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Validation of titration methods

Validation of titration methods

Manufacturing products of the highest quality is a must, especially in the pharmaceutical and food industries. This requires accurate, reproducible, and simple analysis methods that eliminate human errors as much as possible. Automated titration is one such solution that offers additional time and cost savings to laboratories.

After applying automation to a titration method, how can you ensure that the chosen method also delivers a reliable result? And how do you know that it is suitable for the analysis of your analyte(s)? This requires method validation of a titration, which includes standardization of the titrant as well as determination of accuracy and precision, linearity, and specificity.

USP General Chapter <1225> Validation of Compendial Procedures and ICH Guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology define the validation elements – some of the most important ones are described in the following article.

These include (click to go to each section):

Standardization

Dilution and weighing errors as well as the constant aging of all titrants lead to changes in the concentration of the titrant. To obtain results that are as reliable as possible, the most accurate titrant concentration is a prerequisite. Standardization of the titrant is therefore an integral part of a titration method validation. The standardization procedures for various titrants are described in the Volumetric Solution section of USP – NF as well as in the Metrohm Application Bulletin AB-206 regarding the titer determination in potentiometry.

The titrant to be used in the validation must first be standardized against a primary standard or a pre-standardized titrant. It is important that the standardization step and the sample titration are carried out at the same temperature.

Primary standards are characterized by the following properties:

  • high purity and stability
  • low hygroscopicity (to minimize weight changes)
  • high molecular weight (to minimize weighing errors)

The use of a standard substance (primary standard) allows accuracy to be assessed.

For more information about titrant standardization, check out our blog posts «What to consider when standardizing titrant» (for potentiometric titration) and «Titer determination in Karl Fischer titration».

Accuracy and precision

Accuracy is defined as the proximity of the result to the true value. Therefore, it provides information about the bias of a method under validation. Accuracy should be determined over the entire concentration range.

Precision is usually expressed as the standard deviation (SD) or relative standard deviation (RSD). It expresses how well the individual results agree within an analysis of a homogeneous sample. Here, it is important that not only the analysis itself but also all sample preparation steps are performed independently for each analysis.

Precision is evaluated in three levels:

  1. Repeatability: the precision achieved by a single analyst for the same sample in a short period of time using the same equipment for all determinations.
  2. Intermediate precision: analysis of the same sample on different days, by different analysts and with different equipment, if possible, within the same laboratory.
  3. Reproducibility: precision obtained by analyzing the same sample in different laboratories.

Determination of both accuracy and precision is necessary, as only the combination of both factors ensures correct results (Figure 1).

Figure 1. Only when both precision and accuracy are high can correct results be obtained, as high precision does not necessarily mean good accuracy, and vice versa.

For titration, accuracy and repeatability are usually determined together. At least two to three determinations at three different concentration levels (in total six to nine determinations) are recommended. For assays, the recommendation is to use a concentration range of 80% to 120% of the intended sample weight.

Linearity

Linearity expresses whether a particular method gives the correct results over the concentration range of interest. Since titration is an absolute method, linearity can usually be determined directly by varying the sample size and thus the analyte concentration.

To determine the linearity of a titration method in the range of interest, titrate at least five different sample sizes and plot a linear regression of the sample volume against the titration volume consumed (Figure 2). The coefficient of determination (R2) is used to assess linearity. The recommendation is to use a concentration range of 80% to 120% of the intended sample weight.

Figure 2. Linear regression curve for the assay of potassium bicarbonate.

Specificity

Impurities, excipients, or degradation products are among the many components that may be present in a sample. Specificity is the ability to evaluate the analyte without interference from these other components. Therefore, it is necessary to demonstrate that the analytical procedure is not affected by such compounds. This is the case when either the equivalence point (EP) found is not shifted by the added impurities or excipients, or in the event it is shifted that a second EP corresponding to these added components can be observed when a potentiometric sensor is used for indication.

Specificity may be achieved by using suitable solvents (e.g., non-aqueous titration instead of aqueous titration for acid-base titration) or titration at a suitable pH value (e.g., complexometric titration of calcium at pH 12, where magnesium precipitates as magnesium hydroxide).

How can this be implemented in practice? The titrimetric determination of potassium bicarbonate with hydrochloric acid will serve as an example here.

In this case, potassium carbonate is expected as an impurity with pkb values of 8.3 and 3.89. This makes it possible to separate the two species during the acid-base titration. Figure 3 shows the comparison of a curve overlay of the titration curves of potassium bicarbonate with and without added potassium carbonate.

