Therapeutic Artificial Organs (TAO) Research and Its Clinical
Applications in Korea
Prof. Byoung Goo Min
Dept. of Biomedical Engineering, Seoul National University
SMEBA 2006 in KAIST
Biomedical Devices
Biomedical DeviceBiomedical Device
Measurement andDiagnosis Device
Measurement andDiagnosis Device Therapeutic DeviceTherapeutic Device Medical
Information SystemMedical
Information System
X-ray DeviceMRI
Bone Density MeasurementPET
Ultrasound DeviceEndoscope
ElectrocardiographyElectroencephalography
Patient Monitoring SystemBlood Pressure Measurement
(Sphygmomanometer)
X-ray DeviceMRI
Bone Density MeasurementPET
Ultrasound DeviceEndoscope
ElectrocardiographyElectroencephalography
Patient Monitoring SystemBlood Pressure Measurement
(Sphygmomanometer)
Laser Therapy (Nd:YAG, Excimer)
ShockWave Lithotripsy Radiotherapy Device(X-ray therapy device
Gamma-knifeIMRT)
Artificial Organ(Artificial HeartArtificial KidneyArtificial LiverInsulin Pump)
Laser Therapy (Nd:YAG, Excimer)
ShockWave Lithotripsy Radiotherapy Device(X-ray therapy device
Gamma-knifeIMRT)
Artificial Organ(Artificial HeartArtificial KidneyArtificial LiverInsulin Pump)
PACS(Picture Archiving and
Communication System)
PACS(Picture Archiving and
Communication System)
Why Therapeutic Artificial Organs ?
• Many people die of major organ failures– Economical Loss– Social Loss
• Absolute Shortage of Donor Organs– Bridge to Transplantation– Alternative to Transplantation
• From emergency to the surgery and recovery
• Ethical Problems– Xenogenic Organs– Fetal Stem Cells
Artificial Organs
• Artificial Joint• Artificial Valve• Artificial Heart• Artificial Kidney (Dialysis)• Artificial Graft• Artificial Skin• Artificial Blood • Artificial Lung• Artificial Liver• Artificial Eye• Artificial Ear• Artificial Nose• Artificial Bone• Artificial Hand• Artificial Brain• Other Prosthetic Devices
Artificial Heart–Ventricular Assist Devices–Total Artificial Hearts–Korean Artificial Hearts
•Hemopulsa•KorTAH•AnyHeart•T-PLS
Classification of Cardiac Assist Device: Assist Type
• Intra-Aortic Cardiac Assist Device– IABP (Intra-aortic Balloon Pump)
• Ventricular Assist Device (VAD)– LVAD (Left Ventricular Assist Device)– RVAD (Right Ventricular Assist Device)– BVAD/BiVAD (Bi- Ventricular Assist Device)
• Totally Implantable Artificial Heart (TAH)– With weaning natural heart
Classification of Cardiac Assist Device: energy, mechanism, location, pulse
• Energy Source that make actuating motion – Pneumatic– Electronic
• Actuating Force or Mechanism– Pneumatic– Mechanical– Centrifugal
• Location of Device– Implantable– External or Extracorporeal
• Pulsatility of Blood Flow– Pulsatile– non-Pulsatile or Continuous
Intra-aortic Balloon Pump [IABP]
Extracoporeal Centrifugal Pump
• Available since 1977• approved by FDA for cardiopulmonary bypasscardiopulmonary bypass
(CPB)• frequently used as VADs because of availability,
low cost, simplicity
Extracoporeal Pulsatile Pneumatic Ventricular Assist Device
•• Indication: Indication: –– postcardiotomy cardiogenic shockpostcardiotomy cardiogenic shock
•• Application:Application:–– bridge to transplantationbridge to transplantation
• external power supply and console limit patient mobility
Implantable Pulsatile Ventricular Assist Device
• Long-term use• bridge to transplantation• Criteria for circulatory assist
– cardiac output < 2L/min/m2– systolic blood pressure < 90mmHg– atrial pressure > 20mmHg– systemic vascular resistance > 2100 dynes-sec/cm5– urine output < 20ml/hour
Implantable Continuous System
• Disadvantages of pulsatile mechanical assist devices– size– noise– infection of the power/vent line
• Advantages of continuous flow pump– small size– low noise– absence of a compliance chamber– small priming volume
Total Artificial Heart
• Mechanical & Polymeric Parts– Actuator– Blood Sac– Valves
• Electrical Parts– Implantable Controller– Wireless Energy Transmission
System– Wireless Information Transmission
System– Internal & External Battery– Portable Monitoring System
무선정보전송장치
무선에너지전달장치
체외 감시장치체내외 축전지 시스템
이식형 제어장치
인공심장Wireless information transmission system
Wireless Energy Transmission System
Internal & External Battery
Portable Monitoring System
Implantable Controller
Artificial Heart
History of Korean Artificial Heart
• Extracorporeal Ventricular Assist Device (Hemopulsa) (1991 – )
– Biomedlab, Inc.
