20130618 tjames principles of automation

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Automation

Tim James

Head BMS, Clinical Biochemistry,

Oxford University Hospitals NHS Trust

Visiting Professor, Oxford Brookes University

Overview

• Historical development

• General chemistry components

• Automated immunoassay

• Standalone automation

• Linking analytical systems throughtracking

• Procurement



Historical development

• 1957 Skeggs introduces continuous flow analysis, commercialised by

Technicon as the autoanalyser

• 1960 – 1970 Growth in application of biochemical methods to the autoanalyser

• 1969 Sequential Multiple Analyzer (SMA)

• 1970 Dupont produce the Automated Clinical Analyser (ACA)

• 1974 Sequential Multiple Analyzer with Computer (SMAC)

• 1978 Kodak produce the Kodak-Ektachem an analyser employing dry chemistry

slide technology

• 1980 - 1990 Convergence and standardisation of chemistry analysers

• 1990 – 1995 Automation of non-isotopic immunoassay methods

• 1995 – 2000 Development of combined general chemistry and automated

immunoassay within a single instrument.

• 2000 - 2005 Widespread utilization of total laboratory automation and tracking to

link multiple analysers together

Early Autoanalysers

• Continuous flow analysis: – A defined volume of sample introduced at regular intervals into a

continuously flowing stream of reagent.

– A chemical reaction would take place typically producing a changein absorbance monitored through a flow cell detector.

– Air bubbles introduced at regular intervals to prevent lateral flowaffects

– Coils used for standardised mixing

– Dialysis membranes to provide a protein free sample solutionthereby reducing interference.

– Reaction sequences could be modified by longer mixing coils to

provide extended incubation and or heating blocks to achievehigher reaction temperatures.



Continuous flow analysis schematic

High throughput chemistry systemsdevelopment :

Example - American Monitor Parallel

Heavy engineering with platten

above a water bath containing 3600

reusable reaction vessels30 channels

30 sample probes

15 paired spectrophotometers each

with their own

Flame photometer (later version

with ISE)

7200 tests per hour max

Same era as SMAC and Vickers

M300



Early Autoanalysers

• Continuous flow analysis relevance today:

– Original application of most of the common methods we usetoday were first applied using this type of automation

– Basic components similar and have influenced the

development of other analytical systems – coagulation,

immunoassay,…

– Origin of terms used today – discrete, discretionary, random

access – are comparative descriptors to this technology

– Process with respect to analysis identical:

• Sampling

• Reagent addition and mixing

• Reaction incubation

• Reaction monitoring

• What is the main chemistry analyser inyour lab?



2013 analyser characteristics

• Limited number of suppliers

• Convergent evolution of components and reactionsequences

• Reagents often made by the same manufacturers but

badged and packaged

• Family of analysers with variable capacity

Sampling

A mechanism by which a defined volume of the specimen is transferredfrom the sample tube into the reaction vessel of the instrument.



Sampling• Two types - disposable tip for each individual specimen or a fixed probe that is

only changed when it is damaged or has been used for a fixed number of

sample cycles.

• In general chemistry analysers typically transfer 1 to 20 µL.

• Dead volume.

• Specimen probes incorporate a number of design features

– liquid level sensing,

– probe crash detection,

– clot detection.

• Cycle time

• Cap piercing

• Carry over - Broughton P. Carry-over in automatic analyzers. J Autom Chem

1984;6: 94–5

• Sample integrity checking for haemolysis, icterus, lipaemia

Cuvettes



Cuvettes

• Can be:

– reusable – requires a laundry mechanism

– or disposable – individual, segments, racked – requires a feedmechanism and a removal mechanism

• Optically clear at the wavelengths used for detection (typically 340 to800nm)

• Vary in path length

• The reaction temperature is controlled at a constant 37oC, by

incubation. Water bath, an oil bath or warmed air. The temperaturecontrol is critical to ensure reproducible results.

• Compare with “dry” chemistry systems – characterised by highreproducibility.

Reagent compartments



Reagent addition

• Compartments usually temperature controlled.

• “on-board” stability

• Liquid height assessment to calculate remaining reagent shots.

• Typically 50 reagents at one time in cartridges/wedges

• Carry over of reagents – usually well defined by manufacturers

and minimised by general and specific washing protocols or

scheduled avoidance within parameters. Examples include pH

effects, or triglyceride reagent effect on lipase. Many others.

• Mixer probes or paddles - failure of mixing results in poor

precision and is notable by a slowed, inconsistent reaction

profile.

Reaction monitoring

• Many (not all!) have a typical reaction

cycle – around 10 minutes during which

the reaction can be monitored.• Data extracted can be utilised as kinetic

or endpoint to derive results

• Spectrophotometer unit of varyingcomplexity



Access to information

• Analyser manuals/user guides are nowexcellent

• Analysers often have electronic

guidance with diagrams andphotographs

• Read and understand the analyser inyour own lab

Automation in a wider context

• Immunoassay

– Very wide applicability

• Combined Chemistry: immunoassaysystems

• Coagulation

• Haematology

• Linking in a coordinated manner



Integration of processes androbotics

• Increased instrument capacity by linking two or more analyser units togetherwith a single sample presentation mechanism

• Increased assay diversity, by combining general chemistry and immunoassay

units within an apparently single instrument.

