurate the diagnosis. are able to give medical imaging techniques a sharper resolution, making it easier to identify disease.

The

Nanoparticles

Drug delivery systems


The

choice of system depends on the way they bind with the drug and the type of drug treatment. These are pods that encapsulate drugs, which ensures the drugs are released more slowly and steadily in the body

Nanocapsules:

Liposomes: Artificial

vesicles made up of a lipid bilayer so they can fuse with and penetrate membranes easily. These have been used to treat diseases such cancer, fungal infections, hepatitis A, and influenza

Dendrimers:

tree-shaped synthetic nanomolecules that carry drugs in the tips of the branches.

Buckyballs:

spherical nanoparticles can carry more than one drug at a time.

They are useful in the treatment of diseases such as cancer and other diseases where monotherapy can lead to drug resistance
which carry drugs, for cancer for instance, into the body and are held at the target site by an external magnet. purpose of this is to concentrate the drug at the tumour site for long enough for it to be absorbed.

Nanobiomagnets

The

Nanotechnology

can also provide alternatives to injectable vaccines if the inactive virus is bound up with nanoparticles to increase the immune response.

Nanotechnology and Cryo preservation


[Nanotechnology]

will revolutionize the process of ensuring the compatibility of blood products and the reduction of the risk of infectious disease transmission

Research

in cyrobiology focuses on understanding how freezing affects the viability of cells.

Storage

of frozen blood products is critically important to the maintenance of an inventory of rare blood types and also to the storage of hematopoietic stem cells for transplantation.
Blood Services scientists have unravelled some of the mysteries surrounding the freezing process and have developed new strategies to minimize the damage to cells caused by this freezing process.

Canadian

They

have developed new freezing processes and identified unique protectant solutions that will improve the recovery of live cells after the thawing process. collaboration with the University of Alberta, Canadian Blood Services researchers are investigating the opportunity presented by nanotechnology to analyse samples from blood donors in a new way.

In

The

miniaturization of blood donor testing of all types onto a single chip will revolutionize the process of ensuring the compatibility of blood products and the reduction of the risk of infectious disease transmission. efficiency of the blood system will be improved by immediate testing prior to donation rather than the present system of testing postdonation.

The

Nanotechnology

will permit the rapid genetic analysis of a blood donation for the full range of blood group antigens rather than simply the ABO and Rh groups that are typed at present. information will make the process of crossmatching blood for transfusion purposes more complete and safer for patients.

This

Health monitoring
Nanotubes

and nanoparticles can be used as glucose, carbon dioxide and cholesterol sensors and for in-situ monitoring of homeostasis, the process by which the body maintains metabolic equilibrium.

In

developing nations, the use of nanotechnology is also being explored in the fight against infectious diseases such as HIV and TB.

Nanotechnology in cancer
Nanotechnology

advances have been heavily focused on cancer, mainly on diagnosis and drug delivery. carried by polymer-coated nanoparticles have been used to treat multidrug-resistant breast and ovarian cancer with the chemotherapies

Drugs

Tuberculosis

and nanotechnology

The

Central Scientific Instruments Organisation of India has designed a nanotechnology-based TB diagnostic kit, currently undergoing clinical trials. would cut both the cost and time required for TB tests, and also require a smaller amount of blood for testing.

This

Artificial cells
The

general principles of artificial cells can form the basis of a large number of artificial systems addition to being of cellular dimensions in the micron range, they can also be in the macro range, nano range or molecular range

In

The

membrane material includes polymer, biodegradable polymer, lipid, crosslinked protein, lipid-polymer complex, lipid-protein complex and membrane with transport carriers. is the assembling of biological molecules into nanodimension structures, membranes with nanodimension thickness or nanotubules with nanodimension diameter.

Nanobiotechnology

An example of assembling of biological molecules to form polyHb and conjugated Hb

Examples of different types of nanobiotechnology-based polyHbenzymes

There

are three steps in the development of a complete artificial RBC i.e. developing: dimension artificial red cell lipid membrane artificial red

1) A micron

2) A submicron

blood cell
3) A nanodimension

biodegradable membrane

artificial RBC.

Micron

Dimension Artificial RBCs with Ultrathin Polymeric Membrane


first attempt at preparing an artificial red blood cell involved replacing the red blood cell membrane with an ultrathin polymeric membrane

The

Submicron Lipid Membrane Artificial RBCs


Preparation

larger lipid membrane artificial cells where the lipid is supported in the form of lipid-protein membrane and lipid polymer membrane 1980 Djordjevich and Miller submicron 0.2 micron diameter artificial RBCs using lipid membrane vesicles to encapsulate hemoglobin
increased the circulation time significantly, although it was still rather short.