Figure 3. Curve overlay of the specificity test using 1 g KHCO3 with and without 0.5 g K2CO3 (green and orange = no K2CO3 added; blue and yellow = K2CO3 added). Click to enlarge.

The lower titration curve corresponds to the solution containing both potassium bicarbonate and potassium carbonate. Two EPs are found here: the first EP can be assigned to the added potassium carbonate, while the second corresponds to the sum of potassium bicarbonate and potassium carbonate. The curve at the top of the figure clearly shows only one EP for the potassium bicarbonate solution without impurities.

Find out more about the proper recognition of endpoints (EP) in our previous blog post.

Conclusion

If you follow the recommendations above, you will be ready for titration method validation – and now it`s time to get started!

Using potentiometric autotitration instead of manual titration increases the accuracy and reliability of your results. In addition, the use of an autotitrator ensures that critical regulatory compliance requirements, such as data integrity are met.

Right from the start, Metrohm products provide peace of mind and confidence in the quality of the data you produce with proper IQ/OQ.

If you would like to learn more about Metrohm Analytical Instrument Qualification, have a look at our two blog posts dedicated to this important topic.

Additional security is also provided, e.g., by Metrohm Buret Calibration which ensures that the accuracy and precision of your dosing device are within the required tolerances. Traceable monitoring of the performance and function of the instrument through regular re-qualifications and tests is therefore a given.

Watch our free webinar

available on demand!

How to convert from manual to automated titration procedures

Post written by Doris Hoffmann, Product Manager Titration at Metrohm International Headquarters, Herisau, Switzerland.

How much do pipes rust in a year?

How much do pipes rust in a year?

Why is corrosion important?

According to the Association of Materials Protection and Performance (AMPP) the total estimated annual cost of corrosion is as high as 3.5% of a country’s GDP [1]. An AMPP international study [2] found that in the United States alone, the corrosion related cost can be as high as $1.4 billion USD annually in the oil and gas exploration and production sector. This figure climbs even higher, up to $40 billion USD for gas and drinking water distribution plus sewer systems. This is an unavoidable problem with a high cost to bear.

Even though the corrosion itself isn’t unavoidable, it can be controlled by using the right material in the right place. Using a reliable test method that evaluates the material’s resistance against corrosion and predicts its potential failure is of the utmost importance. This test method should also be cost-effective and practicable.

What is corrosion?

Corrosion refers to a naturally occurring process that involves the deterioration or degradation of metals and alloys through a chemical reaction. The corrosion rate is highly dependent on the type of material, ambient temperature, contaminants/impurities, and other environmental factors. Most corrosion phenomena are electrochemical in nature and consist of at least two reactions on the surface of the metals or alloys.

For example:

These electrochemical process require three main elements:

  • Anode: where the metal corrosion occurs.
  • Cathode: the electrical conductor, which is not consumed during the corrosion process in the real-life electrochemical cell configuration.
  • Electrolyte: the corrosive medium that enables the transfer of electrons between the anode and the cathode.

Depending on the materials and environment, corrosion can occur in different ways, such as uniform corrosion, pitting corrosion, crevice corrosion, galvanic corrosion, or microbiologically induced corrosion to name just a few. Learn more about the different types of corrosion in our free white paper.

This white paper also includes details about relevant electrochemical techniques including Linear Sweep Voltammetry (LSV), Electrochemical Impedance Spectroscopy (EIS), and Electrochemical Noise (ECN or ZRA). These techniques allow for the exploration of corrosion mechanisms, the behavior of different materials, the rate at which corrosion occurs, and also to determine the suitability of the corrosion protection solutions such as protective coatings and inhibitors, among others.

Find out more about these subjects individually with our selection of free Application Notes (AN).
Calculation of corrosion parameters with NOVA – Tafel plot corresponding to corrosion behavior of iron in seawater. (Click to enlarge)

Creating pipe-flow conditions in your corrosion laboratory

Internal corrosion is the most problematic cause of pipeline failure. To understand the fundamentals about corrosion failure and its root causes within pipelines, a similar environment should be created in the lab.

The Rotating Cylinder Electrode (RCE) is an integral part of creating hydrodynamic electrochemical experiments in the lab that create turbulent flow conditions which realistically simulate the situation for liquids flowing through pipes. The RCE can be used with most electrochemical techniques such as chronoamperometry, chronopotentiometry, and potential sweep.

Study of the corrosion rate as a function of rotation speed (convective flux) is one of the most common applications for the RCE. Corrosion studies can be performed using linear or cyclic polarization measurements (LP, DPD, CP), electrochemical impedance spectroscopy (EIS), and electrochemical noise (ECN) with respect to the rotation speed.

