Louise Smyth reports on the latest developments in microplates and microplate readers
Although they aren’t necessarily the most exciting weapons in the lab technician’s armoury, microplates and their associated readers nonetheless remain a fundamental part of everyday lab operations. Among the various technical trends and new applications in the sector, there is also the overwhelming trend that can be observed across all lab equipment right now: the need for the products themselves to be ever smaller.
Here, we catch up with some experts in microplate technology to gain an overview of the current market and hear how they are responding to industry demands.
High-throughput screening (HTS) in microplate readers is especially used in drug discovery and relevant to the pharmaceutical industry as well as academic core facilities. HTS allows researchers to quickly conduct millions of chemical, biochemical, or pharmacological tests and establish a basis for drug design.
To maximise efficiency, screening facilities must constantly strive to increase throughput and minimise sample expenditure, while controlling costs. This leads to the key factors in HTS, which are highest speed and flexibility without compromising in sensitivity.
Dr Tobias Pusterla from BMG Labtech explains that, “To meet these requirements, we developed the new multi-mode microplate Pherastar FSX reader. This reader was specifically conceived for fast read times, advanced sensitivity and excellent flexibility.”
Pusterla explains that that the trend towards assay miniaturisation for high-throughput requires the ability to measure the smallest possible quantity. “The outstanding sensitivity of the Pherastar FSX is based on an innovative optical design that is composed of a free air optical path, three independent light sources, simultaneous dual emission detection, and high transmission filters.” He adds: “To ensure the best performance for any HTS assay the reader comes with a high energy xenon flash lamp, a special laser for Alpha Technology and the next-generation laser for TRF/TR-FRET. The new TRF laser with a frequency of 60 flashes per second increases throughput and precision of measurement and allows for a full 1536-well plate to be measured in only 36 seconds.”
Numerous HTS assays require detection of two emission wavelengths. For this reason, BMG Labtech pioneered the technique of simultaneous dual emission detection for microplate readers. Pusterla says: “Thanks to this and two pairs of matched photomultiplier tubes (PMT) detectors, the Pherastar FSX can simultaneously detect two separate emission wavelengths in one single measurement. This offers a speed advantage by cutting read times in half. Moreover, simultaneous dual emission corrects flash-to-flash variations, photobleaching, decaying kinetic signals, or fluctuating conditions such as temperature, pH, and evaporation. Simultaneous dual emission detection can be used in any assay that measures two emission wavelengths or polarization vectors, including FP, FRET, HTRF and AlphaPlex.”
The advantage of miniaturisation allows rapid, inexpensive and effective measurement in 384, 1536 and 3456 well microplates. Pusterla comments that, “The Pherastar FSX offers a combination of features to support all major existing applications and future needs. The reader easily performs applications such as protein-protein interactions, affinity binding assays, compound and inhibitor screening as well as DNA, RNA, and protein quantification.
Moreover, the microplate reader is suitable for enzyme activity, kinetic, cell based and reporter gene assays. The Pherastar FSX especially provides excellent performance in all HTS applications, including NanoBRET, Alpha Technology and HTRF assays.”
Readers with research in mind
Another well-known name in the world of microplate technologies is Molecular Devices, which currently has more than 40,000 units installed in laboratories worldwide. The company offers microplate readers and washers with a variety of detection modes and field-upgradability. Systems range from simple single-mode readers such as the EMax Plus Absorbance Reader, to the SpectraMax i3x Multi-Mode Microplate Reader, the firm’s flagship product.
Celeste Glazer from Molecular Devices says, “Designed with today’s constantly changing research priorities in mind, the SpectraMax i3x measures spectral-based absorbance, fluorescence and luminescence with the added functionality of modular cartridge-based upgrades including western blot and fast kinetics with injectors. Increasingly popular is the option for scientists to perform quick imaging and analysis of their cells using the MiniMax 300 Imaging Cytometer option. The SpectraMax i3x allows scientists to protect their initial investment by purchasing a system with the flexibility to add novel detection capabilities as their research expands, without the need for service engineers or costly system downtime.
