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TECHNOLOGICAL ADVANCES IN
TRANSFUSION MEDICINE
Dr.Neha Singh
Dr.preeti Sharma
Dr.Anjali Sharma
VMMC And Safdarjung Hospital,New Delhi
OUTLINE
 Introduction
 Advancements in :
 Hb screening
 Blood Collection
 Preservative solutions
 Blood Bags
 Component Processing
 Storage
 Advancements in Immunohematology
 e-Blood Banking
 Artificial Blood
 Nanobots
 Various innovations have taking place in the field of transfusion
medicine since the last few years, some of which are being
increasingly adopted in different parts of the world while some of
them are still in the initial stages.
 These can be generally grouped into the following categories:
1. Advancements at the collection, processing and storage level
2. Testing technologies
3. Better Patient Blood Management
4. Futurism
NONINVASIVE
METHODS
EVOLUTION OF HEMOGLOBIN SCREENING IN
DONORS
•Copper sulphate
gravimetric method
•Cyanmethhemoglobin
method
•Spun microhematocrit
method
Problem-
•Time
consuming
•need of reagent
solution
•Non – portable
•Donor
discomfort
•Portable device
•Result within 10 secs
•HemoCue 301 system
•Based on
spectrophotometry
•No finger prick
•No risk of infection
•Use spectrophotometry for
Hb measurement
3 tech:-
Occlusion
spectrophotometry
Pulse CO – oximetry
Transcutaneous reflection
spectroscopy
COMPOLAB TS -
BIOMIXER
1916 – First anticoagulant preservative introduced by Rous and turner
Citrate-glucose solution (Rous Turner’s solution)
Storage of human blood during 1st World war
Storage time -2weeks
1943- Loutit and Mollison
2nd world war
Acidified citrate dextrose(ACD)
Drawback-decrease in pH
decrease red Cell 2,3 –DPG(2,3-Di phosphoglycerate)
increase Hb-o2 affinity
impaired o2 deliver to tissue
Culprit – calcium
Need - ATP
1957-Gilbon et al
Citrate-phosphate-dextrose(CPD)
act as buffer(increase storage time)
maintain 2,3 –DPG
storage- 2-4degree C,21 days
1978-Citrate –phosphate-dextrose with adenine (CPDA-1)
Adenine – synthesize ATP
Shelf life increased to 42 days at 2-4 degree C
 With the advent of component therapy – use of red cells increased.
 Problem- In preparing red cell concentrates 40% adenine and glucose removed with plasma
Red cell conc relatively devoid of plasma – more viscous – difficult to infuse
Solution- Red cell concentrates with Hematocrite<80%
 Problem – lower plasma yield for FFP and cryoprecipitate production
Solution-ADDITIVE SOLUTIONS –resulting in hematocrit of about 60%
42 days at 2-6 degree C
1.Adsol(AS-1)
2.Nutricel(AS-3)
3.Optisol(AS-5)
4.SAGM(Saline-adenine-glucose-mannitol)
NEW BLOOD COLLECTION SYSTEM=PRIMARY BAG WITH ANTICOAGULANT + SATELLITE BAG WITH ADDITIVE
SOLUTION
ADDITIVE SOLUTIONS
AS-3 SAGM
Each 100 mL contains: Each 100 mL contains:
Dextrose (Anhydrous), 1.000
g
Dextrose (monohydrate),
0.900 g
Sodium Chloride, 0.410 g Sodium Chloride, 0.877 g
Adenine, 0.030 g Adenine, 0.0169 g
Citric Acid (Monohydrate),
0.042 g
Mannitol, 0.525 g
Sodium Citrate (Dihydrate),
0.588 g containing 15 mEq of
Sodium.
Monobasic Sodium
Phosphate (Monohydrate),
0.276 g
Bag made of PVC + DEHP – shelf life of platelet – 3 days
New bag – Polyolefin with no plasticizer / thin walled PVC TRI-(2-ETHYLHEXYL TRIMELLATE PLASTICIZER(TOTM)
Shelf life – 7 days (recommended – 5 days)
 Problem-Traditionally,platelet stored in plasma but unnecessary substances like antibodies,allergens,foreign
protein,sometimes drug present in plasma
Current opinion suggests- TRALI caused by antibodies present in donor’s plasma.
Solution- PAS (PLATELET ADDITIVE SOLUTION )
1.T-Sol(PAS II)
2.InterSol(PASIII)
3.Composol
4.M-Sol
Recommended composition – approx 30% plasma + 70% PAS
PENTA BAG
DOUBLE BAG TRIPLE BAG QUADRIPLE BAG
• Plastic bags-permiable to CO2
Polyolefin with no plasticizer / thin walled PVC TRI-(2-ETHYLHEXYL TRIMELLATE PLASTICIZER(TOTM)
TERUMO PENFOL
Manual Component Separation
Automated Component Separators
COMPONENT PROCESSING
CENTRIFUGATION MACHINE
MANUAL PROCESSING FOR TAT BAGS AUTOMATED MACHINE -TAB
•A medical technology in which the blood of a person is passed through an apparatus
that separates out one particular constituent and returns the remainder to the
circulation
MANUAL METHOD APHERESIS MACHINE
INTERMITTENT FLOW CENTRIFUGATION
APHERESIS MACHINE one arm procedure
6-8 cycles for good yield of platelets
CONTINUOUS FLOW CENTRIFUGATION
two arm procedure
isovolemic status of donor maintained
AMICUS – new generation cell seperator
provision of both single venous access and double venous access
• Plasmapheresis - blood plasma- collecting FFP
Commercial uses aside from FFP for this procedure include
immunoglobulin products, plasma derivatives, and collection of rare WBC and RBC
antibodies
• Erythrocytapheresis - red blood cell diseases such as sickle cell crises or severe
malaria
• Plateletpheresis (thrombapheresis, thrombocytapheresis)
• Leukapheresis – leukocytes (white blood cells)
• Neocytapheresis – relatively young red cell(neocytes) harvesting-survive longer
after transfusion
younger,larger and less dense red cells
Thallessemia major patient-decrease transfusion frequency
APPLICATIONS:-
 DONATION
 THERAPY:
• Plasma exchange – remove harmful substances. The plasma is replaced with
a replacement solution.
• LDL apheresis – removal of low density lipoprotein in patients with familial
hypercholesterolemia.
• Photopheresis – blood treated with photoactive drug which are then activated
with UV light treat graft-versus-host disease, cutaneous T-cell lymphoma,
and rejection in heart transplantation.
• Leukocytapheresis – removal of malignant white blood cells in people with
leukemia and very high white blood cell counts causing symptoms.
