Inductively-Coupled Plasma Mass Spectrometry … Plasma Mass Spectrometry (ICPMS) – The New...

11 © 2009 PerkinElmer© 2009 PerkinElmer© 2009 PerkinElmer© 2010 - 2013 PerkinElmer, Inc.

Dr. Mark ParmanSenior Product Specialist, Atomic Spectroscopy

Inductively-Coupled Plasma Mass Spectrometry (ICPMS) –

The New Elemental Analysis Workhorse

22

Metals analysis over the years 1930’s – Atomic Emission Spectroscopy developed, first

emission spectrometers (Arc / Spark excitation sources)

By the 1950’s emission spectrometers were commonly used in metals / alloys industries

Early 1960’s Flame Atomic Absorption Spectroscopy (AA) becomes a

routine technique to perform trace metals analysis, displacing wet chemistry techniques (titration, gravimetric analysis) and many emission spectrometers because it was so much easier to use

The PerkinElmer Model 303 was the first widely used AA

Mid- late sixties the ICP debuts as an excitation source

1970 – First Graphite Furnace AA (PerkinElmer HGA 70) Lower detection limits

33

More history

1970’s - ICP Emission Spectroscopy becomes widely accepted and compliments Flame AA with multielement capability, gives lower detection limits for some elements

By the early 1980’s, ICP, Flame AA and Graphite Furnace AA are well established for trace metal, and even major matrix element analysis.

1983 – First ICP Mass Spec (Sciex, quickly in a joint venture with PerkinElmer)

Into the 1990’s ICPMS gained a reputation for high sensitivity, ultra-trace analysis.

Drinking water, “clean” environmental samples, and the semiconductor industry embraced ICPMS

44

NexION 350 ICP-MS: 7th Generation

30 Years in ICP-MS

PerformanceVersatility

Ease of Use

55 Sample introduction components easily accessible (front)

90 degree (orthogonal) design

66

NexION 350 Orthogonal Design

Detector

Main Filtering Quadrupole

Universal Cell

Quadrupole Ion Deflector

Triple Cone Interface

Torch

Defines narrow ion beam

Plasma atomizes and ionizes samples

90 degree bend reduces maintenance requirements

Turns (+) ions 90 degrees

Removes interferences

Filters ions by mass

“Counts” ions

77

NexION Triple Cone Interface

88 10x improvement in low mass sensitivity

Benefits of a Triple Cone Interface

Well confined beam (~2-3 mm)

Almost no deposition inside mass spectrometer

NexION

Pressure drops in two smaller steps:

• less beam divergence,

• dirt prevented from entering mass spectrometer – very little drift, reduced maintenance

Sampler cone

Skimmercone

Hyper-skimmer cone

pres

sure

distance

Large beam divergence

Lots of material deposits inside mass spectrometer

Older ICP-MS systems –

Pressure drops in one large step:

• large beam divergence,

• more dirt into mass spectrometer – creates more drift and required maintenance

Legend: Blue = beam from plasma (ions + neutrals + dirt);

Red = pressure drop per cone

Sampler cone

Skimmer cone

pres

sure

distance

Material that never enters mass spectrometer

99 No maintenance beyond the cones

Front Access for Easier Cone Maintenance

Skimmer Hyper-skimmerSampler

1010

NexION 300 Quadrupole Ion Deflector

1111

Unique combination of Triple Cone Interface and Quadrupole Ion Deflector provide:

Benefit of a Quadrupole Ion Deflector

Incredible stability Mass spectrometer (including cell)

remains clean when analyzing dirty samples

Ion Optics require very infrequent cleaning

More time running samples, less time cleaning or recalibrating

Very low background noise 10x improvement in low mass

sensitivity No maintenance past the cones

Sampler

Skimmer

ICP

Hyper skimmer

QID

Photons, Neutrals and un-ionized particles

Analyte ions

1212

Exceptional Stability – 9 Hour Drinking Water Analysis

80

85

90

95

100

105

110

115

120

0 1 1.4 2.1 2.8 3.5 4.2 4.9 5.6 6.3 7.0 7.7 8.4 9.1Elapsed Time Since Calibration (Hours)

