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Mass Spectrometry – a Powerful Tool for Metabolomics Sandy Nargund Manager, MS & Chromato Shimadzu [Asia-Pacific] Pte Ltd

Mass Spectrometry – a Powerful Tool for Metabolomics Sandy Nargund Manager, MS & Chromato Shimadzu [Asia-Pacific] Pte Ltd

Mass Spectrometry – A Powerful tool for metabolomics Sandy Nargund Manager, MS & Chromato Shimadzu [Asia-Pacific] Pte Ltd

1 2 Biomarkers Identification and Validation

3 Mass Spectrometry –For Metabolomics

GCMS-QP2010 Ultra GCMS-TQ 8040 LCMS-8060

Nexera UC- Online SFE/SFC

iDPlus-Performance Bacterial Identification

MALDI -7090 High Resolution TOF iMScope-Trio –Mass imaging 4

t Triple Quadrupole MS/MS

Product ion scan

t MRM- Multi Reaction Monitoring

SIM (single analysis) MRM (MS/MS analysis)

50000 10 ppb 7500 10 ppb 40000 5000 30000 20000 2500 10000 0 0 1.0 1.5 2.0 2.5 min 1.0 1.5 2.0 2.5 min Eliminates background for High sensitivity but high trace-level quantitation with background high S/N GCMS- Gold Standard for Metabolomics

7 Metabolomics Research Using GC-MS/MS

Metabolomics Research

Discovery phase Validation phase

Scan measurement MRM measurement MRM measurement (GC-MS/MS) (non-targeted analysis) (wide target analysis) (target analysis)

Detect marker candidates Quantitate marker candidates and identify compounds with higher accuracy Accurate quantitation GC/MS Metabolite Database

Ready to use method for quick start your Research

1. Method files Registered Measurement Number Derivatives 2. Library (scan) Compounds Mode Registered Organic acids, fatty Scan 428 3. Smart MRM database acids, amino acids, TMS , etc. MRM 193 (automatic method creation tool) Scan 50 4. Instruction manuals Fatty acids Methylation MRM 50

Amino acids EZ:faastTM Scan 33 Easy Work Flow

AART function for Automatic Adjustment of Retention Indices with just one injection

Select components for measurement from the database.

Smart MRM database Method is created Automatically

Start acquisition. GCMS-TQ8040

1. Smart Productivity  Analysis of 400 pesticides that used to require 2 or 3 methods, can now be accomplished in a single acquisition Three Smart functions improve analytical method by the new firmware protocol. productivity in your laboratory. 2. Smart Operation  Smart MRM technology creates optimal MRM methods automatically. The “MRM Optimization Tool“ automates best MRM transitions for new compounds. 3. Smart Performance  ASSP achieves high sensitivity at scan speeds of 20,000 u/second. Fastest MRM 800trans/sec. Single GC/MS mode with the maximum possible sensitivity and repeatability.

Confidential 11 Advantages of GCMSMS

Comparison of Reproducibility for Measuring Metabolites in Human Blood Serum Using MRM and Scan Modes 3-Hydroxyisovaleric acid-2TMS (100,000) (1,000) 7.5 131.10>73.00 247.00 247.10>73.00 205.00 2.0 5.0 %RSD (n=6) 2.5 1.0 Compound name MRM Scan 3-Hydroxyisovaleric acid-2TMS 3.99 14.0 15.0 15.5 16.0 15.0 15.5 16.0 -3TMS 5.04 23.4 Kynurenine-3TMS -3TMS 5.98 N/A (10,000) (100) 4.0 307.10>218.10 7.5 424.10 Kynurenine-3TMS 6.48 24.5 307.10>192.10 307.10 3.0 5.0 2.0 2.5 1.0 0.0 43.5 44.0 43.5 44.0 44.5 MRM is able to eliminate the effects of interfering substances so that it can measure trace components accurately. 193 types of trimethylsilylated metabolites 50 types of fatty acid methyl esters (compatible with EI/PCI ionization) Advantage of GCMSMS

Scan (Non-targeted) Discovery

Scan/MRM data

(x100,000,000) 2.25

2.00

1.75

1.50

1.25

1.00 0.75 MRM (Targeted) 0.50 0.25 Validation

12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 37.5 40.0 42.5

Measurement of Scan/MRM mode Ex. TCA Cycle (SmartMRM) Scan section: Comprehensive search of metabolites MRM section: Accurate quantitation of target compounds Metabolites in urine using Scan/MRM

