Commercializing Multi-Angle Light Scattering Instruments

Interview conducted by Will SoutterMay 23 2016

In this interview, Philip Wyatt of Wyatt Technology talks about the development of multi-angle light scattering technology, the inception of the company, and what it's like to run a family business at the cutting edge of the analytical instrumentation industry.

First of all, you were the first to produce a commercial instrument for multi-angle light scattering – can you give us a brief overview of this technology and its applications?

Multi-angle light scattering, MALS, is fundamentally based on measurements of light scattered into a plurality of scattering angles, from a sample illuminated by a monochromatic light source.

From these unique measurements, a variety of the physical properties of the scattering particles/molecules that comprise the sample may be derived. These include molar mass, size, and interactive features of the constituent molecules.

If the samples are fractionated, for example by size exclusion chromatographic techniques, the molar mass and size distributions may be obtained directly with the addition of an in-line refractive index detector.

By measuring the scattering of laser light, the molar mass, size, and interactive features of particles or macromolecules can be determined. Image credit: shutterstock.com/Michal Steflovic

This technique has a long history. A sample of particles was prepared in a cylindrical glass cuvette which was then placed on a stage and into which a fine light beam passed along a diameter. A single detector was then rotated around the cuvette to record the scattered light as a function of angle. Such measurements were often used to determine the average size and related properties of particles and molecules in solution.

Once separation methods (e. g. GPC and FFF) had been developed such that sizes could be separated, it became necessary to make such measurements “on the fly” so to speak, i.e. to make measurements of samples as they were flowing through a special type of cell.

Scanning the range of important scattering angles from such samples using a single detector could not keep up with the high flow rates of the ever-changing fractionated samples. Accordingly, an array of detectors covering the whole range of scattering angles was needed, to capture the whole picture at once.

Can you tell us a bit about your own background, the process of making this technology ready for commercial use, and how Wyatt Technology was founded?

My education included undergraduate work at the University of Chicago and also at Christ College Cambridge. Then I ended up doing a PhD in theoretical physics at the Florida State University. I started working at a few industrial firms shortly after graduating, and began getting interested in the use of lasers.

Eventually, I started a company called Science Spectrum, with a focus on being able to detect the presence of a biological threat. There was a lot of concern in that area at the time, so the US government was more than willing to support the work.

Through that company, which lasted about 14 years, we developed the first scientific instrument that incorporated a laser light source. Those first instruments were based on the traditional single detector, scanning a range of scattering angles (which would have limitations as a technique for flowing samples, as I explained previously).

Unfortunately, the concept of using a laser to make such measurements never caught on and Science Spectrum had to close down due to lack of funds. In its final year, while working on a contract for the Food and Drug Administration to build a device to detect antibiotic residues in meat products, we introduced into the instrument an array of detectors surrounding a glass capillary through which samples were flowing. The first MALS device was born, but never publicized except through a brief “new product” release in a trade journal that no one would read… except one person.

Light scattering patterns from wine were found to correlate with taste and quality. Image credit: shutterstock.com/lenetstan

As Science Spectrum closed its doors, a few employees decided to meet and toast the dead company with a few glasses of wine. While at it, they decided to put some of wines being consumed into a Science Spectrum light scattering instrument that lay abandoned nearby. The results looked interesting as the light scattering patterns seemed to have some correlation with the comments on the quality of the wines made by the toasting ex-employees.

In the process of closing down the loose ends of some of the Science Spectrum contracts, I decided to write up the experiments and submit the article to Science. Virtually every major newspaper in the world picked up the story, many claiming that these scientists were going to take all the joy out of tasting wine by using lasers!

Surprisingly, a French magazine (Science et Vie) was actually very enthusiastic about this method of judging wine quality. This lucky burst of publicity gave us the chance to start building the new company – a piece of luck which brought us to the attention of our first customers.

What were the first projects that you worked on at Wyatt Technology?