In

This

The

most successful approach to improve the circulation time is to incorporate polyethyleneglycol (PEG) into the lipid membrane artificial RBCs resulting in a circulation halftime of more than 30 h

Nanodimension Biodegradable Polymeric Membrane RBCs


To prepare nanodimension artificial RBCs with the following properties:
Aim

1.

Contains little or no lipid in the membrane.

2.

Persist in the circulation after infusion for a sufficiently long time. Be stable in storage.

3.

4.Remains

stable after infusion for the duration of its function as a blood substitute but it has to be biodegraded soon after the completion of its action in the body. The membrane material and its degradation products have to be nontoxic. In addition to hemoglobin, the nano artificial cells should contain important RBC enzymes like superoxide dismutase, catalase, carbonic anhydrase and methemoglobin reductase

5.

6.

7.

The membrane should be permeable to reducing agents and/or glucose. the availability of methods to prepare artificial cells of nanometer dimensions started to prepare hemoglobin nanocapsules of less than 0.2 micron mean diameter using polylactic acid (PLA) membrane, PEG-PLA membrane and other biodegradable polymers

With

Characterization of Nano Artificial RBCs


Electromicroscopic membrane thickness is 515 nm.

appearance

Size distribution of polylactide membrane artificial rbcs


The

diameter and size distribution of the biodegradable hemoglobin are determined by using the Nicomp Size Analyzer (Model 370). instrument operates by light scattering.

The

The

mean diameters of the biodegradable hemoglobin nanocapsules can be shown to be as low as 74 nanometers.

Other properties

Safety and Efficacy of Nano Artificial RBCs


Amount

and fate of PLA membrane

The

membrane material of Poly Lactic Acid nano artificial RBCs is made up mostly of biodegradable polymer with a minimal amount of lipid. polymer is stronger than lipid and is also porous, much less membrane material is required.

Since

Polylactic

acid is degraded in the body into lactic acid and then to carbon dioxide. These are all normal body metabolites.

Efficiency in nanoencapsulating hemoglobin


At

present, the hemoglobin nanoencapsulation efficiencies range from 13 to 29% of the starting quantities of hemoglobin, depending on the polymer used artificial RBCs prepared with poly(D.L.)lactic acid contained fewer defects in the membrane than that prepared using poly(L)lactic acid

Nano

Circulation Time of Nano Artificial RBCs


Circulation

half-life of PLA nano artificial RBCs is evaluated in anesthetized male rats.


Each

rat received 1/3 of its blood volume via intravenous top loading. red blood cell is removed very rapidly from the circulation.

PLA artificial

Immunohematology
The

QWALYS 3 is a new generation of fullyautomated and high-throughput systems for immunohematology; grouping, phenotyping, donor antibody screening, antibody screening, identification and cross-matching can all be easily performed.

The

QWALYS 3 is the only system using E.M. Technology, an innovative nanotechnology based on the magnetization of red blood cells. throughput - Up to 105 Grouping or 110 Antibody Screening or 250 Antibody Screening donors per hour.

Higher

HIV
Nanotechnology-based

techniques are being widely evaluated in medical testing and could provide a new generation of diagnostic assays due to their high degrees of sensitivity, high specificity, multiplexing capabilities, and ability to operate without enzymes

A nanoparticle-based

biobarcode amplification (BCA) assay for early and sensitive detection of HIV-1 capsid (p24) antigen by using antip24 antibody-coated microplates to capture viral antigen (p24) and streptavidin-coated nanoparticle-based biobarcode DNAs for signal amplification, followed by detection using a chipbased scanometric method

Respirocyte
The

artificial red blood cell or "respirocyte Proposed here is a blood borne spherical 1micron diamondoid 1000-atm pressure vessel with active pumping powered by endogenous serum glucose, able to deliver 236 times more oxygen to the tissues per unit volume than natural red cells and to manage carbonic acidity

Artificial platelets (Clottocyte)


An

artificial mechanical platelet appears to halt bleeding 100-1000 times faster than natural hemostasis.

A single

clottocyte, upon reliably detecting a blood vessel break, can rapidly communicate this fact to its neighbors, immediately triggering a progressive controlled meshrelease cascade.

Artificial Platelet

vasculoid
The

vasculoid is a single, complex, multisegmented nanotechnological medical robotic system capable of duplicating all essential thermal and biochemical transport functions of the blood, including circulation of respiratory gases, glucose, hormones, cytokines, waste products, and cellular components.

This

nanorobotic system, a very aggressive and physiologically intrusive macroscale nanomedical device comprised of ~500 trillion stored or active individual nanorobots, weighs ~2 kg and consumes from 30-200 watts of power in the basic human model, depending on activity level.

The

vasculoid system conforms to the shape of existing blood vessels and serves as a complete replacement for natural blood.

References
Internet

Regenerative

Medicine, Articial Cells and Nanomedicine Thomas Ming Swi Chang McGill University, Canada

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