Automation

Automation

• 1.
  Automation in ClinicalChemistry Tapeshwar Yadav (Lecturer) BMLT, DNHE, M.Sc. Medical Biochemistry
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  What is Automation Useof 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”.
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  History  Began-1950  Escalationof 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 simplification Manual- Machine (Various stages of Analytical Procedures)
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  Evolution  Fixed Automation-repetitivetask 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
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  Automations Extending:  Processingand transport of specimens  Loading in to analyze  Assessing the results
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  Processes used inAutomation  Continuous flow  Discrete Processing
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  Continuous flow analysis: By:Leonardskeggs in 1950 • Pioneered device  Single-channel  Continuous flow  Batch analyzer Throughput: 40-60 specimen/hour One result /analyte for each specimen
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   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)
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  Discrete analysis: (1970) Widelyused  Each specimen in a batch – “Separate from every other specimens” Discrete processing is used by-  Centrifugal  Random access Analyzer
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  Centrifugal Analyzers:  1970–Norman Anderson  Oak Ridge National laboratory-US
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  What happens : Discretealiquots 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)
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  Early analyzers:  Analysisof 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).
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  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)
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  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.)
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   Most currentchemistry and Immunoassay analyzers are Random access. Steady Improvement -Mechanical reliability. -Software technology Easy Operation
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  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.
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   Total LabAutomation:  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 belt Tube recapping machine Storage system.
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  Modular Automation (1990) Selected Modules -Analyzers -ISE  Marketed successfully  LAS (Laboratory Automation System).  TLA Require extensive software  Module.
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  Steps in AnalyticalProcesses  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.
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  Specimen Acquisition.  Samplecollection- Automation (In process of Development)  Zivonovic and Davis –Robotic System. -Flat headed probe – location of vein. -Automatic needle withdrawal.
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  Specimen Identification  Identifyinglink  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.
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  Labeling • Test order •Electronic Entry • Generating Unique identity of specimen • Unique lab accession number • Records • Till reporting
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  • Labeling oftubes • Critical for processing • Log in procedures • Technical handling • Secondary labeling (If needed)
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  Bar-coding • Major automationof specimen identification • LIS • Bar-coded label • Specimen container • Read-Barcode reader • Identification information (By software)
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  Advantages • Elimination ofwork 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.
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  Specimen delivery tolab • Courier • Pneumatic tube system • Electric track vehicles • Mobile robots COURIER: • Human courier • Batch process • Specified timings • Delay in Services • Specimen loss . Etc..
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  Pneumatic- Tube system •Rapid transport • Reliable • Point to point services • Mechanical problem • Damage of specimen • Limited carrying capacity • Cost effective Electric track vehicle: • Larger capacity • No specimen damages • Larger stations • ?Rapid specimen transport Mobile Robots: • Studies- Establish usefulness • Delays • Batched pick up. etc, • Cost effective
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  Specimen Preparation • Clottingof blood • Centrifugation (Serum) Time Consuming - Delays • Secondary tube Developments- Note worthing • Use of whole blood 1.Assay system-Analyzer whole blood • Specimen preparation time-Elimination Eg. ISE- with in minutes 2.Application of whole blood to dry reagent films. • Visual • Instrumental observation (Quantitative)
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  Specimen loading andaspiration Specimen- 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 degradation Temperature labile-Refrigeration loading zone Photo labile –Semi opaque containers
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  Loading Zone- Areas ofspecimen holding- • Circular tray • Rack/ Series of racks • Serpentine chain No Automatic specimen identification • Loading of Specimens- correct sequence as per loading list Automatic Specimen Identification- Reposition of Specimens Loading- 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.
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  Transmission of InfectionsDisease • Common concern 1.Splatter-Acquisilion by Specimen probes Prevention -Level Sensors -Restriction of Penetration -Smother motion control 2.Aerosols- -Potential for contamination -Specimen Transfer -Spillages • Prevention- Closed Container -Sampling system.