While at work completing those last Science Spectrum tasks (under the aegis of what I thought would be a temporary company, Wyatt Technology), an unexpected phone call arrived from the Department of Defense telling me that we had been awarded a contract based on a proposal I had submitted almost a year earlier. It concerned a technique we had developed at Science Spectrum to detect the presence of metabolic poisons or carcinogens in drinking water within an hour to determine, thereby, if it was safe to drink.

We had figured out a method using light scattering, and what we used to call micro-canaries (bacteria susceptible to toxins and carcinogens—think of a canary in a coal mine) to detect the presence of these toxins in drinking water. It worked out very well, and we looked forward to selling many special instruments to the Government for this purpose. Unfortunately, the government decided that the threat of sensitive water supplies being poisoned was not high enough to warrant commercializing the project.

Returning now to the MALS concept we had incorporated into our instrumentation for the FDA project mentioned earlier, that last minute press release had been spotted by a scientist from S. C. Johnson & Son who wanted to try MALS as a means to measure the size of particulate samples following separation by hydrodynamic chromatography. They placed an order sight unseen, and the first MALS instrument was delivered to them several months later. A viable business was launched!

The second sale of a MALS instrument, to the Amoco Production Company in Tulsa, OK, came in from another simple “new product” release. This one was a game changer, as the Amoco scientist wanted to combine it with samples separated by gel permeation chromatography (GPC), a concept we had never heard of at the time!

With the Amoco order, we developed new packaging and a revolutionary MALS flow cell which, to date, has been used in all our MALS instruments (HELEOS & TREOS families). We have just recently begun production on the successor, a new innovation with an extremely small flow cell, called the microDAWN or simply μDAWN.

The HELEOS and μDAWN MALS instruments from Wyatt Technology

Are these initial applications still reflected in the main fields your instruments are used in? Are there any other major applications that have arisen since?

The instruments that we currently produce have become essential tools for just about every major pharmaceutical and biotech company in the world.

They are used in the development of new biologicals, and particularly by many firms to ensure the quality of the products they make—especially in the field of vaccines. There are many firms using them on the manufacturing line to make sure that the product is correct before it's bottled and sold. So we're very proud of that.

It’s now over 30 years since Wyatt Technology was founded—what are the advantages in the modern marketplace of having this legacy of innovation and unique technologies?

Our original MALS instruments provided the basis for our further developments in the areas of liquid chromatography.

With the cachet of these exceptional instruments, we developed a variety of ancillary instruments including the world’s most sensitive differential refractive index detector, an intrinsic viscometer, and several instruments based on dynamic light scattering that are so unique that we supply them on an OEM basis to a major instrument company.

The reputation we have developed over these three decades has resulted in our providing these “products of choice” to many of the world’s leading firms and, of course, the universities that continue to produce the world’s most renowned scientists.

Wyatt Technology is a family business, which is relatively unusual for a technology business. Does this have an impact on the company dynamic, and how it is run?

Yes, this company is an exception to the often expressed objective of small startups to “be acquired once successful”. The outcomes for small successful companies that are acquired are not always great for the employees, so we decided a long time ago to make sure that would never happen. The company has been established in such a manner that its acquisition is essentially impossible.

By making sure we remain a family company, this ensures that caring for our customers becomes our first objective. We have no shareholders to please, as is the case for publically traded firms. Increasing profit indices is always secondary to serving our customers. They remain our life blood and we will never forget our obligations to them.

As part of this strategy, we also continue to try and develop instruments that complement, rather than compete with, some of the world’s larger instrument firms. We don’t actually compete directly with any major companies in the same field.

As mentioned earlier, we do have an on-going OEM agreement with a large instrumentation firm with whom we do not compete. This has been a very successful association, as indirectly, it permits us to serve quite different customer bases, in different markets.

We’re quite proud of the fact that a little company like ours is producing OEM products for some very large corporations!

Philip's sons Geof (left) and Cliff (right) are heavily involved in the running of the company.

