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ACADEMIA ROMÂNĂ
Revue Roumaine de Chimie
http://web.icf.ro/rrch/
Rev. Roum. Chim.,
2015, 60(5-6), 403-414
ANALYTICAL CONTINUOUS FLOW SYSTEMS. WHERE TWO WORLDS
COLLIDE! FROM GRAVIMETRY AND TEST TUBES TO FLOW SYSTEMS
TO FIA TO SIA TO PAT
AND FROM ORSAT TO CONTROL ROOM TO PAT TO TAP
Jacobus (Koos) Frederick VAN STADEN
Process Analytical Technology Laboratory (PATLAB) Bucharest, Splaiul Independenţei Str., 202, Bucharest-060021, Roumania
E-mail: koosvanstaden2012@yahoo.com; Website: www.patlab.ro
Received November 10, 2014
Manual analysis plays a dominant role in most of the Analytical World from the 17th century up to most of the 19th century,
dominantly used in the 1940-1970 and even later into the 20th century. Therefore the first part of the talk will start with “weighing”
analysis in the AlChemy era around 1350 BC, followed shortly by flow analysis with chromatography starting in 1905, some non-
segmented inventions in 1911 and the road of Leonard T. Skegss in the early 1950 to the AUTOANALYSER era in the 1960’s. FIA
started with Jarda Ruzicka and Elo Hansen in the mid seventies on LEGOs. The first practical FIA for the water authorities was soon
after built in the Chemistry Department at UP in South Africa, followed by various different configurations up to the first process
analyzer. A normal ink pen led to the first concept of SIA in Pretoria followed by the collaboration with CPAC and Jarda Ruzicka at
the University of Washington, USA with Graham Marshall as PhD student who completed his PhD at the University of Pretoria in
the early nineties. This was followed by numerous developments of process analyzers leading eventually to the PAT concept from
the continuous flow viewpoint. This is road one in the analytical world. I started my career at SASOL with manual analysis in a
routine laboratory, where I also came in contact using the ORSAT gas analyzer that was patented before 1873 by Mr. H Orsat.
Various instruments play a dominant rule in gas analysis in the 1970-1980, with GC most of the time the front runner. In the 1980s
and early 1990s, various aspects of automated non-destructive spectroscopy and the first version of scanning spectroscopy was
introduced by the Chemistry Department in Pretoria leading to the first PAT type configurations with chemometrics and the second
road crossing road one. These types of innovations were followed by some initial work in TAP that cultimated currently to the
modern technology with TAP technology in gas systems. The talk highlighted various innovation aspects from chromatography, flow
systems, FIA, SIA, PAC and PAT to Real-time Integrated Industrial Monitoring and Control Information Management Systems and
eventually to the temporal analysis of products (TAP) concept with the latest TAP concept and a future vision of invasive and non-
invasive non-destructive real-time integrated multi-analyte fully automated interactive process analyzers as incentives and new
paradigm concepts of innovative, low cost, easy to operate, portable sensing platforms with an interrogative kinetics approach for
fast, transient measurements and a high time resolution in industrial processes.
INTRODUCTION AND THE BACKGROUND, THE BEGINNING
Retrieval of data revealed that manual analysis plays a dominant role worldwide from the 17th century
up to most of the 19th century and strange also forms part of the early 20th century. “Weighing” analysis or a
rough form of direct “gravimetric” analysis was probably performed around 1350 BC when the Babylonians
start to use fire assay to test the purity of gold by comparing the “weight” before and after fire assay.
Gravimetry is among the most accurate analytical techniques and gravimetric determinations form for a long
period part of chemical analysis as a basic reference standard method, but although it was part of most
analytical university practical courses during the 19th century,1-5 the technique lost it place in Analytical
Chemical assays due to the tedious and time consuming procedures that are followed. Mohr’s argentometric
method of determination of chlorides (published by Karl Friedrich Mohr in 1856) by titration of silver nitrate
is one of the oldest titration methods still in use. It is a very simple method. Chlorides are titrated with silver
404 Jacobus (Koos) Frederick van Staden
nitrate solution in the presence of chromate anions and the end point is signalled by the appearance of red
silver chromate.1-5 Titrimetry is another analytical concept that is for a long period with us as illustrated on
the cover of the thesis of a Danish historian (Fig. 1) of Analytical Chemistry.6 What is furthermore
interesting is that the volumetric glassware and concepts of solution handling have changed very little during
the last 200 years except that we are now moving to the micro scale with micropipettes.
