At A Glance
Name: Mark Chandler
Position: CEO of as-yet unnamed Luminex spin-out to commercialize the applications of Luminex's technology to medicine
Prior Experience: Founder and CEO of Luminex, founder and CEO of Inland Labs
Just prior to announcing his intention to leave Luminex for an unnamed spin-off designed to apply xMAP technology to medicine, ProteoMonitor spoke with Luminex founder Mark Chandler about the company’s “suspension arrays” and their progress in the marketplace
How did you get involved in doing protein analysis?
I got a PhD in immunology at [the University of Texas] Southwestern Medical School in Dallas, and in getting that PhD I worked on a class of toxic compounds called ribozome inactivating proteins. They're a group of substances that are about the most toxic on earth. They include ricin, and a few other toxins. I'm not sure if you're familiar with the old case, where a [spy] got stuck in the back of his calf with an umbrella tip. They implanted a little ball, killing [the spy] that way. In that tiny little pellet was this compound called ricin, which is highly lethal, but [a form of it] was being used as a cancer drug in the late 80s and early 90s. We are the largest producer of that toxin in the world. [We being] Inland Labs, the company I started right out of grad school.
The need for Luminex' technology evolved out of a need for us to very accurately detect contaminants in the ricin preparations we were giving to pharmaceutical companies. We had to do a lot of protein purification, and any contaminants of the ricin A chain would make it a highly toxic substance to the cancer patients who were receiving the drug. Needing a highly sensitive detection method that could detect multiple contaminants led us to the creation of the Luminex technology. Eventually Luminex grew to exceed Inland, but Inland is still around and doing well. But we were driven to create the Luminex technology by the demand within Inland labs.
You were looking for biological contaminants?
Right, proteins. If these proteins were in the drug mixture, the drug became about a million times more toxic.
How does the Luminex technology work?
To look at multiple proteins in a single sample simultaneously, we use different colored microspheres. Each microsphere has a unique fluorescent signature. Right now we have 100 fluorescent signatures, but as the need for more evolves we can create more.
But having a unique fluorescent signature allows us, for example, in a blood bank application, to put a hepatitis A test on a red colored bead, a hepatitis B test on a purple bead, and a hepatitis C test on another colored bead. With 100 different colored beads, you can have 100 different colored tests that all take place in the same tube. These beads, after reacting with the patient sample, are run through the paths of lasers, where now another fluorescent dye on the surface of the bead quantitates the reaction. For instance, if you’re looking for an antibody to hepatits A, you would use a green fluorescent compound to detect the presence of hepatitis A antibody on the surface of the bead. The intensity quantitates the reaction.
How does this compare with microarrays placed on a solid substrate?
We do get compared with the two dimensional microarrays quite often. We call ours a suspension array, and there a lot of benefits that accrue to a suspension array. Most importantly, [the benefit] is the speed of the reaction. If you compare us to a biochip, we generally have reaction kinetics that can be 10 to 100 times faster. [It’s also] much less expensive – about one percent the cost of a conventional two-dimensional array.
The best part about it is that we can create lot numbers that are traceable. When you create a microarray, each one is its own lot number, so quality control of a 2D microarray is very difficult. When we make a lot, there can be 10,000 or 10 million tests in one lot, so we make it very easy for quality control. So it’s probably something that would be looked on very kindly by the FDA – the ability to so thoroughly control our product.
When you talk about a lot of 10,000 or 10 million, are you referring to repeating the test over and over again?
It would be repeating the same 100 tests over and over again. And all 100 tests would be one lot.
Are there limitations to the technology right now?
The limitations primarily for our customers are the menu. They would like there to be many more tests available on the system so they don’t have to build their own tests. Right now with some exceptions that’s what they have to do. There are cytokine MAPs – multianalyte profiles – available from about five different commercial vendors.
There are kinase assays, there are autoimmune tests that have already been FDA approved, and there are allergy tests that have already been FDA approved. So I think just as that menu grows, the acceptance of our technology will grow with that.
Is there a theoretical limit to the number of different [colors] you can associate with the beads?
No, there really isn’t. It’s more of a practical limit, especially if you look into doing something like SNP analysis, or most genetics analyses. They generally require PCR reactions or some sort of amplification, and that is much more of a limitation than putting a lot of different color beads together on a sample. Nobody is going to want to do a thousand different PCRs to look at a thousand different SNPs. That’s the limitation.
How does it work right now? Do researchers do the protein expression or antibody production themselves?
The researchers can do it themselves. There are also companies that will do it for the customer on a contract basis. So we do have ways to get our customers up and running if they don’t want to build the assay themselves. But it’s on a contract basis.
What’s required for actually working up a test? Is there a lot of chemistry involved?
No there isn’t. We haven’t done anything really unique on the bead chemistry. We use the same chemistries that almost everyone in diagnostics has used for 30 years on beads. You just activate the surface of a bead with one chemical, wait about an hour, add enzymes, proteins, DNA, or whatever you want, and those will be bound to the bead. You wash it and it’s ready to go. You can make millions of tests in that one simple [procedure].
What’s the ideal application for proteomics?
One of the most exciting applications is in large scale multianalyte profiles, where you look at a serum sample from somebody who maybe just came in with a heart attack. You look at hundreds of different blood chemicals to find out what new diagnostic markers are found in the blood that could be useful for not only diagnosis, but also prognosis and even directing drug therapy or toxicology.
With a drug like Baycol [an anticholesterol therapy], if [Bayer] had done a very wide screen of serum proteins, they might have found that myoglobin and [creatine kinase] were elevated in the patients taking Baycol that were going to have muscle degeneration. That could have enabled Bayer to save billions of dollars by either checking for that or taking the drug off the market [earlier].
Any future plans to add capabilities to xMAP?
We’ll expand the number of bead sets that are routinely available when the need arises. We are always working on advances to the instrumentation. There’s a lot that can be done.
What are the challenges with trying to get people to adopt the platform? In speaking with Leigh Anderson, he indicated it was difficult for one company to get all the pieces together for a platform technology.
I think he’s absolutely right about that. The way we have gotten around that is we license our technology as an open platform. We have well over 40 partners now, I think nearer to 50, that operate in all areas of the life science industry – pharmaceutical, diagnostics, environmental. We’ve got people developing our platform for almost every life science bioassay application there is. [Anderson] had it just right. That’s why we didn’t think we could be all things to all people. We’ve turned our technology over to people who are specialists in those different areas, and they are now creating tests for their own markets that they understand much better than we do.
What’s an example of the kind of companies you work with?
We’re in discussions with every one of the major diagnostics companies. We have deals signed with Bio-Rad, we have deals signed with several specialty players in autoimmune disease, and we are expanding into infectious disease. We are becoming very widely adopted. I think in the coming month or two, you will begin to see announcements from major players in the diagnostics industry who are also moving to our platform.