Bioreactor type

What mode of Operation?

What type of bioreactor?

Bench-scale research fermentor Medium-scale beer fermentor

Biological Reaction Engineering

The largest L-Lactic Acid fermentation plant in Asia: http://www.bglactic.com/UK/news0610.htm

Raw Material Processing Biotransformation Separation & purification

Chemical & Biochemical Processing

Ordering Information Description BIOSTAT® PBR 2S Cat. No. 120 VAC RPBRP02LECR-H1 Cat. No. 230 VAC RPBRP02LECR-H2 Sterilization autoclave Basic unit Digital controller color display with touch screen • Control capabilities Temperature, pH, DO • Recirculation rate • Illumination • Illumination via Turbidity • Substrate (Note: configurable via integrated pump) • Turbidity measurement • Gasmixing Exclusive Flow Gasmixing of Air, O2, N2, CO2 • Rotameter Sparger • Rotameter for Overlay • Peristaltic pumps (integrated) 2 (Acid|Base) Thermostat system (integrated) • Recirculation Pump Peristaltic pump • Photosynthesis device Illumination unit • Single wall glass pipe • Helix design • Recirculation Vessel Includes Stainless steel head plate • Jacketed glass vessel • Recirculation fitting • Air Inlet and Exhaust filter • Aeration tube with μ-sparger • Exhaust Cooler •

Microalgae and the bacterium A. brasilense coimmobilized in alginate beads

Develop concepts and technologies on how to recycle used water (wastewater) in arid lands with unique combinations of microalgae and microalgae growth-promoting bacteria.

UC Berkeley scientist Anastasios Melis experimented on algae cultures and discovered sulfur deprived algae can produce hydrogen through photosynthesis.

20L Bioreactor

Ginsenoside

What size?

Ampicillin Amoxicillin

6x15'000 L cell culture bioreactors Construction site

Pharmaceutical Production in Bioreactors

Synthetic Genomics announced a $300 million agreement with Exxon to research and develop next generation biofuels using photosynthetic algae. And according to the New York Times, Exxon is going to invest another $300 million in in-house research.

Raw Material Processing Biotransformation Separation & purification

Chemical & Biochemical Processing

SUBSTRATE(S) PRODUCT

(Glucose) (Ethanol)

Heat

Transfer

Mass

Transfer Fluid

Mechanics

Reaction

Kinetics

Thermodynamics

What’s involved in bioreactor design

REACTOR

SUBSTRATE(S) PRODUCT

(Glucose) (Ethanol)

Heat

Transfer

Mass

Transfer Fluid

Mechanics

Reaction

Kinetics

Thermodynamics

What’s involved in bioreactor design

(Cells - Enzymes) REACTOR

Bioreactors

Bioreactors are designed to influence metabolic pathways

Bioreactor characteristics Bioreactors support or control biological entities In Bioreactors higher selectivity is of primary importance Rate of reaction is of secondary importance

Products of Bioreactions: Intracellular – extracellular metabolites Cell biomass Biotransformation

Ampicillin

Amoxicillin

What is a bioreactor? A “controlled” device in which change in composition of matter occurs by chemical/biochemical reactions. It is also used as a tool for determining something about the reacting system

Chemical Reactions inside the cell

Do reactions really occur?

At which rate?

Are they instantaneous reactions?

• Two factors control the outcome of chemical reactions:

Bio/Chemical Thermodynamics

Bio/Chemical Kinetics

• Chemical Kinetics: study of rates of chemical reactions and mechanisms

by which they occur.

- concerned with description of how fast a reaction occurs.

- concerned with factors affecting reaction rates

- used to derive better ways of achieving desired chemical reactions

- used for designing chemical and biochemical reactors

Bio/Chemical Kinetics

Kinetics of Enzyme-Catalyzed Reactions

The Enzyme-Substrate Complex

The Basic Equations of Enzyme Kinetics

The Effect of Other Parameters on Enzyme Activity

Enzyme Immobilization

Cell Cultivations & Cell Kinetics

Experimental Kinetic Studies

Growth Kinetics

Unstructured/Unsegregated Kinetic Models

Structured/Segregated Kinetic Models

Kinetics

Transport Phenomena in Bioprocess Systems

Mass Transfer in Cellular Systems

Oxygen Transfer Rates in Bioreactors

Mass and Heat Transfer Correlations

Transport

• We can use thermodynamics to tell if a reaction is product- or reactant-favored.

