modern raman spectroscopy: has the sleeping giant finally awoken?*
TRANSCRIPT
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Modern Raman Spectroscopy:Has the sleeping giant finally awoken?*
Richard McCreeryUniversity of Alberta
National Institute for Nanotechnology
thanks to: Bonner Denton*Keith CarronChris BrownJun ZhaoSteve ChoquetteAndrew Whitley
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Stated differently: Has Raman spectroscopy made the transitionfrom research tool to widely used routine analytical technique?
(Note: Vendor names are informational, and do not implyan endorsement or “rating”)
To get your attention:
1985: Raman sales ~ $5 million/year FTIR: ~$400 million
2008: Raman ~ 200 million
FTIR: $600 –
800 million
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Rayleigh scattering, no frequencychange. Intensity proportionalto ν4
488 nm rejectionfilter in front ofcamera
Raman scattering, at longer wavelength(lower frequency) than input light
488 nm laser
cyclohexane
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Raman spectroscopy in 1985:
• double monochromator• single channel (PMT)• high f/#• tricky alignment required
• low sensitivity• slow (~20 min/spectrum)• often high background• intensities strongly dependent
on alignment and focusing
Problems:
Main vendors:
• Spex• ISA/Jobin-Yvon• Dilor• Jasco
Sales: ~ $5 million/year, compared to ~$400 million/year for FTIRNon-research applications: negligible
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Some factors underlying Raman growth:
1983: Fiber optic Raman for remote sampling
1986: FT-Raman at 1064 nm greatly reduced background
1989: Diode laser/ CCD Raman at 785 nm
1990-92: Holographic laser rejection filters
1995: Low f/#, holographic spectrometer and integrated fiber optic sampling
1996: ASTM Raman shift standards
1994-98: Low f/# imaging spectrographs with CCD detectors
1997: Luminescent intensity standards
2000-
Automatic Raman shift calibration
2002-
NIST Luminescence standards
2004-
Hand-held portable spectrometer
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laser
collection fiber(s)
18 around 1photo
1 mm
sample
1983: Fiber optic Raman for remote sampling (McCreery, Hendra, Fleischmann)
McCreery, Hendra, Fleischmann, Anal. Chem. 1983, 55, 146.Schwab, McCreery, Anal. Chem. 1984, 56, 2199.
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Kaiser Optical:
BW Tek:
Bruker:
Commercial examples of fiber optic probes:
Horiba-JY:
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488 nm laser, with 488 rejection filter preceding camera
cyclohexaneRaman(9 M)
Even a very lowconcentration of a
fluorescer can overwhelm Raman scattering, due to
much greater cross section
fluorescein
fluorescence(10-5 M)
Fluorescence was a big problem for practical samples:
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1986: FT-Raman at 1064 nm greatly reduced background (Chase, Hirschfeld)
Chase, D. B.; Fourier transform Raman spectroscopy; JACS 1986, 108, 7485.Hirschfeld, T.; Chase, B.; Applied Spectroscopy 1986, 40, 133.
fluorescein
anthracene
514.5 nm dispersive
1064 nm FT-Raman
FT-Raman
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Raman signal
(Raman + “fluorescence”
+ dark signal)1/2
Good news: fluorescence usually much smaller at 1064 nmthan with 400-633 nm lasers
Bad news: dark signal higher for NIR detectors, multiplex “disadvantage”and weaker Raman scattering at 1064 nm
Important practical consequences:
• broadened utility of Raman to many commercially important samples(impure organics, polymers, pharma)
• added significantly to vendors and sales(Bio-Rad, Bruker, Nicolet, Perkin Elmer, Varian)
S/N ratio =
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785
nm Raman scattering
Raman shift, cm-1
2500 0 500 1000 1500 2000
inte
nsi ty
514.
5 nm
fluorescence
ener
gy
excitedelectronic
stateRhodamine
6G:
1989: Diode laser/ CCD Raman at 785 nm (Williamson, Bowling, McCreery)
Williamson, Bowling, McCreery, ; Applied Spectros. 1989, 43, 372Allred, McCreery, Applied Spectroscopy 1990, 44, 1229..