Glutaric acid-2TMS (MRM) -3TMS

Adipic acid-2TMS (MRM)

17.5 20.0 22.5 25.0 27.5 30.0 32.5

147 Measurement spectrum 233.00 Malic Acid-3TMS Scan 189.00 Measured 133 189 101 233 307 335

100 200 300 73 library spectrum 147 Library 133 233 101 189 307 335 21.25 21.50 21.75 22.00 100 200 300 Semi-quantitation Identification Metabolomics Solutions – Measurements to Pathway Analyses

Scan

Negative Negative Positive Positive Positive ID Name Serum001 Serum002 Serum003 Serum004 Serum005 GC/MS Metabolite 1 2-Aminoethanol-2T 1927822 1574800 1017918 1904832 1850236 2 Pyruvic acid-meto-T 10448 5442.353 9897.21 7413.618 8810.286 Database Ver. 2 3 Lactic acid-2TMS 147827 104531.8 109895.2 98769.1 88488.87 4 Glycolic acid-2TMS 216069 170218.9 210625.3 144679.6 152893.4 5 Alanine-2TMS 26855 20167.9 22414 17969.86 25549.17 6 2-Keto-isovaleric ac 71265 65720.31 63684.02 59946.26 51291.02 7 Glycine-2TMS 14620 10804.38 11295.5 9904.312 9789.166 8 2-Hydroxybutyric ac 35699 27065.86 27361.46 20173.2 30344.84 MRM Identify compounds Measure by GC-MS(/MS) Output data

Enter PubChem ID

Handbook From PubChem, link to Multivariate Analyze pathway KEGG (Detect marker analysis data candidates)

Conventional Metabolomics

M. W. Large LC-MS Peptide , Coenzyme, , Lipids

Steroid, Vitamin

Terpene ,

Hydrocarbo Sugar, Amino acids, Ester Organic acids, Fatty acids Ketone

Small GC-MS Volatility Non Volatility LCMSMS – Readymade Solutions LCMSMS- Readymade Solutions

18

-cyclicmonophosphate -cyclicmonophosphate

-cyclicmonophosphate

-Aminobutyric acid -Aminobutyric acid 4 acid Adenylsuccinic Argininosuccinic acid Cholic acid Creatine acid Nicotinic Ophthalmicacid acid Orotic acid Pantothenic acid Taurocholic acid Uric 3',5' Adenosine 3',5' Cytidine 3',5' Guanosine Thymidinemonophosphate FAD FMN NAD 2 Acetylcarnitine Acetylcholine Allantoin Carnitine Carnosine Choline Citicoline Creatinine Cysteamine Dopa Dopamine Epinephrine Histamine Kynurenine Niacinamide Norepinephrine Serotonin

Organic acids , Coenzymes Others

Morpholinoethanesulfonic acid Morpholinoethanesulfonic Ketoglutaric acid -Ketoglutaric -Hydroxyproline -Glutamylcysteine - Lacticacid acid Pyruvic 2 acid Aconitic acid Malic acid Succinic 4 Alanine Asparagine acid Aspartic Asymmetric dimethylarginine Cystine Dimethylglycine Glutamicacid Glutamine Glycine Histidine Homocystine Isoleucine Leucine Lysine Methionine sulfoxide Ornitine Phenylalanine Proline Serine Symmetric dimethylarginine Threonine Tryptophan Tyrosine Valine Cystathionine Cysteine Homocysteine Methionine 5 Glutathione Oxidizedglutathione S-Adenosylhomocysteine S-Adenosylmethionine 2 Methionine sulfone

Methylation cycle Glycolysis TCA cycle Amino acids Transsulfuration pathway Standards Non-ion pairing method compounds) (97 cyclic cyclic cyclic cyclic - -

Morpholinoethanesulfonicacid - Adenosine 3',5' monophosphate Adenosine monophosphate Cytidinediphosphate Cytidinemonophosphate Cytidinetriphosphate Guanosine 3',5' monophosphate Guanosine monophosphate Thymidinediphosphate Thymidinemonophosphate Thymidinetriphosphate Uridinediphosphate Uridinemonophosphate Uridinetriphosphate NAD NADH NADP NADPH 2 Methionine sulfone