• Erythrocytapheresis – removal of erythrocytes (red blood cells) in people
with iron overload as a result of Hereditary haemochromatosis or transfusional
iron overload
• Thrombocytapheresis – removal of platelets essential
thrombocythemia or polycythemia vera.
The Collection System for collection of two
units of Leucodeplited Red Cells
ALYX
Hemonetics MCS+
A portable automated component collection system that produces double (2) units of leukoreduced RBCs
(DRBCs) from a single donation.
INDICATIONS FOR USE OF FROZEN RED CELLS:-
•Long term storage of rare blood group and supply on a regional and national basis.
•Storage for autotransfusion ,specially in patient with rare blood group
•Prevention of non-haemolytic febrile transfusion reaction in patients sensitized to
leucocytes,platelets or plasma protein.
 PROBLEM:Freezing damages red cells due to intracellular ice formation
SOLUTION-Cryoprotective agent-Glycerol
ADVANTAGES HIGH GLYCEROL LOW GLYCEROL
Initial freezing temp -80 degree -196 degree
Need to control
freezing
No Yes
Type of freezer Mechanical Liquid nitrogen
Maximum storage temp -65 degree -120 degree
Shipping requirement Dry ice Liquid nitrogen
Manual processing from glycerolizing,deglycerolizing (decreasing conc.of
saline),thawing,washing – consumes the valuable human time,man power.
Automatic cell washing system
Ur ACP®215 automated cell processor
a self-controlled and automated cell processor with an integrated shaker for
proper mixing of red cells/solutions for glycerolization and deglycerolization,
washing in a closed disposable system
automatically re-suspended in additive solution to permit extended product
storage post washing.
integrated printer to record each procedure on a summary sheet.
Extra shots:-
•Generally cells are glycerolized and frozen within 6 days of collection of blood in
CPDA.
•With additive solution - 42 days
•Frozen red cells can be stored for 10years.
•Outdating period of the thawed red cells stored at 2-6 degree C is 24 hours.
•Deglycerolized red cells consist of red cells in electrolyte solution .Virtually all
plasma,anti-coagulants and most of the leucocytes and platelets have been removed
GREAT STRIDES IN IMMUNOHEMAT
PAST PRESENT FUTURE
CAPTURE – SOLID PHASE RED CELL ADHERENCE TECH(SPRCA)
Antigen(cell panel for antibody screening- pre coated on the test wells
especially sensitive for detection of IgG antibodies (Anti – Jka and Anti Jkb)
BLOOD GROUP TYPING
OVER THE YEARS
ABO Rh
Extended
Phenotyping
PreciseTypeTM HEA (human erythrocyte antigen) - NEW Test of Record for Extended
Blood Cell Antigen Typing:-
The first and only FDA-approved in-vitro diagnostic (IVD) for molecular typing of red blood cell antigens
• Identifies the most relevant 35 red blood cell antigens from 11 blood groups
• Detects 24 gene mutations
• require no confirmation with antisera—which may save time
• PreciseTypeTM HEA Test Kit provides 96 tests in two formats:
8-chip slides (12)
96-chip microplate (1)
• The Kit is supplied in two boxes:
i. PCR, post-PCR, signal-development reagents, and a negative control
ii. Barcoded BeadChip slides/microplate and a disk with the chip-specific bead-map key for post-assay analysis
Advantages:-
Simplifying the identification of rare antigens
Providing phenotype-matched products for special patient populations
Enabling efficient delivery of antigen-negative products for patients with
alloantibodies
 Data from PreciseType™ HEA Tests will also enable the creation of a
detailed database containing antibody and molecular antigen typing
information.
Viral
RNA/DNA
Detection
Viral Antigen
Detection
Antibody
Testing
Progress in Detection
of Transfusion-Transmitted Pathogens
Surrogate
Marker
 Serum ALT
 T-cell count
 Anti-HIV
 Anti-HBc
 Anti-HCV
 Anti-HTLV
 HIV p24 Ag
 HBsAg
 HCV Ag
 NAT
 HIV-1
 HCV
 HBV
 WNV
NAT is the only direct test for the infectious agent
Shorter window period to detection
Rapid
Assays
ELISA CMIA MP NAT ID NAT
ELISA(Enzyme-linked immune sorbent assay)
First-generation - viral lysate-based immunoglobulin G (IgG) tests.
Second-generation - recombinant and/or synthetic peptide antigens
Ab detection -6 to 12 weeks after infection
Third-generation - detect IgG and IgM (antigen sandwich techniques)
Abbot AxSYM test
Ab detection -3 – 4 weeks after infection
Fourth Generation - CMIA(Chemiluminescent microparticle immunoassay )
newer tests for simultaneous detection of p24 Ag (HIV-1 Ag) and HIV-1/HIV-2Ab.
Window period shortened to 2 weeks
 NAT is a highly sensitive and advanced screening technique that detects which has reduced the window
period of HBV to 10.34 days, HCV to 1.34 days and HIV to 2.93 days
 Detects very low level of viral RNA or DNA that may be present in donated blood.
 It is based on amplification of targeted regions of viral ribonucleic acid or deoxyribonucleic acid (DNA)
 First introduced in Germany in 1997 and it was performed on pooled samples of 96 blood donations
(Minipool NAT [MP-NAT])
 . NAT is also available for testing each donation individually (ID-NAT)
 Different techniques of NAT:
a)Polymerase chain reaction
b)Branched Dna(bDna)
c)Transcription mediated Amplification (TMA)
d)Nucleic Acid Sequence Based Amplification(NASBA)
 Most popular commercially available FDA approaved NAT assay for blood screening - PCR and TMA
•Rapid plasma reagin Card Test
• non-treponemal slide agglutination test
which means
•antibodies detection against substances released by
cells when they are damaged by T.
pallidum(cardiolipin and lecithin)
chromatographic
immunoassay for
qualitative detection of
the surface antigen of
hepatitis B virus
qualitative detection of
antibodies to hepatitis C
virus
Malarial antigen detection
Universal shift to
Leucoreduction
WHY LEUCOREDUCE ?
(Variant Creutzfeldt-Jakob disease) –neurological disease
METHODS
 Filteration-105 -106 WBC/unit (3-4 log) leucodepletion.
•The original leucocyte depletion filter contained sterile cotton wool and
designed by Diepenhorst who published his work in 1972.
1st generation(Clot Filters): cellulose acetate filters
pore size-170-250 µm
help in clot retention
2nd generation (Micro aggregate filters):
pore size – 20-40 µm
traps white cells,platelets and fibrin thread
3rd generation(Leucocyte filters);-Presently depth and screen-type filters.