Results obtained by electrochemical methods are more accurate and are obtained much faster than conventional corrosion investigation methods (e.g. salt spray), providing more efficiency and productivity to any corrosion measurement laboratory. Learn about the RCE and how to simulate realistic pipe-flow conditions in the lab combined with electrochemical corrosion techniques in our free white paper.

One typical method in electrochemical corrosion studies is linear polarization (LP). With this method, it is possible to evaluate the corrosion behavior of a sample under pipe-flow (i.e. turbulent flow) conditions and learn about the corrosion rate of the sample at a specific flow rate.

Metrohm offers two Application Notes that use this technique specifically:

The Tafel plot obtained from LP measurement gives an indication of the corrosion potential. Using dedicated analysis tools in the NOVA software from Metrohm Autolab, the corrosion rate analysis can be performed and corrosion rate can be calculated, giving an indication of how much the pipe will rust in a year (in mm/year) under given conditions. Once this information is available for a certain material, a more corrosion resistive environment can be developed by applying a certain coating or a corrosion inhibitor.

Tafel plot created by Metrohm Autolab’s NOVA software. Blue line is measured without corrosion inhibitor and red line is measured with corrosion inhibitor.
Tafel plot created by Metrohm Autolab’s NOVA software corresponding to the measurements done in quiescent electrolyte (blue) and under 500 RPM rotation rate (red). All other experimental parameters were kept the same.

A second evaluation can be performed to learn how much the pipe will rust in a year, under these resistive conditions. In the example below, under standard conditions, the corrosion rate of carbon steel is measured at 0.25 mm/yr. However, when a specific corrosion inhibitor is used (tryptamine in this case), the performance is significantly improved and the corrosion rate drops to 0.065 mm/yr. These results can be achieved in a matter of minutes by using electrochemical methods, whereas by conventional methods (e.g., salt spray chamber combined with weight loss analysis), it takes up to a few months to conclude the results. That is a huge difference in efficiency!

Corrosion Parameter No Inhibitor With Inhibitor
Ecorr (V) from linear regression -0.479 -0.392
Ecorr (V) from Tafel analysis -0.482 -0.396
Rp (Ω) from linear regression 42.62 135.96
Rp (Ω) from Tafel analysis 43.32 136.39
Corrosion rate (mm/year) from Tafel analysis 0.25 0.065
Linear regression and Tafel analysis data resulting from experiments with and without corrosion inhibitor.

Summary

Understanding the corrosion behavior of a material under real-life conditions helps manufacturers to more quickly optimize the material design in terms of corrosion resistance, either by using a more suitable material for the pipes or by using adequate corrosion protection methods (i.e., coatings or corrosion inhibitors), which results in significant cost savings and safer operation.

Post written by Dr. Reza Fathi, Product Specialist at Metrohm Autolab, Utrecht, The Netherlands.

The importance of titrations in pharmaceutical analysis

The importance of titrations in pharmaceutical analysis

If you are in the pharmaceutical industry and wonder if a conversion from a manual titration to an automated titration is suitable for your work, this blog post should give you all the answers you need.

I will cover the following topics in this article (click to go directly to the topic):

Applicability of modern titration methods in pharmaceutical analysis

Perhaps you have already heard or read about automated titration and its benefits in comparison to manual titration, but are now wondering whether those guidelines are also applicable to pharmaceutical analysis.

Getting straight to the point: Yes, it is true that many USP monographs as well as USP General Chapter <541> Titrimetry still refer to the manual visual endpoint titration. But there’s good news! USP-NF General Notices and Requirements Section 6.30 states:

As long as the alternative method is fully validated and you can prove that both methods are equivalent, you are allowed to use alternative methods.

Since titration still plays an important role in pharmaceutical analytical procedures and processes, Metrohm offers a variety of applications for innumerous API monographs of the United States Pharmacopeia as well as pharmacopeia-compliant analytical instruments.

Automated titration procedure

Have you wondered about how to perform the procedure of an automated titration—how does it differ from a manual titration? Working with a pharmacopeia compliant analytical instrument from Metrohm is not so different:

 

  1. Titrant is added with an automated piston buret that safely controls the delivery of titrant to a precise level.
  2. The sample is homogenized with a stirrer.
  3. The electrode detects the titration endpoint, removing subjectivity of color changes.
  4. Results are automatically calculated and displayed allowing no room for human error.
Figure 1. Anatomy of an automatic titrator.