Nucleotides Coenzymes Standards

phosphate phosphate bisphosphate phosphate

phosphate phosphate phosphate phosphate phosphate phosphate

Bisphosphoglyceric acid Phosphoglyceric acid) Phosphogluconicacid Phosphoglyceric acid - - - A coenzyme Acetyl Alanine Arginine Asparagine Cysteine Glutamic acid Glutamine Glycine Histidine Lysine Methionine Phenylalanine Serine Threonine Tryptophan Tyrosine 6 4- Erythrose Ribose5- Ribulose5- Sedoheptulose7- Succinyl Glyceraldehyde 3- Dihydroxyacetone phosphate Dihydroxyacetone Fructose 1,6- Glucose1- Glucose6- Glycerol 3- acidPhosphoenolpyruvic Pyruvicacid Fructose 6- 2,3- 3 (2

Glycolysis Amino acids phosphate pathway TCA cycle ion pairing method. pairing ion compounds) method pairing Ion (55

Ion pairing method contains metabolites in in carbon the central metabolites contains Ion method pairing and amino some as compounds pathway target metabolic in compounds as target added are acids and organic acids non-

 Metabolites for major pathways in singlemethod Method Package for Primary Metabolites

Ion pairing method Non-ion pairing method (55 compounds) (97 compounds)  Glycolysis, TCA cycle (CoA), Amino acids, TCA cycle (organic acid), Target Pentose phosphate pathway, Bases, Nucleosides, Nucleotides, compounds Amino acids, Nucleotides Transsulfuration pathway, Methylation cycle LC  Usage of ion pairing reagent  Ion pairing reagent is not used conditions  Separation by ODS column  Separation by pentafluorophenylpropyl (PFPP) column Targeted  Medical researcher in  Medical researcher in pharma and Application pharmaceutical company and academia (ion pairing reagent is not academia allowed to use)  Quality assessment by quantifying amino acids, organic acids etc. 57 Standards Mix: Ion Pair Method

An aliquot of 57 STDs Mix was injected at a volume of 3 µL and separated using an ion-pairing chromatography.

60000 Tyrosine -6-phosphate Erythrose-4-phosphate TMP ADP 55000 MES (2-Morpholinoethanesulfonic -5-phosphate Ribulose-5-phosphate AMP TDP acid) Sedoheptulose-7- Pyruvate cGMP Phosphoenolpyruvate 50000 Glutamate phosphate CMP cAMP CTP Aspartate Fructose-6-phosphate NAD CDP GTP 45000 Phenylalanine Tryptophan Dihydroxyacetone- 6-Phosphogluconate UTP Glycerol-3-phosphate phosphate GDP ATP 40000 Glucose-1-phosphate UMP UDP TTP Glyceraldehyde-3- GMP 3-Phosphoglycerate NADPH 35000 phosphate /2-Phoshoglycerate 2,3-bis- 30000 NADP Phosphoglycerate Fructose-1,6-bis- Succinyl-CoA 25000 phosphate Acetyl-CoA NADH 20000

15000 Lysine Alanine Arginine Glutamine 10000 Histidine Threonine Glycine Cysteine 5000 Serine L-Methionine Asparagine sulfone 0 Methionine

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 min

Column : Mastro C18 (2.0 X 150 mm, 3 mm) Tributylamine Mobile phase: A : 15 mmol/L Acetate, 10 mmol/L Tributylamine - Water B : Methanol Injection vol. : 3 uL (100 nM 55 STD Mix) Dwell Time : 10 ms Ionization mode : ESI negative 97 Standards Mix: Non-ion pair method

(x1,000,000)

L-Methionine sulfone (IS) Opthalmic acid Adenosine (x0.5) MES (IS) Nicotinamide 1.0 ADMA Epinephrine Carnitine Standards mix at 500 nM was Pantothenate Isoleucine Methionine Leucine analyzed at a injection volume 0.9 Histamine Cytidine Dopamine of 3 µL.

