Nano Quantity Analyte Detector (NQAD)

1. Nano Quantity Analyte Detector (NQAD) A New Aerosol-based HPLC Detector February 2008

2. Quant Technologies LLC Quant Technologies was founded in 2003 as a subsidiary of Power Engineering & Manufacturing, Inc. (PEM) Our primary focus is engineering design & instrument development, and manufacturing Our Mission: To bring to market high quality, innovative and affordable aerosol instrumentation for applications in basic and applied research, environmental studies, process and quality control, and occupational health and safety.

3. A History of Success In 2003, Quant licensed a remarkable new technology from Aerosol Dynamics, Inc. for laminar-flow water-based condensation particle counting. Our first commercial product was developed within one year of licensing. Product line includes: A family of four Water Condensation Particle Counters (WCPCs) for basic and applied aerosol research ,and are marketed exclusively by TSI Incorporated A Nonvolatile Residue Monitor for measuring impurity levels in ultrapure water systems for the semiconductor industry; marketed exclusively by Fluid Measurement Technologies, Inc. The new Nano Quantity Analyte Detector (NQAD)

4. Design & Development • Successful partnering with inventors and technology leaders • Skilled senior-level engineering design team with almost 30 years experience developing state-of-the-art scientific aerosol instrumentation • In-house expertise in electronics, optics, mechanical design, firmware, software, modeling, and cost-effective manufacturing • Well-equipped engineering development and aerosol test laboratory

5. Manufacturing • 16,000 sq. ft. facility in a light industrial park in Blaine, Minnesota; half dedicated to Quant Technologies and half to our parent company PEM • State-of-the-art production areas, raw material storage, prototype machine shop, and analytical chemistry laboratory • Low to medium volume manufacturing in quantities from 10’s to 100’s annually – PEM volumes of electro-mechanical devices ranges 1,000’s to 10,000’s annually. • ISO 9001 Quality System with certification on February 5, 2008 • ISO 14644 Class 5 clean room and ASTM D1193, Type 1 Microbiological Grade A water system

6. Key Employees • Fred Quant President • Derek Oberreit Development Engineer • Laurencia Kyariga Applications Chemist • Chuck Bille Marketing/Sales/Distribution • Andrew Amighi CEO • Jim Blesener CAO and operations support

7. Acknowledgements The NQAD development was funded, in part, through an SBIR grant from the National Institutes of Health awarded to Fluid Measurement Technologies, Inc. and Southern Illinois University Carbondale (SIUC) Quant Technologies wishes to acknowledge the pioneering work of Professor John Koropchak and his colleagues at SIUC The patented WCPC technology is licensed from Aerosol Dynamics, Inc. US Patent # 6,712,881

8. What is NQAD? A new and very different aerosol-based universal HPLC detector Heart of the instrument is a patented Water Condensation Particle Counter (WCPC) WCPC technology is well-known and widely used in other scientific fields such as climate research and nanoparticle technology Nano Quantity Analyte Detector (NQAD) – original work at SIUC in mid-90s

9. How NQAD Works Particle numbers not volume or mass • Very Sensitive • like counting photons vs light intensity • like counting electrons vs analog electric current

10. How NQAD Works • Nebulized Aerosol Distribution • Log Normal • Stable

11. How NQAD Works • Evaporation • 2-3 order of magnitude shift in particle size • Nonvolatile Residue

12. How NQAD Works Size shift of aerosol distribution – basis for aerosol based detectors

13. Water Condensation Particle Counters (WCPCs) How CNLSD Works • Measures the number concentration of very small airborne particles above a minimum size. • Uses water as the condensing fluid – non-toxic, odorless, non-flammable, non-contaminating • Ultra-sensitive particle size range – from 2.5 nm to over 3 µm diameter • Wide dynamic concentration range – from 0 to 107 particles/cm3

14. WCPC • Water Condensation Particle Counter • Grows seed particles into droplets • Supersaturation occurs because of the difference between the thermo and mass diffusivities of water vapor • Counts Particles – Doesn’t size them • 6 Order of magnitude counting range

15. WCPC • Water Condensation Particle Counter • Very high signal to noise ratio

16. WCPC • WCPC Detection Efficiency • Stable

17. How NQAD Works Low baseline requires ‘clean’ mobile phase and volatile buffers NQAD signal based on the particle count rate - #/sec

18. How NQAD Works

19. How NQAD Works

20. NQAD Recap Nebulization HPLC column effluent is sprayed into an ultra fine mist of droplets Droplet size distribution is bell shaped on log scale

21. NQAD Recap Evaporation Mobile phase and additives evaporate leaving small residue particles Choice of evaporator temperature ensures evaporation of mobile phase - minimizes evaporation of analyte Baseline curve – pure mobile phase plus additives Analyte curve – curve shifts to larger particle size with analyte present

22. NQAD Recap WCPC – Condensational Growth Supersaturated water vapor condenses on particles to form large droplets Only particles above critical size act as condensation nucleation sites (WCPC Detection Efficiency curve) Baseline signal is small compared to analyte Analyte detection down to 1 ng and below possible

23. NQAD Recap Optical Detection Laser optical detector computes the quantity of droplets Dynamic range is over four orders of magnitude NQAD signal is particle number concentration as function of time Peak area under curve represents analyte concentration level

24. What Makes NQAD Better? • Ultra-high Sensitivity • Excellent Dynamic Range • Good Linearity • Reproducible • Small Size, Robust, Reliable • Easy to Set Up and Operate

25. Ultra-high Sensitivity Reliably detect from 1 nanogram to 100 micrograms, or more - LOD in the sub-nanogram range Ideal for searching for drug impurities, degradation products, excipients and when industrial hygiene is a concern

26. Reproducible Results NQAD response is stable, precise and reproducible Example shows six repeated injections of a solution of cations -- the chromatograms are identical

27. Applications • Analysis of nonvolatile and semivolatile compounds: • Amino acids • Carbohydrates • Steroids • Caffeine • Cations • Cholesterol • Amine • Artemisinin (ART) and Dihydroartemisinin (DHA) • PEG 1000 and PEG 20000 • Sulfonic Acid and Sulfanilamide • Saccharin, Theophylline and Sucrose • Ovalbumin • Dipalmitin isomers • Use in a variety of fields including: • Pharmaceutical • Environmental • Agricultural / food / beverage • Industrial products • Life sciences • Energy / petroleum • Forensics / narcotics

28. NQAD Thank you