As shown in Figure 1, an automated titration procedure mainly consists of four steps. These steps are repeated until the end of the titration (Figure 2).

In addition, all Metrohm devices that run with proprietary tiamo® or OMNIS® software are 21 CFR Part 11 compliant meeting all ALCOA+ requirements. Thanks to improvements in productivity, accuracy, and precision, the human influence on analysis is reduced to a minimum.

Figure 2. The titration cycle illustrating the different steps in an automated titration procedure.

If you are wondering how to transfer a manual titration to automated titration, then check out our earlier blog posts on this topic. Also, download our free white paper comparing manual and automated titration.

Choice of electrodes for pharmaceutical titrations

For autotitration, either an electrode or a photometric sensor is used to detect the point of a sample analyte neutralization. Metrohm offers a wide range of different electrodes for titrations that are extremely suitable for various pharmaceutical applications. The electrode choice depends on the type of reaction, the sample, and the titrant used.

Download our free brochure to learn more.

If you want to know more about how endpoints are recognized using electrodes or photometric sensors, read our previous blog post to find out how the endpoint is determined during an autotitration.

Maybe you are not quite sure which is the best electrode for your application. Therefore, Table 1 shows an interactive electrode guide for different pharmaceutical titrations.

Type of titration Electrode Close-up view Pharma Application / API

Aqueous acid/base titrations

e.g. titrant is NaOH or HCl

phenolphthalein indicator

Combined pH electrode with reference electrolyte c(KCl) = 3 mol/L

e.g. Ecotrode Plus, Unitrode

Water-soluble acidic and basic active pharmaceutical ingredients (API) and excipients

API: Benzbromaron, Potassium carbonate, Potassium bicarbonate

Non-aqueous acid/base titrations

e.g. solvent is organic or glacial acetic acid

crystal violet indicator

Combined pH electrode with alcoholic reference electrolyte LiCl in EtOH

e.g. Solvotrode easyClean

Water-insoluble weak acids and bases

Assay of API

Acid value (free fatty acids)

API: Caffeine, Ketoconazole

Redox titrations

e.g. titrant is sodium thiosulfate

starch indicator

Pt metal electrode

e.g. combined Pt ring electrode, Pt Titrode

 

Antibiotic assays

Peroxide value in fats and oils

API: Captropril, Paracetamol, Sulfonamide

Precipitation titrations

e.g. titrant is silver nitrate

ferric ammonium sulfate indicator

Ag metal electrode

e.g. combined Ag ring electrode, Ag Titrode

Chloride content in pharmaceutical products

Iodide in oral solutions

API: Dimenhydrinate

Complexometric titrations

e.g. titrant is EDTA

hydroxy naphthol blue indicator

Ion-selective electrode

e.g. combined calcium-selective electrode with polymer membrane

Calcium content in pharmaceutical products

API: Calcium succinate

Photometric titration

e.g. titrant is EDTA

Eriochrome black T indicator

Photometric sensor

e.g. Optrode

Assay of various metal salts in APIs

API: Chondroitin sulfate, Bismuth nitrate, Zinc sulfate

Table 1. Electrode guide for pharmaceutical titrations.

To help you select the best electrode for your titrations, we have prepared a poster for you to easily find the perfect electrode for USP monographs. Additionally, you will find information about proper sensor maintenance and storage.

If you prefer, the Metrohm Electrode Finder is even easier to use. Select the reaction type and application area of your titration and we will present you with the best solution.

As documentation and traceability are critical for the pharmaceutical industry, Metrohm has developed fully digital electrodes, called «dTrodes». These dTrodes automatically store important sensor data, such as article number and serial number, calibration data and history, working life, and the calibration validity period on an integrated memory chip.

Conclusion

Metrohm is your qualified partner for all chemical and pharmaceutical analysis concerns and for analytical method validation.

In addition to full compliance with official directives, Metrohm instruments and applications comply with many of the quality control and product approval test methods cited in pharmacopoeias. Discover the solutions Metrohm offers the pharmaceutical industry (and you in particular!) for ensuring the quality and safety of your products.

Learn even more about the practical aspects of modern titration in our monograph and visit our Webinar Center for informative videos.

Need a reason to switch

from manual to automated titration?

How about FIVE?

Post written by Doris Hoffmann, Product Manager Titration at Metrohm International Headquarters, Herisau, Switzerland.

