James Walton
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Chromatography has a long and interesting history. To discuss such a vast subject is a challenge, people are understandably passionate about such a subject. There is huge potential of not charting or discussing an area another person believes to be critical, for example we are discussing here Liquid Chromatography, we didn’t feel there would be room or time to discuss Gas Chromatography (GC) in an appropriate amount of detail.

So before we begin, please do let us know if you have any additions or corrections, we are always open to learning more from experts within any industry as that helps us to grow and learn.

Since the mid-19th century multiple types of chromatography have been developed. To start at the beginning, the word ‘Chromatography’ stands for ‘color writing’ and was initially used for the separation of plant pigments such as chlorophyll (which is green) and carotenoids (orange and yellow). However, it soon became apparent that it could be used for a wide range of separation processes as new forms of chromatography were developed starting in the 1940s.

In the modern analytical solutions discussed here, from HPLC to GC and SCFC we have an instrument that is currently in use, allowing the finished Analytical Instruments to achieve their full potential. We have provided solutions for liquid and gas applications, using thermal mass flow technology allowing manufacturers to achieve their end goals and meet the customer’s expectations.

As solutions providers we have relationships with all of the leading manufacturers around the world, these relationships are based on partnership where we provide the flow expertise. Our goal is to deliver the solutions of the future by listening to and understanding the trends in the market now.

One of those techniques is High Pressure Liquid Chromatography (HPLC).

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Schematic drawing of a typically HPLC instrument

HPLC stands for High Performance Liquid Chromatography and is a technique used to separate and allow the user to quantify different compounds. A high pressure pump is used to push the solvent through a column, due to the interaction between the compounds and the column material a separation of different compounds is possible. From here you can analyse the time taken to elute the compund ot the amount of compound detected.

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Schematic of our instruments installed in the HPLC system

UPLC stands for Ultra High Performance Liquid Chromatography and is a special version of HPLC. Compared to HPLC, UPLC columns contain smaller particles sizes (2 um for UPLC vs 5 um for HPLC), which results in a better separation of compounds. The pump pressure in UPLC can go up to 100MPa in comparison to HPLC where this is 40MPa. UPLC has, in some applications, improved chromatography significantly. The run times are much shorter; therefore very fast analysis is possible. UPLC is the abbreviation mostly used in writing; however this is a trademark technology of one of the major corporations in this field and is officially called UHPLC (Ultra High Performance Liquid Chromatography).

SCFC, the last trend we will discuss today is the growth of research into the way that liquid CO2 can be used as a super-solvent. With the ever increasing cost of chemical solvents used in the mobile phase, both purchase and disposal is increasing yearly. Developing a system that utilizes a solvent, such as CO2, that can elute different compounds and provide a gradient effect purely through adjusting and controlling the system pressure is an incredible potential cost saving development. However as with all things, the cost reduction has to be off-set by the cost of installation of such systems. That day is only getting closer, but we are not yet at the point of wide-spread liquid CO2 solvent usage.

  • Working with liquid CO2 can be a real challenge and one that we take seriously, our Coriolis and EL-Press instruments are perfect for this application giving flow and pressure control without the need for a thermal based system that would affect system integrity.

The industry is changing, that’s obvious! We will be on top of this………

James Walton
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Having worked in both the Life Sciences and Analytical industries I am sympathetic to the ever increasing demands for small foot prints and faster instruments. It has been a continuing trend for many years that lab real-estate has become more and more expensive; this led to a drive for footprint reduction of instruments. You had to make sure that size didn’t make you expensive in bench space.

One of the drivers behind this process was the NeSSI system initiative (New Sampling/Sensor Initiative), sponsored by the Centre for Process Analysis and Control. The aim was to reduce the overall costs of engineering, installing and maintaining chemical process analytical systems.

In the NeSSI system, mass flow and pressure meters/controllers needed a standard footprint of 1.5’’.

This footprint is perfect for a large number of applications and end users, even for some of the Life Science OEM companies that have room to spare in their systems. However when you are re-designing your system and you have the chance to incorporate new technology, look at the placement of existing technology and maybe add more it helps if you can reduce the footprint of the components that you use even further.

Reducing the footprint of a known, working technology has challenges of its own. The design and function of which will be driven by the physical characteristics of the measurement principle and therefore the sensor that it uses. To change this you need to look at alternative measurement technologies as a way to achieve the end goal of the industry, same functionality, same signal, smaller package.

