The THT micro reaction calorimeter RC CHEM ICAL APPLICATIO NS BRO CHUR Titration E calorimetry isothermal calorimetry and scanning calorimetry - all in one instrument Introduction and reaction kinetics The THT Micro Reaction Calorimeter ( RC™) has a wide range of All chemical, physical and biological reactions are accompanied application in the chemical, pharmaceutical and related markets. by heat change. These reactions, though sometimes subtle, can This brochure shows how using a micro calorimeter can help be measured using calorimetry. This is the only analysis method chemists and engineers in everyday tasks. that works without modification of the sample or process. Some of the applications detailed within this brochure include: The THT Micro Reaction Calorimeter is based on power • Reaction Kinetics compensation technology making it faster in both signal response • Process Development and temperature variation. Designed for maximum flexibility, the • Scanning Calorimetry RC has the capability to measure both kinetic and • Thermal Stability thermodynamic parameters in both rapid and slow reactions and • Heat Capacity Measurement in solids, liquids or gases. • Adhesive Curing Reactions • Waste Management Measurements made by calorimetry are non-destructive and • End Point Determination non-invasive making it valuable for initial analyses and for • Hazard Analysis systems where other techniques fail. With the RC there is minimal sample preparation and no limitation on the physical state of the material. Systems can be studied under ambient or modified environmental conditions. Kinetics Determination Kinetic analysis can be tedious and time consuming. The use of micro calorimetry to obtain kinetic parameters has been recognized Internationally and is an essential tool in kinetics research. Since reaction rate is directly proportional to heat-flow, it is possible to utilise the data from a RC calorimeter to calculate reaction conversion at any point. From here, every data point within the experiment can be used for an “initial-rate” type determination. Fitting of models to the calorimetric data can also Heat flow vs time at different temperatures be used to elucidate detailed kinetic mechanism. hydrolysis of pharmaceutical material A kinetics fitting and modelling package ( RC-KIN) is available as an option with the Micro Reaction Calorimeter. This software is specifically written for use with the THT RC and contains automatic data importing, advanced data correction, kinetic fitting and modelling. Complex models may be used to provide fitting to consecutive, non-integral, parallel and auto-catalytic kinetics with highly efficient data optimisation routines. For slower reactions the Micro Reaction Calorimeter can be used as an isothermal (or step-isothermal) calorimeter giving rapid access to traditional kinetic methods. Simple Arrhenius kinetics from micro reaction calorimeter data Process development & hazard analysis Heat Capacity Measurement Process deviation studies have never been easier. Instead of generating several litres of waste over several hours for each The RC can be used to rapidly and accurately measure the heat variant considered, the micro calorimeter can generate the same capacity of solids, liquids and mixtures. Applying small information in a few minutes. This will allow proper consideration temperature steps to the material in question allows the heat of all possible mal-operations where before, time, cost and required to be measured. Using these data can significantly material availability may have limited the application. improve the data measured using larger reaction calorimeters. The more considerations of credible mis-operation that are performed the safer a plant and process are. THT aim to re-empower the safety professional by providing new technologies which can considerably improve the way hazard studies are performed. Heat Capacity measurement of Acetone Accuracy better than +/-0.5% of Literature value Process Hazard Analysis Additional options such as a pressure handling option and high pressure cells will allow users to monitor pressure and gas The Micro Reaction Calorimeter provides hazard analysis with formation either as a function of reaction conversion or, in the both speed and flexibility. Working with less than 2ml total case of scanning experiments, as a function of temperature. The volume reduces costs, waste and time. The RC is capable of system can also function with disposable syringes for use with reducing the time requirement of a reaction calorimetry study on highly aggressive materials. a process from several days to a few hours. Process Development The RC is easy to use which allows any chemist or engineer the ability to rapidly investigate whatever reaction parameters they desire. Combining modern DOE approaches to experimental design of calorimetry tests can provide users with information on reactant conversion, material accumulation, competitive reactions, inhibition and catalysis. Conversion and heat-flow from hydrolysis reaction Power compensation calorimetry measures in units of power meaning that calculation of reaction enthalpy is simply performed by dividing heat-flow integral (automatically produced) by quantity. Using the different modes of injection (single, multiple or timed) allows batch and semi-batch processes to be simulated under safe controlled conditions. Kinetic controlled reaction in RC Automated addition of materials allows unattended, walk-away operation and the options of disposable reactors and syringes keeps costs to the minimum when conducting many reactions. Catalysts, cements, & pharmaceuticals Catalyst Screening Adhesive Curing Although many reactions run better when catalysed it is very difficult to know the best catalyst to use. A recent survey of Materials studies including adhesive curing, cement hydration and catalyst manufacturers suggested that in excess of 1000 versions other such processes can be easily studied using the micro of alumina supported platinum exist. The question of which the reaction calorimeter. The disposable vials make the system an best system is and what the best conditions ideal tool for chemistries where materials harden, set or gel. Being able to study these processes as a function of temperature The ability to measure both kinetics and thermodynamics is an ideal way of gaining valuable thermokinetic data which is simultaneously allows users to select the parameters which are otherwise unavailable. important to their process and monitor those as the catalyst is changed. Waste Management High pressure vessels (up to 20bar) now available with the Micro The ever increasing pressure on natural resources means that the Reaction Calorimeter allow gas phase reactions (e.g. optimisation of waste handling is becoming more important. hydrogenation) to be examined. The RC can be supplied with a Combining