Carnosine Guanosine S-Adenosylhomocysteine 0.8 (x0.5) Glutamine Uridine Phenylalanine Cystathionine Hypoxanthine Kynurenine Metabolites related to 0.7 Valine Hydroxyproline transsulfuration pathway Gamma-Glu-Cys Acetylcarnitine (x0.2) and methylation cycle were 0.6 cAMP Glycine Choline added as new targets. cGMP Asparagine Homocystine Tryptophan 0.5 Proline Cystine Arginine Acetylcholine AMPAMP 0.4 Serotonin

0.3

0.2

Cholic acid (x40) 0.1

0.0 Argininosuccinate Creatine Cysteamine cCMP

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 min

Column : Discovery HS F5-3 (2.1 X 150 mm, 3 mm) Mobile phase: A : 0.1% formic acid – Water, B : 0.1% formic acid – Acetonitrile Pentafluorophenylpropyl Injection vol. : 3 mL (1 mM 97 STD Mix) Dwell Time : 5 ms, Ionization mode : ESI/positive/negative

Shimadzu series of LCMSMS

LCMS-8050 LCMS-8060 First mass spectrometry A new vision in sensitivity. company to achieve 5msec It simply changes everything. polarity switching time and a Increased sensitivity by 90 times GLOBAL LAUNCH LCMS-8040 scan time of 30,000u/sec. compared to LCMS-8030 Increased sensitivity by a Increased sensitivity by 30 times LCMS-8030 compared to LCMS-8030 First mass spectrometry company factor of 5 compared to to achieve a scan speed of the LCMS-8030 15,000u/sec and polarity switching time of 15msec

2015 2010 2012 2013 ASMS 2015 AUGUST MAY AUGUST MAY

LCMS-8030 LCMS-8040 LCMS-8050 LCMS-8060 SAP wins the 2015 MS Company of the Year

Frost & Sullivan, which is one of the worlds leading business intelligence giants, has highlighted in its prestigious white paper on best industry practises that:

•Shimadzu has established a strong presence in the APAC mass spectrometry market leveraging on its strengths in product innovation, high value-added and quality mass spectrometers, and excellent promotional activities.

•Shimadzu is working towards increasing its production capacity, thus ensuring the stable and reliable supply of products for years to come.

•Shimadzu's outstanding cost structure will further fortify its position as a leading participant in the MS market.

•Frost & Sullivan considered 2 key factors while deciding on the Company of the Year Award: Shimadzu’s Visionary Innovation and Performance (This included criteria like Addressing Unmet Needs, Visionary Scenarios Through Mega Trends, Implementation Best Practices, Blue Ocean Strategy and Financial Performance) and Customer Impact (This included criteria like Price/Performance Value, Customer Purchase Experience, Customer Ownership Experience, Customer Service Experience and Brand Equity).

LCMS-8060: Changes Everything

Increased ion production 1. Highest Sensitivity Changes to the desolvation line capillary have increased ion production by a factor of >3 2. Ultra Fast Technologies UF Qarray Redesigned to deliver a meaningful impact on ion 3. Unsurpassed Robustness focusing capability and higher sensitivity Enhanced vacuum New vacuum designed to increase ion transmission

MRM chromatograms of rat’s kidney

• Extraction corresponds to 5 mg of kidney tissue followed by 100 times dilution • Sample amounts being measured: 3 µg of tissue 1. Quickly freezing a rat tissue by LN2

22500000 2. Weighing the frozen tissue and homogenizing 3. Adding 70% MeCN which is 10 times of sample volume

20000000 4. Collecting supernatants after centrifuging 5. Collecting supernatants by MeOH / CH3Cl

17500000 6. Filtration 7. Drying it up by SpeedVac 8. Reconstitution 15000000 9. Dilution and injection onto LCMS-8060

12500000 LCMS-8060

10000000

7500000

Column Discovery HS F5 (3.0 μm, 2.1 X 150 mm) 5000000 Inj. Vol. 3 μL MPs A: 0.1% Formic acid-Water 2500000 B: 0.1% Formic acid-Acetonitrile

