automation in clinical laboratory

AUTOMATION IN CLINICAL CHEMISTRY

Dr. Gangadhar ChatterjeeMBBS;MD

Assistant ProfessorRCSM Govt. Medical college, Kolhapur, MH, India

WHAT IS AUTOMATIONUse of laboratory instruments and specimen processing equipment to perform clinical laboratory assays with only minimal involvement of technologist .

Automation in clinical laboratory is a process by which analytical instruments perform many tests with the least involvement of an analyst.

The International Union of Pure and Applied Chemistry (IUPAC) define automation as "The replacement of human manipulative effort and facilities in the performance of a given process by mechanical and instrumental devices that are regulated by feedback of information so that an apparatus is self-monitoring or self adjusting”.

History Began-1950 Escalation of Demand for test. Larger work loads : -Increase in 15 % /Annual -Doubling- 5 Yrs.How to handle ? Increase in Staff Improvement in Methods Use of Automation.Shortage of trained technicians- Work simplificationManual- Machine (Various stages of Analytical Procedures)

Evolution Fixed Automation-repetitive task by itself Programmable Automation-Variety of different tasks. Intelligent Automation-Self monitoring and appropriate response to

changing condition.

Historical Overview: Incremental – over 50 year

Key to success: Incorporation of

continuous flow Discrete processing step

Development: LIS Robotics Concept of total and modular automation

Automations Extending:

Processing and transport of specimens

Loading in to analyze

Assessing the results

Processes used in Automation

Continuous flow

Discrete Processing

Continuous flow analysis:

By:Leonard skeggs in 1950 Pioneered device Single-channel Continuous flow Batch analyzer

Throughput: 40-60 specimen/hour One result /analyte for each specimen

Reaction - Tubing (Flow container & Cuvet) Specimen reagent mixing – roller pump (Assay Specifics) Volume control –Different internal diameter of pumping tubes Mixing – Through Coils. Minimizing Carryover – Injection of air bubbles into

specimen stream Temperature control –water bath Timing reaction –Distance the stream Travelled. Provision of Protein free filtrate- Dialyzers

Mainstay – for > 20 years

2nd and 3rd - Generation (Multiple test result on same specimen)

Discrete analysis: (1970)

Widely used

Each specimen in a batch – “Separate from every other specimens”

Discrete processing is used by- Centrifugal Random access Analyzer

Centrifugal Analyzers:

1970 –Norman Anderson

Oak Ridge National laboratory-US

What happens : Discrete aliquots of specimen & Reagent Pipetted Discrete chambers in a Rotor

Spinning of rotor Centrifugal force Transfer & mix aliquots specimen/reagent

Cuvet (radially located) Rotator motion (Move- Cuvet) Optical path Integration computer system Multiple absorbance reading software Enzyme Activity (Substrate concentration)

Early analyzers: Analysis of Multiple specimens for single analyte in

parallel.

Later: (Selection of Different wave length) Several analysis in parallels at different wave length

Rotor: - Specimens of several tests at same time. -Scheduled of appropriate tests

(keyboard entry bar coded label).

Random access analyzer:

Sequential Analysis on Batch of specimens.(Each specimen different tests.)

Measurement of Variable No. and varieties of Analytes in each specimen.

(Profiles of Groups of Test)

Tests are defined: Keyboard LIS with conjunction with Barcode

Selection of Appropriate Reagent Packs Absorbance Measurement- Computer Incorporation-

“ Walk away “- Instruments can be left for a brief period. Software programming.

(Single Technician – can operate more than one analyzer at a time.)

Most current chemistry and Immunoassay analyzers are Random access.

Steady Improvement -Mechanical reliability.

-Software technology

Easy Operation

Types of Automation Total Modular

Total Laboratory Automation (TLA).Early model 1980 Kochi Medical School. Nankoku,Japan-Dr Mesahide Sasaki.

Samples: Conveyer belts – carriers Work station. Automated pipette. Required lab test.

Total Lab Automation: Large lab Large scale -very expensive.

Pre-analytical automation functions. Centrifugation. Aspiration of serum. De-capping of tubes. Splitting of specimen Barcode of aliquot tubes. Sorting of tubes.Transport system. Conveyor beltTube recapping machineStorage system.

Modular Automation (1990)

Selected Modules -Analyzers

-ISE Marketed successfully

LAS (Laboratory Automation System).

TLA Require extensive software Module.

Steps in Analytical Processes Individual steps – “Unit operations” Specimen acquisition Specimen Identification. Specimen delivery to lab. Specimen preparation. Specimen Loading and aspiration. On – analyzer specimen delivery. Reagent handling and storage. Reagent delivery. Chemical reaction Phase. Measurement approaches. Signal processing , data handling and process control. In most – Sequential. In some – Combined & Parallel.

Specimen Acquisition. Sample collection- Automation (In process of Development)

Zivonovic and Davis –Robotic System. -Flat headed probe – location of vein. -Automatic needle withdrawal.

Specimen Identification Identifying link Maintained throughout -Transport -Analysis

-Reporting. Technology:Labeling , Bar-coding ,Optical character recognition.Magnetic stripe, Radio frequency identification.Touch screen, Optical Mark Reader, Etc. Bar-coding – Technology of choice.