% R

ecov

ery

of C

alib

ratio

n St

anda

rds

Be9

V51

Zn66

As75

Cd111

Hg202

Pb208

U238

1313

Elements & Interferences

Ca(Ar)

K(ArH)

V (ClO)

Cr(ArC/ClO)

As(ArCl, CoO)

Se(Ar2,Kr )

Cu(ArNa, NaCa)

Ni(ArO/CaO/NaCl)

Cd(MoO)

Zn(ArMg, CaO)

Fe(ArO/CaO)Mg

(C2)

Al(CN/CNH, N2 spread)

1414

Scanning quadrupole in Universal Cell

1. Quadrupole can be a passive ion guide2. Quadrupole can create a band pass

(Multi-pole can only be a passive ion guide)

1515

Universal Cell - Introduction of Modes

1616

The STD mode is most suitable for: Applications with few interferences on analytes of interest Low mass or high mass elements

… BECs for interfered elements can be in the ppb range

Universal Cell Technology (UCT™)

1717

Correction equations work quite well with low levels of interference EPA 200.8 still does not allow cell technology for drinking water

Some correction equations have multiple terms Lowers precision of final result High levels of interference introduce more uncertainty

Some interferences cannot be corrected mathematically e.g. Br on Se and Ar

Mathematical Correction for Interferences in STD mode

1818

For subtracting the effect of ClO+ on V51: -3.127*(ClO53-(0.113*Cr52)) BUT . . . Cr52 measurement can be wrong because of ArC+

For subtracting the ArCl+ interference on As75: -3.127*(ArCl77-(0.874*Se82)) BUT, BrH+ increases the Se82 measurement Presence of Br can make BOTH Se (reported at mass 82 in STD

mode) and As answers wrong

Mathematical Correction for Interferences in STD mode

1919

Universal Cell - Collision Mode

2020

The Collision (KED) mode is most suitable for: First row transition elements Applications susceptible to common interferences at moderate

levels

… BECs for interfered elements are in the ppt range


2121

Universal Cell - DRC Mode

2222

The Reaction (DRC) mode is most suitable for: Applications with the highest level of interferences that require

the lowest BECs

… BECs for interfered elements are in the sub-ppt range


2323

NEW! Comprehensive software for ICP-MSEasy setup of instrument, methods and sample analysesIn depth reporting of calibration, sample results, QC’s, internal standardsIntegrated instrument diagnostics for troubleshooting

Syngistix for ICP-MS

2424 Real-time monitoring of > 200 test points, maintenance reminders

Instrument Control

2525

Method Development

2626

Sample Run List

2727 Concentrations Tab

Data Reporter

2828

Routine EPA 200.8, 6020 (KED mode usually sufficient)

High sample throughput FAST autosampler prepFAST complete autodilution and preparation system

Specialized Speciation, e.g. Cr and As Direct seawater analysis with seaFAST

Requires DRC Single nanoparticle analysis

Unique to NexION due to ultra fast analysis time

Environmental Applications

2929

Three 200.8 Method Application Papers

2

The Analysis of DrinkingWaters by U.S. EPA Method200.8 Using the NexION300Q ICP-MS in StandardMode The Analysis of Drinking

Waters by U.S. EPA Method200.8 Using the NexION300X ICP-MS in Standardand Collision Modes The Analysis of Drinking

Waters by U.S. EPA Method200.8 Using the NexION300D ICP-MS in Standard,Collision and Reaction Modes

Each application note has:IDLs, MDLs and linear rangesResults for SRMs12hour stability runs

3030

Environmental – Flue Gas Desulfurization (FGD), Solid Wastes

© 2013 PerkinElmer, Inc. All rights reserved.

Use of ICP-MS for USP <232> and <2232> Laboratory Compliance

3232

The United States Pharmacopeial Convention (USP)

Established 1820, The United States Pharmacopeia Convention (USP) is a non–governmental, official public standards–setting authority for prescription and over–the–counter medicines and other healthcare products manufactured or sold in the United States. USP also sets widely recognized standards for food ingredients and dietary supplements.The USP sets standards for the quality, purity, strength, and consistency of these products–critical to the public health. USP's standards are recognized and used in more than 130 countries around the globe.

