Dr.

Gangadhar Chatterjee
MBBS;MD
Assistant Professor
RCSM Govt. Medical college, Kolhapur, MH, India
Use 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 simplification
Manual- 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

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
 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 belt

Tube recapping machine

Storage system.
 Selected Modules
-Analyzers
-ISE
 Marketed successfully

 LAS (Laboratory Automation System).

 TLA
Require extensive software
 Module.
 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.
 Sample collection-
Automation
(In process of Development)

 Zivonovic and Davis –Robotic System.

-Flat headed probe – location of vein.
-Automatic needle withdrawal.
 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.
  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)

 Major automation of specimen identification
 LIS

 Bar-coded label

 Specimen container

 Read-Barcode reader

 Identification information (By software)

 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.
 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 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
 Clotting of 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)
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
Areas of specimen 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.
 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.
Continuous flow Discrete analyzer

Sample probe Sample Probe

Continuous reagent stream Reaction cup

 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)

Liquid-(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)
 “ 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
 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.

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
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.
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
 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=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 cuvettes:
 Continuous flow systems- Tube- Flow container
- Cuvet
 Discrete Systems
Discrete System
 Each specimen- 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)
Requirement
 Large scale production
 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
Wash station –Aspiration of reaction mixture
 Detergent –Alkaline
-acid wash
 Repeated Dispensing/Aspiration
 Rinsing- Deionizer.
 Drying –Vacuum , Pressurized Air.
Optical Clarity is verified
 Unsatisfactory -Flagging
- Replacement
Reusable Cuvettes:
Economical Increased complexity
Requirement of cleaning liquids

Centaur- Individual cuvettes 200-1000 can be loaded.

Dimensions- Manufacturer by instrument surlyn clear plastic.
Rate of 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.
 Controlled –Temperature Environment
 Close contract to reaction container
 Efficient heat transfer environment- Reaction
mixture.

 Air Baths
 Water Baths
 Cooling plate
Chemistry Analyzer-
- Photometers
-Spectrophotometer
Alternative Approaches-
- Reflectance Photometry
-Fluorometry
Immunoassay:
-Florescence
-Chemilluminiscence
-Electro chemilluminiscence
Electrolytes:
 ISE- Electrochemical
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 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.
 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.
 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
 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 ……