Fig. 1 – Volumetric glassware and concepts. Cover of the thesis of a Danish historian
of Analytical Chemistry. Reproduced from Ref. 6.
CHROMATOGRAPHY INVENTION
The idea of flow analysis was first employed by Ramsey in 1905 with chromatography to separate
mixtures of gases and vapours.7,8 This was followed by Mikhail Tswett in 1906 when he obtained a number
of colored bands of plant pigments on a chromatographic column packed with finely divided calcium
carbonate.9 Martin and Synge enunciated the concept of Gas-Liquid Chromatography (GLC) in 1941 in a
pioneering theoretical study of theoretical plates,10 introduced GLC11 and received the Nobel Prize in 1952.12
The first Gas-Chromatography (GC) instrument appeared on the market in 1956. The sensitivity, speed,
accuracy, identification, and determination of volatile compounds have resulted in a phenomenal growth in
the 1960’s. SASOL was one the first petroleum and petrochemical industries that installed a number of GC
instruments in their special laboratory and it was estimated that around 60,000 gas chromatographs were
already in use at the end of the 1960’s in the world.7
Analytical continuous flow systems 405
NON-SEGMENTED FLOW SYSTEMS
Non-segmented flow systems (NSFS) were first recorded by Dr Albert Griffiths of Birkbeck College
in 1911 when he measured viscosity of water at very low flow rates using a drop of fluorescein solution as
marker in a carrier stream of water flowing slowly through a capillary tube.13 At slow flow rates radial
diffusion plays the dominant role, and the colouring matter travels along the tube approximately as if the
liquid moved in a solid column. Therefore with the introduction of a short length of fluorescein solution into
the carrier stream in the tube, a symmetrical coloured column of slowly increasing length is obtained, the
centre of which indicates the mean speed of the liquid. Sir Geoffrey Taylor studied the dispersion of an
injected portion of soluble matter in water flowing through a tube14 and his theory on the effect of molecular
diffusion on dispersion forms one of the basic aspects that was considered on the development of the initial
theory of Flow Injection Analysis.6
THE AUTOANALYZER ERA
The concept of air-segmented continuous-flow analysis was pioneered by Leonard Skeggs (Fig. 2)15 in
the early 1950s due to an ever increasing workload of urine and blood samples in a large clinical laboratory
that could not cope anymore with tedious and time consuming manual analysis with the larger intake number
of samples into the large clinical laboratory. In this origin of wet-chemistry automated analysis the main
instrumental development was dedicated to liquid transport under dynamic flow conditions. His design of an
automatic analyzer presented several novel features on the automatic analysis of blood for urea nitrogen,
glucose, calcium, chloride, alkaline phosphatase, and acidity. In the first prototype version of an
AutoAnalyzer in 1953 (Fig. 3)15 presented by Skeggs, the main unique features of the instrument in addition
to the continuous peristaltic flow of samples (from an automatic disc sampler tray) and reagents from
(reagent bottles), were the manifold of the system that featured a dialyzer membrane to remove suspended
solids and proteins before tubing transport of liquids by a sort of peristaltic pump. An operational feature of
Skeggs’s air-segmented flow system was the introduction of an air segment in addition to sample and
reagents where an air bubble separates each sample/reagent mixture in the liquid stream once it has been
merged with it. The introduction of air causes each individual sample/reagent mixture to be divided into a
number of small segments. The manifold of the instrument was further made of mixing glass coils as reactors
where the different segments of samples were mixed with reagent solutions with heating or heat incubation if
necessary to form reaction products of the different sample/reagent segments for photometric detection. This
segmentation is retained through the succeeding stages of the analysis up to the photometer at a certain
wavelength where the air is removed in a vented flow-through cell and a continuous solution phase is
reformed.15-17 These principles of invention of Skeggs AutoAnalyzer SFA instrument have been exploited,
extended and commercialized by Jack Whitehead’s Technicon® Corporation in the Technicon
“AutoAnalyzer” with the first commercial “AutoAnalyzer” launched in 1957 (Fig. 4)15 which dominated the
continuous flow field during the sixties and the first part of the seventies.16-22 In the conventional Technicon
AutoAnalyzer measurements are based on steady-state situations in which the physical and chemical
processes in the aliquots of sample and reagent are able to reach equilibrium, resulting in steady-state signals
that are more accurate and reproducible. There were also some critical remarks on the “AutoAnalyzers”,23