• http://www.usp.org/• http://en.wikipedia.org/wiki/United_States_Pharmacopeia

The United States Pharmacopeia (USP) is the official pharmacopeia of the US, and is published dually with the National Formulary as the USP-NF.

3333

USP <231> Heavy Metals General Chapter

Detects metals colored by sulfide ion (Pb, Hg, Bi, As, Sb, Sn, Cd, Ag, Cu, Mo)

Color of sample compared to standard

Very non-specific Very labor intensive Large sample size

required (2 grams) Ashing sample

preparation step for solids

US Pharmacopeia <231>Heavy Metals ~ 100 year old Qualitative method

3434

Overview of New Chapters USP 232, 233 and 2232

USP is authoring 2 NEW “General Test Chapters” to replace the old USP 231

Publication Date in USP 35-NF 30: December 2012Pharmaceutical lab Implementation Date: May 2014

Chapter 232 is titled “Elemental Impurities-Limits”Chapter 233 is titled “Elemental Impurities-Procedures” ICP-OES Referee Procedure ICP-MS Referee Procedure

USP <2232>: Dietary Supplement specific chapter Uses the <233> method chapter and is applicable to ALL DS monographs

USP <1225>: Covers requirements for validation of methods. USP<1226>: Covers verification of the method in your laboratory. Front matter alert

USP specificall sas that o can sbstitte a method as long as o can

3535

Permissible Daily Exposure (PDE) Limits in USP<232>

ElementOralDaily Dose PDE(ug/day)

Parenteral DailyDose PDE (ug/day)

Inhalation Daily Dose PDE (ug/day)

LVPComponentLimit (ug/g)

Cadmium 25 2.5 1.5 0.25Lead 5 5 5 0.5Inorganic Arsenic 1.5 1.5 1.5 0.15Inorganic Mercury 15 1.5 1.5 0.15Iridium 100 10 1.5 1Osmium 100 10 1.5 1Palladium 100 10 1.5 1Platinum 100 10 1.5 1Rhodium 100 10 1.5 1Ruthenium 100 10 1.5 1Chromium 25Molybdenum 100 10 10 1Nickel 500 50 1.5 5Vanadium 100 10 30 1Copper 1000 100 70 25

3636

How Many Elements covered in USP <2232>?

3

3737

The BIG 4 included in USP <2232>

3

1.Lead

2.Arsenic

3.Cadmium

4.Mercury

3838

Permissible Daily Exposure (PDE) Limits in USP<2232>

Are the limits the same for 232 and 2232?

3939

Briefing <233> Elemental Impurities—Procedures. 4 Choices1. Analyze Neat, undiluted if sample is in suitable form2. Dilute in Acidified Aqueous solution if soluble in water3. Dilute in an appropriate Organic solvent4. Closed vessel microwave digestion for insoluble samples

USP 233 on Sample Preparation

4040

Sample Prep: The Power of Microwaves

Heat & Pressure

Solids / Oils / Creams Clear Liquid Digest

4141

Vessel Specifications

Titan MPS Microwave Sample Prep Standard 75mL High Pressure 100mLVessel Material Solid PTFE-TFM™ Solid PTFE-TFM™Volume 75mL 100mLPressure Rating 40 bar (580psi) 100 bar (1450psi)Maximum Temperature 260 oC 260 oCVessels per turntable 16 8DTC™ All Vessels All VesselsDPC™ Reference Vessel Reference Vessel

All vessels come with a one-year warranty.

DTC™ :Reference quality sample temperature sensing in all vessels.

DPC™ : Reference quality sample pressure sensing in a single vessel.