Depth filter (non woven) has filter material in the form of compressed wool
fibers arranged in an irregular fashion.
screen filters (woven type)- arranged in multiple layers in a regular fashion.
Mechanism - charge-based adhesion of negatively charged leukocytes to the
filter material by Vander Waals and electrostatic forces.
Charge modifier - methacrylate polymers
 Centrifugation and buffy coat removal — 108 WBCs/unit (1 log leukodepletion)
easiest and least expensive method
 Washed red cell concentrate with saline — 107 - 108 (1-2 log )leucodepletion
 Frozen deglycerolized red cells —106 107 (2-3 log )leucodepletion
Platelet Rich Plasma
Reduce inflammation
caused byHair growth
Facial glow
Wound healing
RECOMBINANT PRODUCTS
Recombinant factor VIII e.g. Recombinate
Recombinant factor IX e.g. Benefix
Recombinant factor VII (Novoseven)
vWF, ATIII,
Alpha1 protease inhibitor
Hb vaccines,
R Hb
Haemopoietic growth factors
EPO,G-CSF, GM-CSF,TPO,ILS,TNF
BACTERIAL DETECTION OF BLOOD
COMPONENTS ESPECIALLY
PLATELETS
Bacterial Detections Systems
Pall BDS System
BacT/Alert System
Verax PGD Test
VERAX PGD TEST(pan genera detection tech):
 A rapid, qualitative immunoassay based on Pan Genera Detection® (PGD)
technology.
 that detects the presence of aerobic and anaerobic Gram-positive and Gram-
negative bacteria in platelets for transfusion.
 Samples from leukocyte reduced apheresis platelet units and pools of up to six
whole blood derived platelets may be tested.
 is It detects the presence of conserved antigens lipoteichoic acid (LTA) and
lipopolysaccharide (LPS) found on aerobic and anaerobic GP and GN
bacteria, respectively by the use of antibodies.
 detects bacteria in leucodepleted platelet concentrates by measuring the
reduction of oxygen in the sample, due to aerobic bacterial growth.
2ml of the platelet product is transferred into a satellite bag
incubated for 18 – 24 hours at 35°C.
the O2 content in the air is measured using the O2 Analyzer(any time).
Pall eBDS - an enhanced bacterial detection system
 Disadvantage:-does not detect strictly anaerobic bacteria like
Clostridium perfringens or potentially very slowly growing
bacteria.
 Clinical trials show that samples tested at 30 hours and 48
hours showed higher percent positive (sensitivity) results.
BacT/Alert is an automated microbial detection system designed to detect bacteria and fungi in blood products:
 Red Cell Concentrates
 Plasma
 Platelets
 ~ 24 hours after collection*, a Day 1 sample is taken
 The sample** is transferred into a 30cc culture bottle which has culture media (aerobic & anaerobic)
 The bottles are loaded into the incubator at 35°C and inoculated for a minimum of 24 hrs
 The bottles contain colorimetric sensors which change from dark green to yellow in the presence of CO2
 The system than notifies the laboratory with visual & audible alarms
 Sensors scan the bottles every 10 minutes thus ensuring rapid detection of any bacterial contamination
* Delaying when sample is taken = Better detection efficiency
** Higher sample volume = Better detection efficiency
Bac-T/Alert
Positioning Pathogen Inactivation
• Bacterial Detection Systems only detect Bacteria (with significant limitations)
• Pathogen Inactivation is a Comprehensive Approach toward Blood Safety by
directly damaging or modifying organism’s nucleic acids with photochemical
modification
•Commercially available 3 methods:-
AS-PCT(Amotosalen-a photosensitizer + UvA light)/INTERCEPT Method
by Cerus Corporation
RF-PRT(Riboflavin –vitB2 + UV light) / MIRASOL Method
by TerumoBCT
UV C – Latest tech
not include photosensitizer
high energy of narrow band shortwave UV C light
by Macropharma
not approaved
Amotosalen photochemical treatment
Photoexcitation of amotosalen
Covalent modification with thymidine bases
Inhibit transcription
Drawback-defect in platelet signal trasduction-quality
low
Riboflavin pathogen reduction treatment
Redox reaction
Formation of reactive oxygen species(ROS) like
nascent oxygen,superoxide anion ,hydroxly radicals
Damages DNA
Drawback-modifies labile protein like FVIII
One-step illumination with UV C light
energy- delivered -0.2J/cm2 for 30-60 sec
Pyrimidine dimers formation
Prevent replication
Drawback-affects platelet membrane structure
MIRASOL PATHOGEN REDUCTION
e Blood banking
In 2016-17- shortage of 2 million units
>1 million units discarded due to detoriation during storage
Few drawbacks of existing system:-
• Cannot receive the blood on time as the donors are
from various locations.
• Extra clerical works.
• Error handling is not efficient since records are
maintained manually.
• Data management becomes tedious as the records
increase.
• Time-consuming.
A series of
‘rights’
Right Patient
Right Product
Right Reason
Right Time
The E-Blood Bank is an Android application which allows the user to search donors of specific
blood group based on their location, in a short period of time.
•Apps AVAILABLE –
BLOODR
D2D(DONOR2DONOR)
MBLOOD
eRakt Kosh
App features :
1)DONOR:
View blood request
Book appointment
Invite friends
2)Requester:
Send request
View request history
View appointments of donor
3)Admin:
Analyse data
Manage users
eRakt Kosh
•Govt. run web portal.
•An initiative of Ministry of Health and Family Welfare.
•App launched on world health day – 7th April ,2016
•Centralizes blood bank management system for licensed blood banks.
•A/C National AIDS Control Organisation(NACO),out of 2760 blood
banks in India,2711 are already on digital platform.
e-Rakt Kosh has six major components for management of
the blood donation life cycle:
The bio metric Donor Management System for identifying, tracking and blocking donors based on
donor's health, donation history etc.
It provides features such as blood grouping, TTI screening, antibody screening, component
preparation etc. as per the defined processes and rules.
A centralized Blood Inventory Management System for keeping track of the blood stock across
numerous blood banks.
Bio-Medical Waste Management System for disposal of discarded blood and other waste generated
during this process.
Generation of rare blood group donor registries and the generation of regular repeat donors.
Alert and Notification System
BIOMETRICS
The word ‘biometrics’ – two greek words – bio meaning life
- metric meaning – to measure
It refers to metrics related to human characteristics
It is used as a form of individual identification
Automated measurement of Physiological and/or
behavioral characteristics to Determine or
authenticate
identity
 The biggest challenge - donor authentication, identification, and more
importantly, donor filtration based on past eligibility records. This
makes it important to have a centralized platform for blood donors.