– Clinical Trial Stage (64days in animal test, 87days in clinical trial)
• Implantable Bi-ventricular Assist Device (KAH AnyHeart) (1984 – )
– Biomedlab, Inc.
– Clinical Trial Stage (34day in animal test, 12days in clinical trial)
• Pulsatile Extracorporeal Cardiopulmonary Bypass Pump (T-PLS)
(2000 – )– NewheartBio, Inc.
– Approved in KFDA and CE
– Approved in SDA (China)
ImbeddedECG Monitor
2nd controller
1st controller
AutoS/W
Bellow-type Pumping Sac
Pusher-plate
DC motor
Heart
Left Atrium
Aorta
Blood chamberBlood chamber
ActuatorActuator
Integrated ControllerIntegrated Controller
Hemopulsa, Biomedlab, Korea- Extracorporeal Ventricular Assist Device
Water
Hemopulsa, Biomedlab, Korea- Extracorporeal Ventricular Assist Device
Driving UnitDriving Unit
Disposable Unit, ChannyDisposable Unit, Channy--200200
KAH, Seoul National Univ., Korea- Total Artificial Heart (TAH)
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
Cactus Pump
BVAD Configuration LVAD Configuration
TAH Configuration
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
Size : 167 x 170 x 68 mmWeight : 750 gVolume : 600 ccMax Pumping Output : 9 L/min
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
• Control & Electrical Technologies of AnyHeart®– Integrated Controller
• 70 mm diameter 35 mm x 30 mm size
– TET• Efficiency : average 80%• Maximum supply output: 90 W• Li-ion battery system
– Telemetry• RF communication
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
AnyHeart, Seoul National Univ., Korea- Implantable BiVentricular Assist Device
• 12 Days Clinical Experience, Korea Univ. Hospital, 2001
Right Pump : 3.5 ~ 4.5 L/minLeft Pump : 4.5 ~ 5.5 L/min
Artificial Valve, Seoul National Univ., Korea- Polymer Valve
• SNU Polymer Valve– Since late 1980s – Floating Polyurethane Valve [FPV]
• Membrane – partially-open shape in resting state– to minimize the pressure difference across the artificial valve
• Membrane & frame : concave shape– quickly open and completely close when working
• Spokes of valve frame : wedge shape– minimize thrombus formation due to flow separation
– Biocompatible Materials and Surface Modifications• Polyurethane membrane and frame• Lumbrokinase coating with plasma process
Artificial Valve, Seoul National Univ., Korea- Polymer Valve
Pin Ring Membrane Membrane + Ring* adhesive : Pellethane solution
Frame Polymer Valve
Artificial Valve, Seoul National Univ., Korea- Polymer Valve
Normal
Floating
Flapping
Closed
T-PLS, NewHeartBio, Korea
T-PLS, NewHeartBio, Korea
• T-PLS® (NewheartBio. Inc., Seoul, Korea)– Pulsatile, percutaneous, portable, extracorporeal cardio-pulmonary bypass pump– Versatile Extracorporeal Blood Pump
• ECMO + CPB + PCPS + (VAD)
PCPS
CPB
VAD
ECMO
T-PLS, NewHeartBio, Korea
Core Technology of AnyHeart®
Core Technology of AnyHeart®
Moving Actuator TypePumping Mechanism
Moving Actuator TypePumping Mechanism
BiocompatiblePolymer ValveBiocompatiblePolymer Valve
Pulsatile Flow Control & Safety ManagementPulsatile Flow Control & Safety Management
T-PLS®T-PLS®
Animal & Clinical Experiences
Animal & Clinical Experiences
T-PLS, NewHeartBio, Korea
• Product Specification– Weight : 60kg– Dimension (Main body) : 456*437*665 (mm)– Pump mechanism : Tubular-occlusion Mechanism– Designed Stroke Volume : 70 cc– Priming Volume : 300 cc– Maximum flow rate : 6 L/min– Pump rate control : 0-80 BPM(+1/-1 step)
• Auto Control function – Auto Priming setup – Suction Protect mode– Electrical Motor : 50 W brushless DC motor– Battery (UPS) : Lithium-Ion Battery for 4hrs– Tube : Medical-grade silicone rubber– Connector : Medical-grade polycarbonate– Polymer Valve (4EA)
T-PLS, NewHeartBio, Korea
T-PLS®
Oxygen
HeatExchanger
AterialFilter
Oxygenator
Reservoir
Femoral VeinCatheter(21Fr.)