But this gives us no info on HOW FAST reaction goes from reactants to products.

• KINETICS — the study of REACTION RATES and their relation to the way the reaction proceeds, i.e., its MECHANISM.

Chemical Kinetics and Thermodynamics

• Time is a variable in kinetics – not in thermodynamics.

• We may infer about the reaction mechanism from kinetics but not from thermodynamics.

• ΔG of reaction is the measure of the affinity or tendency for the reaction to occur but, it says nothing about ‘how fast’

Differences between Chemical Kinetics and Thermodynamics

Differences between Chemical Kinetics and Thermodynamics

• Chemical Kinetics is concerned with the rate of reaction and factors affecting it.

• Chemical thermodynamics is concerned with the position of equilibrium and factors affecting it

A bioreactor is used to carry out the reactions as a tool for determining something about the reacting system:

- Rate of reaction - Dependency of the rate on various factors.

Information obtained from kinetics is used for determine something about the reactor:

- Size - Flow and thermal configuration - Product distribution - …

System Size to compare the nature of kinetics

Global macroscopic Local Macroscopic

Microscopic (CK)

(CK) (BRE)

Ideal design Real design

Reaction Rate Defined

Reaction rate: changes in a concentration of a product or a reactant per unit time.

[ ] concentration Reaction rate = ——— t

[ ]

t

[ ]

t

change

Average reaction rate

Instantaneous reaction rate Initial reaction rate

1. Physical state of the reactants – states that promote contact have faster rates; homogeneous vs. heterogeneous

2. Concentration of the reactants: conc. ↑, rate ↑ (or pressure for gases)

3. Temperature: temp. ↑, rate ↑ due to higher molecular energy and speed

4. Catalysts: rate ↑ by changing the mechanism and reaction energy

5. pH

6. Other physical things like stirring and grinding solid reactants. Contribution to achieve a homogeneous system

Factors that Affect Reaction Rates

How to measure the rate of reactions?

Rates of reaction is not based on stoichiometry!! It must be determined experimentally

Determine Reaction Rates

To measure reaction rate, we measure the concentration of either a reactant or product at several time intervals.

The concentrations are measured using spectroscopic method or pressure (for a gas). For example, the total pressure increases for the reaction:

2 N2O5 (g) 4 NO2 (g) + O2(g)

… because 5 moles of gas products are produced from 2 moles of gas reactants.

barometer

Expressing reaction rates

For a bio/chemical reaction, there are many ways to express the reaction rate. The relationships among expressions depend on the equation.

Note the expression and reasons for their relations for the reaction

2 A + B = 2 C

[B] 1 [A] 1 [C] Reaction rate = – ——— = – — ———— = — ——— t 2 t 2 t

ri Reaction rate r = —— 𝛎i

+ 𝛎i produced - 𝛎i consumed

Kinetics and Transport Process

• Diffusion and mass transfer.

• Mixing of fluid elements

• Heat transfer

• Fluid flow

Reactor design

• Focus on process design.

• Analysis of performance of an existing reactor

• Rate of process involved

• Motion of elements of fluid

Volume of interest

Mass Balance is made with respect to a “Control Volume”

Mass flow: min mout [kg/time]

Molar flow: Fin Fout [mol/time]

Volumetric Flow: qin qout [m3/time]

inputs outputs

.

. Q

Volume of interest

Mass Balance is made with respect to a “Control Volume”

Mass flow: min mout [kg/time]

Molar flow: Fin Fout [mol/time]

Volumetric Flow: qin qout [m3/time]

inputs outputs

.

. Q

I NPUT – OUTOUT + G EN – CONS = ACC

Volume of interest

Mass Balance is made with respect to a “Control Volume”

Mass flow: min mout [kg/time]

Molar flow: Fin Fout [mol/time]

Volumetric Flow: qin qout [m3/time]

inputs outputs

.

. Q

Volume of reactor?

Volume of liquid medium?

Volume of the packed bed?

Volume of the cell?

I NPUT – OUTOUT + G EN – CONS = ACC

How to Describe a System

• With respect to flow of material

• Continuous flow system

• Semi continuous flow

• Static system

How to Describe a System

• With respect to both material and energy flows

• Open System

• Closed System

• Isolated System