 The gap in demand and supply - On the one hand, the patients
don’t get the components which they are in need of, and on the
other hand some of the components get wasted due to expiry.
STRIDES SOFTWARE SOLUTIONS
‘D-Health app’
India’s first Aadhaar-based centralized donor authentication and identification
application
Brings blood banks, donors, blood camp organisers, hospitals and patients on
one platform.
2017
KEY FEATURES..
Aadhaar (IRIS) Based Donor
Authentication
Centralized Donor Eligibility Check Donor Registration At a
Click With Aadhaar e-KYC
Emergency Donor Management
Aadhaar (IRIS) Based Donor
Authentication
Help in authenticating the donor based on details by Aadhaar e-KYC.
 User just needs the Aadhaar no. and scan iris using Samsung Aadhaar enabled
IRIS tab and application will authenticate the donor from Govt. Aadhaar data
server.
 Once donor data authenticated Centralized Donor Eligibility Check is done.
Donor Self Check-in
 A multi-lingual (English & Hindi) Quiz
view & List view questionnaire is there
to ensure that the donor himself
answers the questionnaire for
screening purpose. This helps in
creating donor awareness, making
donor curious about different
questions & its relevance.
 Once donor data authenticated
Centralized Donor Eligibility Check is
done.
Centralized Donor Eligibility Check
 With the donor personal information details app check it
with existing donor repository for the eligibility of the
donor for blood donation. The eligibility is checked on 2
parameters
 1) Time based –Time since last donation. If less than 90, it
will validate stating ineligible, 2) Past test record based –
If the donor had been found reactive in the past, the
application will validate the same stating ineligible cause
of past test records.
 Centralized donor eligibility check is being done through
the Application based on Real time and past donor
repository, Once eligibility check is done, donor self check
- in will happen.
RFID and Blood Component Tracking
Radio-Frequency Identification (RFID) :-
• automatic wireless scanning system of
bulk quantities of blood bags and
products
• real time tracking of their location
• strict control of inventory and advanced
planning for supplies.
• access card control ensures a restricted
access to blood and other inventories by
authorized personnel only. – A control
over black marketing
Technique:-
Evolution of bar code
Two elements:-
READER- broadcast an electromagnetic field and a radiosignal
TAG(Transponder)
Radiofrequencies:-
• HF Tech –
13.56 MHz
RBC quality not affected by long exposer of RF energy
Approaved by FDA(USA)
Multiple readings
Reading potentialities at medium-long range
• UHF Tech –
865-868 MHz
Lower cost
Hematopoietic Stem Cells
 Hematopoietic stem cells are pluripotent cells capable of indefinite cell revewal and differentiation into
any cell lineage
 1% of B.M. cells and 1/100,000 PBC are stem cells.
 Indication of stem cell transplantation:-
Severe Aplastic Anemia
Red cell disorders:
Thalassemia
Sickle cell disease
Malignant diseases of Bone marrow
CML,Acute Leukemia
Lymphoma,Multiple myeloma
Myelodysplastic Syndrome
Congenital immune deficiencies
Severe combined Immunodeficiency(SCID)
Wiskott-Aldrich syndrome
SOURCES OF
HAEMATOPOIETIC STEM CELLS (HSC)
 Bone Marrow
 Growth Factor Mobilised Peripheral Blood
Stem Cells (Pbsc)
 Placental Umbilical Cord Blood Hsc
PBSC’s COLLECTION
 Hematopoietic G.F(G-CSF,GM-CSF) used to mobilise PBSC’s from B.M.
 Collection targets are > 2 x 106 CD34 cells per Kg.
 Collection Equipments: Apheresis machines like Spectra,CS 3000 Plus,MCS+
 Harvested stem cell product contains a significant number of tumor cells,T cells and
other contaminants along with CD34 cells
Immunoadsorption System(Cell selection with magnets)
 Positive selection(Passive Depletion) – CD 34+ cells magnetically retained and unwanted
cells are removed
 Negative Selection(Active Depletion) – Tumor cells retained and desired cells released
Isolex 300i system(Baxter)
•AntiCD34 + Magnetic
beads(Dynabeads) + Target
cells(CD 34+ cells) = Rossette
formation
Magnetic field
CD34+beads Unwanted
CliniMACS
Super paramagnetic micro beads
Coolmix AS-210
Automated mixing and cooling device for the controlled and reproducible preparation of
hematopoietic stem cells for cryopreservation
 Major limitations of using HLA matched related sibling
donors in HSCT
 Only 30% to 40% of recipients have a HLA - matched
related family donor
 Search for an alternate source of HSC
Enzymatic removal of antigens of red cells to convert groups A, B or AB to group O
Exoglycosidase + Buffer solution(to maintain pH)
GH109 – α-N-acetylgalactosaminidase GH 110-α-galactosidase Glycine buffer
chicken liver green coffee beans 5%glucose
Closteridium perfringes and addition buffer
Artificial blood
Hemoglobin Based Oxygen Carriers (HBOC’s):-
Sources:
Human (expired human blood)
Animal (fresh bovin blood)
Recombinant hemoglobin
Brief concept:-
RBC first lysed to release Hb
stroma removed by various methods,including centrifugation,filteration and chemical extraction
Purification of Stroma free Hb
Modification-chemical / genetic
(without modification ,O2 affinity of stroma-free Hb too high to release O2 in the tissue
Also,outside RBC,Hb rapidly dissociates and filtered in kidney-renal toxicity)
Cross-linked Hb
Polymerized Hb
Hb conjugated to macromolecules
Encapsulated Hb
NANOBOTS
The Artificial Blood
What are Nanobots?
 Nanobots are nanotechnological robot
machines(Nanites).
 Mainly made up of Carbons.
 Size range from 0.1-10 microns.
 Non-shelf replicating.
RESPIROCYTES
Respirocytes are tiny
nanomedical devices of 1
micron diameter designed to
operate on molecular level.
Respirocytes function as
artificial Red Blood Cells
carrying oxygen and Carbon
dioxide molecules from the
body.
How Do They Work?
• Respirocytes destroying bacteria by contrasts.Each
respirocyte stores up to 1.51 billion oxygen
molecules.
• 100% are accessible to the tissues.
Are They Safe?
Respirocytes are extremely reliable.
MICROBIVORES
• Microbivores are oblate
spheroidal nanomedical
devices introduced into the
blood stream would form a
synthetic immune systems.