What are some of the ways that you are able to build close ties with your customer base, that a larger company might not be able to do?

One of the really great ways we have of interacting with the customers is our “Light Scattering University”, a.k.a. “LSU”. This is a three-day training course where the customers come here to Santa Barbara to really learn about the light scattering technique and how to use our instruments. By the end of the course, they can operate their instruments with great confidence.

We even give out graduation diplomas in Latin – based on a suggestion by the great polymer chemist Bruno Zimm who served on our Scientific Advisory Board many years ago. There is a great story about the diplomas concerning a Korean scientist who attended the LSU course, and took his diploma back to Korea, where they are not very familiar with Latin. One of his directors noticed his new diploma and thought it looked like a really good degree, so he got a raise!

So this concept of bringing the customers for training in Santa Barbara has proved invaluable. They represent an exceptional group of scientists from whom we learn a great deal and learn about potential markets for our instruments with which we might not be familiar. It’s a great way for us to interact with them, to find out what they need for the future, as well as what they might like to see improved in the instruments.

Another important feature of our work, and a great testament to the success of our instruments, is the bibliography of peer-reviewed scientific publications that we maintain. Right now there are almost 12,000 reviewed papers based on measurements made with our instruments. An interested researcher can visit our bibliography, select virtually any subject and find a trove of papers on related work. This is a wonderful resource for any new researchers, in a variety of fields.

When did your sons first decide to take a part in the business?

Geof joined the company right out of college as a “temporary job” while he looked for a permanent one! He became so intrigued by what he saw, he decided to stay and help his father “see the light” of business, so to speak. A few years later, he went to the Harvard Business School to get an MBA.

Before he left, he had helped his brother Cliff (a genetics graduate from Berkeley) land his first job with a public finance company. Cliff moved from this firm into the world of sales where, at Becton Dickinson, we learned he had been the recipient of a “Rookie of the Year” sales award. By appealing to family loyalty, we convinced Cliff to return to Santa Barbara and join the company.

He organized a formal sales department and sales have grown continually since he began. We often chide him for not having joined earlier, and ascribe to this the slowness of our early sales!

The family connection looks set to continue as well – one of my grandsons has worked here over the summers in inventory control, while another grandson who is eight years old came to visit, and said, “one day I’m going to run this company!”

What is your outlook for the future – how do you see this area of analytical instrumentation evolving, and how do Wyatt’s plans for development fit into this vision?

Light scattering will always play a major role in analytical chemistry and all disciplines that depend on it. Our wonderful scientific staff (average length of service with the company approaching 7 years!) continue their extensive interactions with our broad customer base, learning from them about the challenges to their research and the types of measurements they would like to see become reality.

The development of new instruments (some have no direct relation to MALS) is guided by our customers, whose frequent interactions with our own staff scientists provide many of our new product ideas and direction. Yet, MALS and DLS will be here to stay for as long as measurement of size and changing size are needed by analytical scientists. We look forward to the next 66 years, and the Centennial celebrations our great grandchildren will be organizing!

Get more information about Wyatt Technology and multi-angle light scattering

About Philip Wyatt

Philip J. Wyatt is the Founder and Chief Executive Officer of Wyatt Technology.

He was nominated by the NAS as one of fifteen finalists for this country's first Scientist-Astronaut Selection Program. In 2003, he was named Graduate of Distinction by the College of Arts and Sciences at FSU. He is the American Physical Society's 2009 recipient of the Prize for Industrial Applications of Physics.

He is a Fellow of the American Association for the Advancement of Science, the Optical Society of America, and the American Physical Society. In addition, he was the Chair (2012-2013) of the American Physical Society's largest unit, the Forum on Industrial and Applied Physics.

The author of more than seventy publications, he has co-authored or contributed to eleven books. He has had over thirty domestic patents issued relating to laser light scattering and other technologies and over sixty derived foreign patents and new filings. He is a Registered Agent before the U.S. Patent and Trademark Office.