Femoral ArteryCatheter(17Fr.)
GasBlender
Air
T-PLS, Three-stage Successive Treatment from Cardogenic Shock to Recovery
CardiogenicShock
Treatment(PTCA, CABG orStent Insertion)
Recovery
EmergentCardiopumonary
SupportAs PCPS
Surgical SupportAs CPB
Heart RecoveryAssist
As VAD
Heart and LungSupportAs ECMO
T-PLS®
T-PLS : Clinical Trial
• Multiple Purpose Pulsatile Blood Pump for Cardiac Surgery and Emergency Treatment– Support during high-risk PTCA– Safeguard against cardiogenic shock pre- and post-PTCA– artial circulatory support in beating CABG surgery with minimal hemodilution– Emergency standby in cases of cardiac arrest during interventional and surgical procedures(Extra-corporeal life
support)– Support the heart during other cardiac surgery(Cardiopulmonary bypass)– ARDS(Acute respiratory distress syndrome)– Hemoperfusion for toxication
Versatile Applications of Dual Pulsatile Blood Pumping Mechanism
Cardiopulmonary Support
Hemoperfusion
Artificial Liver
Hemodialysis
Hemofiltration
Dual Pulsatile Blood Pumping Mechanism
Hemodialysis System(Artificial Kidney)
Hemodialysis System(Artificial Kidney)
• Acute Renal Failure• Chronic Renal Failure
– Peritoneal Dialysis• Mass Transfer through
Peritoneal
– Hemodialysis• Mass Transfer through
Hollow Fiber Membrane– Excessive water– Waste : Urea, Creatine– Required ions– Required dextrose
Hemodialysis Machine
The Principles of Hemodialysis System
Diffusion and Convection through Hollow Fiber
Membrane
Blood
Dialysate
Hollow fiber membrane
Required IonRequired Dextrose
Excessive WaterWaste : Urea, Creatine
Vascular Access of Hemodialysis System
• Vascular Access– AV-fistula
• Requiring vascular surgery
– Implantable venous catheters
Issues of Hemodialysis System
• Development Issues– High-Efficiency Dialysis– High-Flux Dialysis– Daily Dialysis– Home Dialysis– Pulsatile Hemodialysis– Implantable Vascular Access Device– Dialysate Reusable System
The Prospect of Hemodialysis System
• High-Efficiency , High-Flux Dialysis– Incresing middle-size molecule clearance– Incresing water ultrafiltration rate
• A : Membrane with numerous small pores that allow high water flux but no middle-size molecule transport.
• B : Membrane with a smaller surface area and fewer pores, with the pore size sufficiently large to allow middle-size molecule transport.
