application of multi-band uv, visible, near infrared ... · •spectral range: 200 cm-1 to 2000...

BaySpec Proprietary & Confidential 1

PRESENTATION

Application of Multi-Band UV, Visible, Near Infrared, Raman and Hyperspectral Instruments

in Practical in-situ Analysis in Chemical, Pharmaceutical, Forensic, Biomedical, and

Environmental Fields


Company Introduction


BaySpec, Inc.

Located at the heart of the Silicon Valley

Started by optical and laser engineers; invested by Venture Capitals & Cisco, Intel, JDSU and Finisar; Privately held

11+ years in business; 48,000 sq.ft. facility at San Jose, California; 100% Operations in the U.S.A.


Made in the USA 48,000 sq. ft. (4,800 sq. m)

Class 100 Grating Lab

Electronics and Optical prototyping labs

Distributed ITU Laser Bank

Automated Performance Test Equipment

Hermetic Sealing Atmospheric Enclosure, 100% leak detection

Environmental and mechanical reliability testing stations

OEM private labeling and drop shipping to freight forwarders/CMs

Fully Integrated Shop-to-Dock


Evolving Spectroscopic

Instrumentation


Definition of “Spectral Engines”-Traditional

• Light Sources and photon/light inputs and beam manipulations;

• Wavelength (color) separation component(s)-(some kinds of) gratings or some kinds of filters;

• Photo Detectors;

• Data Processing units.

It has NOT changed essentially since Newton’s Time.


Miniaturized (OSA) Development

Multi-disciplinary Technology Advancement make the miniaturization of spectral sensors possible today

– Mini Lasers & Compact Broadband Light Sources

– Holographic Optical Elements

– Low Cost, Sensitive Solid State Optoelectronics

– Cheaper, Faster Computer Chips

+ + +

Enabling real-time monitoring of optical networks


• Highly efficient, as high as 99% efficiency • Transmission mode

– compact light path for smaller foot print instrumentation

• Ruggedized, no affected by shock or vibration – High stability with little maintenance

• Ideal for spectroscopy instrumentation with long term stability and compact size

~5mm

BaySpec Technology - Volume Phase Gratings (VPG®)

Classical

grating VPG grating


VPG

USB to

Host Sensor Array

Control Electronics DSP Memory

Lens

Lens Fiber

Miniature Spectral Engine with InGaAs Arrays-Optical Design

Major Design Considerations • No moving parts; Designed to produce in volume • Environmentally insensitive; Athermal design; 0-50 deg °C operations • Fiber input with SMA or Slit • 3 wavelength regions with InGaAs detector arrays: A) 900-1700 nm; B) 1100-2200 nm; C) 1250-2500nm • Transmission Volume Phase Grating (VPG®) • F# 2 Optics; To Match Multimode Fiber

~ 5-15mm


Modules to Systems

10

• Vertical Integration

• Customized solutions

• Best performance/price


BaySpec Product & Features


Overall Trend in Spectroscopy Instrumentation

• Digital:

• Faster:

progress in microprocessors greatly enhances device control and

computation & signal processing capabilities

• Smaller:

solid state detectors/lasers with much smaller in size

• Multiplexing:

Array detectors with more pixels; 2D array detectors

hyper-spectral imager

• Automation/simplicity

• Lower cost


Miniaturization – the Ultimate Goal

To make spectral instruments pervasively available

Towards Optical “Tricorder”

“TriCorder” is a Registered Trade Mark of CBS Studio “Xantus-mini” is now a Registered Trade Mark of Rigaku Raman Technology Inc.

A mini-1064 nm Raman spectrometer of RRT- Rigaku Raman Technologies, Inc.


The World’s Very First Handheld Dispersive mini-1064 and 532 (785 nm) Raman Analyzer – Xantus-mini

•1064nm or 785 nm or 532 nm excitation with a fiber laser-up (three power level: low, median, high)

•Miniature integrated F#2 spectrograph •Wavelength range: 200 cm-1 to 2000 cm-1 •Resolution: 15-17cm-1 •TE cooled CCD (532nm and 785nm) or InGaAs

(1064nm) •Size= 61 mm × 176mm × 82 mm •Power consumption <=10 W •Less than 2.5 lbs •Raman Library built in •4 hours battery life •One button operation •Wireless control through mobile devices •Very first on the Earth to the best of our knowledge

From Rigaku’s brochure, “Xantus-2” is now a Registered Trade Mark of Rigaku Raman Technology Inc.

Xantus-mini Xantus is a

Trademark of Rigaku Raman Technologies


Raman Spectrometers and Microscope

VPG® Grating Based Spectroscopy Products

Telecom

Products


Raman Spectroscopy

• Observed by C.V. Raman in 1928

• Sunlight passed through a monochromatic filter

• Observed light scattered from glycine solution was shifted to longer wavelength


Vibrational levels

Electronic levels

Raman Spectroscopy

Laser illumination generates a virtual state. Rayleigh

and Raman scattered light is then observed.