but the criticism could not stop the success of the Technicon “AutoAnalyzer”. The first multiple analyzer
was already developed by Skeggs and Hochstrasser in 1964, that led to the very successful Sequential
Multiple Analyzer (SMA 12/60, 1969), an analyzer able to run 60 samples per hour for 12 analyses. In 1973
a computerized version, the Sequential Multiple Analyzer with Computer (SMAC), appeared on the market
which performed 20 analyses on every sample every 20s and both these instruments together with the
AutoAnalyzer II (introduced 1970) were the backbone of many routine clinical and other laboratories and the
best known of Technicon's CFA instruments.15,19-22 Skalar, a Dutch company from Breda, was established in
1965 as a producer of analyzers for the laboratory and process industry and manufactures a range of
automated chemistry analyzers i.e. for the environmental, pharmaceutical, agricultural, detergent, food and
beverage laboratories with worldwide sales, support and distribution. It has since grown into a multinational
organization with its own subsidiaries in most European countries and has extended the product lines to the
very successful San++ Automated Wet Chemistry Analyzer also known as the Continuous Flow Analyzer
406 Jacobus (Koos) Frederick van Staden
(CFA) or also called Segmented Flow Analysis (SFA) technique where up to 16 analytical measurements can
be made on a single sample simultaneously.24 SEAL Analytical has over 50 years experience in
environmental and industrial automated analyzers. SEAL Analytical purchased Bran+Luebbe, who earlier
purchased Technicon Corporation, was the first to commercialize Continuous Flow Analysis and the
QuAAtro39 AutoAnalyzer that is the very latest generation of the original world-class Technicon Continuous
Segmented Flow Analyzer (SFA).25
Fig. 2 – Leonard T. Skeggs Jr. Reproduced from Ref. 15.
Fig. 3 – Prototype AutoAnalyzer version in 1953. Reproduced from Ref 15.
Fig. 4 – First commercial AutoAnalyzer launched in 1957. Reproduced from Ref 15.
Analytical continuous flow systems 407
ORSAT, SASOL, MIMS, CAPILLARY GC, FIRST STEP TO LIMS
When SASOL (Suid-Afrikaanse Steenkool-, Olie- en Gaskorporasie, South African Coal-, Oil- and
Gas-corporation) starts production in the late 1950s to the beginning of 1960s, the ORSAT gas analyzer that
was patented before 1873 by Mr. H Orsat, played a very important role in the determination of CO2, O2 and
CO content in the raw feed-gas composition to the Fischer-Tropsch reactor, especially at start-up processes.
The Orsat apparatus was the only sort of semi-automated batch manual analyzer in a very large routine
laboratory operating around the clock. SASOL like many other large industries in the 1950s and beyond used
a traditional approach of process control with mainly off-site (off-line) analysis and with time-delay
monitoring where samples from the operating system (various plant sections of SASOL) were transported to
a large centralized laboratory for routine analysis.26 As the number of samples from the various plants was
numerous, SASOL initiated one of the first Manual Information Management Systems (MIMS) by using a
recorded indexing of different samples at the entrance into the central laboratory system with distribution to
various laboratory facilities, followed by routine analysis and data reporting back to the different plants. In
the petroleum refinery and petrochemical industries different petroleum products ranging from gases, light
petroleum products, gasoline, diesel etc. are produced from crude oil using mainly refluxing and distilling
towers. Temperature (thermal probe) and pressure were main process variables and real-time monitoring was
already done in the early 1960s at SASOL from large control rooms with on-site in-line analysis base on
temperature and pressure where sampling probes penetrate the process. Commissioned in 1971, the Natref
refinery (National Petroleum Refiners of South Africa) at Sasolburg had been at the cutting edge of refining
technology since its inception. It was therefore no surprise that the first miniaturized analytical manifold of a
flow system, as part of a gas chromatograph, was probably the production of one of the first capillary
columns in the Gas Chromatography Laboratory in the early 1970’s at SASOL in Sasolburg, to separate the
complex hydrocarbon mixture from the Naphta Cracker at Natref. A sample splitter was used to prevent
overloading of the miniaturized GC column and this was also accompanied at the same time with the first
fully automated computerized system of the 38 gas chromatographs in collaboration with Siemens,
Germany.27 Although sampling was done manually, the further steps were fully automated as a first step to
Laboratory Information Management Systems (LIMS). Various instruments play dominant rule in gas
analysis in the petroleum and petrochemical industries with volatile composites in the 1970-1980 and even
nowadays, with GC most of the time the front runner.
