Aber Instruments Introduction Matthew Lee BEng MIET Engineering Director

1. Aber Instruments IntroductionMatthew Lee BEng MIETEngineering Director

2. Contents • Aber Instruments Ltd • The Theory • Typical Data

3. About the Company Aber Instruments Ltd

4. Where is Aber Instruments?

5. The Town of Aberystwyth

6. Aber Instruments Ltd. • Situated in Aberystwyth, Wales, UK • Employs 27 people • Company is 25 years old • Employee owned company (since 2012) • Sustainable business • Market leaders • Completely focussed on measuring Viable Biomass using Capacitance • Technology initially taken up by brewing industry: now standard in virtually all major breweries around the world • Supply systems to all the big biotech company’s all around the World • Many systems in both R&D and Production (over 500 channels in cell culture applications)

7. Any Questions?

8. Measuring Cells Using Capacitance The Theory

9. Why Use Capacitance to Measure Viable Biomass? • An electric field is be used to detect intact Cell Membranes • This is shown in the form of the electronic measurement of Capacitance Probe Electric Field

10. Why is the Cell Membrane Important? • The Cell Membrane • Is impermeable to ions (insulator) • Which, when in an electric field, polarises the cell • This allows a capacitive charge to build up • It is this capacitive charge that is being measured • The capacitance signal is proportional to Viable Biomass because only viable cells have undamaged membranes

11. How does Aber Detect this Capacitance? • The Aber probe and electronics creates and monitors the electric field • The probe’s • Outer electrodes create the field • Inner electrodes measure the voltage • Aber’s complex electronics analyses the very small phase angles between these two signals and thus works out the capacitance value • The electric field is in the Radio Frequency spectrum, typically between 50kHz and 20MHz

12. Key Points • Live cells with intact membranes become polarised and thus measured • Dead cells with porous membranes are not measured • The Resulting capacitance is directly proportional to the total membrane bound volume of the cells • The number of cells, and the size of the cells! • The total biovolume • The system is insensitive to cells with leaky membranes, gas bubbles and other debris • The electric field typically projects about 30mm from the probe into the liquid • Be careful when comparing different methods of determining live and dead cells, this is a grey area, and you can get different answers

13. What are the Detection Limits? • The detection limit depends on the total viable biovolume • Proportional to number of cells • Proportional to cell size • Note: This and the next slide are for Futura measurement technology

14. The Generations of Aber’s Technology • First Generation (1990 - 2002) VCM520, Mux, 800’s • Second Generation (2003 - 2011) BM220, BM230, BM200 • Third Generation (2011 – Present) Futura - SF, SRF, MRF

15. Any Questions?

16. What can you do with Capacitance Measurements? Typical Data

17. Cell Culture Example • Notice how cells have consumed critical nutrients before feed occurs!

18. Using Capacitance to Control Growth • Notice fill level, cells are being harvested!

19. Maintaining Optimum Cell Concentration on Microcarriers

20. Grass Fibre: Lignocellulose Enzyme Digestion

21. Futura, the Next Generation in Biomass Monitors Thank You for Listening Any questions? www.aberinstruments.com