• Indentify Pathogens and other
toxins in Blood and then
destroy them.
CLOTTOCYTES
• Clottocyte is an artificial
mechanical platelet of 2
microns in diameter
• Completes Hemostasis in
as short as one second.
Technological Advancements in transfusion medicine

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Technological Advancements in transfusion medicine

  • 1. TECHNOLOGICAL ADVANCES IN TRANSFUSION MEDICINE Dr.Neha Singh Dr.preeti Sharma Dr.Anjali Sharma VMMC And Safdarjung Hospital,New Delhi
  • 2. OUTLINE  Introduction  Advancements in :  Hb screening  Blood Collection  Preservative solutions  Blood Bags  Component Processing  Storage  Advancements in Immunohematology  e-Blood Banking  Artificial Blood  Nanobots
  • 3.
  • 4.  Various innovations have taking place in the field of transfusion medicine since the last few years, some of which are being increasingly adopted in different parts of the world while some of them are still in the initial stages.  These can be generally grouped into the following categories: 1. Advancements at the collection, processing and storage level 2. Testing technologies 3. Better Patient Blood Management 4. Futurism
  • 5. NONINVASIVE METHODS EVOLUTION OF HEMOGLOBIN SCREENING IN DONORS •Copper sulphate gravimetric method •Cyanmethhemoglobin method •Spun microhematocrit method Problem- •Time consuming •need of reagent solution •Non – portable •Donor discomfort •Portable device •Result within 10 secs •HemoCue 301 system •Based on spectrophotometry •No finger prick •No risk of infection •Use spectrophotometry for Hb measurement 3 tech:- Occlusion spectrophotometry Pulse CO – oximetry Transcutaneous reflection spectroscopy COMPOLAB TS -
  • 7. 1916 – First anticoagulant preservative introduced by Rous and turner Citrate-glucose solution (Rous Turner’s solution) Storage of human blood during 1st World war Storage time -2weeks 1943- Loutit and Mollison 2nd world war Acidified citrate dextrose(ACD) Drawback-decrease in pH decrease red Cell 2,3 –DPG(2,3-Di phosphoglycerate) increase Hb-o2 affinity impaired o2 deliver to tissue Culprit – calcium Need - ATP
  • 8. 1957-Gilbon et al Citrate-phosphate-dextrose(CPD) act as buffer(increase storage time) maintain 2,3 –DPG storage- 2-4degree C,21 days 1978-Citrate –phosphate-dextrose with adenine (CPDA-1) Adenine – synthesize ATP Shelf life increased to 42 days at 2-4 degree C
  • 9.  With the advent of component therapy – use of red cells increased.  Problem- In preparing red cell concentrates 40% adenine and glucose removed with plasma Red cell conc relatively devoid of plasma – more viscous – difficult to infuse Solution- Red cell concentrates with Hematocrite<80%  Problem – lower plasma yield for FFP and cryoprecipitate production Solution-ADDITIVE SOLUTIONS –resulting in hematocrit of about 60% 42 days at 2-6 degree C 1.Adsol(AS-1) 2.Nutricel(AS-3) 3.Optisol(AS-5) 4.SAGM(Saline-adenine-glucose-mannitol) NEW BLOOD COLLECTION SYSTEM=PRIMARY BAG WITH ANTICOAGULANT + SATELLITE BAG WITH ADDITIVE SOLUTION ADDITIVE SOLUTIONS
  • 10. AS-3 SAGM Each 100 mL contains: Each 100 mL contains: Dextrose (Anhydrous), 1.000 g Dextrose (monohydrate), 0.900 g Sodium Chloride, 0.410 g Sodium Chloride, 0.877 g Adenine, 0.030 g Adenine, 0.0169 g Citric Acid (Monohydrate), 0.042 g Mannitol, 0.525 g Sodium Citrate (Dihydrate), 0.588 g containing 15 mEq of Sodium. Monobasic Sodium Phosphate (Monohydrate), 0.276 g
  • 11. Bag made of PVC + DEHP – shelf life of platelet – 3 days New bag – Polyolefin with no plasticizer / thin walled PVC TRI-(2-ETHYLHEXYL TRIMELLATE PLASTICIZER(TOTM) Shelf life – 7 days (recommended – 5 days)  Problem-Traditionally,platelet stored in plasma but unnecessary substances like antibodies,allergens,foreign protein,sometimes drug present in plasma Current opinion suggests- TRALI caused by antibodies present in donor’s plasma. Solution- PAS (PLATELET ADDITIVE SOLUTION ) 1.T-Sol(PAS II) 2.InterSol(PASIII) 3.Composol 4.M-Sol Recommended composition – approx 30% plasma + 70% PAS
  • 12. PENTA BAG DOUBLE BAG TRIPLE BAG QUADRIPLE BAG • Plastic bags-permiable to CO2 Polyolefin with no plasticizer / thin walled PVC TRI-(2-ETHYLHEXYL TRIMELLATE PLASTICIZER(TOTM) TERUMO PENFOL
  • 13. Manual Component Separation Automated Component Separators COMPONENT PROCESSING
  • 14. CENTRIFUGATION MACHINE MANUAL PROCESSING FOR TAT BAGS AUTOMATED MACHINE -TAB
  • 15. •A medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation MANUAL METHOD APHERESIS MACHINE INTERMITTENT FLOW CENTRIFUGATION APHERESIS MACHINE one arm procedure 6-8 cycles for good yield of platelets CONTINUOUS FLOW CENTRIFUGATION two arm procedure isovolemic status of donor maintained AMICUS – new generation cell seperator provision of both single venous access and double venous access
  • 16. • Plasmapheresis - blood plasma- collecting FFP Commercial uses aside from FFP for this procedure include immunoglobulin products, plasma derivatives, and collection of rare WBC and RBC antibodies • Erythrocytapheresis - red blood cell diseases such as sickle cell crises or severe malaria • Plateletpheresis (thrombapheresis, thrombocytapheresis) • Leukapheresis – leukocytes (white blood cells) • Neocytapheresis – relatively young red cell(neocytes) harvesting-survive longer after transfusion younger,larger and less dense red cells Thallessemia major patient-decrease transfusion frequency APPLICATIONS:-  DONATION
  • 17.  THERAPY: • Plasma exchange – remove harmful substances. The plasma is replaced with a replacement solution. • LDL apheresis – removal of low density lipoprotein in patients with familial hypercholesterolemia. • Photopheresis – blood treated with photoactive drug which are then activated with UV light treat graft-versus-host disease, cutaneous T-cell lymphoma, and rejection in heart transplantation. • Leukocytapheresis – removal of malignant white blood cells in people with leukemia and very high white blood cell counts causing symptoms. • Erythrocytapheresis – removal of erythrocytes (red blood cells) in people with iron overload as a result of Hereditary haemochromatosis or transfusional iron overload • Thrombocytapheresis – removal of platelets essential thrombocythemia or polycythemia vera.