Rayleigh

Stokes

Raman

Virtual State

Anti-Stokes

Raman


Raman Spectroscopy

Sample

Laser

Detection

• Spectra are made up of frequencies corresponding to normal molecular vibrations

• Frequency expressed in wavenumbers (n, cm-1)

• Measured as a shift from laser line (0 - 4000 cm-1)


Features for Raman Technique

Raman – with the most desirable feature as analytical tool

• High specificity

• High accuracy

• Direct measurement ideally with little sample preparation, non-destructive and non-contact

• Non destructive with little sample preparation

• finger region, unique for each molecule

• Coupled with microscope for identifying trace forensic evidence in micro scale with chemical specificity

• Application limited due to fluorescence interferences


BaySpec Dispersive Raman Spectrometer

Laser

Sample

Rayleigh

Line Filter

Grating (VPG)

Counts

1600140012001000

Raman Shift cm-1

Form 1 Form 2 Form 3

Polymorphs

Spectrometer

Detector

Dispersive Raman Optical Diagram


Features of VPG® Based Dispersive Raman

• No interferometric type of mechanical moving parts – An alternative for FT-Raman

• High precision and accuracy

• Fast Acquisition: msec

• Compact: suitable for field use

• High sensitivity and high resolution – Full spectral range 200-3200cm-1

– Spectral resolution of 4 cm-1

• 1064nm Raman microscope for Imaging

• Fiber-optic probe for on-line monitoring with real time feedback


BaySpec 1064 Spectrometer Family


Various Models of 1064 nm Raman

Nomadic with 3 lasers

(532, 785, 1064)

MovingLab

Multiple Grating HR1064

RamSpec 1064

Transportable Agility

single/dual Bands


Excited Electronic State (S1)

Fluorescence

Stokes

Raman

Virtual State

Inte

nsity

(Co

unts

)

200015001000500

Raman Shift (cm-1

)

1064nm 785nm

(S0)

785 n

m

1064n

m

Ground State

Raman

Why 1064 Raman? - Reduce Fluorescence

785nm laser – generates fluorescence that obscures Raman signal

1064nm laser – Raman signal without fluorescence interference


FT-Raman vs. 1064 Dispersive Raman

FT-Raman:

- Slow (hrs)

- expensive

- Bulky

1064 Dispersive Raman:

- Fast acquisition (sec)

- portable


Basic Components for 1064nm Raman

• High power 1064nm Laser, typically 500mW

• Highly efficient VPG grating (99%)

– Multiple grating to achieve high resolution

• Fast optics f/2 spectrograph

• Deep cooled InGaAs detector for high sensitivity

Compact 1064 Dispersive Raman suitable for field use


200015001000500

Raman Shift (cm-1

)

532 nm 785 nm 1064 nm

Rhodamine-dyed polypropylene

How effective with 1064-nm’s fluorescence suppression?

Little or no fluorescence with 1064 Raman from highly

fluorescent Rhoadamine Slide.


How fast?

Benzonitrile

msec sampling time


High Resolution RamSpecTM-1064

• BaySpec RamSpecTM –high resolution 1064 system – Highest 1064 Raman spectral quality yet portable;

– 200 to 3200 cm-1 range;

– 4 cm-1 resolution;

– Deep-cooled InGaAs detectors;

– Custom configuration and optimization available.


BaySpec Multi-wavelength Raman Spectrometers Family


BaySpec Raman Spectrometer with multiple laser excitation

• Raman Spectrometers

– Agility Raman Spectrometer

Single grating with no moving part

Single band or dual band option (532, 785, 1064)

– RamSpec bench top Spectrometers

single, dual, three laser systems with multiple gratings for high resolution

deep cooled detectors for high sensitivity

– Raman Microscopes

single, dual, and three laser system; and high resolution options


Multiband Raman Each laser has its own spectrograph

Highly reproducible, and reliable when switching

lasers without changing the light path


Agility™ with Dual Wavelength (532/1064, 785/1064)

•Integrated laser, f/2 spectrograph, TE-cooled detector, and touchscreen computer

•Quick-change sampling inserts for solids, liquids, or fiber probe connection

•Multiple wavelength options:

•532 nm up to 50 mW •785 nm or 1064 nm up to 499 mW

•Dual band capability: •532 nm and 1064 nm •785 nm and 1064 nm

•Wavelength range: 150 cm-1 up to 3000 cm-1 •Resolution: 10-12 cm-1 (532nm), 7-10 cm-1 (785nm)

and 15-18 cm-1 (1064nm)


MovingLabTM Dual-band (785/1064 nm, 532/1064 nm)

•Laser excitation: 532, 785, 1064 nm •Miniature integrated F/2 spectrograph •Spectral range: 200 cm-1 to 2000 cm-1 •Resolution: 7-10 cm-1 (785nm), 12-15

cm-1 (1064nm)

•TE cooled of CCD (785nm) and InGaAs (1064nm)

•Integrated optical microscope and Raman in one compact unit

•Embedded computer


BaySpec’s NomadicTM Raman microscope

– Three laser excitations (532, 785 and 1064 nm);

– 100 to 3200 cm-1 range;

– 2 cm-1 HR for 532/785, 4cm-1 for 1064

– Raman chemical mapping (up to 100 X 100 mm area with 0.5 µm resolution);

– Deep-cooled CCD and InGaAs detectors;

– Various imaging capability available (fluorescence, dark-field, polarizing, etc.)