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  Specimen Delivery Continuous flow Sampleprobe Continuous reagent stream Discrete analyzer Sample Probe Reaction cup
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  Discrete Pipetting • Positive–Liquid-Displacement pipette • Specimens/Calibration/Controls Operational 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)
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  Displacement Medium Liquid-(Diluents orreagent) -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)
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  Carry over- ”Unintended transferof 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
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  Reagent Handling andStorage • Liquid reagents-Plastic/glass containers. • System Packs-No refill • Mostly single reagent • Impregnated slides/Strips • Electrodes Storage • Refrigeration • Reagent storage compartment(40- 100 C) • Stable 2-12 months.
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  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
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  Reagent Identification Labels- Reagent Name •Volume • No. of tests • Expiry Date • Lot No. Barcodes: 1.Facilitation of inventory management 2.Insertion of reagent container in random sequence. 3.Automatically dispense a particular volume of liquid reagent. • In immunoassay system- Key information –Calibrators.
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  Open Vs ClosedSystems Open- Reagent from variety of Suppliers • Flexibility • Ready adaptation • Less expensive • Longer open stability Closed: • 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
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  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.
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  Chemical Reaction Phase •Chemical Reaction=Specimen + Reagent Issues of concern in designing Analyzer. 1.Vessel- Reaction occurs, -Cuvet- reaction monitored. 2.Timing of reaction 3.Mixing and transport of reactants . 4.Thermal conditioning of fluids. Types of reaction vessels and cuvet: • Continuous flow systems- Tube- Flow container - Cuvet • Discrete Systems
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  Discrete System • Eachspecimen- Separate Physical - Chemical space 1. Individual (Dispensable/Reusable) Reaction vessels. -Transported 2. Stationary reaction chamber Cuvets – Reusable / Disposable -Simplification -Avoid carry over -Superior plastic (Acrylic & polyvinyl chloride)
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  Requirement • Large scaleproduction • Excellent dimensional tolerance • Must be transparent in spectral range. Reusable reaction Vessels • B &C Synchron • Abott • Olympus Periodic replacement –Composition • 1 month- Plastic • 2 yrs- Std glass • If Physically Damaged–Pyrex glass
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  Cleaning Cuvets Wash station–Aspiration of reaction mixture • Detergent –Alkaline -acid wash • Repeated Dispension/Aspiration • Rinsing- Deionizer. • Drying –Vacuum , Pressurized Air. Optical Clarity is verified • Unsatisfacting -Flagging - Replacement Reusable Cuvets: Economical Increased complexity Requirement of cleaning liquids Centaur- Individual cuvet 200-1000 can be loaded. Dimensions- Manufacturer by instrument surlyn clear plastic.
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  Timing of Reaction Rateof Transport-Measurement station • Timed events of reagent additive or activation. Discrete systems • Addition of specimen & reagents at timed sequence. Absorbance at intervals Timings- Defined by Manufacturer Mixing of Reactants • Forceful dispensing • Magnetic stirring • Rotating paddle • Use of ultrasonic energy Mixing –Difficult to automate.
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  Thermal Regulation 370C • Controlled –Temperature Environment • Close contract to reaction container • Efficient heat transfer environment- Reaction mixture. • Air Baths • Water Baths • Cooling plate
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  Measurement Approaches Chemistry Analyzer- -Photometers -Spectrophotometer Alternative Approaches- - Reflectance Photometry -Fluorometry Immunoassay: -Florescence -Chemilluminiscence -Electro chemilluminiscence Electrolytes: • ISE- Electrochemical
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  Signal Processing, DataHandling 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)
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  1.Command and Phasethe 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 data Communication integrations between analyzer & operator • Replenish reagents • Empty waste container • Warn operating problems • Status of every specimen Flagging • Exceeding of Linearity • Sub strata exhaustion • Absorbance problem 4. Interfacing Facility 5.Computers incorporated into instruments- Special Capability. QC Calibration curves.
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  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.
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  Questions in ourMind  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
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  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
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  Ten Reasons whyAutomation 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.
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  • Over buildand 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)
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  “Let us ThankAll the Brains Behind Automation “ For Making Our job Easy and Pleasurable and our life Peaceful ……