• More complex integrated :

– Standalone automation units that can undertake pre and post analytical

processes but are physically separate systems from the analysers.

– Tracking systems, in which pre and post analytical processes are

undertaken by units connected to a track which also conveys specimens to

the analysers

• Allows automated centrifugation, removal of sample container caps and

specimen routing, recapping, archiving, seamless cascade and repeat testing

through retrieval

• Pick and place robotics vs point of space sampling.

• Efficiency improvements and TAT benefits

• Health and safety benefits - repetitive strain injury an reduced staff exposure to

clinical infection risk.

Tracking example : ADVIA Labcell

1.38m

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4.20m

1.43m

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C e n t a u r X P C e n t a u r X P

2 . 5

2 m

0 . 8 0 m

2 . 8

2 m

5.78m

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9 m

2.82m

1 . 0

0 m

4.60m3.90m

4.50m

4.55m

22.20m

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R

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Impact on TAT of Immunoassay

Efficient utilisation of staffing and

automation

• Design, review, improve.

• Use the automation 24 hrs a day.

• Needs more breadth of confidence with all automationelements ie chemistry analyser, immunoassay analyser,track, centrifuge…

• Need access to good quality metrics and data on usage

• Need on-going improvements in specimen receptionprocesses

• Post-analytical phase – utilise all the functionality availableon Data Management systems to minimise staff time usedfor data review – reflex testing, QC rules, re-run ability,automated comment addition



Optimisation

• The introduction of automation has

achieved significant improvements in

laboratory efficiency and productivity.

However, the maximum utilisation of

such systems requires careful

management, implementation and on-going review.

Centrifuge utilisation - XL



Instrument status (on-line/ off-line)

Centaur 1 utilisation



Key points

• Automation is constantly evolving and changing

software and hardware in a phased manner provides

opportunities for continual improvements

• Create large open spaced laboratories to allow

continued expansion of automation

• Access to good metrics essential to assess theimpact of investment

• Pre and post analytical re-engineering and on-goingrefinements are critical

• Supplier can give advice on getting the best from

automation systems

Summary• Clinical biochemistry laboratories have benefited significantly from developments in

automation, instrumentation and robotics.

• Two main types of instrument, the general chemistry analyser and the immunochemistryanalyser predominate but a wide range of hybrid and combination analysers are available

• A thorough understanding of the individual analyser components and their relativemechanical and data interactions enables operators to troubleshoot problems moreeffectively

• Consolidation of most of the biochemistry repertoire is now possible on a single system that

comprises a set of integrated analysers.

• Automation of the three phases of laboratory testing, namely pre-analytical, analytical andpost analytical in a continuous process.

• A complex automation system requires monitoring and management to achieve consistentand optimal efficiency.

• On-going maintenance and standard regimes of operation need defining and completion foroptimal operation of automation

• Automation has resulted in significant reduction in manual intervention in the total analyticalprocess.

• Automation produces shorter and more consistent test turnaround times

• For maximum utilisation of automation total laboratory processes need to be reviewedregularly



Procurement of automation

• Plan ahead – 2 years prior to procurement initiation. Get your factstogether – visit sites and talk to colleagues at other centres.

• Define high level scope – particularly which disciplines will be involved

– get buy in from the wider team – haematology, coagulation, virology,estates, IT, procurement, finance.

• New procurements facilitate common processes and gains in efficiency

• Develop fine level detail of an output based specification – mainlywhich tests.

• Ask your lab leads for the copy of the last technical specification – compare this to what you have in the lab

• EU procurement process is well defined – know what it is!

• Risk of challenge high as value and length of contracts has increased

References

Buckley-Sharp MD et al. Introduction of a Vickers M300 analyser into the routine service of ahospital laboratory: Installation, staffing, logistics. J Clin Path. 1976, 29, 322-327

Westgard JO et al. Performance studies on the Technicon "SMAC" analyzer: Precision andcomparison of values with methods in routine laboratory service. Clin Chem.1976 ;22:489-96.

Little AJ et al. Comparative evaluation of a Technicon SMAC2/RA1000 System with an

American Monitor Parallel during normal service work. Journal of Clinical Laboratory Automation1986;8: 207-210Roberts WL. Chapter 5: Principles of Clinical Chemistry Automation.In: Michael L. Bishop, Edward P. Fody, Larry E. Schoeff. Clinical chemistry: principles,procedures, correlations. 5th edition, Lippincott Williams & Wilkins, 2004.

Melanson SEF, Lindeman NI, Jarolim P. Selecting automation for the Clinical ChemistryLaboratory. Archives of Pathology and Laboratory Medicine. 2007; 131: 1063-1069.

The Immunoassay handbook. Editor: Wild D. 3rd Edition 2005. Elsevier Science.

Wheeler M. Overview of robotics in the laboratory. Annals of Clinical Biochemistry. 2007; 44:209-218.

James T. Chapter 2: Automation. In: Clinical Biochemistry. Ed Ahmed N. 2010. OxfordUniversity Press Oxford, UK. ISBN 13: 9780199533930

20130618 tjames principles of automation

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