– Custom configuration and optimization available.

NomadicTM Raman microscope

Multi-wavelength Excitation Raman Microscope


Nomadic High Resolution & Large Frame Nomadic

Nomadic HR - High Spectral

Resolution with Multiple Gratings

Nomadic LF – Large Frame

for wafer analysis


Optical Diagram of Nomadic Raman Microscope

Sample

Trinocular

Excitation

Raman

BF Camera

0

2000

4000

6000

8000

10000

12000

1 2 3 4 5 6 7 8 9 10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

TIME, CHANNELS

PH

OT

ON

CO

UN

TS

0

2000

4000

6000

8000

10000

12000

1 2 3 4 5 6 7 8 9 10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

TIME, CHANNELS

PH

OT

ON

CO

UN

TS

Laser

Grating

(VPG)


Noticeable Trend in Analytical Instrumentation

• Hyphenation - Noticeably, more instruments appear on the market as result of combination of two or several analytical methods in one device; more complex, more function.

• Examples: – AFM-Raman

– NIR-Raman

– Mass-GC/LC


Accessories– fiber probe and heating/cooling stage


NomadicTM with Fiber Port Option

Side panel of the Nomadic Raman

microscope with optional fiber ports


Connection Diagram (using liquid vial holder as an example)

Fiber-port

objective

Excitation

Laser

Nomadic Raman

Spectrometers for

detecting Raman

signal

Data to PC

(Spec2020

software)

Nomadic panel with fiber ports

Vial holder

for Raman

probe

Laser excitation

Raman signal

Sample


Fiber-port Objective and Raman Probe

Fiber-port Objective

Raman Probe

Fiber-port on Microscope

Or

cyclohexane


Near Infrared Spectrometers

VPG® Grating Based Spectroscopy Products

Telecom

Products


BaySpec Spectroscopy Products

• Components for Building your own Spectrometer – Transmittance gratins in house

– Spectrographs (for array detectors) • Single grating with no moving part

• Multiple gratings for high resolution

– Detectors

TE cooled CCD camera for UV VIS range of 200-1100nm

TE Cooled InGaAs camera for NIR,

(900-1700nm, 1100-2200nm and 1250-2500nm)

– Spectrometers UV VIS Spectrometers with CCD detectors

NIR spectrometers with InGaAs detectors


Product Portfolio -Deep-Cooled Detectors

52

Deep-Cooled Detector/Cameras • 4-stage TEC with vacuum sealing

• 2 models

-InGaAs, 900-2500nm

-Silicon CCD, 200-1100nm

Suggested use with: • NIR spectrographs

• Raman spectrographs

• Custom Spectral Imaging Systems


• Keys to Success:

- Fast and Accurate follow up from incoming lead

- Superior specifications and pricing

NIR Spectrometer

• 900-1700nm, 1100-2200nm,

1250-2500nm or custom

• High Throughput f/2 with VPG

Grating

UV-VIS-NIR Spectrometers


Build Your Spectroscopy Solution

Light Sources

•Laser

Narrow band

532 nm

785 nm

1064 nm

• white light

UVVISNIR

Wavelength Range

•UVVIS

200-1100 nm

•NIR

900-1700nm

1100-2200nm

1250-2500nm

High resolution

spectrograph Raman

•Slit Width

10, 15, 25, 50, 100,

200, etc.

•Fast optics f/2 for high

light throughput

•Multiple grating for

high resolution

Detectors

•CCD

200-1100nm

•InGaAs Arrays

900-1700nm

1100-2200nm

1250-2500nm

Many cooling options

uncooled

-25 C

-60 C

-155oC

Spectrograph


NirSpector™ Transportable VIS-NIR Analyzer

•No moving parts reliability

•Turn-key system with embedded computer

•Transportable, battery-powered system enables chemical analysis

•Continuous wavelength ranges from 400-1700 nm

•Standard software switchable active trigger probe or transmittance sampling accessory for flexible spectral collection

•Real-time spectral data acquisition with millisecond response time

•Outstanding optical throughput is achieved with VPG and f/2 design


Case Study: Amphi-Spec (NIR and Raman)

NIR Spectrometer integrated with Raman spectrometer

1) NIR Wavelength 1.3 um ( 7600 cm-1) to 2.2 um( 4500 cm-1)

2) Raman 785 nm excitation- covers 300 cm-1 to 3200 cm-1

3) Switching between NIR to Raman mode automatically


NIR/Raman Probes for simultaneous NIR and Raman measurements

Deliverables:

• Two Optical switches for multiplexing 1x4 points, one for NIR engine, one

for Raman engine

• Up to 4 Stainless steel fiber optic NIR process control probes and 4 fiber

optic Raman process control probes- custom fabrication into desired vials.