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Microwave Digestion for Drugs and Dietary Supplements

Typical Sample Prep Parameters:Sample Weight = 0.1 g to 1gAcids Added = 5 mL HNO3, Transfer to 50-mL autosampler vial, QS water.50 to 500x dilution factor for solids

Titan MPS Microwave Digestion System

4343

USP on Analysis by ICP-MS

Ability to analyze most of the elements in the periodic tableWide dynamic range Part-per-trillion to high part-per-million

Only technique which can detect As, Cd, Hg and Pb at required levelsAnalyze high level elements using Extended Dynamic Range (EDR)Requires One Sample Prep and One Method

Three Modes of Spectral Interference Reduction1. Standard Mode with Correction Equations2. K.E.D. Helium Collision mechanism reduce Polyatomic Interferences3. DRC Reaction mechanism based on specific chemistry

4444

ICP-MS Spectral Interferences

Some spectral interferences found in common matrices with USP metals

Interference Analyte40Ar12C 52Cr98Mo16O 114Cd35Cl40Ar 75As44Ca16O 60Ni40Ar 23Na 63Cu35Cl16O 51V

4545

Measured Elemental Contaminants in Oral Drug Product

Element/Mass Oral PDE(ug/g)

Cold/FluRemedy(ug/g)

(%) Recov. 0.8J Spike

MDL’s500x Dilution(ug/g)

Cd 114 2.5 <MDL 105 0.0004Pb 206+207+208 0.5 5 106 0.0007As 75 0.15 1.5 110 0.0045Hg 202 1.5 <MDL 105 0.0080Ir 193 10 <MDL 105 0.0005Os 189 10 <MDL 105 0.0010Pd 105 10 <MDL 98 0.0025Pt 195 10 <MDL 104 0.0019Rh 103 10 <MDL 105 0.0002Ru 101 10 0.002 106 0.0005Mo 95 10 <MDL 105 0.003Ni 60 50 <MDL 106 0.0026V 51 100 0.054 105 0.0053Cu 63 100 < MDL 103 0.002

4646

Measured Elemental Contaminants in Inhalation Spray

ElementInhalationLimits (ug/g) for 1g/day Max Dose

Inhalation AlergyMed. Measured (ug/g)

(%) Recov. 0.8J Spike

MDL’s50x Dilution(ug/g)

Cadmium 1.5 <MDL 101 0.0001Lead 5 <MDL 106 0.0003Inorganic Arsenic 1.5 <MDL 101 0.0001Inorganic Mercury 1.5 0.0028 104 0.0002Iridium 1.5 <MDL 104 0.0005Osmium 1.5 <MDL 107 0.001Palladium 1.5 <MDL 102 0.0006Platinum 1.5 <MDL 103 0.0005Rhodium 1.5 <MDL 102 0.0002Ruthenium 1.5 <MDL 100 0.0003Chromium 25 0.0013 104 0.0002Molybdenum 250 <MDL 103 0.0001Nickel 1.5 <MDL 102 0.0005Vanadium 300 <MDL 103 0.0001Copper 70 0.0054 102 0.0001

4747

HUMAN HEALTH • ENVIRONMENTAL HEALTH

Screening Plant Materials for Toxic and Nutritional Elements

4848

Application requires a wide dynamic range Low-level toxic elements – As, Cd, Pb, Se, and Hg Macro-level high concentrations – Ca, Mg, K and Na

If needed Extended Dynamic Range (EDR) can be employed

Samples are complex and require preparation Dissolve carbohydrates, minerals and proteins Require homogeneity and sometimes drying of

samples Microwave preparation can be used to digest into

solutions for analysis

Components in the matrix cause spectral interferences Organic components, minerals, digestion acids Universal Cell Technology (UCT) can be used to deal

with interferences

Experimental Challenges in Plant Material Analysis

4949

Microwave (Closed Digestion)

Common in Environmental, Food, Chemical Labs

Benefits:Closed, pressure digestionEasy methods, regulatory complianceSuitable for Mercury USP <232><233>

High temp, high pressuresFast digestionsTemp/Pressure controlData records

Challenges:Higher initial costPower/Ventilation requirements

Titan MPS

5050

Sample Preparation

Digestion Program

Approximately 0.25g of each sample was digested in duplicate with a mixture of HNO3 and H2O2. The addition of a small amount of HF is recommended for total digestion of siliceous material. After digestion, the sample solutions were diluted with deionized water to a final volume of 50 mL. Gold was added to all solutions to stabilize Hg.

