User Meeting 8 or 9 September 2015: Laser diffraction Data … · 2016-11-03 · User meeting 8 or 9 September 2015 | Sysmex Check the obscuration: red and blue obscuration 35 Particle

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User meeting 8 or 9 September 2015 | Sysmex

User Meeting 8 or 9 September 2015:

Laser diffractionData Quality: Do’s and Don’ts

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Things to consider during and after the measurement:

● Result – particle size distribution

● Background

● Raw data

● Calculation *) :

● Model● Fit

● Obscuration *)

● Repeatability *)

● Measurement settings *)

*) Optimized during method development but always good to check duringand after the measurement

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Check the result

3

● Particle size and Particle size distribution:

● Logical, expected distribution?


Check the result

4

● Mastersizer 2000: Result Analysis (M)

● Mastersizer 3000: Analysis


Check the data

5

● Background and data

Sample dataBackground substracted

Background


Check the data

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● Background and data

Background

Sample data


Check the data

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● Mastersizer 2000: Data (M)

● Mastersizer 3000: Data Background data

Sample data


Check de Data and Background

Sample data

Background data


Check the Background data and system cleanliness

● A good measurement requires a clean, stable background

● This should show progressive decrease across the detector range

Less than 20 scatteringunits by detector 20

Less than 100 units on detector 1


Background example 1

● How does the background look like?

● What could be the reason?

● What could be done?


Background example 1 - solution

● How does the background look like? Hump around detector 20

● What could be the reason? Material stuck to the windows

● What could be done? Extra Flush or clean the windows








● Poor background – contaminated dispersant

● Particulate contamination causes fluctuations in the background over time

● Bubbles in the dispersant can also result in a similar background



● View after background measurement, before sample addition







Poor background – misaligned system.

● Castellation indicates a mis-aligned system.

● This may be caused by:

● Dirt on the cell windows. Address these and then re-align.● Changes in the temperature of the dispersant

Castellation


Poor backgrounds: thermal gradients in organic dispersants

● The sample dispersion unit may be at 30°C+, while the solvent is generally much cooler

● This gives rise to thermal gradients resulting in fluctuations in the laser beam, alignment problems and poor backgrounds

Thermal gradient in dispersant








In direct view: wild instability of the scattering on the first few detectors….

● After a few minutes the background should stabilise as the temperature differences equilibrate.

● If it does not stabilise, fit the cover of the dispersion unit to reduce surface evaporation.


Check the data

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Data Graph - Light Scattering

1 3 5 7 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 Detector Number

0

10

20

30

40

50

60

70

Ligh

t Ene

rgy

Background dataPharmaceutical in propanol, 22 September 2004 12:17:21

No Background Signal Data0 53545.938 46460.320 13.2331 67.011 53.034 -5.1102 56.543 40.361 -8.7003 34.427 22.086 -7.7854 31.487 16.457 -10.8635 36.039 19.474 -11.7976 30.898 13.803 -13.0067 31.508 13.554 -13.7858 28.469 10.780 -13.9219 25.682 9.428 -12.856

10 23.907 9.202 -11.54111 21.491 9.316 -9.33112 18.177 8.685 -7.08713 15.684 8.661 -4.948

● The data is already corrected for the background

● Negative data (avoid this!) unstable background

● Results are affected!


Check the raw data, mastersizer 3000

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● The data is already corrected for the background

● Negative data (avoid this!) unstable background

● Results are affected!


Check the data● Idea about the particle size?

● First detectors numbers● Small angle Scatter● Higher light energy● Big particles

● Higher detector numbers● Big angle Scatter● Lower light energy● Small particles

User meeting 8 or 9 September 2015 | Sysmex 23

Check the fit : what is the fit?● The fit page shows the measured scattering data and the data predicted

by the scattering model● The precision of the overlay of these curves is known as the ‘data fit’● The goodness of the ‘data fit’ is quantified by the Residual


1 3 5 7 9 11 14 17 20 23 26 29 32 35 38 41 44 47 50 Detector Number

0

50

100

150

200

Ligh

t Ene

rgy

Fit data(weighted) 10 August 2001 16:52:43


How do we get the size distribution?


Check the fit

● Weighted residual ≈ residual

● Weighted residual and residual < 2% (if possible)

● Bad fit could be caused by:

● Poor selection of Optical properties● Negative data● Too high obscuration (multiple scatter)● Wrong selection of the calculation model● The sample itself (mixture of components etc.)● Etc.

● Optimize the fit, but still look if you use logical optical properties and get a logical particle size distribution

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Example of Unweighted & Weighted fit: Good

●

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Example - Unweighted

Example - Weighted


Assessing the Data Fit: Absorption (MS2000)


7 20 23 26 29 32 35 38 41 44 47 50 Detector Number

TC 1 during 100% u/s, 11 January 2005 13:36:27

Detector 51 and 52: Absorption

● Misfits to the extinction detectors indicate an incorrect absorption value

● 51 in the red light● 52 in the blue light


Assessing the Data Fit: RI (MS2000)

.D a ta G r a p h - L i g h t S c a tte r i n g

14 17 20 22 25 28 31 33 36 39 41 44 47 D e tec to r N um ber

C om pound A , 29 M arc h 2005 15 :16 :52

Other detectors: RI

● A poor fit to the focal plane detectors (<40) suggests an incorrect choice of refractive index


Assessing the Data Fit: Absorption (MS3000)

● Misfits to the extinction detectors indicate an incorrect absorption value● 51 in the red light● 63 in the blue light

Poor data fit here indicates poor choice of

absorption

Poor data fit here indicates poor choice

of absorption


Assessing the Data Fit: RI (MS3000)

● A poor fit to the focal plane detectors (<40) suggests an incorrect choice of refractive index

Poor fit indicates incorrect choice

of refractive index


Check the fit : not good MS3000

● Residuals > then 1-2%; residual and weighted residual not same order.