  • 18. The Collection System for collection of two units of Leucodeplited Red Cells ALYX Hemonetics MCS+ A portable automated component collection system that produces double (2) units of leukoreduced RBCs (DRBCs) from a single donation.
  • 19. INDICATIONS FOR USE OF FROZEN RED CELLS:- •Long term storage of rare blood group and supply on a regional and national basis. •Storage for autotransfusion ,specially in patient with rare blood group •Prevention of non-haemolytic febrile transfusion reaction in patients sensitized to leucocytes,platelets or plasma protein.
  • 20.  PROBLEM:Freezing damages red cells due to intracellular ice formation SOLUTION-Cryoprotective agent-Glycerol ADVANTAGES HIGH GLYCEROL LOW GLYCEROL Initial freezing temp -80 degree -196 degree Need to control freezing No Yes Type of freezer Mechanical Liquid nitrogen Maximum storage temp -65 degree -120 degree Shipping requirement Dry ice Liquid nitrogen Manual processing from glycerolizing,deglycerolizing (decreasing conc.of saline),thawing,washing – consumes the valuable human time,man power.
  • 21. Automatic cell washing system Ur ACP®215 automated cell processor a self-controlled and automated cell processor with an integrated shaker for proper mixing of red cells/solutions for glycerolization and deglycerolization, washing in a closed disposable system automatically re-suspended in additive solution to permit extended product storage post washing. integrated printer to record each procedure on a summary sheet.
  • 22.
  • 23. Extra shots:- •Generally cells are glycerolized and frozen within 6 days of collection of blood in CPDA. •With additive solution - 42 days •Frozen red cells can be stored for 10years. •Outdating period of the thawed red cells stored at 2-6 degree C is 24 hours. •Deglycerolized red cells consist of red cells in electrolyte solution .Virtually all plasma,anti-coagulants and most of the leucocytes and platelets have been removed
  • 24. GREAT STRIDES IN IMMUNOHEMAT PAST PRESENT FUTURE CAPTURE – SOLID PHASE RED CELL ADHERENCE TECH(SPRCA) Antigen(cell panel for antibody screening- pre coated on the test wells especially sensitive for detection of IgG antibodies (Anti – Jka and Anti Jkb)
  • 25. BLOOD GROUP TYPING OVER THE YEARS ABO Rh Extended Phenotyping
  • 26. PreciseTypeTM HEA (human erythrocyte antigen) - NEW Test of Record for Extended Blood Cell Antigen Typing:- The first and only FDA-approved in-vitro diagnostic (IVD) for molecular typing of red blood cell antigens • Identifies the most relevant 35 red blood cell antigens from 11 blood groups • Detects 24 gene mutations • require no confirmation with antisera—which may save time • PreciseTypeTM HEA Test Kit provides 96 tests in two formats: 8-chip slides (12) 96-chip microplate (1) • The Kit is supplied in two boxes: i. PCR, post-PCR, signal-development reagents, and a negative control ii. Barcoded BeadChip slides/microplate and a disk with the chip-specific bead-map key for post-assay analysis
  • 27. Advantages:- Simplifying the identification of rare antigens Providing phenotype-matched products for special patient populations Enabling efficient delivery of antigen-negative products for patients with alloantibodies  Data from PreciseType™ HEA Tests will also enable the creation of a detailed database containing antibody and molecular antigen typing information.
  • 28.
  • 29. Viral RNA/DNA Detection Viral Antigen Detection Antibody Testing Progress in Detection of Transfusion-Transmitted Pathogens Surrogate Marker  Serum ALT  T-cell count  Anti-HIV  Anti-HBc  Anti-HCV  Anti-HTLV  HIV p24 Ag  HBsAg  HCV Ag  NAT  HIV-1  HCV  HBV  WNV NAT is the only direct test for the infectious agent Shorter window period to detection Rapid Assays ELISA CMIA MP NAT ID NAT
  • 30. ELISA(Enzyme-linked immune sorbent assay) First-generation - viral lysate-based immunoglobulin G (IgG) tests. Second-generation - recombinant and/or synthetic peptide antigens Ab detection -6 to 12 weeks after infection Third-generation - detect IgG and IgM (antigen sandwich techniques) Abbot AxSYM test Ab detection -3 – 4 weeks after infection Fourth Generation - CMIA(Chemiluminescent microparticle immunoassay ) newer tests for simultaneous detection of p24 Ag (HIV-1 Ag) and HIV-1/HIV-2Ab. Window period shortened to 2 weeks
  • 31.
  • 32.  NAT is a highly sensitive and advanced screening technique that detects which has reduced the window period of HBV to 10.34 days, HCV to 1.34 days and HIV to 2.93 days  Detects very low level of viral RNA or DNA that may be present in donated blood.  It is based on amplification of targeted regions of viral ribonucleic acid or deoxyribonucleic acid (DNA)  First introduced in Germany in 1997 and it was performed on pooled samples of 96 blood donations (Minipool NAT [MP-NAT])  . NAT is also available for testing each donation individually (ID-NAT)  Different techniques of NAT: a)Polymerase chain reaction b)Branched Dna(bDna) c)Transcription mediated Amplification (TMA) d)Nucleic Acid Sequence Based Amplification(NASBA)  Most popular commercially available FDA approaved NAT assay for blood screening - PCR and TMA
  • 33.
  • 34. •Rapid plasma reagin Card Test • non-treponemal slide agglutination test which means •antibodies detection against substances released by cells when they are damaged by T. pallidum(cardiolipin and lecithin) chromatographic immunoassay for qualitative detection of the surface antigen of hepatitis B virus qualitative detection of antibodies to hepatitis C virus Malarial antigen detection
  • 36. WHY LEUCOREDUCE ? (Variant Creutzfeldt-Jakob disease) –neurological disease
  • 37. METHODS  Filteration-105 -106 WBC/unit (3-4 log) leucodepletion. •The original leucocyte depletion filter contained sterile cotton wool and designed by Diepenhorst who published his work in 1972. 1st generation(Clot Filters): cellulose acetate filters pore size-170-250 µm help in clot retention 2nd generation (Micro aggregate filters): pore size – 20-40 µm traps white cells,platelets and fibrin thread
  • 38. 3rd generation(Leucocyte filters);-Presently depth and screen-type filters. Depth filter (non woven) has filter material in the form of compressed wool fibers arranged in an irregular fashion. screen filters (woven type)- arranged in multiple layers in a regular fashion. Mechanism - charge-based adhesion of negatively charged leukocytes to the filter material by Vander Waals and electrostatic forces. Charge modifier - methacrylate polymers
  • 39.  Centrifugation and buffy coat removal — 108 WBCs/unit (1 log leukodepletion) easiest and least expensive method  Washed red cell concentrate with saline — 107 - 108 (1-2 log )leucodepletion  Frozen deglycerolized red cells —106 107 (2-3 log )leucodepletion
  • 40.