FIA AND SIA
The first generation of flow-injection analysis (FIA) was introduced in 1975 by Ruzicka and Hansen6
as a simple and convenient concept, which is suitable for increasing sample output in most analytical
laboratories. This pioneering innovation marked an important breakthrough in unsegmented automatic
continuous flow analysis and has developed over four decades as a simple, convenient, feasible analytical
technique with the capability of a high sample frequency and degree of automation.26,28-40 Our main aim was
however to develop multiple-component process analyzers and our first achievement in 1980 was the
simultaneous FIA determination of sodium, potassium, magnesium and calcium in surface, ground and
domestic water (Fig. 5),41 followed by the simultaneous determination of protein, phosphorus and calcium in
animal feedstuffs by multi-channel flow-injection analysis.42 We were also very successful with our main
goal in flow systems in the second half of the 1980s with the achievement of further steps towards process
industrialization with the development and implementation of a fully automated on-line flow system for the
manufacturing of a very important drug where the raw feed materials were non-toxic, but the intermediate
products were very toxic (but inside the manifold tubes and did not come in contact with human beings) and
the final curable drug product was used as medicine.43 The early stages of Laboratory Information
Management Systems (LIMS) in FIA from the mid-1980s up to the new millennium in 2000 were marked by
time-delayed monitoring, semi-automated flow systems, but with a continuous sample feed on-line and even
from in-line.44-48 A normal ink pen led to the first concept of SIA in Pretoria followed by the collaboration
with CPAC and Jarda Ruzicka at the University of Washington in Seattle, USA with Graham Marshall as
PhD student who completed his PhD at the University of Pretoria in the early nineties. The introduction of
sequential injection analysis (SIA)29,34,49-52 broadened the scope of flow analysis. SIA is a technique that has
408 Jacobus (Koos) Frederick van Staden
great potential for on-line measurements and process control with computer control that is essential. The
system is simple and robust and convenient in the way sample manipulations can be automated, it is reliable
with low frequency of maintenance and very low reagents and sample consumption.
Fig. 5 – Schematic diagram of the simultaneous determination of sodium, potassium, magnesium
and calcium. Reproduced from Ref 41.
REAL-TIME INTEGRATED PROCESS CONTROL, RIIMCIMS AND PAT
Our group is however further interested to move the Laboratory Information Management System
(LIMS) to a better version implementing a new innovation development as Real-time Integrated Industrial
Monitoring and Control Information Management Systems (RIIMCIMS) to take advantage of low cost
microprocessors with wireless communication53 to transform and/or upgrade the analytical and control
functions in industrial processes. Our research was initially influenced by interests of an existing base of
monitoring in the petrochemical industry where the initial steps and concepts of PAT was originally used in a
traditional form in and around the large pipe-lines of the industrial continuous flow plant reaction (mostly
organic) processes. An example is SASOL, established in 1950 in South Africa, which is still one of South
Africa largest investors in technological research and development and still one of the world’s largest
producers of synthetic fuels.54 Sasol’s decision to proceed with the front-end engineering and design phase of
an integrated, world-scale ethane cracker and downstream derivatives units and a 96 000 barrels per day gas-
to-liquids (GTL) facility in the US, is the largest foreign direct investment in Louisiana, in the united state’s
(USA) history.55,56 It will be second largest plant of its kind in the world. My viewpoint on the development
of Smart Process Control Analyzer Systems (SPCAS) for relevant industries (Real-time integrated process
control) is that the distance between a truly representative sampling point and a detection probe and the
timing between sampling and detection with final process data in process analyzer systems should be as short
as possible for industries to function optimally and sustainably to deliver high-quality products using either
Process Analytical Technology (PAT) or Performance Product Measurement Techniques (PPMT) or a
combination of both in closed-loop process control for Total Quality Industrial Sustainable Management
(TQISM). The ideal situation will be an interactive real-time sampling, detection probe inside the industrial
process. Some basics in Good Industrial Process Management are the following. In any well-defined
functional industry the following unit operations:- sampling, sample processing, detection, data assembling
and data processing are essential tools for high-quality efficient sustainable production. Relevant industry in
tact dictates the way these operational units are handled and should function properly to satisfy specific
requirements. The sampling environment can range from very high temperatures (up to near 1000 ºC in gas
to liquid refineries) to far below freezing point (in space shuttles), from gas, liquids and solids to solutions
and mixtures thereof, from simple single entities to simple complex matrices, from static difficult complex
Analytical continuous flow systems 409
matrices to rapid dynamic changing difficult complex matrices, from elemental to inorganic to organic
substances and mixtures thereof (homogeneous or heterogeneous and mixtures thereof). What is however
very important, is that timing is essential for fast and very good decisions in the whole process environment.