(Vials measure 20mm diameter, 2-3 inches tall so probe needs to fit inside)


In Situ Lyophylization Monitoring

Chemical information monitoring:

• Near Infrared: Moisture and others during freezing dry

• Raman: Chemical components and their forms in cake, such as API

Raman NIR


Introduction to Hyperspectral Imaging and the New OCI Product

Line

OCI-1000TM Finalist in Category of:

Detectors, Sensing, Imaging, and Cameras


BaySpec’s History in Miniaturization

Xantus-mini (“Xantus-mini” is now a Registered Trade Mark of Rigaku Raman Technology Inc. )

1980s

To make spectral instruments pervasively available

BaySpec’s VPG® grating

Raman spectrometer

OCI-2000 “Snapshot”

Hyperspectral imager

< 2014 2014

2010


Hyperspectral Imaging Realization

Spatial X

Spatial Y

Lines scan

“push-broom”

Data structure Acquisition method

Snapshot

NM. Short, Sr.,Graphic representation of

hyperspectral data, 2007, NASA


Typical Applications

Explosives Detection

Sorting

UAV/ROV

Remote

Sensing

Quality/Safety Control Precision

Agriculture

Bio-medical

Sorting


In Handheld Form – the OCITM

OCI-1000 (Push-broom) OCI-2000 (Snapshot)

Fast speed

(real-time cube Acquisition)

High spatial/spectral resolution

Slow cube acquisition

+

+

+

+

950900850800750700650

nm

Conventional

Camera

Pseudo-RGB

Spectra

Classified data


OCI Specifications

OCI-1000 OCI-C OCI-2000

Type Push-Broom HSI engine Snapshot

Wavelength Range 570-1000 nm

600-1000 nm

600-1000 nm

Image size 2048 x N (N depends on

sample length)

2048 x N (N depends on

sample length)

256 x 256 each

Bands ~100 ~100 ~32

Spectral Resolution ~5 nm ~5 nm ~10 nm

Speed Fast Match with the application Fastest (real-time)

Size 3.0 x 5.5 x 1.0 in3

(77 x 140 x 26 mm3)

Application-specific 3.0 x 5.5 x 1.0 in3

(77 x 140 x 26 mm3)

Weight 0.5 lbs (227 g) Start with 0.5 lbs (227 g) 0.8 lbs. (363 g)


OCI-U

8 cm

3 cm

USB 3.0 to

onboard computer


OCI-UAV Package

"Thin shell" monocoque

construction is lighter and much

more durable

Active gimbal maintains stable,

vertical orientation of imaging

Powerful single-board computer

controls and synchronizes OCI

imager with autopilot

High efficiency

propulsion for 5 lbs.

payload

BaySpec is working with entrepreneurs

in the UAV industry for a total packaged

UAV hyperspectral imaging solution

Autopilot and OCI imager

are secured in the cargo bay

GPS enables autopilot

and automatic flight

mission


Specs and Control

OCI-UAV hardware specs:

• Weight: 0.6 lb

• Power input: 5V

• Frame rate: up to 120 fps

Hyperspectral imaging mode:

• Pushbroom (OCI-UAV-1000) for

high resolution.

• Snapshot (OCI-UAV-2000) for

large area scan and easy

stitching.

Flight:

• Automatic flight and imaging

planner;

• Real-time flight control and

viewing of RGB imaging.

Automatic flight and hyperspectral imaging

mission planner

Hyperspectral image segmentation based on plant spectral

characteristics


Don’t Wait for Answers!

12 am Monday 9/29/2014 We are launching

PortabilityTM Mass Spec!


PortabilityTM Mass Spec

KEY FEATURES • Person portable

• 24V, 12V, and battery power options

• Linear Ion Trap (LIT) Technology

• Sample analysis in 1 to 10 seconds

• Detection of positive and negative ions

• Compatible with ambient desorption and ionization methods (ADI-MS)

• Atmospheric pressure sampling

• Autonomous data analysis, and direct result reporting

• No need to re-optimize instrument for sequential detection

• Parts-per-billion (ppb) detection levels

• MS/MS (MSn mode)


Direct Measurement at ppb-level


Wish We Could Say More!