0

0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 min

Metabolites Profiling in Rat Kidney 300

250 ■No Administration ■Drug A ■Drug B

200 ・ Area ratio against ITSD

150 ・ 85 compounds are detected among 97 compounds

100

50

0 NAD Uracil Proline Uridine Inosine Cystine Alanine Cytidine Arginine Guanine Thymine Histidine Tyrosine Allantoin Cytosine Citrulline Xanthine Carnitine Citicoline Citricacid Malic acid Threonine Isoleucine Creatinine Carnosine Thymidine Lactic acid Lactic Cholicacid Tryptophan Glutathione Epinephrine Pyruvic acid Pyruvic Niacinamide Asparticacid Homocystine Glutamic acid Cystathionine Phenylalanine Acetylcarnitine Dimethylglycine Pantothenic acid Pantothenic Methionine sulfone Methionine Adenylsuccinic acid Adenylsuccinic 4-Aminobutyric acid 4-Aminobutyric 2-Aminobutyric acid 2-Aminobutyric Oxidized glutathione Oxidized S-Adenosylhomocysteine Thymidine Symmetric dimethylarginine Symmetric Cytidine monophosphate 3',5'-cyclic Cytidine

Metabolite Variation by Drug

• The level of ophthalmic acid, glutathione and 5-Glu-Cys were changed by the administration of drug A

Glutamine Ophthalmic acid 5-Glutamylcysteine 35 0.25 1.4 30 1.2 0.2 25 1 20 0.15 0.8 15 0.1 0.6 10 0.4 0.05 5 0.2 0 0 0 未投与 薬剤 薬剤 未投与 薬剤 薬剤 未投与 薬剤 薬剤 NA Drug AA Drug B NA Drug AA DrugB B NA Drug AA Drug B

Glutamic acid Glutathione Oxidized glutathione 300 7 3 250 6 2.5 200 5 2 4 150 1.5 3 100 2 1 50 1 0.5 0 0 0 未投与 薬剤 薬剤 未投与 薬剤 薬剤 未投与 薬剤 薬剤 NA Drug AA Drug B NA Drug AA Drug BB NA Drug AA Drug B

Graph has shown average of area ratio (n=4)

Full Line of Shimadzu Ultra Fast Mass Spectrometers

offers High sensitivity and Enhanced selectivity High-Speed Performance LCMS-8060

GCMS-TQ8040 GCMS-QP2010 Ultra

GCMS-QP2010 SE LCMS-8050

LCMS-8040 LCMS-8030 LCMS-2020

Conventional Metabolomics

M. W. Large LC-MS Peptide , Coenzyme, Nucleotide, Lipids

Steroid, Vitamin

Terpene Nucleoside , Sugar phosphate

Hydrocarbo Sugar, Amino acids, Ester Organic acids, Fatty acids SupercriticalKetone Fluid ChromatographyAlcohol [SFC-MS]

Small GC-MS Volatility Non Volatility

Online SFE/SFC/MS system

Make up solvent pump （Pump C） SFE Unit Make up LC-20ADXR solvent Extraction vessel

CO2 pump Splitter CO2 (Pump A) Column Cylinder LC-30ADSF MS 7% Valve Valve × Injector 93% Column oven BPR-A CTO-20AC etc. (Back Pressure regulator) SFC-30A BPR-B (Back Pressure Regulator) SFC-30A Modifier pump Modifier （Pump B） solvent drain LC-20ADXR etc.

LCMS-TQ (8030/8040/8050/8080)

Advantage of SFC

1 2 3 4 GC/MS Online SFE-SFC-MS system 5 6 7

8 9 10 11 12 13 14 15 LC/MS

0 5 10 15 min

1. Diazinon 8. Aramite 2. Metalaxyl 9. Isouron 3. Tolclofos-methyl 10. Acephate - high sensitivity 4. Lenacil 11. Aminocarb - fast and high separation 5. Mepronil 12. Cyazofamid - suitable for separation of hydrophobic compounds 6. Dioxathion 13. Diquat - possible to change the polarity using modifier 7. Cypermethrin 14. Chromafenozide 15. Imidacloprid

Molecular Imaging - Target Enabling Technology Cell In vitro MS Microscope ?

Tissue/Organ AXIMA & CHIP MALDI -TOF MS Imaging

Small animals Clairvivo PET PET Mouse

Clairvivo CT CT Rat In vivo Clairvivo OPT Optical Imaging

Human LABNIRS

Brain fNIRS

Human Eminence STARGATE Whole body Clinical PET/CT

33 Imaging – Current challenges

Conventional optical microscope iMScope- MS microscope

Laser radiation on a small spot Abnormal cell?

Image obtained with Simultaneous molecular identification by MS optical microscope under microscope observation.