SULFOLIN PROCESS
In the sulfolin process in the Sasol-Lurgi gasification process vanadium in alkaline medium in the
flue-gas scrubbers is used to remove hydrogen sulphide gas from sour gas streams. In the process H2S is
oxidized to elemental sulphur by vanadium (V) which is reduced to vanadium (IV). Vanadium (V)
concentration should be monitored during this absorption stage in order to monitor the efficiency of the
oxidation-reduction process and also to prevent overloading of the circuit by V(IV), since this leads to a loss
of vanadium from the process. In the reoxidation circuit, V(IV) is oxidized to V(V) with air. During this
phase it is also important to monitor the V(V) concentration, in order to speed up the return of the reoxidized
vanadium to the absorption circuit. A method was required that would be capable of determining V(V) in an
alkaline medium, in the presence of up to a 10-fold excess of V(IV). The monitoring and control was
successfully applied in a process analyzer with an FIA manifold illustrated in Fig 6.44, 57
Fig. 6 – FIA manifold and sampling system used in the process analyser. SP=centrifugal pump; F=0.2pm ceramic cross-flow
filter; SV=selection valve; P=peristaltic pump; W=wash solution; Std 1-4=calibrant solutions; CS1=5 mmol/l CDTA stream;
R=6.8x10-5 mol/L PAR, 5 mmol/l CDTA, 0.1 mol/l phosphate buffer pH 5.3; E=effluent; IV1, IV2=injection valves; SC=stirred
chamber; RC=2.5 m reaction coil; D=LED photometer at 550 nm. Reproduced from Ref. 57.
CPAC AND NeSSI
Process Analytical Chemistry (PAC) and PAT is not new and has been applied in the petroleum and
petrochemical industries since the 1950s, but the demands for real-time quantitative chemical information
near chemical plants on a growing list of manufacturing processes presented new challenges to analytical
chemists, instrument engineers and plant supervisors. In respond to these needs, the Center for Process
Analytical Chemistry (CPAC) was established in 1984 at the University of Washington in Seattle as the
Brain-child of Bruce Kowalsky to work with industry.58 NeSSI (New Sampling/Sensor Initiative) was born
from CPAC in focus group meetings held in 1999 followed with early work that was started in July, 2000 by
Peter van Vuuren (ExxonMobil Chemical) and Rob Dubois (Dow Chemical) with the initial aim of adopting
new types of modular and miniature hardware which were being addressed as a standard for industry being
developed by an ISA (Instrumentation, Systems and Automation Society) technical committee. Both Peter
van Vuuren (ExxonMobil Chemical) and Rob Dubois (Dow Chemical) introduced and promoted the vision
and future concepts of a communication/power bus specifically designed for process analytical control (the
NeSSI-bus) and fully automated sampling systems at a presentation at the International Forum of Process
Analytical Chemistry (IFPAC) at Amelia Island, Florida, USA in January 2001 with the idea to implement
modular, miniature and automated (smart) sample system technology using the mechanical design based on
410 Jacobus (Koos) Frederick van Staden
the American National Standards Institute/Instrumentation, Systems and Automation Society (ANSI/ISA
SP76.00.02-2002) standard.59 The vision and mission of the Nessi concepts include 3 generations with Nessi
I in the time-frame 2000-2002 implementing mechanical, passive components on a SP76 BUS (train)
substrate, Nessi II in the time-frame 2000-2002 with “electrified” passive & active components on a SP76
bus substrate, integral heating and temperature control of the substrate, all electrical components integrated
with a sensor/actuator manager (SAM), sensors and actuators communication via a sensor bus and smart
(self-diagnostic) sample systems and Nessi generation III from 2003 onwards having many analytical sensors
and micro-analytical systems and also wireless sensors. In the presentation of Peter van Vuuren at