See it at Booth 28


Real-world Sample

Measurements with Multi-Wavelength Raman

72

http://images.google.com/imgres?imgurl=http://www.cnn.com/TECH/science/9806/12/yoto/monitor.jpg&imgrefurl=http://www.cnn.com/TECH/science/9806/12/yoto/&h=237&w=275&sz=19&tbnid=JxONtJMsxLsJ:&tbnh=93&tbnw=108&start=19&prev=/images?q=ocean+monitor&hl=en&lr=&rls=GGLD,GGLD:2005-08,GGLD:en


Energy


Grow

Extract

Analyze

In situ Raman Measurement in Fuels

• Dispersive Raman is not traditional methods in liquid fuel analysis due to fuels’ fluorescence. Example: research in biofuels (microalgae-based) was based on grow-

extract-analyze low-efficiency wet chemistry process.


Gasoline

Inte

nsity (

A.U

.)

140012001000800600

Raman Shift (cm-1

)

#87 #89 #91

Octane ratings can be readily read

from AgilityTM -1064 Transportable

Raman Spectrometer, in a few

second.


% Methanol in Gasoline

Methanol percentage in blended gasoline, based on the ratio of

their characteristic spectra peaks of 1030 cm–1 and 1465 cm–1,

can be simply measured down to 0.1%.


Engine Oil Quality

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

200 700 1200 1700 2200 2700 3200

Co

un

t

Raman Shift (cm-1)

Engine Oil

Engine Oil Spent

Plastic Bag

New and spent engine oil

in plastic bag.


Lubricant samples

For all three samples, fluorescence induced by 532 and 785 nm laser overwhelms Raman peaks and saturates detector. Only 1064 nm Raman works.

2500200015001000500

Raman Shift (cm-1

)

Process Lubricant (PL)

532 nm 785 nm 1064 nm

180017001600150014001300120011001000900800700600500400

100% 18.0% 10.2% 6.58% 0

719 1443 100

80

60

40

20

0

% G

rea

se

in

PL

1.00.80.60.40.2Int. 719 / Int. 1443

Curve Fit ResultsFit Type: least squares fitFunction: lineCoefficient values ± one standard deviation

a =-6.1231 ± 1.11b =89.34 ± 2.01

R2 = 0.9985

% grease in lubricant


Instant oil characteristics by Raman spectroscopy

Chain length

Unsaturation

Melting Temp.

Wu, et. al., PNAS, 108:3809, 2011


Microalgae Biofuel Application

Only 1064 nm Raman is good for microalgae monitoring and research.

0 500 1000 1500 2000 2500

Raman Shift (cm-1)

Normal

10-day Starvation

20-day Starvation

Carotenoids Bands

Oil band


Instant Lignocellulosic Biomass Characterization

14x103

12

10

8

6

4

2

0

Cou

nts

200015001000500

Raman Shift cm-1

Red Oak Treated 25mW, 400ms, 30 avg yROC_300mW, 5s, 1 avg

Lignin

Cellulose

Cellulose Lignin


Biofuel Samples on Market In

ten

sity (

A.U

.)

2500200015001000500

Raman Shift (cm-1

)

Diesel Biodiesel B20 E85


Solar Cell -- Raman Mapping


Material


Raman Chemical Mapping of Carbon Nanotubes 532 nm

Raman shift (cm-1) 500 1000 1500 2000 2500 3000

500

1000

1500

2000

2500

3000

3500

Raman Shift (cm -̂1)

Mean+

Std

Dev 5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

202 cm-1

5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

260 cm-1

5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

289 cm-1

5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

860 cm-1 5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

1296 cm-1

5 10 15 20 25 30 35 40 45

5

10

15

20

25

30

35

40

45

1594 cm-1

Inte

nsity (

Counts

)

D

G

RBMs Mean ± Standard deviation

100 µm

Bright-field Image


532 Is Best for Non-fluorescence Samples (e.g., semiconducting materials)

320030002800260024002200200018001600140012001000800600400200

Raman Shift (cm-1

)

532 nm 785 nm 1064 nm

Graphene Sample

785 and 1064 nm excite

fluorescence from Si.


500 1000 1500 2000 2500 30000

0.5

1

1.5

2

2.5

3

Variable

Com

p.

1 (

0.9

7%

), C

om

p.

2 (

5.3

5%

), C

om

p.

3 (

93.2

1%

)

Variables/Loadings Plot for Multiple SPC Files

Component Image of Graphene on Si (100um/pixel)

Multi-variant analysis

BaySpec Proprietary & Confidential 92 92

Stress Characterization of Through-

silicon Via Structures

532nm Raman


Inte

nsity

2500200015001000500

Raman Shift cm-1

785 nm Excitation Calcite Ulexite Kaolinite Alunite

Inte

nsity

350030002500200015001000500

Raman Shift cm-1


Inte

nsity

200015001000500

Raman Shift cm-1


Mineral Samples


Inte

nsity (

a.u

.)