Labeling Test order

Electronic Entry

Generating Unique identity of specimen

Unique lab accession number

Records

Till reporting

Labeling of tubes

Critical for processing

Log in procedures

Technical handling

Secondary labeling (If needed)

Bar-coding Major automation of specimen identification

LIS

Bar-coded label

Specimen container

Read-Barcode reader

Identification information (By software)

Advantages Elimination of work list on the system. Prevention of mixed-up of tubes placements. Analysis of specimen in defined sequences. Avoiding tube mix-up –in case of serum transfer Auto discrimination Operator intervention is less. Ensures- integrity of the specimen identity.

Specimen delivery to lab Courier Pneumatic tube system Electric track vehicles Mobile robots COURIER: Human courier Batch process Specified timings Delay in Services Specimen loss . Etc..

Pneumatic- Tube system Rapid transport Reliable Point to point services Mechanical problem Damage of specimen Limited carrying capacity Cost effectiveElectric track vehicle: Larger capacity No specimen damages Larger stations ?Rapid specimen transportMobile Robots: Studies- Establish usefulness Delays Batched pick up. etc, Cost effective

Specimen Preparation

Clotting of blood Centrifugation (Serum) Time Consuming -Delays Secondary tubeDevelopments- Note worthing Use of whole blood

1.Assay system-Analyzer whole blood Specimen preparation time-EliminationEg. ISE- with in minutes2.Application of whole blood to dry reagent films. Visual Instrumental observation (Quantitative)

Specimen loading and aspirationSpecimen- Serum/ Plasma -Primary collection tubes

-Sample cups-Secondary tubes

1.Evaporation of Specimens (Cups- 50 % over 4 hrs) Analytical errors- -Loading zone-covered -Cups-Paraffine film /caps.2.Thermal /Photo degradationTemperature labile-Refrigeration loading zonePhoto labile –Semi opaque containers

Loading Zone-Areas of specimen holding- Circular tray Rack/ Series of racks Serpentine chainNo Automatic specimen identification Loading of Specimens- correct sequence as per loading listAutomatic Specimen Identification- Reposition of SpecimensLoading- Second run (Separate tray) Optimal Efficiency Provision of Continuous loading.

Ideal/ Desirable features: (STAT Mode) New sample insertion at anytime/ all the times. Ahead of already running sample Timely analysis -Emergency samples.

Transmission of Infections Disease Common concern1.Splatter-Acquisilion by Specimen probesPrevention -Level Sensors

-Restriction of Penetration -Smother motion control

2.Aerosols--Potential for contamination-Specimen Transfer-Spillages

Prevention- Closed Container -Sampling system.

Specimen DeliveryContinuous flow

Sample probe

Continuous reagent stream

Discrete analyzer

Sample Probe

Reaction cup

Discrete Pipetting

Positive –Liquid-Displacement pipette Specimens/Calibration/ControlsOperational Modes:

1. To dispense only aspirates specimen in to reaction receptacle.

2. To flush out specimen together with diluents.3. Plastic or glass syringe with plunges (Teflon)

Displacement MediumLiquid-(Diluents or reagent) -Highly reproducible measurement.Air: Less accuracy (Viscous fluid) Lipaemia/ Hyper protinemia.Categorization: -Fixed -Variable

-Selectable- Predetermined volumes widely used in systems.

Inaccuracy/ Imprecision-Not >1 %(Specimen and Reagent)

Periodic Verification of Accuracy & reproducibility.

Delivery of Specimens- Built -in Conveyor Track or Specimen Carrier (Robotic)

Carry over-”Unintended transfer of a quantity of analyze or

reagent by an analytical system from one reaction into sub sequent one”

“ Error in analysis”Protocols to minimize Adequate flush to specimen ratio-4: 1 (Wash station /Sample

probe) . Choice of sample probe materials . Surface conditions Flushing internal/ External surface of sample probe. Wiping of outside. Disposable sample probe tips for the Pipetic Systems Stringent requirement- For Immunoassays. -Additional washes /devices.

-Additional rinsing function

Reagent Handling and Storage Liquid reagents-Plastic/glass containers. System Packs-No refill Mostly single reagent Impregnated slides/Strips ElectrodesStorage Refrigeration Reagent storage compartment(40- 100 C) Stable 2-12 months.

Liquid Reagent system:

Large volume –Adequate for operation Container- Reagent (Test by Test) Limited stability- Preparation (fresh)

Non-Liquid Reagent System:

No/Very little liquid Dry systems- Multilayered slides-Reagent emulsions

Multilayered film chip-Reagent impregnation.

Reusable Reagents-Immobilization in reaction coil or chamber.-Immobilization of enzymes on membrane –Buffer - wash solution

Reagent IdentificationLabels-Reagent Name Volume No. of tests Expiry Date Lot No.

Barcodes:1.Facilitation of inventory management2.Insertion of reagent container in random sequence.3.Automatically dispense a particular volume of liquid reagent. In immunoassay system- Key information –Calibrators.

