Multimode Microplate Readers

 Multimode Microplate Readers

Microplate readers come in two main forms: Those that detect a single type of signal (single-mode readers) and those that can detect multiple types (multimode readers). There’s no shortage of either class of instrument, and new offerings are continually coming to market. Here we review some of the newest entries in the multimode microplate-reader category and highlight features to consider when selecting an instrument for your own lab.

Key features

Several considerations should be factored in when choosing a multimode microplate reader. The most obvious, of course, is current and future application needs. Common reading modes include absorbance, luminescence and fluorescence intensity, but there also are more specialized modalities, such as AlphaLISA and bioluminescence resonance energy transfer (BRET).

But there’s more to the decision than that, says Michael Bjerke, global product manager for detection at Promega. “Scientific discoveries not only require the right type of assay to achieve the necessary sensitivity, dynamic range and reproducibility—they also require the right type of instrument. Instruments with poor optical performance hinder assay performance and experimental design.”

Also important is ease of use—how simple is it to set up an experiment, and how easily can new users be trained, for instance—as are customer service and support. Carl Peters, applications scientist at BMG Labtech, suggests asking, “Is the company committed to service and available to help you when needed? Will you receive support and training after installation?”

Those in high-throughput environments should consider compatibility with lab robotic systems or automated workflows as well as with laboratory information management systems, says Bjerke.

Finally, ask your colleagues about their own experiences, especially if they’ve owned and used their readers for a long time. “A good track record of successfully and reliably working instruments is a big plus, as it proves the robustness and longevity of an instrument,” says Bernd Hutter, marketing and product management for bioanalytical instruments at Berthold Technologies.

Select multimode plate readers

Berthold Technologies

Berthold Technologies offers the TriStar² LB 942, Mithras LB 940 and Mithras² LB 943 microplate readers. All instruments read absorbance, fluorescence, luminescence and fluorescence resonance energy transfer (FRET). Each model is modular, such that users can add advanced reading modes, if needed. These include BRET, time-resolved fluorescence, fluorescence polarization, HTRF® (homogeneous time-resolved fluorescence) and Alpha. The TriStar² uses plates with 6 to 384 wells, and the Mithras and Mithras² use plates with 6 to 1536 wells.

Berthold also offers a proprietary, built-in reagent-injection system—up to four frictionless JET injectors “with the injection tips being located in measurement position for simultaneous inject-and-read operation,” says Hutter. “Variable volume and speed, together with inert material, allow for dispensing of even critical cell suspensions.”

BioTek Instruments

BioTek’s extensive family of microplate readers range from the 384-well-compatible Synergy™ HT to the Synergy Neo, a high-speed, 1536-well plate reader for high-throughput screening. Basic reading modes include absorbance, fluorescence and luminescence, and advanced modes include fluorescence polarization, TR-FRET and Alpha.

BioTek’s Cytation™ 3 is a cell-imaging microplate reader with automated microscopy functionality. “What makes Cytation 3 unique is its digital microscopy optics that allow multicolor imaging with objectives from 2.5x to 60x,” says Xavier Amouretti, product marketing manager at BioTek Instruments. The system’s imaging capabilities include four fluorescent and one brightfield channel. Amouretti says customers use the imaging functions for phenotypic screening, cell viability and cytotoxicity and cell-cycle and cell-migration research.

BMG Labtech

BMG Labtech’s CLARIOstar® offers customers multiple reading modes. For measuring fluorescence intensity, users can choose the wavelength (from 320 nm to 850 nm) and bandpass (8 nm to 100 nm) settings. The CLARIOstar also can measure luminescence and absorbance, and it can perform FRET, time-resolved FRET (TR-FRET), BRET, fluorescence-polarization and AlphaScreen®/AlphaLISA® assays.

The CLARIOstar can read plates in 6- to 1536-well formats as well as BMG Labtech’s LVis Plates containing 16 low-volume microspots. For labs looking to boost throughput, BMG Labtech also offers a plate stacker and plate-handling robot that are compatible with the CLARIOstar.

Peters says many BMG Labtech customers use the CLARIOstar for monitoring gene expression. “This can be accomplished in a variety of ways, including absorbance, fluorescence, luminescence and AlphaLISA,” he says. “Detecting changes in enzyme activity is also very important [using] fluorescence polarization, TR-FRET and AlphaScreen.”