Working in conjunction with the TNO, the Netherlands organisation for applied scientific research we designed a new range of mass flow and pressure meters/controllers built around MEMS technology. This allowed us to offer solutions with a footprint of 0.75’’, halving the footprint and offering ultra-compact flow controllers.

This has given our customers:

  • Compact assembly ensuring space efficiency
  • Analog or digital communication
  • Top mount modules, easily accessible
  • Pre-testing ‘’Plug and Play’’ manifold assemblies, reducing customer test requirement

To maintain the usefulness of the new instrument you have to have the same functionality. Along with a sensor on a chip, we need a new, smaller control valve, filter options and a smaller pneumatic shut-off valve. To save even more space and build time, customers requested a down-ported version.

The final addition that makes full use of the space saving created by the addition of new technology was to create a manifold system where a customer can design a number of flow channels into a manifold, all well within the internal space limitations they have for their instrument.

IQ+ Manifold Solution

This is one of the key themes of our blogs and it is referred to time and again. The Solutions based approach, ending up with a bespoke solution not a standard product with compromises. Innovation in technology must be driven by the customer. If you do not think that a standard flow or pressure solution will meet your needs then let us know and challenge our team, we will be your low flow fluid handling specialist.

Check out our smallest mass flow and pressure meter/controller

Check out our Ultra Low Flow Coriolis Instruments

James Walton
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Everyone wants to have greater accuracy, it is desirable and achievable. It has been the push of R&D and marketing teams for years, describing in minute detail how accurate their new instrument is, the work, new technology and time spent to achieve it.

Of course, accuracy is very subjective depending on the industry and even application, I will leave you to apply your own numbers but the definition remains the same.

Accuracy: How close a measurement is to the true value Precision: How repeatable measurements are to the true value

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But, does everyone ask the question; how accurate do you need the instrument to be?

This question can create options for the end user often missed because it is assumed that greatest accuracy is the desired parameter, or the supplier does not have the facility to offer alternatives.

In terms of Mass Flow, accuracy requirements can change the type of sensor being discussed. If you need very high accuracy you can have a Coriolis device, if you don’t need high accuracy you may need a CTA or other sensor type.

These choices can have a high impact on the cost of the instrument and therefore the final solution. To achieve high accuracy requires a higher degree of engineering capability, extremely capable R&D engineers to precisely model the behaviour of the instrument across its range. This creates a very robust set of standards that future instruments can be calibrated against to ensure the end user sees that promised capability. All of this has to be applied with strict quality processes to ensure it happens every time.

When the conversation widens in this way, the conversation becomes very application specific and consultative, it could be very high accuracy in a low throughput application, or it could be lower accuracy, high repeatability in high throughput applications. Every change can result in a cost impact on the instrument, often making an instrument less expensive as many companies only offer their flagship model as standard.

Working with people that have more than one sensor type available is helpful in this situation. If you only have access to one sensor type then your options are greatly reduced. The opposite of working with someone who has access to a suite of sensor types to fit different accuracy and cost requirements.

Understanding this principle can alter the way that you purchase your instrumentation, it is also a good way to check if your flow provider is paying attention!

If you enjoyed the blog I would ask you to investigate our YouTube channel and website.

James Walton
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Metering and dosing of ultra-low flow rates (g/hr) requires a different approach and understanding of the measuring principle compared to metering and dosing of higher flow rates. At these low levels physics start to play a significant role. In this article I will reveal some of the successes for measuring stable ultra-low flow rates.

Working with people to achieve stable and accurate low and ultra-low flow metering and dosing you learn that little things can make a big difference to the process output.

The first thing to do is understand the measuring principle that is being used, please see the video below for a short explanation on Coriolis measurement theory.

Once the principle has been understood then the challenges that we will face become easier to understand.

Due to the ultra-low flow nature of the application the influence of one area can affect the rest of the system, because of this we have broken our advice down into specific areas of discussion.