30002500200015001000500

Raman Shift (cm-1

)

Benzene

Polarizer parallel Polarizer perpendicular

Raman with Polarizer

Example of cyclohexane’s 532

Raman spectra with different

polarization Polarizer in

Raman emission

path


Bio & Biomedical


Raman for Biomedical

• Fingerprinting a molecule

• Non-destructive and painless

• Potentially non-invasive

• Detection (health condition)

• Prevention (early diagnosis)

• Monitoring

• Diagnosis (under investigation)

• 1970: Lord and Yu record 1st protein spectrum from lysozyme using HeNe excitation

• 90s: fast dispersive Raman


Tooth, 1064nm HR fiber

1064nm can penetrate further than785nm

Application: dental implant monitoring


Inte

nsity (

Cou

nts

)

30002500200015001000500

Raman Shift (cm-1

)

Checkin Skin Pork Skin

Skin

Application: Abnormal skin cell diagnosis


Kidney Tissue

30002500200015001000500

Raman Shift (cm-1

)

40x103

30

20

10

Inte

nsi

ty (

Co

un

ts)

1064nm

785nm

Fluorescence from the pigment in kidney tissue is highly reduced with 1064nm excitation laser

Application: In situ tumor cell diagnosis during surgery


Bones

Inte

nsity (

Co

un

ts)

30002500200015001000500

Raman Shift (cm-1

)

Regular Bone, 1064nm, 400mW, 30s Demineralized, 1064nm, 400mW, 30s

Application: bone health detection


Blood Samples

Application: protein related illness diagnosis


6000

5000

4000

3000

2000

1000

Inte

nsity (

Co

un

ts)

30002500200015001000500

Raman Shift (cm-1

)

Urine 1064nm300mw 45s

Human Urine

Application: health condition monitoring


Human skin - NIR

600 800 1000 1200 1400 1600-2.5

-2

-1.5

-1

-0.5

0

0.5

1

1.5

Wavelength (nm)

Absorp

tion c

oeff

icie

nt


Single Cell Imaging - Lipids

20 µm


Food & Beverage


Oxidized Red Wine (Through Bottle)

30000

25000

20000

15000

10000

5000

0

Inte

nsity (

Cou

nts

)

30002500200015001000500

Raman Shift (cm-1

)

1064nm 785nm

30000

25000

20000

15000

10000

5000

0

Inte

nsity (

Co

un

ts)

30002500200015001000500

Raman Shift (cm-1

)

1064nm 785nm


30000

25000

20000

15000

10000

5000

0

Inte

nsity (

Co

un

ts)

30002500200015001000500

Raman Shift (cm-1

)

1064nm 785nm

Dark Rum (Tattoo®)

60x103

50

40

30

20

10

0

Inte

nsity (

co

un

ts)

2500200015001000500

Raman Shift (cm-1)

0.5 s

acq. time

5 s

acq. time


Agility 1064nm – Distinguishing Olive Oil from Other Cooking Oils

Arb

itra

ry Inte

nsity

18001600140012001000800

Raman Shift cm-1

Extra Virgin Oilve Oil Sample #1 Corn Oil Sample #173 Soybean Oil Sample #178 Tea Oil Sample #190 Sesame Oil Sampl e#180


Corn Flour

35x103

30

25

20

15

10

5

0

Inte

nsity (

a.u

.)

18001600140012001000800600400200

Raman Shift (cm-1

)

785nm 1064nm


Forensic & Art


Forensic

• Major targets: – Drug & Toxic chemical

– Explosive & firearms discharge residue

– Body fluid

– Trace evidence

• Analytical methods: – Wet chemistry

– Microscopy

– Chromatography

– Spectroscopy

– DNA Analysis


Why Raman?

• Non-destructive

• Inorganic and organic identification

• Virtually no sample preparation

• Small particle size collection - 1m

• Fast

• Sample through glass and plastic

• Complementary to FT-IR - sharp spectral features


Forensic - Yaba Pills (Street Drugs)

18001600140012001000800600

Raman Shift (cm-1

)

50x103

40

30

20

Inte

nsity (

Cou

nts

)

1064nm

785nm


OCI – Narcotic Identification


Forensic and Homeland Security - Explosive Identification

Composition B, mixture of RDX and TNT

15

10

5

x1

03

2200200018001600140012001000800600

Raman Shift (cm-1)

15

10

5

0

x1

03

1064 nm 785 nm

Fluorescence caused by 785 nm excitation overwhelms Raman spectrum, only 1064 nm Raman can deliver a high SNR, background-free Raman spectrum.

All spectra shown are unprocessed.


17001600150014001300120011001000900800700600500400

Raman Shift (cm-1

)

Tree pollen Flower

pollen

Forensic – Trace - Pollen


Forensic – Trace – Lipstick on Glass In

ten

sity (

A.U

.)