Developing the electrochemical sensors of your dreams

Developing the electrochemical sensors of your dreams

«Measurement is the first step that leads to control and ultimately to improvement. If you can’t measure something, you can’t understand it. If you can’t understand it, you can’t control it. If you can’t control it, you can’t improve it.»
H. James Harrington

 

The statement above relates very well to the demand to measure more and more about our lives—one option available to achieve this improvement is through the development of electrochemical sensors. Sensor manufacturing is in high demand and is expected to grow exponentially in the coming years.

Everything around us gives valuable information, including the chance to discover and the ability to know how we need to act. Developing sensors opens up new opportunities to develop and customize powerful and accurate solutions for specific applications in multiple fields, as well as being able to monitor different parameters outside the laboratory on the spot.

Electrochemical sensors and biosensors that are developed in small sensor strips allow for many measurement and monitoring possibilities. Sensors with new strategies have evolved by working with new materials, substrates, and formats that improve their accuracy, miniaturization, and portability in response to new analytical paradigms in various markets.

Why are electrochemical sensors needed?

Electrochemical sensors are a sensitive, fast, accurate, and cost-effective solution for point-of-care measurements. Such characteristics make these solutions suitable for integration into various monitoring or automation systems which, combined with a data communication structure, can generate considerable advances in the field of biosensing, creating new and important possibilities for the market as practical and future-proof solutions.

The latest advances in the miniaturization of electrochemical sensors is another reason for their growing use and popularity. These portable and simple formats are geared towards the end user—technical and non-technical—to obtain results in their daily work. This makes electrochemistry very attractive to anyone thinking of taking an idea or research to the next level and commercializing their findings.

This progress makes the development of electrochemical sensors one of the most active areas of analytical electrochemistry. These sensors are capable of providing information with superior features such as: real-time data generation, disposability, high accuracy, or wide-range linearity that make these small sensor strips an advanced alternative to conventional, bulky and expensive analytical instruments.

Multiple possibilities for production of electrochemical sensors

Your dream sensor is now possible thanks to expert manufacturing from Metrohm DropSens that allows customization and production according to your required quantity and specifications. Using an innovative and experienced production process, large quantities of customized sensors can be produced while maintaining high product quality and scalability stability as well as an attractive price-performance ratio.

Optimized design

Metrohm DropSens R&D experts understand the application concept in depth. The engineering and design departments assist in the development process to implement a final prototype, always finding a solution in which all specifications converge.

 

Custom-made solutions

The development of these sensors allows their miniaturization while at the same time allowing the possibility of modifications in terms of spatial distribution, shape, area, substrate, or the use of a wide range of materials, to name just a few. In addition, flexible sensors, textile sensors, biosensors or other types of solutions can be manufactured to suit the biochemical and electronic process needs of each individual application.

 

 Manufacture on demand

Take advantage of this capacity to produce custom-made electrochemical sensors on demand efficiently and quickly, regardless of the quantity ordered, meeting future needs without ever running out of supply.

 

High performance market-ready solutions

Be the first to bring a sensor to market, avoiding long processes and an abundance of partners. Count on the fast and professional manufacturing capability from a company positioned directly in the launch and production of electrochemical sensors to the market.

 

The highest quality standards

Production is carried out with the highest quality materials, printing, and finishing. In addition, the solutions are approved by quality management systems, which allows the highest levels of reliability and stability to be achieved in each product, guaranteeing its scalability.

From small-scale prototyping to large-scale sensor production, Metrohm DropSens offers support throughout the entire process: initial conceptualization, in-depth prototype design, and helping to achieve results that meet your goals.

This expert manufacturing is backed by the global support of Metrohm’s extensive worldwide network of partners. With more than 75 years of experience, Metrohm offers the highest standards of product and service quality, providing all you need for chemical analysis support.

Sensors for infinite uses

Progress and improvement cannot be adequately defined without the use of sensors. Everything can be measured (and usually quantified), which gives many opportunities to grow. State-of-the-art sensors based on the most recent scientific accomplishments excel in their customer-friendliness, allowing sensors to become part of everyday life as they are accessible to more people. Furthermore, the development of these decentralized devices can leverage R&D in many different industry sectors by addressing their specific applications and needs, giving them the option to reach the market.

The measurement of human health, pollution, information about foods and beverages, environmental analysis, water contamination, illicit drugs, or viruses, among other things, can be performed with electrochemical techniques and solutions. Sensors also play a fundamental role in industrial sectors such as agriculture and livestock farming, being able to measure an infinite number of parameters applicable to their improvement and development.

Another aspect to be taken into account regarding the development and growth of relevant sectors is the capacity of sensors for continuous electrochemical monitoring of different biomarkers. Combined with automated wireless data communication systems, this has represented a considerable advance in the field of biosensing towards new market possibilities.