Eppendorf

Eppendorf’s AF2200 microplate reader is built to be reliable and user-friendly. It reads absorbance and fluorescence and has preconfigured filters and easy-to-use software that offers users the option for both preprogrammed and user-defined methods. A distinguishing feature, according to Jessica Geisler, product manager for PCR, detection and cell technology at Eppendorf North America, is that “the software populates the raw results into Microsoft Excel, where it performs automatic calculations, analyses and graphs of your data.”

Geisler says most customers use the AF2200 for nucleic-acid normalization, either with direct absorbance at 260 nm or using fluorescent quantification kits like PicoGreen (using a preprogrammed software feature). The AF2200 also typically is used for protein quantification with the preprogrammed Bradford, BCA or Lowry Assays. The AF2200 can read plates with six to 384 wells as well as Eppendorf’s micro-volume μPlate G0.5, which uses 16 quartz dots for 2-microliter samples.

Molecular Devices

Molecular Devices’ newest microplate reader is the SpectraMax® i3, which researchers can expand “beyond the standard plate-reading functionality without a technician visit or taking the instrument off-line,” says Brian Quast, director of product marketing for microplate readers at Molecular Devices.

Expansion is accomplished by snapping in an individual add-on cartridge (currently more than 40 cartridges are available). For example, the MiniMax 300 Imaging Cytometer Cartridge adds cellular-imaging functionality, and the ScanLater™ Western Blot Detection Cartridge adds fluorescence-based protein-Western blot protein detection functionality. “The ScanLater cartridge compresses protein-detection workflows, from Westerns to ELISAs and numerous other assays, to a single instrument and software platform,” says Quast.

The base SpectraMax i3 system can read fluorescence, absorbance and luminescence and also perform BRET and FRET assays. Add-on cartridges let researchers add capabilities for time-resolved fluorescence, AlphaScreen and fluorescence-polarization assays. The SpectraMax i3 base platform uses 6- to 384-well microplates, and some detection cartridges expand to a 1536-well format. The low-volume SpectraDrop enables researchers to use up to 64 2-microliter nucleic acid samples.

Revvity

For users interested in switching to label-free reagents, Revvity’s most recent model, the EnSpire® Multimode Plate Reader, is equipped with Corning’s Epic® label-free technology. It also can run high-throughput assays based on Revvity’s Alpha technology (AlphaLISA and AlphaScreen), LANCE® and LANCE Ultra TR-FRET and DELFIA® time-resolved fluorescence platform.

Revvity’s EnVision® Multilabel Plate Reader is designed for ultra-high-throughput work. According to Volker Eckelt, portfolio director for multimode detection at Revvity, the company’s microplate readers are mainly used in drug-discovery labs for screening small molecules and studying biologics, such as peptides. But they also have roles in other areas of research, including epigenetics, biotherapeutics and biomarker discovery.

Promega

Promega’s new GloMax® Discover system includes a new software design that uses simple touch controls on a tablet via a wireless connection. It features a wide dynamic range that enables detection of low- and high-signal samples in the same microplates. “To do this on other instruments requires gain adjustment, but our instrument automatically adjusts to accommodate this broad range,” says Bjerke.

Compatible with single tubes and 384-well plates, GloMax instruments can measure absorbance, fluorescence and luminescence, as well as FRET and BRET.

Promega also designs its microplate readers with multiplexing in mind. Multiplexing allows users to read multiple assay signals from the same well, such as cell viability, cytotoxicity and apoptosis, for example. “Our instrument is designed with a flexible protocol builder to control filter slides automatically for fluorescence, luminescence and absorbance,” says Bjerke. “Therefore, you can seamlessly switch filters and detection modes to measure multiple assays’ signals without user intervention.”

The final word

Clearly, the market has a lot to offer, and keeping track of all those specifications may seem intimidating. As you consider your own lab's needs, this advice may help: 

“A plate reader is a plate reader, and it has to read microplates with good sensitivity, and even more important, with high reliability,” says Berthold Technologies’ Hutter. “You want the instrument to perform the same even after many years of use.”

Caitlin Smith has a B.A. in biology from Reed College, a Ph.D. in neuroscience from Yale University, and completed postdoctoral work at the Vollum Institute.

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