IFPAC2008, NeSSI Day, Baltimore, MD, USA, 29 January 2008 with a title of the New Sampling/Sensor
Initiative (NESSI)- An enabling platform for the reduction in Total Cost of Ownership (TCO) of process
analytical systems, he presented a NeSSI BUS Platform with the sampling system and flow channel substrate
with all the components included to move samples to a micro GC analyzer and the spectroscopic
microanalyzers.59 The NeSSI BUS Platform system was and is still very successful with the implementation
in numerous petroleum and petrochemical industries. The current technology of NeSSI uses on-site (at-site)
on-line analysis where the sample is automatically sampled and fed into a dedicated analysing system where
analysis is automatically performed with an automatic feedback to the operating system (for example,
process stream for industrial chemical processes) for adjustment and corrective action with their analytical
system (sensors, detectors) close to the sampling point (by-line) with close-time monitoring or near real-time
monitoring.26
FROM PAT TO TAP
The increasing demand from the petroleum and petrochemical and other relevant industries in the
1990s to real-time integrated process monitoring and control was followed by numerous attempts,
developments and implementation of process analyzers leading eventually to the PAT concept from the
continuous flow viewpoint and various aspects of automated non-destructive spectroscopy with the first
version of non-destructive scanning spectroscopy introduced by the Chemistry Department in Pretoria that
lead to the first PAT type configurations with chemometrics and the second road crossing road one. These
were the first attempts to integrated real-time process monitoring and control with the future vision of in-line
analysis, where the analysing probe is situated inside the operating system (or plant) as part of the operating
system (or process stream). Transduction is performed inside the operating system with a feedback to the
processor inside if possible or outside the operating system with facilities for fast automatic adjustment and
fast immediate corrective action.26
THE TAP ERA
There was also an increasing need from industries to follow the kinetics of very fast reactions in
heterogeneous catalytic reactors and membrane reactors and this led to the idea concept of temporal analysis
of products (TAP). The TAP reactor system was originally initiated by John Gleaves in the late 1980’s60 as
an interrogative kinetics approach to assist the catalytic development approach and is proving to be a
powerful tool for unraveling complex catalytic reactions and other surfaces processes and a powerful
technique to investigate the mechanism and kinetics in heterogeneous catalysis. With fast, transient
measurements and a high time resolution it is possible to determine single reaction steps during a reaction
over real catalysts. Interrogative kinetics (IK) is based on the application of novel high speed transient
response experiments (TAP pulse response experiments)60,61 in conjunction with traditional kinetic
measurements (steady-state, TPD, step-transient. etc.). IK uses a battery of kinetic measurements to probe
the kinetic characteristics of a catalytic surface, and to monitor how these characteristics change in response
to changing reaction conditions (pressure, temperature, surface coverage, reactant composition, etc.). A
simplified schematic diagram of a TAP Knudsen pulse response experiment is outlined in Fig. 7.62 A narrow
gas pulse is injected into an evacuated reactor containing a packed bed of catalyst particles. The gas flow
exiting the reactor is detected by a quadrupole mass spectrometer (QMS), and is determined as a function of
time. The resulting transient responses of reactor output reflect the transport and kinetic processes that occur
Analytical continuous flow systems 411
Fig. 7 – Simplified schematic diagram of a TAP Knudsen pulse response experiment. Reproduced from Ref. 62.