Step TargetTemp (o

C)

Pressure Max (bar)

RampTime (min)

Hold Time (min)

Power (%)

1 150 30 5 5 60

2 200 30 5 20 90

3 50 30 1 10 0

5151

Speciation Capability – LC/ICPMS

5252

Arsenic in Apple Juice

5353

SP-ICP-MS for Nanomaterials

www.perkinelmer.com

Environmental•Fate studies•Drinking water•Surface water•Water treatment•Remediation studies •Bioavailability studies•Bioaccumulation studies•Distribution in the ecosystem

Consumer•Health and Fitness•Energy •Food and Beverage•Textiles•Paint•Semiconductor•Automotive•Electronics and computers •Sunscreen•Nanocomposite materials

Biological/Biomedical•Early diagnosis•Cancer treatment•Drug design and delivery •Toxicological studies

Single Particle ICP-MSSyngistix™ Nano Application Module

5454

Environmental Studies and SP-ICP-MS

SP-ICP-MS is now becoming a “conventional” analytical technique for the detection of metal-based nanoparticles Theory overview Syngistix Nano Application Module

Published environmental studies include: Release Fate (Dissolution, agglomeration, etc…) Bioaccumulation Biodistribution

5 NexION 350D with Syngistix Nano Application Module

5555 © 2009 PerkinElmer© 2009 PerkinElmer© 2009 PerkinElmer© 2010 PerkinElmer

SP-ICP-MS Theory Overview

5

5656 Differentiation between Dissolved and Particles Signal

Steady-state Signal

Individual Signal EventsParticle Size Information

Concept of Single Particle-ICP-MS

5757 Particles = Pulsed Signal

... ....... ..

..... ....... ......

..

... ...... ...

... ....... ..

..... ....... ......

..

..........QuadrupoleDetector

Time

Counts at mass 197 (Au)

Dwell Time

NanoparticulateMetals (Au)

Plasma

Pulse

• Tune Mass Spec for material• Intensity of pulse relates to

particle mass • Number of pulses relates to

particle concentration• Baseline = dissolved

300-500 µs

ICP-MS Schematic of General Analysis for Nano Metals

5858 NexION 350 Single Particle Mode

Overlap of ion plume transit with dwell time

ICP

-MS

Cou

nts

Time

Fast Continuous Data Acquisition = No Settling Time

Dwell Time Shorter than the Particle Transient Time

Fast Continuous Data Acquisition

5959 The faster the better!

Fast scanning ICP-MS Min. Dwell: 10 µs Max. 6 million data points/min Continuous data acquisition Integrated software: Syngistix Nano

Application Module Real-time particles visualization Particles composition, concentration,

size, size distribution and dissolved concentration

StandardCollision/KED

Reaction/DRC

Universal Cell Technology Axial Field Technology

avoids damping High interference

reduction No loss in sensitivity

Quadrupole Ion Deflector Minimizes particle

spikes

Hardware Meets Software


NexION 350 ICP-MS

Syngistix Nano Application Module

6161

Real-World Sample

Continuous Data Acquisition at 100 µs Dwell Time

0

50

100

150

200

250

300

350

400

0 1 2 3 4 5 6 7 8 9 10

I (19

7 Au)

, cou

nts

Time (s)

020406080

100120140160180200

7.7835 7.784 7.7845 7.785 7.7855 7.786 7.7865 7.787

Coun

ts

Time (s)

0

20

40

60

80

100

1.557 1.5575 1.558 1.5585 1.559 1.5595 1.56 1.5605

Coun

ts

Time (s)