● No good fit for detector 51 and 63 (extinction red and blue)

● optimize optical properties absorbance

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Check the fit : not good MS3000

● Residuals > then 1-2%; residual and weighted residual not same order.

● No good fit for other detectors

● optimize optical properties refractive index

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MS3000 development: The optical property optimiser (OPO)

● Offers a quick way to adjust optical properties and assess the fit and result

Optical Property Selection Data & Result views


Check the obscuration

● Stable between measurements?

● Compare obscuration red/blue

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Check the obscuration: red and blue obscuration

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Particle Size Distribution

0.01 0.1 1 10 100 1000 3000 Particle Size (µm)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

5.5

6

6.5

7

7.5

Volu

me

(%)

testx, vrijdag 7 mei 2010 12:02:41


0.01 0.1 1 10 100 1000 3000 Particle Size (µm)

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

5.5

6

6.5

7

Volu

me

(%)

testy, vrijdag 7 mei 2010 13:09:24


0.01 0.1 1 10 100 1000 3000 Particle Size (µm)

0 0.5

1 1.5

2 2.5

3 3.5

4 4.5

5 5.5

6 6.5

7 7.5

8 8.5

9 9.5 10

10.5 11

Volu

me

(%)

testz, dinsdag 29 juni 2010 12:12:01

X Y

Z


Check obscuration

● Stable between measurements?

● Compare obscuration red/blue (indicative information)

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Check the obscuration

● Obscuration too high:

● Multiple scatter● Obscuration too low:

● Signal/noise ratio low● Bad reproducibility

● Blue>Red:

● Small particles, risk for multiple scatter.● Avoid blue > ca. 15%● Test right obscuration with an

obscuration titration

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Guideline Obscuration Ranges for Sizes

Dv(50) Value Obscuration Range

Submicron 2-5%

1-10um 5-10%

Over 10um 5-15%


Obscuration guidelines

● Obscuration is tested during method development.

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Method Distribution Particle size Obscuration

Dry Wide Coarse 0.5 - 6%

Dry Narrow Fine 0.5 - 3%

Wet Narrow Nano 5 - 6%

Wet Narrow <4 µm 10%

Wet Wide Coarse 15 - 25%


MS3000 development: Data Quality

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Check the Repeatability

● A good measurement is repeatable

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0.01 0.1 1 10 100 1000 3000 Particle Size (µm)

0 2 4 6 8

10 12 14

Volu

me

(%)

Solvent1, 11 May 2010 12:43:33 Solvent1, 11 May 2010 12:44:10 Solvent1, 11 May 2010 12:44:48Solvent1, 11 May 2010 12:45:25



● If not repeatable:

● Did the measurement settings change?● Did the calculation change?● Did the dispersion change?

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0.01 0.1 1 10 100 1000 3000 Particle Size (µm)

0

2 4

6 8

Volu

me

(%)

product1, 13 January 2011 13:17:38 product1, 13 January 2011 13:18:24product1+, 13 January 2011 13:19:50 product1+, 13 January 2011 13:20:35product1+, 13 January 2011 13:21:21 product1++, 13 January 2011 13:22:40product1++, 13 January 2011 13:23:25 product1++, 13 January 2011 13:24:11


Check the Repeatability – ISO guide line

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● Limits suggested in ISO13320:

● Dv(50): RSD < 3%● Dv(10) and Dv(90): RSD < 5%● “Below 10µm, these maximum values should be doubled.”

● In ideal conditions● 0.5% COV on parameters >1μm● 1% COV on parameters <1μm

● Limits suggested within USP<429> and EP 2.9.31:

● Dv(50): RSD < 10%● Dv(10) and Dv(90): RSD < 15.0%● “Below 10µm, these maximum values should be doubled.”



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Check Repeatability

● A good measurement is repeatable

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Check Repeatability

● If not repeatable:● Did the measurement settings change? ● Did the calculation change?● Did the dispersion change?

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Summary - data quality● Background data

● Make sure that:● Material is not stuck to the cell windows● There is no dispersant contamination● There are no thermal gradients● That the system has been properly aligned ● The inner detector data is free from castellation

● Sample data● Check that

● There are reasonable signal to noise levels● There is no multiple scattering● There is no negative data● There is no noisy data ● There is no beam steering


Questions?

Please contact:Sandra Remijn – Application [email protected]

Tineke Mink – Application Specialist [email protected]

www.sysmex.nl www.sysmex.be

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Documents

User Meeting 8 or 9 September 2015: Laser diffraction Data … · 2016-11-03 · User meeting 8 or 9 September 2015 | Sysmex Check the obscuration: red and blue obscuration 35 Particle