Certified by ISO 13485 for the manufacture of sensors for medical devices

In the clinical setting, point-of-care (POC) testing dominates as an end-user application. The main areas of development focus especially on POCs for home monitoring of chronic diseases and POC testing of infectious pathologies, among others.

The COVID-19 pandemic, caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a threat to global public health. Therefore, the development of a rapid, accurate, and easy-to-apply diagnostic system for the detection of the virus has become crucial to control the outbreak of infection and monitor the progression of the disease. 

Metrohm DropSens manufactures electrochemical sensors under ISO 13485 certification, which attests to the ability to provide production that consistently meets customer and regulatory requirements applicable to medical devices and related services.

The sectors of medical and diagnostic services are driven by a strong interest in rapid point-of-care testing and monitoring devices. In addition, the integration of biosensors into medical diagnostic equipment will offer endless opportunities for the market for prevention and control of the spread of disease.

Moreover, the proliferation of biosensors employing electrochemical sensing technology has been gaining ground due to the strong demand for rapid and non-invasive POC applications. These are market-ready sensors that can be used by anyone.

Electrochemical test strips are a suitable canvas and format for the creation of a motorized diagnostic and testing system in this area and can provide a solution to these new analytical paradigms. The development of non-invasive sensors for decentralized and continuous monitoring has received a great deal of attention from researchers in different industries for painless analysis of important health parameters.

These are extraordinary times for sensor development

We constantly look for ways to mark our progress, and having the ability to measure parameters is one way to achieve this. The development of electrochemical sensors opens up a wealth of possibilities, and thanks to the customization and mass production capabilities of Metrohm DropSens, you will be able to produce high quality electrochemical devices that are tailored to specific applications. This production process is designed to meet the long-standing market demand for end-user-oriented sensor solutions with features such as: portability, wireless functionality, and simple usability without any loss in measurement accuracy.

Electrochemical sensors, based on small sensor strips, are now simpler, smarter, more user-oriented, and cheaper than conventional electrodes, which rely on cleaning or recovery tasks and have lower reproducibility in many areas of analysis. These devices are also characterized by the ability to acquire data in real time, which, combined with portability and ubiquitous availability, makes them practical and powerful tools for measurement purposes. In addition, they can provide an alternative solution for applications where complexity is involved, as they can be developed to adapt to infinite specifications.

Electrochemical sensors guarantee optimum quality, excellent measuring accuracy, and use perfectly bonded materials, prints, and substrates. They can be developed in various formats and are reproducible on flexible or even wearable materials, always maintaining good conductivity and preserving the correct alignment of the different sensor elements in all cases.

Metrohm DropSens is able to produce these electrochemical sensors in large quantities on a customized basis while still maintaining all the benefits and features scaled up from the customer-developed application. This is possible while guaranteeing market-ready production, an efficient price-performance ratio, and no risk of stock-outs – always with continuous global and specialized support service. Contact us to make your dream sensor a reality!

Dream of your sensor

and together we will make it true

Post written by Belén Castedo González, Marketing Communication at Metrohm DropSens, Oviedo (Asturias), Spain.

Decarbonizing chemical processes with Thor

Decarbonizing chemical processes with Thor

The chemical manufacturing industry consumes approximately 10% of the energy produced worldwide and is responsible for more than 5% of global carbon emissions. Nearly all chemicals are synthesized using thermal energy generated by fossil fuel combustion, leading to the significant carbon footprint from this sector. What if there was a way to reduce the carbon footprint without requiring significant amounts of energy or high costs? That is where the 2021 Metrohm Young Chemist Award winner, Ryan Jansonius, comes in.

Ryan Jansonius is a Ph.D. candidate at the University of British Columbia and a co-founder of ThorTech. He received his BSc (Hons) in Chemistry from the University of Calgary in 2016. He then went on to work at the Automotive Fuel Cell Cooperation, a subsidiary of Ford and Daimler, developing ion exchange membranes for hydrogen fuel cell vehicles. His research in the Berlinguette group at UBC has centered around developing technologies that use inexpensive and abundant renewable electricity to drive otherwise environmentally costly chemical transformations. ThorTech is bringing to market a unique membrane reactor technology that uses water and electricity to hydrogenate molecules relevant to the biofuel, pharmaceutical, and specialty chemical industries.

The Metrohm Young Chemist Award

Metrohm values the spirit of innovation and believes in the value of novel research performed by pioneering young scientists. At Metrohm USA, the tradition of holding a yearly contest for early career researchers has gone on for nearly a decade! Every year, between 50 and 75 entries are received to try and win a grand prize of $10,000 USD.

