Course Information
Course Title: Nanoliter Sample Handling: From TLC to MALDI, DART and SIMS for the Analysis of Proteins, Agents, Toxics, Polymers and More Using Syringes, Pipettes, Pumps and Other Induction Based Fluidic Devices
Categories: 1 - Biomedical Engineering
2 - Life Sciences
3 - Liquid Chromatography-Mass Spectrometry
4 - Mass Spectrometry
5 - Microscopy
6 - Proteomics
7 - Sample Preparation
Instructor(s): Andrew Sauter/Julie P. Harmon Course Number: 24
Affiliation: Nanoliter
Course Date: 03/13/2011 - Sunday Course Length: 1/2 Day Course
Start Time: 08:30 AM End Time: 12:30 PM
Fee: $225 ($325 after 2/14/11) Textbook Fee:

Course Description
In this course, we present the basics of Induction Based Fluidics (IBF) and exciting new peer review published by NIST, JEOL, University or Wisconsin and others that show ca. 10 to 100x improvement in MS sensitivity when nanoliter volumes of liquids are employed instead of uL quantities for MALDI, SIMS and DART techniques. We also show video of 384 channel parallel dispensing and pipette/MS data as well as more mundane IBF applications like TLC, sample handling and source introduction which may replace, we predict, ESI.

Target Audience
Researchers, chemists, technicians, managers, QA and safety personnel. The course highlights where nanoliter, green technology has application and how using lower volumes of chemicals can help organizations save money on reduced solvent usage as it increases lab safety and as one can do important "new things."

Course Outline
We discuss five new papers over the last year that have shown that IBF can be used to: 1. increase the sensitivity of MALDI for proteins, peptides and synthetic polymers by up to 100x, literally  as it increases reproducibility (3 to 20 x),  2. that can increase the sensitivity of SIMS for RDX and cocaine by 100 to 1000x and drugs by DART Accu TOF MS by factors of 10 to 100x., 3 that one can  measure/verify the volume of liquids (nLs) dispensed in real time and 4. that IBF can be used to fly liquids directly into instruments like TOF’s and other instruments....like ICP’s yielding 100% sample introduction efficiency. We also show that IBF is useful for more mundane tasks like depositing liquids for TLC, preparing standards, dispensing drugs, agents of other liquids into or onto targets (humans/animals/plants, microtiter plates or spectroscopy sample cells) using handheld devices (e.g., the nanoLiter Cool Wave SyringeŽ or Pipette) or in msec timeframes using robotic platforms. We presente other unique IBF attributes like making charged polymers. Finally, we discuss why this is important, green and of significant interest to labs and chemists of all types.

We discuss other mundane IBF topics e.g., dispensing statistics, to more exciting aspects of IBF, like electric field enhanced synthetic polymer MALDI. We also show even newer IBF applications to LC/MALDI, SIMS applications to sampling humans in forensics applications on blood, serum and samples (evidence.).
 
We show how IBF can morph syringes, pipettes, pumps & LC’s into non-touch handheld dispensers or highly parallel sample prep devices. We address practical issues across the macro, micro and nano regimes like evaporation after Maxwell, electrochemistry after Adams/Bard, particles, viscosity, surfaces, joule heating, environmental factors and non ideal consideration in micro/nanofluidics briefly.

Finally, we discuss calibration techniques, quality control of IBF devices in various applications, answer questions and discuss future possibilities of IBF... like leadiing labs worldwide into the Green nanoliter world.

Nanoliters: From Sample Preparation To Instrument Introduction. Applications To Proteins, Peptides, Synthetic Polymers, NCB Agents, Explosives, Pollutants, Evidence, Drugs  & More via IBF 

(Note: This outline is abbreviated for our 4 hour Pittcon course.) 

Why nanoliters and IBF?
Economics, health, aesthetics and practicality
Do new tasks, most important
Traditional/non-traditional fluidic devices considered
Limitations of pipettes, syringes, mechanical systems
IBF history described
     Studying ESI w/Agilent, Affymax and Chem Space.
                        Traditional microfluidics
                        Traditional microfluidics constrasted to ESI
                        ESI contrasted to IBF
Other liquid movement approaches addressed and contrasted, e.g., inkjets, piezo, chips
Example IBF Applications with Video
Simple useful functions, parallel dispensing, parallel LC/MALDI sample placement, million fold dilution, e-spotting, TLC, etc.
NCB sample handling benefits.
DNA/RNA prep. Samples fly to humans for dispensing medication.  Others.