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• 785 nm lasers enable much of the reduction in fluorescence available withFT Raman, but retain the advantagesof CCD detectors
• diode lasers are also compact, withlow power and cooling demand
• multichannel (512 -
2000 in parallel)
• very low dark signal (< 0.001 e-/sec)
• sensitive (QE> 95% in visible)
• 2D imaging possible
• CCD’s
are OUTSTANDING Raman detectors:
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1990-92: Holographic laser rejection filters (Carrabba, Owen)
1995: Low f/# spectrometers and integrated fiber optic sampling(Owen, Battey, Pelletier, Kaiser, ISA, Chromex, Andor,…)
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1985
2008
Improvement(PMT/Double)
(CCD/Single)
Quantum efficiency
0.15
0.95
6.3 X
Collection (AD
Ω) 4 x 10-4
5 x 10-4
1.2
Transmission
0.1
0.6
6
# Channels
1
1600
1600
Total signal gain 72,000(same acquisition time)
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Raman shift, cm-1
glassy carbon:
Scanning/PMT
20 minutes
SNR ~ 28
ca. 1985
CCD multichannel
5 seconds
SNR ~ 280
Scanning/PMT
20 minutes
SNR ~ 28
2000
SNR improvement for sameacquisition time: 100-
500 X
Decrease in acquisition timefor same SNR: 103
to 104
Comparable to or greater improvement than that for
FT-NMR and FTIR
Raman shift, cm-1
1985
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1996: ASTM Raman shift standards (Carrabba, McCreery, 7 labs for input)
2000: Automatic Raman shift calibration (Allen, Zhou, US pat. 6,141,095)
500 1000 1500 2000 2500 3000 Raman shift, cm-1
213.
3
390.
9
857.
9
1168
.513
23.9
1561
.6
1648
.4
2931
.130
64.6
3326
.6
1105
.5
651.
6
329.
246
5.1
504.
071
0.8
797.
296
8.7
1236
.8
1371
.5
3102
.4
4-acetamidophenol(i.e. Tylenol)
4-acetamidophenolcyclohexanenaphthalenetoluene/acetonitrilesulfurbis-methylstyrylbenzenebenzonitrileindenepolystyrene
Raman shifts from 7labs, all with standarddeviation < 0.5 cm-1
ASTM E 1840 Standard Guide for Raman Shift Standards for Spectrometer Calibration
ASTM E 1840:
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Automatic Raman Shift calibration:
Bruker
“Sure-Cal”
Allen, Zhou, US patent 6,141,095 (2000)Zhao, Carrabba, Allen, Applied
Spectroscopy 2002, 56, 834
Days
1164.5
1168.5
1172.5
0 2 4 6 8 10 12 14 16 18 20
Ram
an S
hift Tylenol, intentionally unstable diode laser at 785 nm standard deviation of
Raman shift = 0.066 cm-1
over 20 days
(Data from Jun Zhao)
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3000 2500 2000 1500 1000 500
C6
H12
same laser wavelength, 3 spectrometers
1997: Luminescent intensity standards (Ray, Frost, McCreery)
2002-
NIST Luminescence standards (Choquette, Etz, Hurst, Blackburn)
The consequences:
• true relative intensities usually unknown• uncorrected libraries are instrument dependent• validation of regulatory data (e.g. pharma)
1064 nm
785 nm
514.5 nm
3000 2500 2000 1500 1000 500 0
CHCl3
The problem:
(spectra from Steve Choquette)
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NIST standard reference material luminescent standards
Cr-doped glass with calibrated luminescent output in responseto Raman laser
Hurst, Choquette, Etz, Applied Spectroscopy 2007, 61, 694.Choquette, Etz, Hurst, Blackburn, Leigh, Applied Spectroscopy 2007, 61, 117.