Open Vs Closed SystemsOpen- Reagent from variety of Suppliers Flexibility Ready adaptation Less expensive Longer open stabilityClosed: Reagent –Unique container Formats by manufacturer Hidden cost advantage Avoidance of variability arising from reconstitution of

reagent. Open variable stability short.Most Immunoassay system -Closed

Reagent Delivery Liquid Reagent Pumps (Through tubes) + ve displacement syringes devises. Mixing and reaction chambers

Pumps: Peristaltic pumps -Compressing and releasing of reagent tubes. -Deliver the fluids. -Determination of the proportion of

reagent to specimen. Syringes Devices- Reagent and Specimen common + ve displacement. Volumes –Programmable. Reproducible ±1 % Washing and Flushing facility.

Chemical Reaction Phase Chemical Reaction=Specimen + ReagentIssues of concern in designing Analyzer.1.Vessel- Reaction occurs, -Cuvet- reaction monitored.2.Timing of reaction3.Mixing and transport of reactants .4.Thermal conditioning of fluids.Types of reaction vessels and cuvettes: Continuous flow systems- Tube- Flow container - Cuvet Discrete Systems

Discrete System Each specimen- Separate Physical - Chemical space1. Individual (Dispensable/Reusable) Reaction vessels. -Transported2. Stationary reaction chamber

Cuvets –Reusable / Disposable -Simplification -Avoid carry over -Superior plastic (Acrylic & polyvinyl

chloride)

Requirement Large scale production Excellent dimensional tolerance Must be transparent in spectral range.

Reusable reaction Vessels B &C Synchron Abott OlympusPeriodic replacement –Composition 1 month- Plastic 2 yrs- Std glass If Physically Damaged–Pyrex glass

Cleaning CuvettesWash station –Aspiration of reaction mixture Detergent –Alkaline -acid wash Repeated Dispensing/Aspiration Rinsing- Deionizer. Drying –Vacuum , Pressurized Air.Optical Clarity is verified Unsatisfactory -Flagging

- ReplacementReusable Cuvettes:Economical Increased complexityRequirement of cleaning liquids

Centaur- Individual cuvettes 200-1000 can be loaded.Dimensions- Manufacturer by instrument surlyn clear plastic.

Timing of ReactionRate of Transport-Measurement station Timed events of reagent additive or activation.

Discrete systems Addition of specimen & reagents at timed sequence.Absorbance at intervalsTimings- Defined by ManufacturerMixing of Reactants Forceful dispensing Magnetic stirring Rotating paddle Use of ultrasonic energyMixing –Difficult to automate.

Thermal Regulation 370 C

Controlled –Temperature Environment Close contract to reaction container Efficient heat transfer environment- Reaction

mixture.

Air Baths Water Baths Cooling plate

Measurement Approaches

Chemistry Analyzer-- Photometers-SpectrophotometerAlternative Approaches-- Reflectance Photometry-FluorometryImmunoassay: -Florescence-Chemilluminiscence-Electro chemilluminiscenceElectrolytes: ISE- Electrochemical

Signal Processing, Data Handling and Process Control

Computers-Integral Components -Analysis -Reporting Process

-Control of Data inputs -Monitoring -Data Reporting

Work Station- Integration Interphasing of individual Analyzer.Acquisition Processing of Analytical Data Software (Sophisticated)

1.Command and Phase the electromechanical operations Transfer of Solution Placement of proper filter Regulation of speed of rotation

2.Operational features: Calculation of results Increase Reproducibility

3.Acquire, assess, process and store operational dataCommunication integrations between analyzer & operator Replenish reagents Empty waste container Warn operating problems Status of every specimen

Flagging Exceeding of Linearity Sub strata exhaustion Absorbance problem4. Interfacing Facility5.Computers incorporated into instruments- Special Capability.QC Calibration curves.

Computer Work station Monitoring & Integration Accept test order, Monitoring of testing process Assisting with process quality Review and verification of results. Display of L J Chart. Troubleshoot monitoring Auto verification of results.

Questions in our Mind Increase in our work load ? Tackling increase work load ? Quality Result Reporting ? Error Prevention ? Complete control ? Improve TAT ? Adding new assays ? Stream lining the processes ? Improving Services ? Over coming shortage of trained technicians ?

Single Answer is -Automation

Benefits: Reduction - variability of results -Errors of analysis

Avoidance- -Manual- boredom or inattention

Improved reproducibility-Quality improvement Skill fully designed automated instrument Good analytical methods Effective QA program

Cost Effectiveness

Ten Reasons why Automation Fails to Meet Expectations

Incomplete understanding of current environment, processes, cost, customer expectation.

Loss in flexibility because of fixed process and limited throughput

Unrealistic Expectations of system-Cost reduction, throughput returns on investment.

Unplanned and poorly developed “work around” require to interfere automation with manual processes.

Unclear expectation s of system functionality.

Over build and Unnecessarily complicated system design.

Inadequate technical support Credible and realistic impact analysis never

conducted. Hidden costs-Labor, supplies, maintenance Failure to optimize current processes before

automation (Never automate a poor process)

“Let us Thank All the Brains Behind Automation “

For Making Our job Easy and Pleasurable and

our life Peaceful ……