A panel of judges from inside and outside of the company reviews the submissions and scores the applicants’ responses to the questions on the application. Finalists are then asked a series of follow up questions from the judges and asked to summarize their role in the work and its future potential. A winner is chosen, who then presents their research at PITTCON. Watch Ryan’s presentation at PITTCON 2021 below!

Past winners of the MYCA  have gone on to continue their research and broaden their horizons using the prize money to do things they otherwise would have had to pass on.

Learn more about the Metrohm Young Chemist Award here! Applicants do not have to use Metrohm instrumentation to be considered, and it plays no part in winner selection.

Decarbonizing the chemical industry

Ryan’s doctoral research at UBC focuses on finding ways to decarbonize chemical manufacturing. The production of fuels, plastics, fertilizers, pharmaceuticals, and specialty chemicals consumes a significant amount of energy and is responsible for 5% of all greenhouse gas emissions. By developing ways to produce these useful chemicals using only abundant feedstocks and renewable electricity, there is an opportunity to offset these emissions.

To decarbonize chemical processes, Ryan and his group are developing a reactor that can use renewable electricity to drive chemical reactions that would otherwise require fossil fuel inputs. The type of reaction they are targeting is called «hydrogenation», and it is used in about 25% of all chemical manufacturing across several industries. Hydrogenation is a simple chemical process where hydrogen atoms are added to an unsaturated chemical feedstock.

Normally, this requires high pressure, high temperature hydrogen gas to achieve, which is extremely dangerous to handle. Conventional technology requires capital intensive hydrogenation plants for this purpose and has not changed for nearly a century.

The reactor, called «Thor», produces hydrogen through the electrolysis of water, which then passes through a thin membrane and hydrogenates an organic feedstock. What makes Thor unique is the use of a palladium membrane as a cathode, hydrogen-selective membrane, and hydrogenation catalyst simultaneously. This architecture enables the electrolysis to proceed in aqueous electrolyte while hydrogenation is mediated in organic solvent. Both reactions proceed efficiently as a result.

Team Thor (left to right): Ryan Jansonius, Natalie LeSage, Roxanna Delima, Mia Stankovic. Not pictured: Arthur Fink, Camden Hunt, Aoxue Huang, and Aiko Kurimoto. The technological innovation is defined by the large number of female group members, as shown by their lead authorship on several peer-reviewed articles (listed at the bottom of the page).

This process circumvents the use of fossil-derived H2, and the natural gas heaters required for conventional thermochemical hydrogenation reactors used industrially today. The ultimate goal is to use Thor to produce renewable diesel, pharmaceuticals, and a host of bio-derived specialty chemicals in a way that is cleaner, safer, and more cost-effective than conventional methods.

The legend of Thor(Tech)

Where did the name «Thor» originate?

Studying the palladium-hydrogen system led the Berlinguette research group to develop the Thor reactor in 2018. The inventor of the technology, Rebecca Sherbo (currently a postdoctoral fellow at Harvard), came up with this idea after studying the bizarre hydrogen absorption properties of palladium. The first setup and proof of concept was a tandem hydrogenation oxidation reactor. Now, instead of the paired electrolysis method they use water hydrolysis as a hydrogen source, but kept the great name to remind them of the history.

What is ThorTech? Ryan and his research team explain their project in a nutshell:

Earlier iterations of the prototype reactor developed by Ryan’s research group at UBC.

Potential commercial impact of greener technology

Thor solves key challenges with conventional hydrogenation methods by using water as a hydrogen source. Therefore, pressurized H2 gas is no longer required, which is challenging to handle and store. The reactivity of hydrogen atoms delivered to the organic feedstock in the reactor is on the order of hundreds of atmospheres. Hydrogen sourced from water can therefore be used to hydrogenate organic molecules without the use of dangerous reagents or high temperatures. Using electricity as the only energy input also enables the device to be carbon neutral if is coupled to a renewable electricity source.

A close-up view of the Thor benchtop reactor.
An expanded view of the internal parts in the flow cell.

Why choose Metrohm?

So, why choose Metrohm over other providers? I asked Ryan about his experiences with our line of potentiostats for his doctoral research in the Berlinguette lab group at UBC.

«All of the potentiostats that we use are Metrohm potentiostats in the lab. The only piece of fancy equipment or scientific equipment we need to run it [Thor] is a potentiostat. We have one big multichannel potentiostat with five or six individual channels in it, and we run all of our reactions off of that.»