Fluid Storage:

  • For pressurised containers avoid using gas that dissolves in liquid, e.g. N2/Air
  • If fluid is water, use Di-Water

Filter Advice:

  • Always use a filter
  • Ensure filter has a large internal volume to minimise pressure drop
  • Outlet needs to be position up to ensure trapped AiR comes out during flush

General Advice:

  • Make sure there are no leaks
  • Make sure the entire system is filled with the same medium
  • Ensure environment stability (temp, humidity, vibration)
  • Use small volume tubes to avoid compliance
  • Use a degasser to remove entrained AiR from the fluid

Image: example of pressurised container with degasser Example pressurised container with degasser

Set-up for success

Firstly, you have to be able to pass the fluid through the tube. This is why you will always be asked to discuss the following points:

  • Pressure
  • Viscosity
  • Density

Knowing these three fluid parameters allows you to calculate (www.fluidat.com) the performance envelope that exists. This is something that is critical in instrumentation to ensure that you size a sensor correctly to achieve optimum performance following installation.

Once the above conditions have been considered and a sensor has been found to meet the requirements of both the fluid and the application you have only the conditions surrounding the sensor that can affect the quality of the readings generated.

All Coriolis instrument reading can be susceptible to external influence from vibration; this is why metering at low and ultra-low flow rates is such a challenging design process. If the environment around the application produces a vibration similar to that of the instrument it can cause false and inconsistent readings. Alongside external vibration issues it is possible to create ‘cross-talk’ where Coriolis instruments mounted next to each other incorrectly can cause interference.

Using mass blocks, considering your environment and allowing for physical functions of instruments in the design process will ensure you can achieve maximum performance.

It is important to discuss these limitations because they exist, however having seen Coriolis instruments on helicopters, at the bottom of the ocean and in submarines it just proves that due care and attention will mitigate low and ultra-low flow liquid metering challenges.

Watch our video explaining the principle of our Coriolis flow meters
Check out our Coriolis flow meter product line

James Walton
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Ultra low flow splitter techniques for Analytical Chemistry

I have been working with analytical chemists for a long time, whenever that happens it gives you a unique insight into the challenges they face and the methods employed to overcome them. There is a particular technique that causes problems the world over, it is hard to do and it can have varying results and levels of success. However, people do persevere with it and it currently has no long term successor, of course I am talking about ultra-low flow splitter techniques.

People I frequently speak to are challenged to deliver solutions for low, repeatable flow measurement, especially when employing hybrid techniques. These combinatory analytical techniques put multiple instruments in-line to be used in the detection and separation of chemicals from a solution, of course this means that the sample, unless split out, could be destroyed and with it any further chance to re-analyse the sample.

Splitting the sample has long been possible and is used in analytical chemistry to try and preserve original samples where possible, there are 2 main techniques currently in use and they both have issues.

Resistance splitting is one of the oldest and most reliable methods of continuous flow splitting employed by laboratories; the split is created by using a tube of smaller diameter as a split off from the main flow, creating a known resistance, or delta P, and a fairly accurate continuous split of sample.

Time splitting is similar to resistance splitting but with the added advantage of being able to collect a particular specific compound from a sample. The method is built in much the same way as the earlier resistance split, however the time part of the method title refers to the time taken for your specific compound of interest to pass through the separation column. Once you know this it allows you to give a delta T to a flow switch following the column so that it splits the flow at the right time to split the flow and collect the now separated compound in an allocated vessel.

As I am sure you can see there are multiple problems with both of the above techniques. The set-up of both these methods is very static and there is not much room for flexibility. In conversation these techniques I have found that to change the fluid profile by using a different mobile phase or defining a different compound of interest it is possible to render the original set-up redundant.

While it is possible to re-time the separation of the new compound of interest, or same compound different mobile phase, it may be necessary to re-cut the tubes and re-make the connections from scratch.

I have found that along with being hard to run as a live technique it also creates problems for routine service and maintenance, any replacement of tubes on a calibrated system needs the tubes to be of exactly the same type and length, any change, particularly at low flows can have a huge effect on the velocity of a fluid in a tube and therefore changes in the performance of the system as whole.

Other techniques have been released onto the market, some include a fast acting piezo valve but the cost to performance balance has never lead to a surge away from the old tried and tested methodology.

It is an area that people are showing a great amount of interest in, I am sure it is on the development plan of end users and manufacturers alike, people are asking for an improvement and it is now up to the industry to deliver it.

With the ever increasing use of fluid independent flow technology, please see upcoming blog about utilising the Coriolis force for metering and control, and its ability to increase the simplicity of such an under developed method. New and dynamic advances are surely over-due in this important field of analytical chemistry. I am sure that it will be a hot topic over the next 18-24 months and one that I will revisit to provide a more detailed and in-depth look at the future of analytical flow splitter technology.

If you enjoyed the blog I would ask you to investigate out Youtube channel and website, both linked below.