Gas & liquid phase matter movement. 
               Laminar  flow, capillary action, adhesion and cohesion,  
               Other very common approaches to mass transport.   
               IBF and Mass Spectrometers {ions, gasses, liquids} 
                        Forces considered-contrasted. Liquid trajectories calculated? 
Explaining energy of flying nanoliters in one application  
                            Simple explanation of IBF in a capillary  
Simple explanation of IBF flying liquids to humans, parallel IBF dispensing other examples 

Instrumentation 
           Liquid transport specification (Simple or complex task.) 
           Plumbing, manifold or chip considerations 
           Energy sources Electrokinetic 
Pneumatic, peristaltic, ultrasonic, other for hybrid systems 
Detection 
Robotic considerations 
Interface/s 
Morphing your devices into the nanoliter regime  
Other aspects 
 
Traditional microfluidics presented, discussed, contrasted by Dr. Mitch Johnson, ca. 45 min. 
 
Polymer Sample Preparation Observations in recent paper. 
       Overview 
       IBF polymer devices
       IBF polymer MALDI
      Videos of MALDI polymer drying.  E field enhanced MALDI, new paper.
      Measuring charge and volume, new paper of polymers.
      IBF and polymers.

IBF Practical Issues

Consideration of practical issues in liquid transport, across the macro and nano regimes.
Evaporation after Maxwell
Electrochemistry after Adams/Bard.
Particles
Viscosity 
Surfaces
Joule heating
Environmental factors
Non ideal consideration in nanofluidics briefly considered

Calibration
   Approaches
      Photoshop/Paintshop Pro demo
      Calibration software demo
      Accuracy and precision estimates for various modes/devices
      Newer approaches
      Discussion and cautions.  Straight-forward comparisons

Other IBF based liquid movement techniques, outside the box. As time allows. 
       Nanoliter-sicles, making frozen charged spheres of liquid/s  
       Writing the word "picoliters" with pLs and IBF. The picoliter regime 
       The New Nanoliter/Microliter syringe (Patent Pending.) 
       Printing with monolithic LC columns for MALDI sample preparation 
       More morphing syringe pumps, peristaltic and other pumps into the  
       nanoliter regime 
       Passive/active focusing.   
Summary. 
       Why and where having the ability to manipulate nanoliters easily has merit 
       Why having the ability to manipulate nanoliters by you at your facility has value  
       Competitive techniques 
       Questions and answers 
       Manipulating nanoliters affords new, simple, very useful and practical capabilities and an interesting future we predict.

Course Instructor's Biography
Mr. Andrew D Sauter, Jr. developed and applied GC/MS, ICP/MS, LC/MS and MS/MS technologies since the 70’s. He developed the first priority pollutant GC/MS protocol, receiving awards for this work. These methods have been at the core of the implementation of federal environmental regulations, methods and contracts in the USA across federal environmental laws for the last 35 years. He also acquired funding for and worked on early LC/MS projects, funded early ICP/MS federal projects, and he purchased and applied Finnigan’s first built LC/MS/MS, hands on, demonstrating the first HTS LC/MS/MS ever, presenting that work at ASMS and in the literature. He has consulted, collaborated with most MS firms and to clients as diverse as Los Alamos, WMX, DOD, Lockheed, DOJ, Kraft and now through Nanoliter, LLC he is collaborating with 14 projects at major universities, government agencies and major corporations. In the last year, he has coauthored three papers on IBF and quantitative MALDI showing major improvements in sensitivity (up to 100x !) and reproducibility for proteins, peptides and synthetic polymers, attempting to moved MALDI to technique that is routinely quantitative. In the past, he has published in signal processing, pattern recognition and data base building in applied MS on national multi-laboratory MS projects, publishing three interlaboratory MS studies. He has also published basic, applied papers on ionization and detection of MS technology including EI, CI, PB, ESI and MALDI. Currently, he is working on IBF applied to LC/MALDI, parallel dispensing, DART/DESI sample introduction and standardization and on pipette/MS and two very cool projects for the US Army. Sauter invented, patented and is now selling nL devices and licensing IBF technology including the nanoliter syringe, the nanoliter pipette, and OEM ing parallel nanoliter dispensing heads for highly parallel LC/MALDI. Nanoliter also sells dispensers for DART, DESI, SIMS and other sample introduction and standarization tools. He holds chemistry degrees from Duquesne (BS) & Marquette (MS) and he continues to develop/apply liquid handling technology to interesting problems, as he grows Nanoliter, a Nevada based LLC. Julie P. Harmon is a Professor in the Chemistry Department at the University of South Florida in Tampa, Florida. Prior to joining USF she worked for Eastman Kodak Company, PPG Industries and Union Corporation. One facet of her ongoing research focuses on studying the effects of electric fields on morphology and properties of materials.