1 / 50

Real-Time Raman-Based Analytics for Small-Scale Reactor Applications

Explore the innovative Raman-based analytics developed by Stuart Farquharson and colleagues for real-time chemical detection in micro-systems, including small-scale reactors and lab-on-a-chip separations. Our technology enhances rapid optimization of esterification reactions, improving yield and time-to-market in pharmaceuticals. Compatible with various industries, our fiber optic probes enable continuous monitoring and analysis without sample preparation, even in harsh environments. This breakthrough facilitates compliance with process analytical technology standards, ensuring safety and efficacy in drug development.

bette
Download Presentation

Real-Time Raman-Based Analytics for Small-Scale Reactor Applications

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Stuart Farquharson, Chetan Shende, Frank Inscore, and Wayne Smith • Real-Time Raman-Based Analytics • for Micro-Systems: • Small-Scale Reactors • Lab-on-a-chip Separations www.rta.biz Contracts: NIH: 1R43CA94457-01 US Army: DAAD13-02-C-0015, NSF: DMI-0215819, DMI-0349687, DMI-0512701, NASA: NNA05CP04C, NNC05CA09C USDA: 2006-33610-1683

  2. We Do Raman – All analyses performed by Raman & SER Spectroscopy Mission: Provide analyzers that perform continuous, real-time, trace chemical detection with the ability to operate in harsh environments. Our fiber optic probes allow easy installation and use in all industries employing chemicals. Such as: Agriculture Petrochemical Biopharmaceutical Pharmaceutical Chemical Polymer Environmental Medical Homeland Security R&D

  3. Rapid Optimization of New Reactions/Processes • Micro-Reactors => thermal & mass transport reduced • Numbering-Up => 2 years earlier to market, Improve yield • Process Analytical Technology => In spec, safety • New drugs improve health… • A blockbuster drug makes >$1 million/day! • Profits limited by patent expiration • Eliminate delays to market (5-7 years lab-to-pharmacy) • 16% of drugs out-of-specification (= $1.1 million/year loss) • 50% of production time = analyzing intermediates/product Project Goal: Project Drivers:

  4. Esterification Reaction (Demonstration) Protection of a carboxylic acid group by esterification, represents one of the most often used reaction steps during the synthesis of pharmaceuticals.

  5. Small-Scale Reactor: (5 mL coil)

  6. Dr. Brian Marquardt University of Washington Small-Scale Reactor: Photograph Capillary Volume = 5 ml

  7. RTA’s Raman Analyzer It’s an Interferometer…no x-axis drift! $75,000 • Advantages: • No sample preparation • Simple integration via fiber optics • Remote analysis, multi-component • No fluorescence interference • Complete spectral coverage • Wavelength stability • Confident spectral subtraction • and library search/match • Real-time, On-demand analysis • Long term stability • Temperature and vibration immune • Shock resistant

  8. RTA Advantage: No Fluorescence Diesel Fuel 785 nm Laser Excitation 1064 nm Laser Excitation Virtually all natural materials fluoresce using 785 nm 8

  9. RTA Advantage: No X-Axis Shift Aspirin Aspirin Shifted Ibuprofen X axis shifts limit: quantitation, multi-component analysis, and unknown identification 9

  10. 1 mm glass capillary Sample Cell: 1-min, 375 mW of 785 nm Glass background = noise

  11. Benzoic Acid Methanol Sulfuric Acid Chemicals:

  12. Benzoic Acid (BA) Methyl Benzoate (MBZ) Chemicals: Reactant & Product 780 and 817 cm-1 => COO deformation mode

  13. Benzoic Acid (0.5-4M) Methyl Benzoate (0.5-4M) Calibration:

  14. Peak Height Peak Area Calibration:

  15. 60 oC Real-Time Monitoring by Raman Spectra generated using 375 mW of 785 nm and stored every 30 sec (every 3 min shown).

  16. 40 oC 50 oC 60 oC Small discrepancy between rate constants Reaction Rates:

  17. Activation Energy: SPIE, 6371 (2006)

  18. NeSSI-Based Small-Scale Batch Reactor Mike Cost Parker-Hannifin

  19. Raman Probes: Swagelok

  20. NeSSI-Based Small-Scale Batch Reactor Methanol BA LOAD H2SO4 Syringe Pumps

  21. NeSSI-Based Small-Scale Batch Reactor Raman Probe Monitor & Control REACT Peristaltic Pump

  22. NeSSI-Based Small-Scale Batch Reactor Syringe Pumps Raman Probe EMPTY MBZ

  23. Batch mode small-scale reactor built & used • Esterification reaction successfully monitored • Limits of detection: BA = 0.9%, MBZ = 0.75% • Various acid catalysts used, sulfuric acid best • Rate constants easily determined from 25-65 oC • Activation Energy determined at 50.1 kJ/mole • Best yield, 91% obtained at 60 oC • Continuous Reactor requires 72 m tube Summary:

  24. Lab-On-a-Chip Separations & Surface-Enhanced Raman Spectral Detection Basic SERS Concepts Anthrax Spores on Surfaces Pesticides in Fruits & Vegetables Chemotherapy Drugs in Saliva

  25. Surface-Enhanced Raman Spectroscopy

  26. Simple SERS Sample Vials 2001 U.S. Patent Number 6,623,977

  27. Which do you want: Sensitivity or Reproducibility? SERS: silver particles in sol-gel 1 square micron = 12.6 silver particles Laser spot (325 micron diameter) = 83,000 square microns i.e. contains 1.04 millionsilver particles Or the equivalent of 1 perfect hot spot generating 1012 enhancement 10 microns

