Automatic Analyzer

 Automatic Analyzer

Complete automation will lead to human prohibition in pharma industries.

“One machine can do the work of fifty ordinary men, no machine can do the work of one extraordinary man”

automation as the use of combinations of mechanical and instrumental devices to replace, refine, extend or supplement human effort and facilities in the performance of a given process, in which at least one major operation is controlled without human intervention, by a feedback mechanism.

Benefits of Automation

  • Faster analyses up to 120 samples per hour.
  • Up to 300 samples can be analyzed in batch.
  • Automatic data recording and preparation
  • Being a closed system, automation reduces contamination, for e.g., from atmospheric gases.
  • Greater accuracy and reproducibility of results as all samples are subject to same processes.
  • Smaller sample and reagent volumes which reduces cost.
  • Automatic range changing, drift control and automatic sample preparation.

Need for automation

  • The partial or complete replacement of human participation in laboratory process is a growing trend.
  • Increasingly stricter control of growing number of samples in which a large number of analyts are to be determined at increasingly low concentration.
  •  Cost reduction.
  • In research for increased accuracy, precision, and productivity, the pharmaceutical analyst seeks to select optimal measurement and to automate as appropriate.

Automated device

 They are defined as those encasing automation.

They are conceived to make decisions with the aid of feedback system, without human intervention. There is a different operation sequence for each situation (sample).Some system are self-monitoring and self-adjusting ,have greater independence than automatic devices and are sometimes called ‘completely automatic’.

Automation is used for

  • Facilitating an analytical technique or method.
  • Processing of large number of samples.
  • Determination of several components in the same sample.
  • Reduction of human participation to. 
    • Avoid error.
    • Cut costs.
  • Increasing sample throughput.
  • Process (industrial or otherwise ) control.
  • Lowering consumption of sample and/or reagent(s).
  • Samples, occasionally dealt with in large number or valuable to deal with manually.
  • Analyts, which are sometime present in very dissimilar or low concentration in sample. 
  • Reagents, some of which are rare or expensive even unstable.
  • Rapidity, frequently essential in large laboratories such as those in hospitals, urgently requiring the analytical result, and of industrial and other laboratories require in constant availability of data for process controls.
  • Economy, in personnel and material expenditure.
  • Precision, closely related to the elimination of both definite and indefinite errors arising from the so-called ‘human factor’ (tiredness, mood, prejudice, pathological, complaints and so forth).
  • Data generation , some analytical technique are based on the acquisition of a large number do data, especially in the drug discovery and development stages.

Classification of automatic analyzers

  • According to the degree of automation
    • Automatic
    • Semi-automatic 
  • According to the way in which samples and reagents are transported 
    • Batch (discrete)
    • Continuous
      • Segmented
      • Unsegmented
    • Robotics
  • According to the number of analytes per sample
    • One parameter
    • Multi-parameter
  • According to flexibility
    • Specific
    • Flexible
  • According to source
    • Commercial
    • Hand-made
  • According to the state of aggregation of sample
    • Gas analyzer
    • Liquid analyzer
    • Solid analyzer
  • According to sample frequency
    • One-off
    • Periodic
    • Continuous

Types of Automatic Analysis Technique

Basically there are two types of automatic analysis techniques/instruments

Discrete sampling instrument- In discrete sampling, each sample undergoes reaction and measurement in a separate cuvet or chamber. These samples may be analyzed sequentially or in parallel.

Continuous –flow sampling instrument- In continuous flow sampling, the samples flow sequentially and continuously in tube perhaps being separated by air bubble. They are each sequentially mixed with reagent in the same tube at the sample point down stream and then flow sequentially into a detector 

Discrete Analyzers ( Batch Analyzer)

A discrete analyzer handles each individual sample as a separate entity and is usually a single channel instrument. In some designs both sample and reagent are metered into discrete reaction vessels. However , most of the system have specially design cells that already contain pre pack amount of required reagent for given analyte and thus making sample introduction only the necessary step. In both cases reagents are combine with sample in discrete cuvettes where mixing, incubation and final color measurement occurs.

Continuous Flow Analysis

There are two kind of Continuous Flow Analysis:

  • Segmented flow analysis
  • Flow Injection Analysis

Segmented flow analysis

It includes a peristaltic pump that continuously aspirates sample and reagent, a variable no. of tubes constituting a manifold to circulate liquid and a detector system. Aspirated sample are segmented by injecting air bubbles that should be remove before they can be reaching to the detector. At detector air bubble are removed and thus each sample is separated by washing solution, thus a square shaped detector response is obtained, the height of rectangle is directly proportional to conc. of analyte.

Flow Injection Analysis (FIA)

FIA is like a HPLC without a column. It is low pressure and without separation. The injected sample mixes and reacts with the flowing stream. A transient signal is recorded. FIA is based on the injection of a liquid sample into a moving continuous nonsegmented carrier stream of a suitable liquid. The injected sample forms a zone which is then transported towards a detector. Mixing with reagent in the flowing stream mainly occurs by diffusion-controlled process and a chemical reaction occurs. Detectors continuously record the physical parameter as it changes as a result of passage of sample material through flow cell.

