Week2

Week 02 Overview

  • Course: Recovery and Purification of Biological Products (DTU 28233)

  • Institution: DTU Chemical Engineering Department

Course Structure

  • Processes covered include:

    • Biomass Removal (Centrifugation and Filtration)

    • Intracellular Products (Flocculation and Cell Lysis)

    • Product Concentration (Precipitation, Extraction, Ion Exchange)

    • Product Purification (Chromatography)

  • Schedule highlights:

    • Key dates for sessions (e.g., reports, quizzes, presentations)

Process Design

  • Definition: Conceptual work prior to building or expanding a process plant.

  • Main Activities:

    1. Process Synthesis: Selecting and arranging unit operations to produce a product at a desirable cost and quality.

    2. Process Analysis: Comparing and analyzing different process solutions for efficiency.

Industry Economics

  • Commercialization Chances:

    • Ranges from 1-3% to 40-60% (for pilot plants)

    • New drug development costs can vary significantly from $50 million to over $1 billion.

  • Capital Investment: E.g., new facilities for monoclonal antibody production can average around $460 million.

Separation and Purification Techniques

  • General Process Design Steps:

    • Removal of cells, concentration of products, and solvent removal.

  • Production Types: High-value, low-volume products that are batch produced, versus continuous production of commodity biochemicals.

  • Extracellular vs. Intracellular Products:

    • Easier recovery of low molecular weight extracellular products, whereas intracellular recovery is more complex due to impurity levels.

Downstream Processing (DSP) Economics

  • Percentage of Total Production Costs:

    • Varies significantly by product type (e.g., fermentation cost vs. DSP cost).

  • Process Yield: A critical parameter that can be enhanced through integrated operations.

  • Product Purity: Required for market specifications; can be influenced by the number of processing steps.

  • Product Concentration: Affects size and effectiveness of unit operations, can be optimized through fermentation conditions.

  • Productivity: Must align with fermentation output to optimize efficiency and avoid degradation.

Filtration in Bioprocesses

  • Applications:

    • Used for cell and protein separation from liquid solutions.

  • Challenges:

    • Risk of blockage due to cell characteristics; fouling at high concentrations necessitates high-pressure operations.

    • Membrane lifespan is limited.

Centrifugation for Biomass Removal

  • Applications:

    • Primary step in DSP for extracellular products; efficiently separates microbial cells and debris.

  • Challenges:

    • Operation can be costly and produce noise; shear forces may damage larger cells.

Liquid-Liquid Extraction Techniques

  • Applications:

    • Extraction of small molecules into organic solvents or separation of proteins in aqueous two-phase systems.

  • Challenges:

    • Organic solvent selection must factor in costs and environmental impact; phase separation can be problematic, especially with high protein concentrations.

Precipitation Techniques

  • Usage:

    • Effective for separating proteins based on differing solubility characteristics.

  • Challenges:

    • Requires careful solubility data management and separation of tiny particles suspended in solution.

Distillation for Product Concentration

  • Operational Principle:

    • Utilizes differences in boiling points to separate components within a mixture.

  • Challenges:

    • High energy costs and potential molecular degradation necessitate lower pressure operations.

Sedimentation Techniques

  • Applications:

    • Used to settle dense particles; more commonly, centrifugation is preferred due to microbial size and water density proximity.

Chromatography for Product Purification

  • Function:

    • Allows separation of very similar proteins based on interactions in the column bed.

  • Challenges:

    • Scale-up limitations; costly media and pressure-drop considerations are critical for efficiency.

Integration of Chemical Engineering Principles

  • Overall Goal:

    • Optimize upstream and downstream processes for effective recovery and purification of biological products.