  28. Separation and Analysis 1 2 3 4 5 6 1 2 3 4 5 6 PABA PA 800 1000 1200 1400 1600 1800 2000 Wavenumbers (cm-1) Farquharson & Maksymiuk Appl Spec, 57, 479 (2003), US Patents 6,943,031 & 2

  29. Performance: reversibility 30 second “plug” of benzoic acid 8 second spectra, 100 mW 785 nm

  30. Analysis: SERS of Pesticide Mixture Carbaryl on gold Chlorpyrifos on silver

  31. Professor Jay F. Sperry University of Rhode Island Trace Detection of Bacilli Spores on Surfaces using a Portable SERS-Based Analyzer • Anthrax LD50 ~10,000 spores • Goals: 100 spores/cm2 • 1-min • No False Positives

  32. Approach: measure anthrax signature - CaDPA CaDPA

  33. B. cereus Raman Spectroscopy Pure samples 500 mW of 1064 nm 5-min acquisition time CaDPA J Raman Spec, 35, 82-86 (2004)

  34. SERS and RS of dipicolinic acid (DPA) SERS 1 mg/L (1 ppm) 150 mW, 10 sec Raman 5.5 g/L (55,000 ppm) DPA in KOH 300 mW, 25 min Enhancement Factor = 105 Appl Spec, 58, 351 (2004)

  35. Extraction & Identification of DPA in 2-min! 0. Dried 2200 spores from 1 microliter (~0.2 cm2) 1. Added 10 micoliters of SporeDestroyer (1-min digestion) 2. Suck 1 microliter into SER-active capillary (10-sec) 3. Measure SERS of DPA (10% = 220 pg/microliter) (10-sec placement, 30-sec scan)

  36. RTA’s Raman Analyzer • Advantages: • No sample preparation • Simple integration via fiber optics • Remote analysis, multi-component • No fluorescence interference • Complete spectral coverage • Wavelength stability • Confident spectral subtraction • and library search/match • Real-time, On-demand analysis • Long term stability • Temperature and vibration immune • Shock resistant RTA’s Portable Raman Analyzer SERS-Active Capillary

  37. SERS: 220 Spores 1 spore = 10 pg, DPA =10% spore weight 220 pg/microL DPA 100 pg/microL (ppb) reference spectrum Internal Reference IJHSES, 20, 12-18 (2007)

  38. Rapid Analysis of pesticides on or in fruit & vegetables by SERS • Need pesticides to meet food demand • US imports 40-45% fruit & vegetables • 6.1% of imports exceed guidelines • Only 1% is tested • 3 Million tons of contaminated fruits & • vegetables reaches the market each year • Goals: • 10 ppb-1 ppm (0.01-1 mg/L) • 1-minute • No false positives • Minimum Reagents • Field-usable

  39. Sensitivity: 10 ppb 75 mW of 785 nm 1 min

  40. Pesticide: chlorpyrifos (methyl) SERS: 10 & 5 ppm (mg/L) RS: 50,000 ppm (50g/L), 350 mW-25 min

  41. Standard Method vs SERS Method 10 min 1 hour

  42. Gas Chromatography After step 5a After step 7b Professor James Stewart, U. Connecticut

  43. Chlorpyrifos: 50 ppb 1) In dichloromethane 2) In OJ after evaporation & SPE 3) In OJ after SPE

  44. Method: 10-minute analysis sma

  45. Prototyping SERS-chip A B C A) Endosulfan SERS-Active Lab-on-a-Chip Sample Injection Syringe B) Thiabendazole A B C C) Phosmet 500 750 1000 1250 1500 1750 Wavenumbers (cm-1)

  46. Controlling Chemotherapy Drug Dosage • 1,334,100 new cancer cases each year • >0.5 million Americans died of cancer in 2003 • Lung and bronchus – 28% Colon and rectum – 10% • Breast – 7% Prostate – 6% • Treatment involves Surgery, Radiation and Chemotherapy • Chemotherapy drugs also kill non-cancer cells • Dosage is critical • No clinical trials to establish statistical based dosage • Current analysis of drugs and metabolites use 10-20 ml blood • Consequently, measurements made on an “as needed” basis

  47. Detection of 5-fluorouracil in saliva using SERS • 5-FU, one of most widely used chemotherapy drugs • Wide genetic-based variation in metabolism,15-80% inactive • 10% of patients die the first time administered • Need: Monitor metabolism on individual basis • Solution: SERS of saliva • Concentrations in saliva 10-50% of blood plasma (1-10 microg/mL) • Saliva is 99.5% water, few interfering physiological chemicals • But Currently analyses require 10-20 cc - unsafe • Raman – chemical specificity • SERS – increased sensitivity • Simple SERS Syringe - 100 microL, 5-min total analysis time

  48. Analysis: 5-Fluorouracil Normal Raman Surface-Enhanced Raman J Raman Spec, 36, 208-212 (2005) Vibrational Spec, 38, 79-84 (2005)

  49. Simple Separation Devices 5FU & 5FUH2 5FdUrd Leucovorin A B C A B C 600 800 1000 1200 1400 1600 Wavenumbers (cm-1)

  50. Simple Separation Devices 100 micron

More Related