0
0.2
0.4
0.6
0.8
1
1.2
500 750 1000 1250 1500 1750Wavelength (nm)
Inte
nsity
(arb
)
SRM 2242SRM 2244SRM 2241SRM 2243SRM 2245
488/514 Ex 532 nm Ex 785 nm 1064 nm Ex
632.8 nm Ex Standard is run like any othersample, then software mathematically corrects spectrum.
>230 sold so far, mostly for 785 nm
(spectra from Steve Choquette)
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Uncorrected SRM 2241 on 4 commercial Systems.
λex = 785 nm
785 nm
0
1000
2000
3000
4000
3000 2500 2000 1500 1000 500
Raman Shift
Instrument response function significantly distorts relative intensities
(spectra from Steve Choquette)
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corr. with SRM 2243
2241
2244
(spectra from Steve Choquette)
sign
al (a
.u.)
(much of remaining differences due to ν4
factor)
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Major progress toward widespread Raman use, 1985-2005:
• 104
to 105 sensitivity increase, 100-500 X in SNR
• Compact, low power, integrated systems available
• Much broader applicability
• Standards for frequency and intensity, automatic shift calibration
• Variety of sampling modes: fiber optic, through glass, in-vivo
• Proven industrial applications in process control and QC
HOWEVER:
• spectrometer prices bottomed out at ~ $50K due to laser and CCD
costs
• not yet suitable for field applications, not really portable
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2004-08 Hand-held portable spectrometer (Carron, DeltaNu, Ahura)
• 785 nm laser• < 1 –
5 lbs weight• > 4 hrs battery life• built-in library for rapid ID• portable and shock tolerant• vials, non-contact, through-bag• $15,000 -
$35,000
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DeltaNu/Intevac Photonics
remote observation to 3 meters
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Ahura
Scientific
0 500 1000 1500 2000 2500 3000Raman shift, cm-1
Inte
nsity
toluene + acetonitrile
(slide from Chris Brown)
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Has the “giant”
woken up ?
1985: ISA/HoribaSpexDilor
~ $5 million sales(~$400 million for FTIR)
2008:
Vendors*:
Ahura
ScientificBruker
OpticsB&W TekCenticeDeltaNuFoster&FreemanHoriba/ISAJascoKaiser OpticalOcean OpticsPerkin ElmerPI/ActonRenishawRiver DiagnosticsSEKI TechnotronThermoVarian
*Mukhopadhyay, Analyt. Chem. product review, May 2007 (in part)
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2008 Raman sales: $201 million (>40 X since 1985, CPI was 2X)
Some APPROXIMATE sales numbers:
2008 FTIR sales: $600-800 million (slow growth since 1985)
• largest segment in dollar value is microscopes with dispersive
spectrometers
• portable systems dominate in terms of number of systems (> 2000
since 2006)
• 10-15% annual growth for all but FT-Raman, much higher for portable
• 785 nm most popular laser
• still looking for “killer”
application, although fairly wide use in QC, pharma, polymers, drug and hazmat ID, forensics
A final, and persistent question:
Why don’t we do dispersive Raman with a 1064 nm laser, to obtain the same fluorescence reduction as in FT-Raman?
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Silicon detectors (i.e. CCDs) are not sensitive to light beyond ~1100 nm, where nearly all of the Raman scattering exists from 1064 nm lasers
Detector Spectral Response Curves
.5 1 1.5 2.0 2.5.3
CCD(dispersiveRaman)
Wavelength (μm)
Ge (FT-Raman)
InGaAs I
InGaAs II
(slide from Keith Carron)
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SN 5
SN 13
SN 60
SN 300500 1000 1500 2000 500 1000 1500 2000
250 mW 1s
250 mW 30s
40 mW 1s
40 mW 30s
Captain Morgan Rum
Combine a 1064 nm laserwith a dispersive spectrographand specialized InGaAs
arraydetector (DeltaNu/Intevac)
FT-Raman, 1064 nm
Dispersive Raman, 1064 nm
(slide from Keith Carron)