of waste streams and batches may reduce volumes, high pressure transducer for direct measurement of gas uptake costs and handling issues but safety dictates that these simple during reaction or gas evolution measurement. operations must be fully investigated as unexpected reaction may occur. The new RC-KIN, dedicated kinetics package gives users the ability to easily import data directly into a specialist kinetics analysis software and then to model the reaction using a wide range of purpose designed systems. RC-KIN is compatible with the CISP software products which allows full-scale models of reactions to be implemented for reactor modeling, runaway prediction and other useful parameters. Excipient Compatibility Screening The three temperature modes of the RC make it a very useful and flexible tool for excipient compatibility assessment. Using the device in an isothermal mode allows auto-catalytic and slow reactions to be monitored. Interaction of Propan-2-ol and water Comparison of the thermal response between Aspirin and two standard excipients, Talc and Magnesium Sterate Step-isothermal calorimetry will provide an accelerated method by which thermal stability assessments can be reduced from weeks to hours. Temperature scanning can also be used to detect reaction onset. Working as a macro-scale DSC, the RC can provide onset information where lack of material consistency requires the use of larger volumes of material. Titrations, scanning, solids addition and dissolution End Point Determination The ability of the RC to measure small heats of reaction means that it can be used to detect subtle changes in heat output (and therefore reaction) where other indicators may prove unavailable or unreliable. The titration function of the micro calorimeter can be used to determine the exact stoichiometric quantities of reactants required to achieve full conversion. Plunger Sample Schematic of calorimeter cell & sample insert Dissolution Experiments The enthalpy of solution is an important parameter in both Binding exotherms as equivalence is reached chemistry and pharmaceutics. Using the new Solid Addition System, heats of solution can be measured reliably and As well as binding exotherms titrations can be conducted with repeatedly without error. The solid is loaded into the addition traditional acid-base type experiments to determine acidic system and the base of the system sealed using Parafilm™. The concentration and other parameters where traditional plunger is then lowered at the appropriate time in order to colorimetric determination is not possible (in highly coloured introduce a well-equilibrated material into the solution. solutions). Scanning Calorimetry The power compensation system used in the RC means that temperature scanning may be used as a means of determining many process variables. From reaction onset to melting and crystallisation points the RC has the ability to detect chemical and physical processes as a function of temperature. Enthalpy of solution experiment for KCl KCl Enthalpy of solution(kJ/mol) Endothermic result from temperature scan = +17.22 at 1°C/min /kJ.m /mg ol-1 Solid Additions 7690.5 33.5 0.000450 17.10 7915 34.2 0.000459 17.24 Although the liquid titration system supplied with the micro reaction calorimeter is very efficient to use and very useful 7631 32.5 0.000436 17.49 sometimes, it is necessary to add solids into a liquid. THT have Average 17.28 now developed a specialised system for the addition of solids to Standard Deviation 0.20 the RC during an experiment. The image shown below illustrates the operation of the system. % Error (w.r.t Literature) Enthalpy of solution results for KCl Biology education and specification Biological Applications The RC can be used for a wide range of bio-chemical applications including binding studies (of proteins, lipids and enzymes) cell growth, organism metabolism and denaturation. Several features of the RC make it unique for study of these classes of materials including the incremental titration, temperature scanning, and stirring which, with the removable cells of the micro reaction calorimeter mean that if your Specification experiment precipitates or forms a gel you can simply dispose of the vial and start the next experiment with a clean one. Baseline Noise From 5µW Dynamic Range 5µW to 100mW Temperature Range -5°C to 150°C Standard Modes of Operation Isothermal Titration Scanning Optional Modes Pressure - pressurise cell up to 10bar Solid Addition Accessory Scanning Rate Up to 2°C/min Isothermal Stability +/- 0.0001°C Growth curve showing bacterial activity in Milk The biochemical applications of the RC are detailed in a Cell Volume 1.5 ml separate applications brochure. Cell Type Removable glass vial Injection Volume 1 to 250 µl Educational Applications Temperature Control Peltier based The Micro Reaction Calorimeter, as can be seen in this brochure, has a very wide range of applications. This versatility makes the Stirring Speed 0 - 400 rpm RC the ideal instrument for an academic environment as a range Measurement Principle Power compensation of varied users can perform different experiments on it. Connection to PC via USB cable In the teaching laboratory the RC provides an elegant method Footprint (width x depth x height) 15 x 40 x 35 cm of performing kinetics experiments without polystyrene cup calorimeters and watching iodine clock experiments in a water bath. As a research tool the RC gives a rapid, accurate and unique way of studying a range of parameters which may not be Certain other specifications may be possible by discussion. measured by other methods. New applications are being Contact us with your exact requirements. discovered all the time - don’t hesitate to enquire. Options The RC benefits from a small footprint, lack of external service requirements (no water bath or chiller) and a simple PC The RC is available with a range of options. These vary from connection (only a USB connection to any PC running Windows changes to the specification (for high sensitivity application, rapid XP). The RC is designed to operate in any chemical or response or large heats) to specific cell types (dissolution cells, biochemical laboratory and conforms to modern safety standards. high pressure cells, low tau cells) and others (external pump options, pressure handling systems). 1 North House • Bond Avenue • Bletchley • MK1 1SW • England T: +44 1908 646800 F: +44 1908 645209 E: info@thtuk.com W: www.thtuk.com PO Box 25 • Whitestown • Indiana • 46075 • USA T: +1 317 222 1904 F: +1 317 222 1904 E: info@thtusa.com W: www.thtusa.com Suite 1416 • No 1101 Pu Dong Road (S) • Shanghai • 200 120 • China T: +86 21 5836 2585 F: +86 21 5836 2581 E: info@thtchina.com W www.thtchina.com 808, Eighth Floor Tower - I • Pearl Omaxe) • Neta Ji Subhash Place • Pitampura • Delhi - 110034 India T: +91 95 6065 5656 E: info@thtindia.com W www.thtindia.com