in the reactor.63-65 In a publication on the recent advances in technology for kinetic analysis of multi-
component catalysts the TAP-3 reactor system (Fig. 8)66 is comprised of (1) a pulse-valve manifold assembly
that supplies gas reactants for pulsed and flow experiments at user defined temperatures and pressures, (2) a
microreactor assembly that can be operated isothermally or in a temperature programmed mode, (3) a mass
spectrometer detector contained in a high-throughput ultra-high vacuum system, and (4) a computer based
control and data acquisition system. The TAP-3 menu of experiments includes, high-speed vacuum pulse-
response experiments (TAP Knudsen pulse-response experiments, TAP pump-probe experiments, and TAP
multi-pulse experiments, pulse experiments with a change of time within a pulse and between pulses),
atmospheric pressure steady-state, step-transient and Steady-State Isotopic Transient Kinetic Analysis
(SSITKA) experiments, temperature programmed desorption (TPD), and temperature programmed reaction
(TPR). In addition, newly developed software allows the user to create programmed experimental sequences,
which can be stored in memory, and then performed automatically. Sequences may include complex
temperature treatments, switching back and forth between atmospheric pressure and vacuum experiments,
switching from continuous flow to transient response experiments, or combinations of step-transient, pulse
transient, steady-flow, and temperature programmed experiments. The development and implementation of
412 Jacobus (Koos) Frederick van Staden
various commercial versions of the TAP reactor system indicate the success of the concept to both academic
and industrial research groups. It opens however a new innovation paradigm of new non-destructive probe
systems and TAP where a variation and adaption of the TAP concept and approach in the future can be
redesigned, developed, applied and implemented in industrial shaped potential areas for non-destructive
invasive and/or non-invasive process analytical technologies with probes of micro-detection systems like
NIR, MIR, UV-Visible, Raman Scattering (SERS), MS, NMR, Tetrahertz microwave, Acoustic techniques,
Sensors, Fluorescence, Chemiluminescence with chemometrics for process optimization and process
intensification either in flow or with discrete systems.
Fig. 8 – The TAP-3 Reactor System. Reproduced from Ref. 66.
CONCLUSIONS
Looking at the various innovation aspects of instruments design, development, implementation and
application from chromatography to flow systems, FIA, SIA, PAC and PAT and eventually to the temporal
analysis of products (TAP) concept with the latest TAP concept, does these innovations and exploitations
satisfied the need of the modern industrial world? A future vision of invasive and non-invasive non-
destructive real-time integrated multi-analyte fully automated interactive process analyzers as incentives and
new paradigm concepts of innovative, low cost, easy to operate, portable sensing platforms with an
interrogative kinetics approach for fast, transient measurements and a high time resolution in industrial
processes up to Real-time Integrated Industrial Monitoring and Control Information Management Systems
should satisfy most of the requirements of industry. However the fully in vitro in situ in-line complete fast
intelligent interactive non-destructive process analyzers to manage complete process reactions at various
positions inside process plant pipe-lines with fully automated non-attending supervision for extended periods
to deliver high quality industrial products still do not exist.
Acknowledgements: The author would like to acknowledge the financial support received from project Program Ideas by PN-
II-ID-PCE-2011-3-0538/2012-2014, financed by contract 100/27.10.2011. The author also acknowledges the support received from
the University of Pretoria and various industries.
Analytical continuous flow systems 413
Abbreviations
ANSI American National Standards Institute
CFA Continuous Flow Analysis (Analyzer)
GC Gas-Chromatography
GLC Gas-Liquid Chromatography
GIPM Good Industrial Process Management
CPAC Center for Process Analytical Chemistry
FIA Flow-injection analysis
GTL Gas-to-liquids
IFPAC International Forum of Process
IK Interrogative Kinetics
ISA Instrumentation, Systems and Automation Society
LIMS Laboratory Information Management Systems
MID Mid-Infrared
MIMS Manual Information Management Systems
NATREF National Petroleum Refiners of South Africa
NeSSI New Sampling/Sensor Initiative
NIR Near Infrared
NMR Nuclear Magnetic Resonance
NSFS Non-Segmented Flow Analysis
SAM Sensor/Actuator Manager
PAC Process Analytical Chemistry
PAT Process Analytical Technology
PPMT Process Product Measurement Techniques
QMS Quadrupole Mass Spectrometer
RIIMCIMS Real-time Integrated Industrial Monitoring and Control Information Management Systems
SASOL Suid-Afrikaanse Steenkool-, Olie- en Gaskorporasie (South African Coal-, Oil- and Gas-
corporation)
SERS Surface Enhanced Raman Scattering
SFA Segmented Flow Analysis (Analyzer)
SIA Sequential Injection Analysis
SMA Sequential Multiple Analyzer
SMAC Sequential Multiple Analyzer with Computer
SPCAS Smart Process Control Analyzer Systems
SSITKA Steady-State Isotopic Transient Kinetic Analysis
TAP Temporal Analysis of Products
TPD Temperature Programmed Desorption
TPR Temperature Programmed Reaction
TQISM Total Quality Industrial Sustainable Management
UV-visible Ultraviolet Visible
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