Nano Quantity Analyte Detector (NQAD)

A New Aerosol-based HPLC Detector

February 2008

Quant Technologies LLC

Quant Technologies was founded in 2003 as a subsidiary of Power Engineering & Manufacturing, Inc. (PEM)

Our primary focus is engineering design & instrumentdevelopment, 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.

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)

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

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

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

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

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

How NQAD Works

Particle numbers not volume or mass

Very Sensitive• like counting photons vs light intensity• like counting electrons vs analog electric current

How NQAD Works

Nebulized Aerosol Distribution• Log Normal• Stable

How NQAD WorksEvaporation• 2-3 order of magnitude shift in particle size• Nonvolatile Residue

How NQAD Works

Size shift of aerosol distribution – basis for aerosol based detectors

How CNLSD WorksWater Condensation Particle Counters

(WCPCs)

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

WCPCWater 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

WCPCWater Condensation Particle Counter• Very high signal to noise ratio

WCPCWCPC Detection Efficiency• Stable

How NQAD Works

Low baseline requires ‘clean’ mobile phaseand volatile buffers

NQAD signal based on the particle countrate - #/sec

How NQAD Works

How NQAD Works

NQAD Recap

Nebulization

HPLC column effluent is sprayed into an ultra fine mist of droplets

Droplet size distribution is bell shaped on log scale

NQAD Recap

EvaporationMobile 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

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

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

What Makes NQAD Better?

Ultra-high SensitivityExcellent Dynamic Range Good Linearity ReproducibleSmall Size, Robust, ReliableEasy to Set Up and Operate

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

Reproducible Results

NQAD response is stable, precise and reproducible

Example shows six repeated injections of a solution of cations -- the chromatograms are identical

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

NQAD

Thank you