No information on compounds Images obtained with Identification of substances MS microscope MS spectra

34 iMScope Trio– Imaging Mass Microscope

35 iMScope – Imaging Mass Microscope

Laser Optical microscope Ion guide Sample inlet QP / Ion trap Time of flight mass spectrometer epi-illumination

Ion Sample

Sample stage Detector

Observation spot Transmission Ionization point lamp

36

t iMScope- How it works Nd:YAG Laser (355nm) Quadrupole Ion Trap Time-of-Flight Mass Analyzer Optical microscope RF Ion Guide with Reflectron

Reflected Light Illuminator Ion

Sample TMP TMP TMP

Transmitted Light Illuminator

Optical Laser Beam microscope SampleSample Optical observation InterfaceInterface Analyzing Observing Position Position Laser irradiation

Transmitted 3-Dimensional Light Illuminator Automated Stage 37 iMScope – Imaging Mass Microscope

Features

Direct MS measurement of tissue slice  visualize a local distribution of compounds High spatial resolution (5um)  observe compounds in a single cell Atmospheric pressure ionization  Suitable for living cell MSn measurement  realize structural analysis of unknown compounds

38 Powerful Software

(1) Optical Microscope Image

(3) Setting of mass analyses parameters MS Analyzing Window (4)-1 Real time mass spectrum Data Analyzing Window

(2) Assignment of analyzing spot / area (4)-2 MS Image 39 Imaging Viewer software

40 iMScope – Drug Delivery System

Targeting of drug to tumor Targeting of drug to cancer cells Controlled release of drug

DDS

15min 1hr 24hrs

Tumor

Taxol in tumor

100% Taxol-Micelle in tumor

0% 41 iMScope – Cancer Diagnostics

MSn analysis of peak m/z 616

Heme b distribution MS imaging 組織切片の光学顕微鏡イメージ with m/z 616

Comparison between normal and cancer area in human cancer tissue Inten.(x1,000,000) 2.25

2.00 616.0

1.75 MS spectrum at 1.50 m/z 616 normal area 1.25 603.9 1.00 651.4 764.3 0.75 792.4 0.50 743.9 758.4 0.25 666.0 790.4 818.2 836.3 716.4 876.6899.5 632.0 689.4 703.4 864.3 0.00 Heme b 600.0 625.0 650.0 675.0 700.0 725.0 750.0 775.0 800.0 825.0 850.0 875.0 m/z Inten.(x1,000,000) 3.5 605.4 3.0 MS spectrum at The peak m/z 616 can be identified as 2.5 Heme b based on MSn analysis 2.0 cancer area

1.5

758.4 1.0 664.0 Heme b concentration is found to be low due to ischemic conditions 621.9 786.4 0.5 689.5 633.4 665.0 806.4 714.2 734.4 841.3 892.2 813.5 834.4 874.2 0.0 at cancer area. 600.0 625.0 650.0 675.0 700.0 725.0 750.0 775.0 800.0 825.0 850.0 875.0 m/z 42 iMScope – Biological Tissue Slice Visualizing the distribution of lipid isomers Optical microscope in the mouse retina to understand the structure of the lipid layers.

200 µm m/z772.5 PC(16:0 16:0)+K m/z798.5 PC(16:0 18:1)+K 25 µm

11 µm Outside of retina

Inside of retina Superimposed

m/z806.5 PC(16:0 22:6)+H m/z872.4 PC(18:0 22:6)+K

150

100

50 intensity [a.u.] intensity

0 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 m/z 43 iMScope – Potential Applications

Medical diagnostics Drug metabolism Distribution of drug A (m/z 313) in tissue Distribution of compounds in lesion area Optical imaging MS imaging

Optical imaging MS imaging Tissue (control)

Tissue (with drug A)

Agriculture Chemical material Distribution of active ingredient in rice Distribution of compound B in rubber sheet MS imaging New rubber Optical imaging MS imaging Old rubber (Distribution of LPC)

germ

44 Summary

 Shimadzu offers wide range of analytical instruments from Research to routine analysis

 In addition to analytical platforms Shimadzu offers readymade solutions to enhance your workflows

 iMScope can be extremely useful in various fields especially in Clinical Metabolomics due to its high spatial resolution.

 Imaging is powerful tool to study the localization of compounds within the cells/Tissues

 Shimadzu is keen to collaborate for your research with its advance instrumentation to ramp up your research

45

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