Silicone o-ring
Conventional Conventional high flux high flux dialyzer, dialyzer,
CHFDCHFD
Modified high Modified high flux dialyzer, flux dialyzer,
MHFDMHFD
The Prospect of Hemodialysis System
• Design of Modified Dialyser– Enhanced Ultrafiltration– Enhanced Molecule
Clearance(Patent Pending)
The Prospect of Hemodialysis System
• Daily-Home Hemodilysis– Benefits of Daily-Hemodialysis
• Better well-being and energy • Better nutritional indices • Higher hemoglobin, less transfusions or erythropoietin requirements • Better blood-pressure control, less blood pressure medications • Much improved intra-dialysis tolerance with fewer: cramps, crashes,
nausea-vomiting, headaches • Less post-dialysis fatigue, cramps, lightheadedness • Better quality of life ratings
The Prospect of Hemodialysis System
• Korea Artificial Organ Center , Seoul National University & Newheartbio Co.– C-PAK(Compact-Pulatile Aritificial Kidney) & N-PAK(Nocturnal)
• Home/Portable Homedialysis• Pulsatile Blood Pumping• Implantable Vascular Access Device• Dialysate Reusable System• Web-based Remote Monitor & Control
PHS system®, AKSYS, USA Prototype of C-PAK9.3 kg
The Prospect of Hemodialysis System
• C-PAK
Design of C-PAK
Configuration of C-PAK during animal experiment
Weight : 9.3 kg
Pulsatile Blood Pump : 0 – 700 ml/min
Fluid Pump : 0 - 5 l/h (2EA)
Air-bubble Detector (ultrasonic)
Blood Leak Sensor (laser)
Blood Pressure Sensor
Main Controller : Samsung ARM9 2410
4.0 inch Color Touch Display
• C-PAK : Animal Experiment– Daily hemofiltration without dialysate– Blood urea nitrogen profile
0
10
20
30
40
50
60
70
80
90
0 50 100 150 200 250
Time [hr]
BU
N [
mg
/dl]
, B
od
y W
eig
ht
[kg
]
Body Weight
BUN(cheju)
BUN(E1)
Artificial Liver
E-liver System
Artificial Liver - Bridge System
• Artificial liver is ‘bridge system’ for the patients who need time until…– liver transplantation surgery; Lack of donor liver;
Waiting list of liver transplantation is increasing every year.
– recovery of liver function.
• In some fulminant hepatic failure (FHF) cases, the lethality reaches 85%.– Proper liver assist device which can replace liver
function is essential.
Types of Artificial Liver
• Non-biological artificial liver
• Biological artificial liver• Hybrid bioartificial liver;
BAL
Liver Support System
• Nonbiological liver system – only toxin removal
• Plasma exchange• Hemodialysis• Hemofiltration• Hemoperfusion• Hemodiadorption
• Biological liver support system – Toxin removal and metabolism– Extracorporeal circulation
• Extracorporeal perfusion with animal or human liver• Artificial liver support systems using hepatocytes (BAL)
– Hepatocyte transplantation• Transgenic xenotransplantation• Human hepatocytes transplantation directly to splenic bed
Bioartificial Liver (BAL)
• DefinitionAll kinds of liver-assist devices which are using hepatocytescome from mammalian animals or human
• BAL - ‘Hybrid system’
- Inorganic bioreactor vessel + Functioning living cells or tissue
- Detoxification + Functional liver support
SNU Artificial Liver System
• E-Liver system – PSAF(Plasma Separation-Absorption-Filtration) – Patent Pending
P1
Water soluble toxins removalElectrolytes balancing
Albumin bound toxins Water soluble toxins
Absoprtion50~150 ml/min
Blood circuit100~300 ml/min
Hemofiltration30 ml/min
Plasm
a Sep
Replacement fluid30 ml/min
P3
Hem
ofilterA
dsorber
P2
plasma circuit50~150 ml/min
SNU Artificial Liver System
• E-Liver– Mock-circulation
Test
Prospect of Artificial Organs Research
• Development of combined treatment of cell-therapy and therapeutic artificial organ
HeartHeartAttackAttack
LifeLife--savingsavingUsing Using
ArtificialArtificialOrganOrgan
(VAD/ECLS)(VAD/ECLS)
ExtractingExtractingMuscle cell Muscle cell
from Patientfrom Patient’’ssLeg MuscleLeg Muscle
Culture Culture MuscleMuscle
Cell into HeartCell into HeartMuscle CellMuscle Cell
For 3~4 weeksFor 3~4 weeks
TransplantTransplantCulturedCultured
MucsleMucsle CellCellOn Patient On Patient
HeartHeart
Differentiation/Differentiation/DevelopmentDevelopment
Of transplantedOf transplantedMuscle cellMuscle cell
Recovery ofRecovery ofDamaged Damaged Heart cellHeart cell
Weaning Weaning Artificial Artificial
OrganOrgan(VAD/ECLS)(VAD/ECLS)
Thank you