Ryan Jansonius

MYCA 2021 Winner and Ph.D. Candidate, University of British Columbia

Learn more about Metrohm’s electrochemical instruments on our website!

A Metrohm Autolab Multichannel instrument. Each channel is a separate potentiostat/galvanostat module, allowing you to perform up to twelve measurements on just as many individual electrochemical cells.

«The thing that sets them apart from other potentiostats I’ve used is that the user interface is really good. The Metrohm software has a lot of default procedures and makes making custom procedures almost brainless, which is great.

You want to use your brain for the hard stuff, not the “set up the instrument” stuff.»

Ryan Jansonius

MYCA 2021 Winner and Ph.D. Candidate, University of British Columbia

We wholeheartedly agree! For more information about potentiostats from Metrohm Autolab, visit the website.

The next steps

The Thor team is currently working to develop membranes that use less palladium, designing flow cells to increase reaction rates and efficiency, and screening catalysts that enable a broader scope of feedstocks to be hydrogenated in Thor.

Dr. Aiko Kurimoto, a postdoctoral fellow on the Thor team has shown that depositing thin layers of different catalysts on the palladium cathode leads to substantially higher reactivities. This work was published in Angewandte Chemie (2021).

Of course, the COVID-19 pandemic has influenced research activities across the globe, and it is no different for our Metrohm Young Chemist Award winner. After spending nearly six months outside of the lab, social distancing measures made it difficult for Ryan to finish up his doctoral work. If an experiment failed, an entire week of work could be lost because of the need to stagger attendance. Ultimately, the team moved to a larger unoccupied space close by in order to continue their work.

How will the MYCA prize money be used?

After completing his doctorate, Ryan had planned to put all efforts into his start-up company ThorTech based on the research he contributed to. However, the transition from graduate researcher to start-up co-founder is quite an expensive one.

«It [the prize] couldn’t have come at a better time! I’m just now starting to appreciate how expensive transitioning [to industry] is.»

Ryan Jansonius

MYCA 2021 Winner and Ph.D. Candidate, University of British Columbia

He wants to take some time off to work on the company before investment capital comes in, and the prize money will be instrumental to help him do this. Additionally, a bit of rest and recharge is needed after finishing his degree!

Ryan defends his Ph.D. at the University of British Columbia in May 2021, and we wish him the very best of luck. To learn more about the research of Ryan and his team, selected peer-reviewed literature is provided below.

Selected literature for further reading:

  • Sherbo, R.S.; Delima, R.S.; Chiykowski, V.A.; et al. Complete electron economy by pairing electrolysis with hydrogenation. Nat. Catal. 2018, 1, 501–507. https://doi.org/10.1038/s41929-018-0083-8

    This is the first article published on the Thor reactor.

  • Sherbo, R.S.; Kurimoto, A.; Brown, C.M.; et al. Efficient Electrocatalytic Hydrogenation with a Palladium Membrane Reactor. JACS 2019, 141, 7815–782. https://doi.org/10.1021/jacs.9b01442

    Thor enables ~65% more energy efficient hydrogenation reactions than can be achieved using normal electrochemical hydrogenation methods.

  • Delima, R.S.; Sherbo, R.S.; Dvorak, D.J.; et al. Supported palladium membrane reactor architecture for electrocatalytic hydrogenation. J. Mater. Chem. A 2019, 7, 26586–26595. https://doi.org/10.1039/c9ta07957b

    This article describes a design for palladium membranes that uses 25x less palladium than conventional Pd foils.

  • Jansonius, R.P.; Kurimoto, A.; Marelli, A.M.; et al. Hydrogenation without H2 Using a Palladium Membrane Flow Cell. Cell Reports Physical Science, 2020, 1, 100105. https://doi.org/10.1016/j.xcrp.2020.100105

    This article shows a designed and validated scalable flow cell architecture, enabling 15x faster, and 2x more efficient hydrogenation reactions.

  • Huang, A.; Cao, Y.; Delima, R.S.; et al. Electrolysis Can Be Used to Resolve Hydrogenation Pathways at Palladium Surfaces in a Membrane Reactor. JACS Au 2021, 1, 336-343. https://doi.org/10.1021/jacsau.0c00051

    Thor can also be used to resolve complex reaction mechanisms by depositing nanoparticles on the surface of the membrane.

Post written by Dr. Alyson Lanciki, Scientific Editor at Metrohm International Headquarters, Herisau, Switzerland.

Special thanks go to Ryan Jansonius for taking the time before his doctoral defense to contribute to this article.