There are mainly five types Flow Injection Analysis

  • Syringe based injection system
  • Injection with rotary valve
  • Proportional injection
  • Merged injection 
  • Hydrodynamic injection 

Automation Approach in Analysis

  • A serial (or sequential ) automation process.
  • A parallel automation process.
  • Hybrid Automation Systems.

A Serial (Sequential) Automation Process

The general characteristic of a serial automation process is that a given determination reaches completion before the next determination begins, although with some serial automation systems, the second determination may be started before the first is completed. Serial automation could also be configured in an on-line arrangement, where tandem processes in the chemical determination are performed by collection from a flowing stream.

Parallel Automation Process

Parallel Automation Process  for chemical analysis is, simply, a process where more than one automated chemical manipulation is performed simultaneously.

These parallel manipulations can encompass some or all of the following discrete analytical chemistry operations: 

Experiment initiation, Sampling (obtaining the samples), Sample preparation, Component separation, Analyts detection and reduction/reporting   

Hybrid Automation Systems

Hybrid automation systems for chemical analysis combine features of both serial and parallel systems. Some processes are conducted in serial, some are conducted in parallel, and all are integrated into a single system. Conceptualized semi automated 96-well liquid–liquid extraction procedure.  

Hybrid Automation = Serial Automation + Parallel Automation.

Hybrid Automation Systems

In Robotic solid-phase extraction method development system, a central robotic arm (XP) which service various arm peripherals, and a 144-port vacuum manifold, used for solid-phase extraction method development. The system and development of the solid-phase extraction columns, which are in parallel. Although a fully parallel system would have been desirable, it was beyond the capabilities of commercially available system at this time. 

Basic Automatic Analysis System

  • Sampling unit
  • Proportioning pump
  • Manifolds
  • Dialyzers
  • Constant temperature bath
  • Detector
  • Recorder

Sampling unit

The sampling unit enables an operator to introduce unmeasured sample and standards into auto analysis system. The unit in its earlier form consisted of a circular turntable. The sample plate carrying these cups rotates at a predetermined speed. The movement of turntable is synchronized with the movements of sampling crook. The crook carries a thin flexible polythene tube, which can dip into cup and allow water, standard or test solution to be aspirated. The samplers are fitted with a sample mixer, which enables the sample to be mixed before and during aspiration. The automatic samplers employs a different washing action between samples.

Proportioning Pump

The function of proportioning pump is to continuously and simultaneously push the fluids, air and gases through the analytical chain. Samples and reagents are driven single peristaltic pump. A series of flexible plastic tubes, one from the sampler the other from reagent bottles or simply drawing air, are placed length wise along the platen spring loaded platform. The roller head assembly is driven by a constant speed gear motor. When the rollers are pressed down and the motor switched on, they compress the tube containing liquid streams against the platen. As the roller advance across the platen, they drive the liquid before them.

Manifolds

A manifold mainly consists of a platter, pump tubes, coils, transmission tubing, fittings and connections. Mixing coils are used to mix the sample/reagent. As the mixture through a coil, the air bubble along with the rise and fall moton produces a completely homogenous mixture. Delay coils are employed when a specimen must be delayed for a completion of chemical reaction before reaching the colorimeter. Various types of fittings are employed to join stream of liquids to split a stream or to introduce a air segmentation to the stream. The reagents line are segmented by introducing air through one or more additional tubes in the manifold. This produces a series of bubbles at a regular intervals in the liquid stream. This is designated as bubble pattern

Dialyzer

Dialysis is accomplished to remove protein cells to obtain an interference free analysis. The dialyzer module consists of a pair of Perspex plates, the mating surface of which are mirror grooved in a continuous channel, which goes in towards the centre on itself and returns to the outside. A semi permeable cellophane membrane is clamped between the two plates. Cellophane membrane use has a pore size of 40-60Å.

Constant temperature bath

On leaving the dialyzer, the stream may be combined by one or more additional reagents. It is then passed to a heating bath. A thermostatically controlled immersion heater maintains a constant temperature within ±0.1.

Detector system Mainly used detector Colorimeter Flame photo meter Flourimeter

Signal Processing and Data-Handling Modern automatic analysis systems make use of a PC as multi tasking data processor and system controller. However such multi tasking is used with the use of microprocessor based analogue interface card which fits neatly into a standard extension slot inside the computer.

Recorder

The most common type of recorder used with automated system is dc voltage null-balance potentiometer recorder. Significant fluctuations in the flow pattern may result in irregularities of the base line on a recorder. Irregularities are also produced due to a drift in the electronic circuit. Pulse suppressor are used to smoothen out fluctuations. 

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