Novel technologies for blood purification Prof. Dr. Dimitrios Stamatialis
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1 Novel technologies for blood purification Prof. Dr. Dimitrios Stamatialis Biomaterials Science and Technology, MIRA institute, University of Twente 1
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5 BST group MIRA: Technology for regeneration 5
6 My research focus Biomedical membranes & (bio) artificial organs Tissue regeneration TE scaffolds - Bioreactors Mass transfer-modeling (Bio)artificial organs (Bio)artificial kidney (Bio)artificial liver (Bio)artificial pancreas Bio-separations Bio-molecule separations Membrane chromatography 6
7 Clearance of all uremic solutes: Kidney water soluble small molecular weight Middle molecules Protein-bound - Continuously
8 Chronic kidney failure Chronic kidney failure Build up of waste products Donor kidney Artificial kidney 8
9 Artificial kidney membrane dialyzer Dutch Kidney foundation 9
10 Current therapy Clearance of solutes: water soluble, small molecular weight (some) middle molecules Not - Protein-bound solutes Not - continuous cleaning Vanholder, Kidney International 2003 Lee, Clinical and Experimental Nephrology
11 Wearable kidney Davenport et al, Lancet
12 Wearable artificial kidney program (consortium of Dutch kidney foundation) 12
13 Protein-bound solutes Hippuric acid Indoxyl sulfate P-cresyl sulfate 13
14 p-cresol / p-cresyl sulfate µm µm µm Meijers et al. CJASN 2009
15 Sorbents Hemoperfusion columns Short term: Intoxications Solute spectrum Wearable artificial kidneys 15
16 Protein bound - binder in dialysate Hemodialysis Patzer et al. Ther Apher Dial, 2006 Hemodialysis with binder in dialysate 16
17 Dual layer mixed matrix membrane Adsorptive particles Porous matrix 0 Particle free blood contacting layer Hollow fiber flat sheet membranes M. S.L. Tijink et al., Acta Biomaterialia 8 (2012)
18 Cu removal from water Packed bed MMM Tetala et al. Sep. Pur Tech 2013.
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20 Flat MMM 20
21 relative concentration Adsorption from human blood plasma 1,2 relative creatinine concentration relative PAH concentration 1,0 0,8 0,6 0,4 0,2 0,0 particle free membrane single layer MMM dual layer MMM activated carbon M. S.L. Tijink et al., Acta Biomaterialia 8 (2012)
22 Hollow Fiber Spinning Polymer solution for MMM Bore liquid Polymer solution for inner layer Triple orifice spinneret Pulling wheel Coagulation bath (H2O)
23 A B SL 200 µm 100 µm MMM PES / PVP Norit AC DL1 DL2 C E 200 µm D F 100 µm DL3 G 200 µm H 100 µm 200 µm 100 µm
24 Hollow fiber MMM Clean water permeance : 60 L/m 2 /h/bar M. S.L. Tijink et al., Biomaterials (2013) in press. 24
25 q (mg/g AC) Adsorption isotherms DL HF indoxyl sulfate creatinine 100 hippuric acid C (mg/ml)
26 p-cresyl sulfate Indoxyl sulfate 1.0 1h 4h 1.0 1h 4h C t / C Initial PCS: 39.9 mg/l Initial PCS: mg/l C t / C o Initial IS: 37.9 mg/l Initial IS: 106 mg/l PES/PVP DL3 AC PES/PVP DL3 AC 0.0 PES/PVP DL3 AC PES/PVP DL3 AC Static adsorption from human blood plasma MMM PES / PVP Norit AC 1.0 Hippuric acid 1h 4h C t / C Initial HA: 76.4 mg/l Initial HA: 79.8 mg/l PES/PVP DL3 AC PES/PVP DL3 AC M. S.L. Tijink et al., Biomaterials (2013) in press.
27 Pressure sensor P Module P Pressure sensor P Module P P Pump Pump Permeate scale Regulated pressure valve Feed scale Dialysate scale Feed scale Diffusion Convection
28 creatinine removal (mg/g AC) DL HF total removal diffusion adsorption total removal adsorption diffusion time (h) 28
29 Removal (mg/g membrane) Removal (mg/g membrane) Diffusion experiment HA 2 PCS Time (h) MMM PES / PVP Norit AC IS Convection experiment HA IS PCS Time (h) M. S.L. Tijink et al., Biomaterials (2013) in press.
30 MMM evaluation Diffusion 2.3 mg PCS/g membrane and 3.6 mg IS /g membrane in 4h Convection 2.7 mg/g membrane PCS and 12.9 mg/g membrane IS Assuming similar removal in vivo: 5-35 gram ( m 2 ) MMM for daily removal of these toxins (healthy subjects excrete 78 mg PCS and 69 mg IS in their urine in 24h).
31 Future work Inner layer can be optimized (diameter, porosity) Higher particle loading Larger modules comparable to: - hemodialysis concerning surface area / size - commercial columns concerning particle content New membrane forming polymer New particles
32 Acknowledgements Dutch Kidney Foundation PhD Marlon Tijink Nephrology dept. UMC Gent R. Vanholder G. Glorieux MTG University of Twente J. Sun S. Saiful Z. Borneman M. Wessling Nephrology and Hypertension UMC Utrecht M. Wester J. Joles K. Gerritsen 32
33 WP2 (P1, P3, P8) Bioartificial kidney device for removal of uremic toxins BIOART ITN WP1 (P1, P2, P8, P9) Artificial kidney devices for prolonged/continuous treatment WP3 (P4-P8, P10) Bioartificial liver devices ensuring viability and function of hepatic cells Kidney and liver disease treatment Coordinator EU BIOART ITN 11 partners - 5 European countries (16 researchers, 3.8 million Euros) 33
34 Bioartificial kidney BioKid project - BMM program
35 Bioartificial kidney
36 NanoNext (PhD project, F. Hulshof) 24/07/
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38 Kidney on Chip MDCK 100 µm KNAW grant / BST, TR, BIOS (UT), UMC Nijmegen 38
39 See you on the road We're gonna get to that place where we really want to go.. But till then, tramps like us.. we were..born to run! (Born to Run, 1975) 39
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41 Clean water flux (L/m 2 /h) Dual layer HF MMM clean water permeance: 58 ± 9 L/m 2 /h/bar transmembrane pressure (bar) 41
42 q (mg/g AC) Creatinine adsorption isotherms single layer MMM dual layer MMM langmuir fit C (mg/ml) Deng et al. Journal of Applied Polymer Science
43 Creatinine C 4 H 7 N 3 O Product of muscle breakdown Measure for glomerular filtration rate 43
44 Para amino hippuric acid C 9 H 10 N 2 O 3 Albumin bound Removal in kidney: tubular secretion 44
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