UltrafiltrationPresented By:

Amar Kher-BearJason ‘The Closer’ WardDavid ‘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 Series Operation

-Largest tank volume and membrane area required.

-Conversion per pass is low, but with multiple passes, virtually any concentration can be achieved

-Fresh medium continually added to feed tank

-Continual re-pressurization required

Membrane Options

Polyethersulfone (Polymeric)

http://www.whatman.com/repository/images/s7/7_57_292_290.jpg

http://www.sterlitech.com/products/membranes/polyethersulfone/images/PolyethersulfoneMembrane.jpg

http://www.accuton.com/img/products/c_drivers/CM2_elec200.jpg

Regenerated Cellulose Ceramic

-Excellent hydrolytic stability

-High flux, high retention

-Wide range of operating pH

-Durable and thus economically efficient

-Expensive

-Susceptible to fouling and deformation

-Good flux and retention

-Comparatively fragile

-Narrow operating pH range

-Lower flux than polymer membranes

Membrane Modules

http://www.millipore.comhttp://www.np.edu.sg/~dept-bio/biochemistry/aab/topics/minitan.gif Perry’s Chemical Engineering Handbook

Spiral Wound Cassette

Hollow Tube

-Cannot produce turbulent flow with the flowrates at which we are operating

-Small footprint

-Produces turbulent flow for better medium-membrane communication.

-Small footprint

-Large membrane surface area

-High packing density

-Susceptible to structural deformation

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:

Simple Area Calculation:Membrane Area = 10.2 m2 # .5m2 Cassettes = 21

Multi-Step Area Calculation:Membrane Area = 6.5m2 # .5m2 Cassettes = 13

SuperPro Calculated Area:Membrane Area = 2.5 m2 # .5m2 Cassettes = 5

..AS

Q

Costing• Capital Costs

• Operating CostsDescription Annual Cost (USD)

Membranes (13 x 4 annual replacements x $800) $41,600Pumps (assume 1 breakdown per year) $4,000Power $2,351Labour $10,000Cleaning Solution and Preservatives $3,000

Total: $60,951

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

Total: $81,000

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

ManufacturersDonaldson – “Filtration Solutions”, Minneapolis, MinnesotaMake 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, CaliforniaTubular Ultrafiltration Membranes from SpinTek provide excellent capabilities for filtering and concentratingdifficult process and waste streams.Maintenance and replacement savings, along with reduced downtime

Millipore - Billerica, MA (but manufacture around the world)Millipore’s Biomax membranes are well suited for applications requiring high flux, low-protein binding, and harshchemical cleaning and sanitization.For high-recovery purification, the patented Ultracel PLC membranes offer high retention and improved integrity

Pall Corporation - East Hills, NYUse a Microza Hollow Fiber Membrane Systems that are designed to integrate with existing infrastructure or as

anew, stand-alone infrastructure package

Koch Industries INC. - Wilmington, MA   Offer both spiral wound and hollow tube UF’s in a wide range of pore sizes

References1. 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; Perry’s 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/~dept-bio/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 Corporation12. “Ultrafiltration – Filtration Overview”, http://www.kochmembrane.com/; Copyright 2004-2005 Koch

Membrane Systems, Inc.

Questions?