The contribution of chemical engineering to biotechnology Professor Howard Chase FREng Professor of Biochemical Engineering Department of Chemical Engineering

Definitions Biotechnology - “the application of scientific and engineering principles to the processing of materials by biological agents to provide goods and services” Biochemical engineering - “the contribution of chemical engineering to biotechnology”.

Where can biotechnology be applied? All applications benefit from an input of chemical engineering principles although the scales may not be the same as that encountered in the traditional oil and chemical industries. Some scales are smaller (e.g. healthcare) and some larger (environmental).

Biological cells: the source of sustainable molecules and more H2, CH4, O2, CO2 Ethanol, butanol, acetone, propane-diol, biodiesel Organic acids, amino acids, flavourings Pharmaceuticals (e.g. antibiotics Biopolymers (plastics and rheology) Proteins: enzymes and therapeutics Gene therapy products (packaged nucleic acid sequences) Vaccines Microbial cells (environmental clean-up; waste treatment) Human cells (stem cells; tissue replacements) Hybrid products: bio/electrical/optical/mechanical (e.g. biosensors)

Why not chemical engineering? The chemical engineer’s tool-box Material and energy balances Thermodynamics and equilibria Separation principles and selectivity Heat and mass transfer Modelling Measurement techniques Processes Microstructure engineering Product design

Some outcomes for biotechnology Bioreactor design and optimization (fermenter mixing and aeration; biocatalysis) Separation and purification of (complex) biomolecules/molecular entities Controlled drug release; targeted drug delivery Scaffolds for tissue culture P &ID, Hazop/Hazan, Batch process scheduling; debottle-necking Systems’ biology

Biotechnology is not new to Chemical Engineering @ Cambridge Peter King: 1953 photosynthethic Chlorella with PVD John Davidson: 1980 member of committee for Spinks Report Deep shaft waste treatment processes & ICI’s Pruteen bioreactor Nigel Kenney: Packed bed processes for antibiotic purification. Nigel Slater: Maintenance of sterility in valves and pipes attached to fermenters

What has this department done recently? Healthcare Purification of molecules and biological assemblies produced in biological systems Targeted delivery of pharmaceuticals to cells. Purification of viruses and constructs for gene therapy. Separation of different types of human blood cells. Bioreactors for the growth of stem cells Separation of differentiated from non-differentiated stem cells.

Energy and the environment Biodiesel production from vegetable oils and algae Gasification of sewage sludge Oil production by pyrolysis of cellulosic materials. Reduced sludge production in activated sludge waste water treatment Biofilm reactors for degrading toxic compounds in aqueous wastes

Case study. Expanded bed adsorption for protein purification. A quasi-packed bed through which particulates in non- clarified feeds can pass U Segregation of beads via distributions of size and density Umf < U < Ut  ~ 0.4  ~ 0.7-0.8 Fluidised Bed Well mixed Poor adsorption Packed Bed Blocks with particulates Expanded Bed

Simplified Downstream Processing Flow Sheets Conventional Process : 50-80% total production costs cascade of 5-6 stages decreasing yield with increasing number of stages Expanded Bed Adsorption : clarification, concentration and purification in one stage increase in yield through reduction in stages

The expanded bed in action: purification of enzymes from yeast cells

Expanding the bed

Applying the feedstock

Washing to remove particulates

Desorbing the desired enzyme

The future of biotechnology: a personal vision New therapeutics; gene therapy; personalized medicine; replacement organs Novel diagnosis Renewable feedstocks for the (petro)-chemical industries Direct biological energy production; photosynthesis Biological information storage: DNA versus silicon Improved environmental clean-up

The future of Chemical Engineering and Biotechnology Chemical engineering has a pivotal role in the delivery of biotechnological discovery and innovation for the benefit of society Biotechnology will continue to provide intriguing challenges for chemical engineers as the range, variety and extent of applications proliferates. Chemical engineers have the appropriate ‘wherewithal’ to meet and surpass those expectations. The right combination at the right time in the right place.