  • 41. Platelet Rich Plasma Reduce inflammation caused byHair growth Facial glow Wound healing
  • 42. RECOMBINANT PRODUCTS Recombinant factor VIII e.g. Recombinate Recombinant factor IX e.g. Benefix Recombinant factor VII (Novoseven) vWF, ATIII, Alpha1 protease inhibitor Hb vaccines, R Hb Haemopoietic growth factors EPO,G-CSF, GM-CSF,TPO,ILS,TNF
  • 43. BACTERIAL DETECTION OF BLOOD COMPONENTS ESPECIALLY PLATELETS Bacterial Detections Systems Pall BDS System BacT/Alert System Verax PGD Test
  • 44. VERAX PGD TEST(pan genera detection tech):  A rapid, qualitative immunoassay based on Pan Genera Detection® (PGD) technology.  that detects the presence of aerobic and anaerobic Gram-positive and Gram- negative bacteria in platelets for transfusion.  Samples from leukocyte reduced apheresis platelet units and pools of up to six whole blood derived platelets may be tested.  is It detects the presence of conserved antigens lipoteichoic acid (LTA) and lipopolysaccharide (LPS) found on aerobic and anaerobic GP and GN bacteria, respectively by the use of antibodies.
  • 45.  detects bacteria in leucodepleted platelet concentrates by measuring the reduction of oxygen in the sample, due to aerobic bacterial growth. 2ml of the platelet product is transferred into a satellite bag incubated for 18 – 24 hours at 35°C. the O2 content in the air is measured using the O2 Analyzer(any time). Pall eBDS - an enhanced bacterial detection system
  • 46.  Disadvantage:-does not detect strictly anaerobic bacteria like Clostridium perfringens or potentially very slowly growing bacteria.  Clinical trials show that samples tested at 30 hours and 48 hours showed higher percent positive (sensitivity) results.
  • 47. BacT/Alert is an automated microbial detection system designed to detect bacteria and fungi in blood products:  Red Cell Concentrates  Plasma  Platelets  ~ 24 hours after collection*, a Day 1 sample is taken  The sample** is transferred into a 30cc culture bottle which has culture media (aerobic & anaerobic)  The bottles are loaded into the incubator at 35°C and inoculated for a minimum of 24 hrs  The bottles contain colorimetric sensors which change from dark green to yellow in the presence of CO2  The system than notifies the laboratory with visual & audible alarms  Sensors scan the bottles every 10 minutes thus ensuring rapid detection of any bacterial contamination * Delaying when sample is taken = Better detection efficiency ** Higher sample volume = Better detection efficiency Bac-T/Alert
  • 48. Positioning Pathogen Inactivation • Bacterial Detection Systems only detect Bacteria (with significant limitations) • Pathogen Inactivation is a Comprehensive Approach toward Blood Safety by directly damaging or modifying organism’s nucleic acids with photochemical modification •Commercially available 3 methods:- AS-PCT(Amotosalen-a photosensitizer + UvA light)/INTERCEPT Method by Cerus Corporation RF-PRT(Riboflavin –vitB2 + UV light) / MIRASOL Method by TerumoBCT UV C – Latest tech not include photosensitizer high energy of narrow band shortwave UV C light by Macropharma not approaved
  • 49. Amotosalen photochemical treatment Photoexcitation of amotosalen Covalent modification with thymidine bases Inhibit transcription Drawback-defect in platelet signal trasduction-quality low Riboflavin pathogen reduction treatment Redox reaction Formation of reactive oxygen species(ROS) like nascent oxygen,superoxide anion ,hydroxly radicals Damages DNA Drawback-modifies labile protein like FVIII One-step illumination with UV C light energy- delivered -0.2J/cm2 for 30-60 sec Pyrimidine dimers formation Prevent replication Drawback-affects platelet membrane structure
  • 51.
  • 52. e Blood banking In 2016-17- shortage of 2 million units >1 million units discarded due to detoriation during storage Few drawbacks of existing system:- • Cannot receive the blood on time as the donors are from various locations. • Extra clerical works. • Error handling is not efficient since records are maintained manually. • Data management becomes tedious as the records increase. • Time-consuming. A series of ‘rights’ Right Patient Right Product Right Reason Right Time
  • 53. The E-Blood Bank is an Android application which allows the user to search donors of specific blood group based on their location, in a short period of time. •Apps AVAILABLE – BLOODR D2D(DONOR2DONOR) MBLOOD eRakt Kosh App features : 1)DONOR: View blood request Book appointment Invite friends 2)Requester: Send request View request history View appointments of donor 3)Admin: Analyse data Manage users
  • 54. eRakt Kosh •Govt. run web portal. •An initiative of Ministry of Health and Family Welfare. •App launched on world health day – 7th April ,2016 •Centralizes blood bank management system for licensed blood banks. •A/C National AIDS Control Organisation(NACO),out of 2760 blood banks in India,2711 are already on digital platform.
  • 55. e-Rakt Kosh has six major components for management of the blood donation life cycle: The bio metric Donor Management System for identifying, tracking and blocking donors based on donor's health, donation history etc. It provides features such as blood grouping, TTI screening, antibody screening, component preparation etc. as per the defined processes and rules. A centralized Blood Inventory Management System for keeping track of the blood stock across numerous blood banks. Bio-Medical Waste Management System for disposal of discarded blood and other waste generated during this process. Generation of rare blood group donor registries and the generation of regular repeat donors. Alert and Notification System
  • 56.
  • 57.
  • 58.
  • 59. BIOMETRICS The word ‘biometrics’ – two greek words – bio meaning life - metric meaning – to measure It refers to metrics related to human characteristics It is used as a form of individual identification Automated measurement of Physiological and/or behavioral characteristics to Determine or authenticate identity
  • 60.