18001600140012001000800600400200

Raman Shift (cm-1

)

1064nm 785nm

Revlon: Cherry Blossom


Raman Imaging of Ball-pen Ink

18001600140012001000800600400

Raman Shift (cm-1

)

No ink Ink


Raman Imaging of Contamination

• Mapping image is based on the spectral intensity of selected region where contains unique features from contamination

Inte

nsity (

Co

un

ts)

30002500200015001000500

Raman Shift (cm-1

)

785nm 10X 30mw 5s

Matrix On white spec


Art and Archeology

– Dyes and Pigments – Jewelry and precious stones – Artifacts – Organic materials and their degradations – others

Aged Rare

Valuable


Once Upon a Time -

.

Pink-headed duck once lived in India and Myanmar


Carotenoid Raman Bands


Significance

• Methodology Pigment information was collected from an extinct bird without sample destruction

• Museum studies: pigments are well-preserved in museum, including the 60 year old feathers from a pink-headed duck

• Zoo archaeology/Evolutionary: biology Pink-headed duck was a very unusual bird – one of only two ducks to known to display carotenoid feather pigments

• Interface between art and science: Study design was guided by the unusual colors in a 1907 painting, which

• Ultimately identify an unusual pigment in an extinct animal


Feather in fluorescent Amber

D.B. Thomas, et al, Scientific Report, 2014, 4, 5226


40x103

30

20

10

0

Inte

nsity (

Co

un

ts)

18001600140012001000800600400

Raman Shift (cm-1

)

009 123 375 503 515 620 651

30x103

25

20

15

10

5

0

Inte

nsi

ty (

Co

un

ts)

1600140012001000800600400

Raman Shift (cm-1

)

009 123 375 503 515 620 651

009

123

375

503

515

620

651

785 nm

1064 nm

Oil Painting Samples


Cross section Raman analysis

Inte

nsity

(A

.U.)

18001600140012001000800600400

Raman Shift (cm-1

)

Inte

nsity

(A

.U.)

18001600140012001000800600400

Raman Shift (cm-1

)

Inte

nsity

(A

.U.)

18001600140012001000800600400

Raman Shift (cm-1

)


Pigment or Dyes

Inte

nsity (

A.U

.)

12001000800600400200

Raman Shift (cm-1

)

Inte

nsity (

A.U

.)

18001600140012001000800600400

Raman Shift (cm-1

)

Barite Red Ochre


Raman Spectra of Emerald and Green Glass

Arb

itra

ry I

nte

nsity

200015001000500

Raman Shift cm-1

1064 nm Excitation Emerald Green Glass

Arb

itra

ry Inte

nsity

200015001000500

Raman Shift cm-1


Arb

itra

ry I

nte

nsity

200015001000500

Raman Shift cm-1


Fluorescence overwhelms Emerald Raman

spectrum with 532, 785 Raman

Emerald shows a distinct Raman spectra with

1064 Raman, notably different then a green

glass imitation.

1064 Raman

532 Raman 785 Raman


OCI – Document Examination

http://www.bayspec.com/videos/oci-1000-qde/








Pharmaceutical


Raman for Pharmaceutical

• Raman advantages for pharmaceutical application

– Specific spectral fingerprints

– In-situ, non contact, non destructive

– No or limited sample preparation

– Amorphous and crystalline phases information

– Fast data acquisition

• Major pharmaceutical applications

– R&D, Quality control and assurance

• Polymorph identification

• API and excipient analysis and mapping

• Quantification

• Raw material identification

• Process monitoring


Polymorphs

Polymorphs

Chemical reactivity

Solubility

Stability

Dissolution rate

Excipient compatibility

Bioavailability


Zantac 1064nm advantage


Ranatadine HCl Polymorphs


API and Coating Identifications


Component Analysis - Excedrin

80x103

60

40

20

0

Inte

nsity (

a.u

.)

18001600140012001000800600400

Raman Shift (cm-1

)

Acetaminophen Aspirin Caffeine

Acetaminophen (250mg), Aspirin (250mg) and Caffeine (65mg) as its APIs


Excedrin – Raman Imaging

970 x 700 µm (97*70 pixels)


API-Estradiol

Inte

nsity (

a.u

.)

30002500200015001000500

Raman Shift (cn-1

)

Estradiol, 532nm, 30mw, 5s

Automatic micro-

plate Raman reader


Raw Material Identification

• Important for QC/QA

• Traditional analytical method: – pH meters

– Balances

– GC

– HPLC

– Infrared spectrometer

– UV spectrometer

– Karl Fischer moisture titration

– Wet chemistry

– …………..

