Although a mature product category, microplate readers are evolving towards greater functionality, flexibility, and throughput. All top instrument makers are focusing at least some efforts on multiplexing.
“Vendors are introducing evolutionary improvements in performance, reliability, user interface, and support,” says Xavier Amouretti, product manager at BioTek Instruments (Winooski, VT). Supporting applications and methods
Users, according to Mr. Amouretti, expect a short learning curve, userfriendly software, and instrument reliability. BioTek maintains an in-house applications laboratory staffed by scientists who develop, run, and publish applications and methods. Each year, this team selects and delves into several broad application areas such as toxicology studies, and makes them available to the public. This year, the applications group has targeted, among others, biofuels and biologics drug discovery. Publications of biofuels methods began in mid-2011. In 2010, the group published 75 application notes and posters and several peer-reviewed papers.
Justifying higher densities?
When plate densities were increasing during the last decade in response to very high-throughput studies, it appeared that plate readers would require upgrades as well. Luckily, experiment densities have stabilized, with life science researchers turning to smaller, “smarter” screens. 384-well plates have become standard in industry, while 96 wells is quite common in academic research.
However, the desire to consume less sample and fewer reagents continues. BioTek has developed the Take3 Micro-Volume Plate accessory that works on principles similar to Thermo’s NanoDrop UV/Visible analyzer. After depositing 2 µL samples on the 16- or 48-spot plate, the second optical surface engages, and the plate is read in the standard manner.
Not that ultra-dense plates are completely out. “The emergence of the 3456-well format has created demand for screening an entire compound library on one plate,” says Dr. Michael Fejtl, international sales and marketing specialist at BMG Labtech (Ortenberg, Germany).
Is it an array or a plate?
One indication of the maturity of the plate reader market is the number of vendors involved. According to the Lab Manager Magazine website, more than 25 manufacturers operate in the United States. The consequence of so many vendors competing for modestly growing research and highthroughput markers has been a steady stream of technologic innovation and price reductions.
“There is significant competition these days among instrument companies within the sub-$20,000 price range,” says Darren Cook, director of business development at Douglas Scientific (Alexandria, MN). “At the same time, I see some of the more complex reading technologies now being offered in that economical format.” Readers have similarly improved in sensitivity, dynamic range, and flexibility. Some offer full visual spectrum read.
The lower-cost instruments lack the throughput of high-end systems, but for their target markets—basic research and academic labs—they offer a level of sophistication that cost two or three times as much just a few years ago. “These are researchers who can afford to wait eight or 10 minutes for a readout,” Mr. Cook adds. “They have the time but lack the capital. Systems that measure much faster than that still command a significant price premium.”
Douglas Scientific is taking an approach that it believes will provide “more than incremental gains” for the high-throughput end of the spectrum, which according to Mr. Cook has hitherto been the norm. Douglas’s ArrayTape is a revolutionary idea. Instead of an injection-molded plastic microtiter plate or microarrays, ArrayTape is a continuous polypropylene (or polystyrene, polycarbonate) strip embossed with reaction wells that hold less than 800 nL of test fluid. Wells are arranged in familiar SBS format (96, 384, 1536, etc., wells), but the savings in reagent and solvent are phenomenal—as much as 90 percent compared with standard microwells.
Every operation associated with Array- Tape—from charging wells to incubation and reading—has been streamlined and miniaturized. “We’ve leveraged the ‘lean’ manufacturing idea that’s been used in automobile manufacturing for decades,” says Mr. Cook.
Douglas is currently pursuing two major upgrades: a multimode detector for its reading system and support for its microplate operations. “Users with existing microplate systems and methods will not need to mothball them if they upgrade to an ArrayTape system,” says Mr. Cook. What purchasers should look for
Anita Kant, Ph.D., application scientist at Molecular Devices (Sunnyvale, CA), says purchasers should consider their specific applications, the number of expected users, sensitivity, current vs. future needs, system versatility, and single- vs. multimode- reading capability; for example absorbance and fluorescence in a single experiment.
“Single mode is less expensive, but that may not satisfy future needs,” says Dr. Kant. Nevertheless, multimode (and some other) capabilities may be added later on, provided the instrument can handle upgrades.
“Multiplexing has become more commonplace for conducting significant numbers of biological assays quickly, cost-effectively, and with improved reproducibility,” notes Mark Torresan, sales director for detection and separation at Tecan US (Research Triangle Park, NC).
Users must also consider reliability, validation capabilities, throughput, automation, user interface, software, and service. Validation capability, once solely the domain of regulated or high-end labs, may be something else to think about.
Mr. Torresan notes that assay reagent providers are continuously introducing new technologies requiring flexible, high performance instruments. Microplate readers should therefore be purchased with “room to grow” into more-complex analysis modes. “Always consider possible future detection modes, sensitivity, throughput, and modularity or upgrade path.”
Dr. Kant describes these factors as starting points for purchasing a plate reader. “Different labs will begin at different points, depending on their specific situations, and work through some or all of the other factors,” she observes. The most common place to begin is price, but labs unconstrained by budgets might look first at throughput or flexibility. “But eventually everyone considers price,” she notes.
For additional resources on microplate readers, including useful articles and a list of manufacturers, visit www.labmanager.com/microplates.