“With the SpectraMax i3x, we’ve created a system that leverages that experience to explore a range of applications including cellular pathway analysis and protein activation and expression with the performance, robustness and flexibility that users need to unleash their research.”
Glazer reveals that the latest edition to the company’s portfolio is the SpectraMax QuickDrop Micro-Volume Spectrophotometer, which addresses the needs of researchers who quantify very small amounts of DNA, RNA, oligos and proteins. Glazer comments: “Researchers have the flexibility to work with micro-volume samples as small as 0.5 µL, preserving their precious samples, or with larger samples using the standard 10 mm cuvette port. In a small-footprint, the system also features a large, high-resolution touchscreen interface that gives users the ability to take advantage of pre-configured analysis methods, easily set up customised experiments, or export data to a USB flash drive for additional analysis.
“The QuickDrop Micro-Volume Spectrophotometer is an excellent addition to any lab looking to quickly determine DNA/RNA and Protein concentrations from small volumes with minimal effort. The additional cuvette port and kinetic read options nicely complement our current reader offerings.”
Some exciting news for Molecular Devices in 2016 came when NanoRacks launched one of the company’s most durable microplate readers, the SpectraMax M5e, to the International Space Station. “We are extremely proud to have the only brand of microplate readers that have passed the rigorous vibration, environmental and ease-of-use testing required by NanoRacks to enable reliable and reproducible microgravity scientific research," says Greg Milosevich, the company’s president.
From cell imaging to plate stacking
US-headquartered Biotek Instruments is another player in the microplates sctor that has had an extremely busy 2016. In April it launched its newest product, the Lionheart FX, which offers microplate-based live cell imaging – something that’s especially necessary in the rapidly-growing 3D cell market.
The Lionheart FX is optimised for kinetic live cell imaging, with up to 100x air and oil immersion magnification in a variety of slides, dishes, microplates and flasks. Imaging channels include brightfield, colour brightfield, phase contrast and fluorescence, with both image-based and laser autofocus. An environmental control cover provides convenience beyond that of typical digital microscopes, allowing for incubation up to 40°C and gas control, while the optional humidity chamber and dual reagent injectors enhance environmental support for live cell imaging workflows. Gen5 3.0 software provides automated image capture and analysis, plus annotation and movie maker functions, offering ease and simplicity across a broad range of live and fixed cell applications.
Augmented microscopy is the combination of all of these features in one compact system. Biotek says that Lionheart FX is ideal for live and fixed cell applications including kinetic live cell assays, 3D spheroid imaging, translocation and colocalisation studies, cell migration and invasion, proliferation, viability, toxicity and many more.
In other product news, BioTek recently announced its new BioSpa 8 Automated Incubator, which is an innovative platform that links microplate washers and dispensers with readers and imaging systems for unattended workflow automation. The company says that real-time temperature and CO2/O2 control and monitoring, plus humidity level monitoring and plate lid handling provide an ideal environment for cell-based and other assays, with minimal manual intervention.
BioSpa 8's robotic arm moves microplates, cell culture dishes and flasks between its environment-controlled drawers and integrated instruments. The system is compact enough to fit within a biosafety enclosure for added protection essential to long term live cell assays, including 3D cell culture studies and other live cell assays. BioSpa 8 is also suited for temperature sensitive and controlled-environment biochemical assays.
The BioSpa system software integrates with the linked instrument's software for efficiency and programming ease, precisely controlling all operations for short or long-term uninterrupted runs. Customisable text or email notifications and alerts relieve the need for onsite monitoring, and session timelines and environmental reports allow quick scrutiny of the process and system status for added confidence.