• Raman – Library search

– Quantification with models

Advantages

• Speed (1-10 s)

• Ease of use

• Low cost

• No waste

Method Developer Operator


Raw Material Identification


Quantitation of Pharmaceutical Incoming Material - Glycerin

147

y = 0.0001x - 0.0065

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00%

0 2000 4000 6000 8000 10000 12000

Co

ncen

trati

on

Gly

ceri

ne

Raman Peak Height

Raman Intensity vs. Concentration

400 600 800 1000 1200 1400

Arb

itra

ry I

nte

nsit

y

Raman Shift cm-1

Raman Spectra Glycerin

6.25%

12.50%

25%

50%

100%


Compliance

• ASTM international standards – E131-05 Standard Terminology Relating to Molecular Spectroscopy

– E1840-96(2007) Standard Guide for Raman Shift Standards for Spectrometer Calibration

– E2529-06 Standard Guide for Testing the Resolution of a Raman Spectrometer

• United State Pharmacopeia USP – Chapter <1120> Raman Spectroscope

– Chapter <851> Spectrophotometry and light-scattering

– Chapter <197> Identification Testing with Spectroscopy Systems

– Chapter <1225> Validation of Compendial Procedures

– Chapter <1158> Analytical Instrument Qualification

• European Pharmacopeia EP – 2.2.48 Raman Spectrometry


Polymer


Mapping of Polystyrene Beads (15um)

10 um

Sample:

Drop of Polystyrene beads

15 um in water suspension

on Silicon wafer, dried in air

Instrument set up:

Laser: 532 nm, ~ 50mW

Emission: 1001.4 cm-1

Motorized stage:

step size: 0.5um


Injection HDPE&PP

12x103

10

8

6

4

2

0

Inte

nsity (

Co

un

ts)

200015001000500

Raman Shift (cm-1

)

Blue sample red sample

HDPE PP


PC and PS

30x103

25

20

15

10

5

0

Inte

nsity (

Co

un

ts)

200015001000500

Raman Shift (cm-1

)

Safety glass light blue transparent sample white half ball

PC PS PS


Polymer classification - NIR


PVC film measurement, 532 nm

30002500200015001000500

Raman Shift (cm-1

)

Green

Transparent

PVC wrap


1200 1400 1600 1800

PVC film depth profiling, 1 µm per scan

500 1000 1500 2000 2500 3000

Raman Shift (cm-1)

15 µm

14 µm

13 µm

12 µm

11 µm

10 µm

9 µm

8 µm

7 µm

6 µm

5 µm

4 µm

3 µm

2 µm

1 µm

0 µm

-1 µm

-2 µm

-3 µm

-4 µm

-5 µm

-6 µm

-7 µm

-8 µm

-9 µm

-10 µm

-11 µm

-12 µm

-13 µm

-14 µm

-15 µm

PVC


Process & Reaction


Raman Monitoring

• Non-contact measurement – avoiding contamination

• No sample preparation – on-line monitoring

• No interference from water

• Specific fingerprint information

• Optical fiber – remote analysis

• Multiple fiber probe

• Fast measurement

• No consumables


Process Control

158

Exemplary picture

InGaAs detector inside

Fiber Optics up to 400 m !

Optical

switch


Polymorph Transformation

• Why mannitol? – Common excipient

– Three anhydrate polymorphs


• β polymorph to δ form transformation – Heating to 170 °C then natural cooling

– Raman spectra acquisition every 3 mins

– 1064nm Raman with Fiber probe

– In situ measurement

Mannitol Polymorph transformation

20x103

15

10

5

Inte

nsity (

a.u

.)

118011601140112011001080106010401020

Raman Shift (cm-1

)

0 min 8 min 16 min 24 min 32 min 36 min 5000

4000

3000

2000

Ram

an

In

ten

sity (

a.u

.) a

t 1

03

8 c

m-1

35302520151050

Time (min)

3500

3000

2500

2000

Ra

ma

n In

ten

sity

(a.u

.) at 1

05

4 c

m-1

Beta Delta


Raman Imaging

• Two polymorphs – β- form

– α- form

• 1064nm Raman Microscope – 10X objective

– 800 x 700 µm (80*70 pixels)

Heating and cooling plate for microscope


Accessories for Process Monitoring

(A) Fiber optical probe for

bioreactor monitoring. Standard

PG 13.5 connector and simple

maintenance.

(B) High temperature fiber probe

for process monitoring. Pressure

sleeve specified to 3000 psi and

up to 600°C.

(C) Optional IP66 NEMA

enclosure provides instrument

protection in outdoor and

industrial environments.

(D) Reaction monitoring set-up

with BaySpec’s RamSpec

Benchtop Raman spectrometer

and high temperature probe


Epoxy Hardening

600 800 1000 1200 1400 1600

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

2500 2550 2600 2650 2700 2750 2800 2850 2900 2950 3000

0

2000

4000

6000

8000

10000

12000

14000

1 2 3 4 5 6 7 8 9 10500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Time (min)

Inte

nsity (

Counts

)

Raman Signal at 2579 cm-1)


Contact

Sales Managers:

•Lynn Chandler, Ph.D.

[email protected]

•Eric Bergles

[email protected]

Application Scientists: •Owen Wu, Ph.D.

[email protected]

•Jack Qian, Ph.D.

[email protected]

BaySpec, Inc. 1101 McKay Drive San Jose, CA 95131

www.bayspec.com Booth #28

application of multi-band uv, visible, near infrared ... · •spectral range: 200 cm-1 to 2000...

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