Dwell = 100 µs Dwell = 100 µs

100 000 data points

6262

NexION 350 ICP-MSSyngistix Nano Application Module

NexION 350 ICP-MS Syngistix Nano Application Module

6363

Analytical Parameters

Method Parameters

Calibration

Real-Time Data

Real-Time Distribution Histogram

Syngistix Nano Application Module – Analysis Tab-Transport Efficiency

6464

Syngistix Nano Application Module – Analysis Panel

Analytical Parameters

Method Parameters Calibration

Real-Time Data

Real-Time Size Distribution Histogram

6565 Sample Containing 20, 50 and 80 nm Gold Nanoparticles

20 nm

50 nm 80 nm

Syngistix Nano Application Module – Adjustable Integration Window

6666 Particle Concentration, Size, Size Distribution, Dissolved Concentration

Syngistix Nano Application Module – Results Tab


Application of SP-ICP-MS in Environmental Studies

6868

Environmental Samples

G. Batley, SETAC Berlin 2012

G. Batley, SETAC Berlin 2012

6969

Environmental Transformation of ENMs

6

7070

Tracking Transformation of Silver Nanoparticles in Surface Water

NexION 350X Silver Nanoparticles In Surface Water – Application Note

7171

Tracking Transformation of Silver Nanoparticles in Surface Water

NexION 350X Silver Nanoparticles In Surface Water – Application

7272

Tracking Nanoparticles Dissolution using Single Particle ICP-MS

Mitrano, D. and Ranville, J., Colorado School of Mines, Department of Chemistry and Geochemistry

7373

L. variegatus was readily digested using the TMAH procedure, allowing for SP-ICP-MS analysis of tissues. The pulses observed in Figure 2A, can clearly be observed above a very low Ag+ background.

Analysis of Nanoparticles in Biological Tissues Using SP-ICP-MS

Bioaccumulation/Bioavailability of Nanoparticles

7474

Environmental Applications – Are Particulates your Lost Species?

Speciation is the combination of two well established techniques

Routine speciation of Se, As and other elements by LC-ICP-MS has become a “turn-key” application

Most quantitation is achievable with a correlation coefficient of >0.999 in the ppb and ppt range

The total concentration isn’t always equal the sum of the various species

As-B

As-III

DMA

MMAAs-V

Could particulates be the lost species in your speciation chromatogram?

http://www.perkinelmer.com/CMSResources/Images/44-171616Altus-UPLC-System.jpg

http://www.perkinelmer.com/CMSResources/Images/44-171616Altus-UPLC-System.jpg

7575


Are particulates the lost form of species?

Why are environmental scientists interested in particulate selenium and mercury?

Can SP-ICP-MS help uncover the lost species?

*Courtesy of Z. Gajdosechova, K. Loeschner, J. Feldmann, EM Krupp, Trace Element Speciation Laboratory (TESLA), University of Aberdeen, Scotland, UK

7676


20 mg of dry tissue

Lipids extraction(DCM:MeOH)

1 mg/mL Protease5 mg/mL SDS

Pre-concentration50 kDa centricon

filtersOvernight incubation at 37 ºC


Sam

ple

Prep

SP-IC

P-M

S A

naly

sis

7777


Adult whales have significantly more particles (Hg and Se) than juvenile whales

No difference between liver and brain


7878


Max particles size increases also with age (Hg and Se)

No difference between liver and brain


7979

Industrial Applications - Consumer Product Testing

AgNP in mineral supplements – Application Note

8080

Overview of Biological Applications

8181

Biological Applications – Detection of Nanoparticles in Biological Fluids

Precise sizing and counting

Great particle number recovery

Straightforward analysis

8282

Biological Applications – Detection of Nanoparticles in Biological Fluids

Blood (1/20 dilution in 0.5% NH4OH + 0.1% Triton)Urine (1/10 dilution in 0.5% NH4OH + 0.1% Triton)

8383

Biological Applications – Detection of Nanoparticles Biological Fluids

AuNP in Biological Fluids

0 10 20 30 40 50 60 70 80 9010

20

30

40

50

60

70

80

90 30 nm Au NP 60 nm Au NP

Siz

e (n

m)

Time (days)

AuNP in Blood

0 10 20 30 40 50 60 70 80 9010

20

30

40

50

60

70

80

90 30 nm Au NP 60 nm Au NP

Siz

e (n

m)

Time (days)

AuNP in Urine

8484

Introduction to the concept of Single Cell ICP-MS

Global Manager, PerkinElmer

Chady Stephan, Ph.D.

[email protected]

8585

... ....... ...

.... ..

..... ........

... ...... ...

... ....... ..

..... ....... ......

..

