An interview with Randy Heyler, on extending Raman Spectroscopy into the THz regime, delivering chemical composition and structural information to form the "structural fingerprint". Conducted at Photonics West 2019.
Please define what is meant by the terms “Structural Fingerprint” and “Chemical Fingerprint” in relation to Raman Spectroscopy.
We coined the term “structural fingerprint” to describe the use of Raman for looking more specifically at the chemical structure, and not just the chemical composition. Raman has become popular and has been accepted widely for compositional analysis. It can quantify what the chemistry is, what the constituents are and what the concentrations are.
However, often molecules can change form. This is very important in pharmaceutical areas where a molecule in one form works as an approved drug, but does not in another form. They have to control and monitor it under FDA regulation, and there are very subtle changes, because the composition is not changing at all. The low frequency region, which covers the terahertz (THz) vibrational energies of the molecule, are very sensitive to form changes, and include what are referred to as phonon modes.
Phonon modes are indicative of the crystal lattice in the structure. Many of these materials are crystalline, and so we get highly sensitive signals to form changes. It is therefore very easy to differentiate polymorphs and detect the form changes, and it is essentially done in real time. People were used to Raman having a “chemical fingerprint”, so we coined the term “structural fingerprint” as a complementary term. It is also important to note that our systems will capture both, at the same time, in a single measurement.
As it is more sensitive to structural changes, the other area that is very important is in measuring crystallinity. Using pharmaceuticals as an example, when you are trying to absorb a drug into your system, it is more easily absorbed if it is in an amorphous form. If it is in crystalline form it takes a while to dissolve, reducing the bio-availability. In pharmaceuticals they are trying to blend or pulverize the material into an amorphous form, but it is hard to know if there is any crystalline material left, and how long it will remain stable in this form.
Because our system is highly sensitive to crystallinity, it can tell and quantitate how much crystalline content is present in a powder or material. Then, it allows you to observe the transition from amorphous to crystalline, or vice-versa. If you leave the material alone, it will eventually recrystallize, due to factors such as temperature and humidity, or it might happen naturally. This can be observed in real time with our system, and is the only system with this capability and sensitivity.
People can use it to monitor crystallinity changes over time, or to watch the manufacturing process in order to manage the level of crystallinity. It is like a “crystallinity-meter”, and it is unlike any instrument that anybody has ever made before. To measure this quantitatively in the past, it had to be taken to an X-ray diffraction (XRD) instrument.
In some cases, you can use the chemical fingerprint to detect some subtle form changes, but our signals are typically 10 times stronger and make detection a lot easier and more reliable.
What are the benefits associated with extending the range of Raman spectroscopy into the terahertz regime? Please introduce the TR-Probe offered by Ondax.
The principal product that we offer for this is called our TR-Probe. THz-Raman® is how we describe the unit, because it adds terahertz vibrational energies (also known as low frequencies) into the Raman signal. The probe is a way to use the product in a modality that can be used in direct contact with a sample, be immersed into a liquid, or to probe something optically through a free space context (for example looking through the side of a vessel). We like the word probe, because then it is something people are used to.
We have also developed options to adapt it to a microscope, so that it can be bolted onto an adaptor to make a microscope version of a THz-Raman system, or alternatively be configured for Transmission Raman measurements, which are good for bulk samples or coated tablets. It is a very universal product that has lots of different sample interface accessories.
What applications can the TR-Probe be used for?
The TR-Probe can be used for continuous monitoring of sensitive processes, and can be used as an active feedback mechanism for example to monitor crystallinity, a reaction, or a change from one form to another. It can also be used for basic materials characterization or even chemical mapping, utilizing a microscope. In addition to pharmaceuticals, customers have been analysing polymer compounds, where crystallinity is important to performance, and advance electronic materials, including photovoltaics and 2D materials like graphene. We even have customers doing forensic analysis on home-made explosive materials, and others observing changes under cryogenic conditions.
What other solutions does Ondax provide as part of the THz-Raman® portfolio?
In terms of the product family, the probe has become a versatile tool kit for virtually any kind of sample interface. Most recently, it has also been adapted for automated measurements. For research chemists who will be measuring many different samples and do not want to have to load every sample, we developed a fully automated, programmable well-plate system. Called the WPS, this platform is flexible to measure any standard well-plate and it is completely programmable and customizable, capturing and storing all the data for future analysis.
For example, the ring around the outside of the well may start to crystallize while the remaining sample does not – and the form can change between the time the materials is placed in the well and the time it has been measured…a key indicator of its stability.This system is unique because it probes this interesting range, meaning that you get both Thz-Raman AND chemical fingerprint signatures out of it, as well as allowing you to “map” the inside of each well to look at what is happening.
These are unique features of the system that allows the customer to put a whole range of materials in our systems and flexibly measure everything….automatically!
Learn how to extend Raman Spectroscopy into the THz regime
How do you hope Ondax Raman solutions will advance our understanding of materials characterization?
Our THz-Raman solutions will advance materials characterization in two areas. Firstly, it gives you an additional simultaneous measurement of molecular structure; instead of having to take the material off-line and destructively test in an X-ray machine, a single Raman measurement can give you both composition AND structure. This will bring real benefit to the people who are trying to understand and measure things in real time.
The other is advancement is that it is very sensitive. In areas outside of pharmaceuticals, for example batteries, photovoltaics, advanced electronic materials and plastics, crystallinity dramatically affects mechanical and electronic properties, and it is one of the things that people have not been able to measure non-destructively, especially in real time. I think that those two attributes are going to bring a lot of value to the field of materials science.
About Randy Heyler
Randy Heyler was President and CEO of Ondax, Inc. from 2010 until its acquisition by Coherent in October 2018. The company is the market leader in the design, manufacture, and marketing of high-performance holographic optical filters, wavelength-stabilized laser sources and THz-Raman® spectroscopy systems for a wide range of industrial, scientific, defense, and life science applications.
Randy has over 38 years of leadership experience in the photonics industry, including nearly 20 years with Newport Corporation and 10 years at Spectra-Physics, where his responsibilities progressed through product development, manufacturing, marketing, strategic planning and general management.
Randy holds both a BSME (Design) and an MS in Engineering Management (Technology Management) from Stanford University.
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