Ultrafiltration

Presented By:

Amar Kher-Bear Jason The Closer Ward David Big Game Lotimer Derek The Rock MacFadden

Outline
Process Goal Definition Design Goals Setup Unit Sizing Alternative Options Cost Analysis Questions

Process Goal
Increase insulin concentration coming from the HPLC unit by a factor of 10 before it enters the crystallizer

Definition: Ultrafiltration
Operates according to principle of diffusion under pressure
Solutes and water are extracted Retains macromolecules i.e. Insulin

Serves two purposes:

Purification Concenration

Differs from diafiltration: diafilters are generally used for simply purification purposes

Design Goals
High flux High retention rate Hydrolytically stable & Biocompatible Turbulent flow Small footprint Durable Economically viable

Operational Setup

Batch, Semi-Batch Operation

-Largest tank volume and membrane area required.
-Conversion per pass is low, but with multiple passes, virtually any concentration can be achieved

Series Operation
-Fresh medium continually added to feed tank
-Continual re-pressurization required

Membrane Options

Polyethersulfone (Polymeric)
-Excellent hydrolytic stability
-High flux, high retention -Wide range of operating pH -Durable and thus economically efficient
http://www.sterlitech.com/products/membranes/polyethersulfone/images/Polyet hersulfoneMembrane.jpg

Regenerated Cellulose
-Expensive
-Susceptible to fouling and deformation -Good flux and retention
http://www.whatman.com/repository/images/s7/7_57_292_29 0.jpg

Ceramic
-Comparatively fragile
-Narrow operating pH range -Lower flux than polymer membranes
http://www.accuton.com/img/products/c_drivers/CM2_elec2 00.jpg

Membrane Modules

Hollow Tube

Spiral Wound
-Cannot produce turbulent flow with the flowrates at which we are operating -Small footprint

Cassette
-Produces turbulent flow for better medium-membrane communication. -Small footprint -Large membrane surface area -High packing density -Susceptible to structural deformation

http://www.millipore.com

http://www.np.edu.sg/~deptbio/biochemistry/aab/topics/minitan.gif

Perrys Chemical Engineering Handbook

Filter Sizing
List of Assumptions: Reference data accurately reflects flux behaviour for Insulin separation with a 1 kDa Polyethersulfone membrane. The rejection coefficient for the Insulin (~6 kDa) retained by a 1 kDa membrane is 1.

Design of Ultrafilters centres upon the flux properties of the membrane. Flux is a function of membrane material, protein type, protein concentration, transmembranous pressure

Protein Concentration (g/L)

Simple Flux Equation:

Q S . A.

Simple Area Calculation:

Membrane Area = 10.2 m2
Membrane Area = 6.5m2 Membrane Area = 2.5 m2

# .5m2 Cassettes = 21
# .5m2 Cassettes = 13 # .5m2 Cassettes = 5

Multi-Step Area Calculation:

SuperPro Calculated Area:

Costing
Capital Costs
Unit Stainless Steel Holders and Cassette Assembly (x2) Pumps (7 x $4,000 each) Fittings and Piping (13 x $1,000 each) Total: Cost (USD) $40,000 $28,000 $13,000 $81,000

Operating Costs
Description Membranes (13 x 4 annual replacements x $800) Pumps (assume 1 breakdown per year) Power Labour Cleaning Solution and Preservatives Annual Cost (USD) $41,600 $4,000 $2,351 $10,000 $3,000 Total: $60,951

Alternative Options
Ion Exchange and Affinity Chromatography - Eluting and buffering chemicals would
introduce additional separation units

Evaporation
High temperatures denature Insulin Utilities cost is three times that of Ultrafiltration

Engineering Schematic

Manufacturers
Donaldson Filtration Solutions, Minneapolis, Minnesota Make several different types of filters from compressed air and water and oil separation, to liquid filters Use hollow tube formation of UF Spintek Filtration, INC. - Los Alamitos, California Tubular Ultrafiltration Membranes from SpinTek provide excellent capabilities for filtering and concentrating difficult process and waste streams. Maintenance and replacement savings, along with reduced downtime Millipore - Billerica, MA (but manufacture around the world) Millipores Biomax membranes are well suited for applications requiring high flux, low-protein binding, and harsh chemical cleaning and sanitization. For high-recovery purification, the patented Ultracel PLC membranes offer high retention and improved integrity Pall Corporation - East Hills, NY Use a Microza Hollow Fiber Membrane Systems that are designed to integrate with existing infrastructure or as a new, stand-alone infrastructure package Koch Industries INC. - Wilmington, MA Offer both spiral wound and hollow tube UFs in a wide range of pore sizes

References
1. Curtis, Morris, Safford, Aqueous Protein Solutions Stable To Denaturation; http://www.freepatentsonline.com/4783441.html; United States Patent 4783441 (2005) 2. Encon Wastewater Systems Inc., Competitive Comparison To Ultrafilters; http://www.evaporator.com/comp_ultra_filters.html; PSI Water Systems Inc., Manchester, NH (2005) 3. Ferry J.D., Ultrafilter Membranes and Ultrafiltration; Dept. of Chemisty, Stanford University, California; Journal of Chemical Reviews, Vol.18, No.3 (October 1936) 4. Government of Ontario, Electricity Prices In Ontario; http://www.oeb.gov.on.ca/html/en/consumerinformation/2005elecrates.htm#3; Ontario Energy Board (2006) 5. Henry J.D., Prudich M.E., Eykamp W. et al., Alternative Separation Processes: Ultrafiltration; Perrys Chemical Engineering Handbook (Section 22-52) 6. Millipore, Pellicon 2 Filters and Holders: Technical Library; http://www.millipore.com/publications.nsf/docs/ds1210en00; Millipore Corporation, Billerica MA (2004) 7. Figure flat plate ultrafiltration system, Advanced Analytical Biochemistry Basic Principles; NgeeAnn School of Life Sciences and Chemical Technology, Singapore; http://www.np.edu.sg/~deptbio/biochemistry/aab/topics/aab_principles.htm 8. Millipore Catalogue. http://www.millipore.com; Millipore 2006. 9. Process and Specialty Liquid Filters, http://www.donaldson.com/; 2002-2005 Donaldson Company, Inc 10. Filtration Systems, http://www.idswater.com/water/us/spintek_filtration; Spintek Filtration Inc. 11. Solutions for Biopharmaceutical Applications, http://www.pall.com/; Pall Corporation 12. Ultrafiltration Filtration Overview, http://www.kochmembrane.com/; Copyright 2004-2005 Koch Membrane Systems, Inc.

Questions?