..........QuadrupoleDetector

Time

Counts at mass 195 (Pt)

Dwell Time

Cell Suspension

Plasma

Pulse

• Element Specific • Intensity of pulse relates to mass content• Number of pulses relates to cell concentration• Baseline = ionic concentration in the Media

ICP-MS Schematic of General Analysis for Nano Metals

8686

Biological Applications – Single Cell ICP-MS

http://connect.acspubs.org/CEN_PerkinElmer_3_22_16?partnerref=CENEmail1&elqTrack=true

8787

Application of Single Cell in Cancer Research

Staff Scientist, National Institute on Minority Health and Health Disparities (NIMHD)

Lauren Amable, Ph.D.

[email protected]

8888

Cisplatin and Platinum-based Chemotherapy

Cisplatin is one of the most widely used chemotherapy drugs in the clinic treating a variety of cancers: ovarian, testicular, lung, head and neck, and several others.

Platinum compounds include: cisplatin, carboplatin, and oxaliplatin

8989

Cisplatin Mechanism of Action

Primary mechanism of action is binding to DNA, producing bulky DNA adducts that bend the DNADNA replication is blocked and the cell must repair the DNA damageIf there is too much damage the cell dies

9090

Patients’ Response to Treatment

Initially patients respond well to treatment but later relapse and display resistance to platinum compounds.

CisplatinResistance

Increased DNA Repair

Altered Cellular Accumulation• Decreased import• Increased export

Increased cytosolic inactivation

Amable L. Pharmacol Res 2016

9191

Traditional Methodology to Measure Cisplatin Uptake

Traditional methods do not reflect cellular variability and distribution

Cisplatin

?

9292

Cell Cycle and Serum Starvation

Cells have 4 parts of the cell cycle G1 phase- First growth phase S phases- DNA synthesis phase G2 phase- Second growth phase Mitosis (M) phase- Cells divide

Serum starvation removes the growth factors needed for cells, stalling them in G1 phase.

Whether varied uptake of cisplatin levels is due to cells in different phases of division?

9393

Uptake of Cisplatin versus Cell Cycle

Cells were serum-starved for 18 hours prior to cisplatin treatment

Serum-starved CP70 show less uptake of cisplatin versus non-starved

0

5

10

15

20

25

30

35

0 1 2 3 4 5 6 7 8 9

Aver

age I

nten

sity

Time (hours)

CP70 Cell line

RegularSerum Starve

9494

Nanoparticle Uptake vs Particle Number

0.0000.0020.0040.0060.0080.0100.0120.0140.0160.0180.020

CP70 A2780 CAOV3

Norm

alize

d up

take

rate

Ovarian cell lines

0.5 M1 M

• Uptake rate was measured by exposing the cells to two concentrations of Nanoparticles (0.5 and 1 M particles/mL) for 21 hours.

• CP70 and CAOV3 exhibit a similar Nanoparticle uptake, regardless of concentration, while A2780 show less Nanoparticle uptake

9595

Nano Application Collateral ICP-MS

Syngistix Nano App Module product note (011657A_01)

NexION 350 ICP-MS brochure(011676A_01)

NexION 350 – nano-specific application collateral available now

NexION 350 ICP-MS Nano Application Materials: Single Particle ICP-MS Theory white paper (011649_01) Iron Nanoparticles SP-ICP-MS app brief (011497_01) Gold Nanoparticles SP-ICP-MS app note (010402A_01) Silver Nanoparticles in surface water SP-ICP-MS app note (011646_01) Element Oxide Slurries Nanoparticles SP-ICP-MS app note (011617_01) Nanoparticles Dissolution SP-ICP-MS app note (011750_01) Silver Nanoparticles in Dietary Supplements SP-ICP-MS (011800_01) Nanoparticles in Biological Tissues SP-ICP-MS (011803_01)

www.perkinelmer.com


DSA-TOF

Hyper DSC

Lambda 1050

NexION 350

Optima 8X00

LC/SQ 300 MS

TGA-IR-GC-MS

http://www.perkinelmer.com/CMSResources/Images/44-69995_FlexarSQ300MSpair_1000x908.jpg

http://www.perkinelmer.com/CMSResources/Images/44-69995_FlexarSQ300MSpair_1000x908.jpg

9797

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Inductively-Coupled Plasma Mass Spectrometry … Plasma Mass Spectrometry (ICPMS) – The New...

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