  • 61.  The biggest challenge - donor authentication, identification, and more importantly, donor filtration based on past eligibility records. This makes it important to have a centralized platform for blood donors.  The gap in demand and supply - On the one hand, the patients don’t get the components which they are in need of, and on the other hand some of the components get wasted due to expiry.
  • 62. STRIDES SOFTWARE SOLUTIONS ‘D-Health app’ India’s first Aadhaar-based centralized donor authentication and identification application Brings blood banks, donors, blood camp organisers, hospitals and patients on one platform. 2017
  • 63. KEY FEATURES.. Aadhaar (IRIS) Based Donor Authentication Centralized Donor Eligibility Check Donor Registration At a Click With Aadhaar e-KYC Emergency Donor Management
  • 64. Aadhaar (IRIS) Based Donor Authentication Help in authenticating the donor based on details by Aadhaar e-KYC.  User just needs the Aadhaar no. and scan iris using Samsung Aadhaar enabled IRIS tab and application will authenticate the donor from Govt. Aadhaar data server.  Once donor data authenticated Centralized Donor Eligibility Check is done.
  • 65. Donor Self Check-in  A multi-lingual (English & Hindi) Quiz view & List view questionnaire is there to ensure that the donor himself answers the questionnaire for screening purpose. This helps in creating donor awareness, making donor curious about different questions & its relevance.  Once donor data authenticated Centralized Donor Eligibility Check is done.
  • 66. Centralized Donor Eligibility Check  With the donor personal information details app check it with existing donor repository for the eligibility of the donor for blood donation. The eligibility is checked on 2 parameters  1) Time based –Time since last donation. If less than 90, it will validate stating ineligible, 2) Past test record based – If the donor had been found reactive in the past, the application will validate the same stating ineligible cause of past test records.  Centralized donor eligibility check is being done through the Application based on Real time and past donor repository, Once eligibility check is done, donor self check - in will happen.
  • 67. RFID and Blood Component Tracking Radio-Frequency Identification (RFID) :- • automatic wireless scanning system of bulk quantities of blood bags and products • real time tracking of their location • strict control of inventory and advanced planning for supplies. • access card control ensures a restricted access to blood and other inventories by authorized personnel only. – A control over black marketing
  • 68. Technique:- Evolution of bar code Two elements:- READER- broadcast an electromagnetic field and a radiosignal TAG(Transponder) Radiofrequencies:- • HF Tech – 13.56 MHz RBC quality not affected by long exposer of RF energy Approaved by FDA(USA) Multiple readings Reading potentialities at medium-long range • UHF Tech – 865-868 MHz Lower cost
  • 69. Hematopoietic Stem Cells  Hematopoietic stem cells are pluripotent cells capable of indefinite cell revewal and differentiation into any cell lineage  1% of B.M. cells and 1/100,000 PBC are stem cells.  Indication of stem cell transplantation:- Severe Aplastic Anemia Red cell disorders: Thalassemia Sickle cell disease Malignant diseases of Bone marrow CML,Acute Leukemia Lymphoma,Multiple myeloma Myelodysplastic Syndrome Congenital immune deficiencies Severe combined Immunodeficiency(SCID) Wiskott-Aldrich syndrome
  • 70. SOURCES OF HAEMATOPOIETIC STEM CELLS (HSC)  Bone Marrow  Growth Factor Mobilised Peripheral Blood Stem Cells (Pbsc)  Placental Umbilical Cord Blood Hsc
  • 71. PBSC’s COLLECTION  Hematopoietic G.F(G-CSF,GM-CSF) used to mobilise PBSC’s from B.M.  Collection targets are > 2 x 106 CD34 cells per Kg.  Collection Equipments: Apheresis machines like Spectra,CS 3000 Plus,MCS+  Harvested stem cell product contains a significant number of tumor cells,T cells and other contaminants along with CD34 cells Immunoadsorption System(Cell selection with magnets)  Positive selection(Passive Depletion) – CD 34+ cells magnetically retained and unwanted cells are removed  Negative Selection(Active Depletion) – Tumor cells retained and desired cells released
  • 72. Isolex 300i system(Baxter) •AntiCD34 + Magnetic beads(Dynabeads) + Target cells(CD 34+ cells) = Rossette formation Magnetic field CD34+beads Unwanted CliniMACS Super paramagnetic micro beads
  • 73. Coolmix AS-210 Automated mixing and cooling device for the controlled and reproducible preparation of hematopoietic stem cells for cryopreservation
  • 74.  Major limitations of using HLA matched related sibling donors in HSCT  Only 30% to 40% of recipients have a HLA - matched related family donor  Search for an alternate source of HSC
  • 75.
  • 76. Enzymatic removal of antigens of red cells to convert groups A, B or AB to group O
  • 77. Exoglycosidase + Buffer solution(to maintain pH) GH109 – α-N-acetylgalactosaminidase GH 110-α-galactosidase Glycine buffer chicken liver green coffee beans 5%glucose Closteridium perfringes and addition buffer
  • 78.
  • 79. Artificial blood Hemoglobin Based Oxygen Carriers (HBOC’s):- Sources: Human (expired human blood) Animal (fresh bovin blood) Recombinant hemoglobin Brief concept:- RBC first lysed to release Hb stroma removed by various methods,including centrifugation,filteration and chemical extraction Purification of Stroma free Hb Modification-chemical / genetic (without modification ,O2 affinity of stroma-free Hb too high to release O2 in the tissue Also,outside RBC,Hb rapidly dissociates and filtered in kidney-renal toxicity) Cross-linked Hb Polymerized Hb Hb conjugated to macromolecules Encapsulated Hb
  • 80.
  • 82. What are Nanobots?  Nanobots are nanotechnological robot machines(Nanites).  Mainly made up of Carbons.  Size range from 0.1-10 microns.  Non-shelf replicating.
  • 83.
  • 84. RESPIROCYTES Respirocytes are tiny nanomedical devices of 1 micron diameter designed to operate on molecular level. Respirocytes function as artificial Red Blood Cells carrying oxygen and Carbon dioxide molecules from the body.
  • 85. How Do They Work? • Respirocytes destroying bacteria by contrasts.Each respirocyte stores up to 1.51 billion oxygen molecules. • 100% are accessible to the tissues. Are They Safe? Respirocytes are extremely reliable.
  • 86. MICROBIVORES • Microbivores are oblate spheroidal nanomedical devices introduced into the blood stream would form a synthetic immune systems. • Indentify Pathogens and other toxins in Blood and then destroy them.
  • 87.
  • 88. CLOTTOCYTES • Clottocyte is an artificial mechanical platelet of 2 microns in diameter • Completes Hemostasis in as short as one second.