Finally, BioTek also recently introduced its Synergy Neo2 microplate reader. This is an advanced, high-performance, high-speed plate reader that incorporates the firm’s Hybrid Technology with its independent optical paths that ensure uncompromised performance. Continuously variable bandwidth quadruple monochromators, sensitive high transmission, filter-based optics and up to four PMTs provide ultra-fast measurements with excellent results. Advanced environment controls, including CO2/O2 control, incubation to 65°C and variable shaking support live cell assays; cell-based detection is optimised with direct bottom illumination. Barcode-labelled filter cubes help streamline workflows and limit errors, and the available BioStackNeo plate stacker is extremely fast, making it ideal for high throughput requirements.
Latest reader empowers research
One recent launch sets out to offer tailor-made solutions to suit “virtually any drug discovery or advanced life science research application.” The Spark 20M multimode microplate reader from Tecan is a freely configurable system that gives researchers access to new techniques and features intended to enhance and streamline biochemical and cell-based workflows.
At the heart of the instrument are Fusion Optics and a powerful, high frequency xenon flash lamp, which can be combined with the user’s choice of high performance detection modules to ensure a perfect match for their workflow. Options include an enhanced fluorescence module designed to improve sensitivity and increase the speed of high-throughput screening, and the newly developed Te-Cool cooling module that allows the measurement chamber temperature to be set below the ambient room temperature for more accurate and reliable results.
The Spark 20M’s cell handling capabilities have also been extended with a new automated cell imaging and confluence measurement feature. This allows incubation and monitoring of cell culture microplates within the measurement chamber, enabling the user to define the confluence at which the assay starts/ends or the substrate is injected, for optimal assay results and greater walkaway operation.
Fully modular microplate reading
Berthold Technologies has extended its TriStar2 multimodal microplate reader platform by adding new functionalities to offer all main detection technologies in one easy-to-use, monochromator or filter-based instrument. Developed for full modularity and equipped with the proprietary One-4-All optical system, the TriStar2 S series combines the user friendliness of a multimodal optical system with the sensitivity and performance of a dedicated optical device. Its maker says that it provides the flexibility for today, tomorrow and beyond in a single system. Users can start with the reading technology they need to master their research today and upgrade when they need it.
The TriStar2 S series is equipped with both, top and bottom reading technology to support a wide range of detection modes, including absorbance (UV/VIS), fluorescence intensity (including FRET), fluorescence polarization, luminescence (including BRET and BRET2), time resolved fluorescence (TRF), and time resolved FRET (TR-FRET / HTRF). Up to three proprietary JET injectors can be installed to dispense multiple activators or detection reagents at any time with high accuracy and precision as well as excellent mixing performance. The option to inject in the measurement position offers highest sensitivity for ultra-fast flash luminescence assays. A temperature controlled microplate compartment ensures stable conditions whenever temperature sensitive enzymes or cells are in use. The optional gas control unit enables adjustment of both, O2 and CO2 gas levels, if required for cell-based applications. The upgradeable TriStar2 S multimode microplate reader offers the flexible all-in-one solution for any lab.
Innovative multimode plate reader
One microplate product proving popular with those working on cell-based assays is the EnSight multimode reader from PerkinElmer. This is being put to use for applications such as comparing transfection reagent efficiency by imaging and cell counting.
Many cell-based assays and biotherapeutic production processes rely on the expression of exogenous molecules in a model cell line. This makes it highly desirable to have robust, reliable methods that are quick to perform and easy to reproduce for both the optimisation of transfection rates and the monitoring of cytotoxic effects in and on the cell lines of interest.
To meet those needs, the EnSight multimode plate reader offers well imaging, label-free and labelled detection technologies on a single system, and is perfectly suited to track and measure transfection efficiency across different cell types and with different protocol variations and optimisations. The combination of brightfield and digital phase contrast (DPC) imaging with up to four fluorescent colours in a high-density plate-based format allows the user to test many conditions quickly and with enough replicates to ensure the quality of the data generated.
Along with Kaleido data acquisition and analysis software, the EnSight system is able to simultaneously measure transfection rate and assess cell health in a rapid, easy to use and reproducible manner.