At A Glance
Name: Randel Marfin
Position: Vice president of business development at Luminex
A report released in August by BioPerspectives consulting company showed that within the protein arrays market, bead arrays are growing at twice the rate of planar arrays. ProteoMonitor caught up with the vice president of business development at Luminex, the leading bead array manufacturer, to find out more about why beads are thriving in the market.
Can you give some history of Luminex as a bead company?
The company was incorporated in 1995. It launched its first commercial product in late 1999. The company began and was founded on a proprietary bead-based technology that took advantages of advances made in digital signal processing and powerful computer algorithms. Basically the technology is a very simple, elegant technology that uses multiple dyes inside of the bead to be able to classify what reaction is taking place, and then uses another dye on the surface of the bead to develop or report the reaction — the quantification of the assay. Given that we work in 10 different intensities of internal dyes for the two dyes, we’re able to construct a set of 100 separately addressable microspheres.
How does the proprietary technology work?
Luminex’s technology is based on four key components. The first component is the biology or chemistry. Any binding event will work well on the surface of our bead. The second component is our bead, which are polystyrene microspheres. The biology and chemistry of working with beads is well established. Your home pregnancy test and several companies have been utilizing beads for many years. So working with beads had already been well established. Then we say the third component is the flow side of this, where we take advantage of technology in the flow cytometry area. The beads flow through a flow stream where they’re pulled into single file, and they’re interrogated by two lasers. One laser excites the two dyes internally, so it tells you — Oh, I have a blue-green bead here, so that’s an IL8 assay — and another laser hits the surface of that bead and it tells you how much IL8 is bound to that bead. From that, because it’s fluorescent, you can quantitate that reaction. Then the fourth component which is the key component to the technology is the high-speed digital signal processing and powerful computer algorithms that allow you to capture, analyze and report that data in real time.
How much multiplexing can be done with the beads?
We can do up to 100 separately addressable beads. And there’s really no limitation. That’s what we offer today. But because we’re dealing in terms of color, instead of spatial or location, we’re really not limited to the amount of multiplexing that we can produce. So if I wanted to put three dyes in a bead, I could do 1,000, or if I wanted to put four, five, six dyes — I could put as many dyes as I wanted into the beads, as long as I had room. Each bead has what we call a spectral address. It has its own color and own spectral characteristics, so we’re able to separate these beads and it’s very easy to do. But it would not have been possible had the advances in digital signal processing not taken place. In 1993, there were not the SP chips capable of doing this. These beads are coming up that flow stream at thousands per second. So it’s happening very fast.
Why did the company decide to work with beads instead of planar arrays?
There’s obvious reasons why we selected beads. One is because the biology and chemistry was well understood in working with beads. They had been around much longer than the planar arrays — beads are old chemistry to other companies — so we decided to stick with something that for assay developers was well understood. Secondly, the beads gave us the ability to do these reactions in suspension, as opposed to a planar array. So instead of having to tether something to the bottom of a surface, our beads are suspended in liquid. So we get near liquid-phase kinetics for the reaction — it’s a faster reaction time. If you can imagine a plate where you have tethered to the bottom of it your probe — in order for the reaction to take place in the planar array, you have to make sure you put enough sample in there so that it accidentally comes in contact with it. Whereas, in a suspension array, we are floating around just like it is in real biology. The other reason was the flexibility associated with beads. Suppose somebody was doing a cytokine assay and they were looking at five cytokines and they decided that they also wanted to look at IL8 — another cytokine. If they were using a planar array, they would have to build a new plate, a new chip that included IL8, or add another special chip that had IL8 in it and run two separate reactions. With us, you just merely drop in a new bead, so you have the flexibility to mix and match and customize your assays. That flexibility is a very important attribute of the technology.
A study done by BioPerspectives consulting company showed that bead arrays are growing at twice the rate of planar arrays in the market. Why do you think the beads are growing faster than the planar arrays?
We’re capturing the space at a much higher rate. I think it’s a combination of the flexibility and the menu available — the number of different applications available. Our model is that we have a number of different partners. We will have a partner like Upstate who has a license to Luminex’s technology, and they’ll put their kinase products on our beads and they’ll sell that out onto the market. And because Luminex has several partners, our partners are able to offer a broad menu to the market. It’s an open system. So you’re able to run an Upstate kit, or a BioRad product on the instrument.
Do you think the beads have as much content as the planar arrays do?
Yes. And you can mix and match. I think our customers like the flexibility and the performance. You’re able to get the sensitivity and the dynamic range that they need, and yet you have all the flexibility to customize your panels. And the other part, going back to that flexibility, is that we’re able to do both proteins and nucleic acid-based assays on the same system. And fluorescence is highly quantitative. Because we are in fluorescence, we’re able to have comparable if not better sensitivity than ELISA and other gold-standard methodologies that are in the market. The other thing is we’re reasonably priced, if not a low-cost solution.
What are some of the downsides to using beads compared to planar arrays?
I guess with the planar arrays, with some of those systems you’re able to dwell on it for a long time, so with those systems you could get some very sensitive assays. Because our beads are flowing, they’re exposed to the light source for just a brief moment. A planar array has got a light source that’s just looking on top of it, and it can just sit there because the planar array isn’t moving.
Can you give some more reasons why the beads market is growing so quickly?
I think that it’s the multiplexing in general is growing. There’s a need to look at multiple pieces of information simultaneously. People want to see how the inflammatory process is upregulated and downregulated and in order to do that you need to look at multiple markers at a time. So you have a need in the marketplace for multiplexing. The best solution is a technology that can get you the assay performance without compromising flexibility that is reasonably priced. When you look at that and you look at all the attributes of being on the surface of a bead, I believe that’s what’s driving the demand for bead-based assays. They’re filling the need for multiplexing because they have the flexibility, they have the speed, they have the cost and they have the menu. In addition, the beads have been used in FDA-approved products. For example, Zeus [Scientific] has an autoimmune panel that is FDA cleared. There’s also other panels that have been FDA-cleared as well. In addition to that, we have molecular diagnostic applications for cystic fibrosis, thrombophelia — those are all being used on the diagnostics side. So if you’re a life sciences researcher and you’re out developing an assay, it’s comforting to know that that assay that you’re developing can be used on the diagnostic side because the technology has already been cleared [in the past with another assay].
How does the number of bead-based clinical assays that have been FDA approved compare with the number of planar array-based clinical assays that have been approved?
You’d be surprised at how few, if any, [planar array tests] have cleared. And that’s because of the quality variations associated with manufacturing. If you look it up, I think you’re going to be surprised when you compare the number of applications of beads compared to the number for planar array — I think you’re going to be surprised at the difference. In terms of quality control, beads are a well-established process. With planar arrays, to get the precision that the FDA requires, the repeatability, has been challenging.