Advances in 3D Cell Culture for High Throughput Drug Screening

27 Apr 2016
Lynsey Forsyth
Post Doc / Research Fellow

Editorial article

Image: Sebastian Kaulitzki/Shutterstock

Dr Timothy Spicer, Assistant Professor of Molecular Therapeutics and Lead ID Director of Discovery Biology & HTS at The Scripps Research Institute, Florida, USA talked to SelectScience® about advances in cancer drug screening, being driven by 3D cell culture automation.

Dr Spicer’s research is focused on developing and optimizing technologies for high throughput screening (HTS) of any biological target, with an unmet therapeutic need. There is a huge drive in the field of cancer research to accelerate screening and maintain disease relevancy.

3D Cell Culture and HTS Screening

3D cell cultures, where cells are allowed to grow in vitro in all three dimensions, compared with traditional monolayer methodologies, are more physiologically relevant. This makes them ideal for compound screening in drug discovery. However, replacing large-scale 2D cell culture has been challenging. Dr Spicer is working in collaboration with Corning Life Sciences to improve 3D cell culture screening technology, by developing and validating non-adherent 1536-well spheroid plates. As Dr Spicer explains, “The work we’re doing now is really focused on improving the technologies. A lot of researchers have been doing 2D or a monolayer format for screening, for a long time, and they’ve found reasonable leads but ultimately most of them have failed.” These new 1536-well plates are designed to enable fast development of spheroids on a large-scale, high-density format to facilitate the screening of a huge volume of compounds. Dr Spicer remarked that it would be possible to screen the entire Scripps Drug Discovery Library, of over 650,000, compounds in less than two weeks, using this technology. The team at Scripps with Corning Life Sciences have developed, tested and validated the 1536-well spheroid plates, which are compatible with existing HTS facilities such as imagers, readers and automated workstations.

Future Perspectives

This successful collaboration is now focused on validating the 1536-well plates by screening potential cancer therapies. However, this technology will be applicable to any area of drug discovery, including central nervous system disorders, infectious, cardiovascular and metabolic diseases. The ability to produce consistent 3D cell cultures, on a large-scale, is set to transform the field of drug discovery. Enormous numbers of compounds can be screened rapidly, in a more physiologically relevant model, which will accelerate their development into the clinic and ultimately lead to new and more efficacious treatments.


Watch the video and visit the website to learn more about Dr Spicer’s work at the Scripps Institute. Find out more about Corning’s high content screening plates in this video.

Do you use Corning’s 96- and 384-well spheroid microplates or 1536-well spheroid microplates? Tell us what you think, leave a review.

Corning® 384-well Black/Clear Round Bottom Ultra-Low Attachment Spheroid Microplate, Bulk Packed 10 per Bag, with Lid, Sterile

Corning Life Sciences

Ultra-Low Attachment microplates feature a covalently bound hydrogel layer that effectively inhibits cellular attachment Surface minimizes protein absorption, enzyme activation and cellular activation Surface is noncytotoxic, biologically inert and nondegradable Sterilized by gamma irradiation Black wall microplates have low background fluorescence, minimal light scatter and reduced crosstalk Opaque walls to prevent well-to-well crosstalk Can be used for both top and bottom reading instruments Bulk packed 10 per bag Novel well geometry aids formation of spheroids in center of well Optically clear round bottom with black opaque microplate body

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Corning® 96-well Black/Clear Round Bottom Ultra-Low Attachment Surface Spheroid Microplate, Bulk Packed, with Lid, Sterile, 10/Bag

Corning Life Sciences

Ultra-low attachment surface with covalently bonded hydrogel that minimizes cell attachment, protein absorption, enzyme activation and cellular activation The surface is noncytotoxic, biologically inert and nondegradable Round bottoms with 300 µL total volume Recommended working volumes of 0.075 to 0.30 mL Sterilized by gamma radiation Novel well geometry aids formation of spheroids in center of well Optically clear round bottom with black opaque microplate body

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Cell / Tissue CultureCell culture or tissue culture is used to study the biology of cells or tissues and to isolate cellular products in an environment which can be manipulated and well defined. Accurately control your culture environment with bioreactors or culture incubators, bind your cells to a surface or together with an extracellular matrix. Distinguish cell types with differential media or proliferate cells with certain characteristics using selective media. Enrich your media with supplements such as growth factors, sera and vitamins. Find the best cell and tissue culture products, kits and equipment in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.MicroplatesMicroplates are multi-well plates used to increase the throughput of biological investigations. The number of wells microplates contain can range from 6 to 3243 wells, with the 96-well format being the most commonly used. Microplates can come tailored for a range of applications including cell culture, PCR, filtration, storage, non-binding surface, protein crystallization, as well as pre-coated, deep well and normal Standard microplates. Additionally, options for microplate colors include clear , black, white or black with clear bottom and white with clear bottom for absorbance microplate reader applications. Find the best microplates for your lab in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.High-Throughput ScreeningHigh-throughput screening (HTS) is an automated drug discovery technique for identification of active compounds against a compound library. Use HTS readers and integrated assay preparation / analysis workstations to screen your compounds. Identify active compounds against various HTS libraries, including membranes, proteins and peptides and HTS cell lines. Find the best high-throughput screening products in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Cell Lines Stem Cells and Primary CellsPrimary cell cultures, established cell lines and stem cells are vital for <i>in vitro</i> and <i>ex vivo</i> experimentation. High-quality cells, optimized for your applications, alongside optimized cell substrates, growth medium and supplements, are critical for experimental success. Explore a range of cells suitable for your applications, including isogenic cell lines, competent cells, induced pluripotent stem cell (iPSC)-derived cell lines, fungal/bacterial/mammalian cell lines, stem cells and cancer cell lines. Find the best cells for your research in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Microplate Readers / DetectorsMicroplate readers are used to automate the detection and analysis of labeled or label-free components in microplates during assays or live-cell monitoring. Microplate readers are generally distinguished by their mode of detection. Types include absorbance, luminescence, fluorescence intensity, fluorescence polarization, TRF / FRET and multimode microplate readers. Microplate readers deliver a high throughput of samples by reading multiple wells simultaneously, with the 96-well format the most commonly used. As a result, microplate readers are often used in the drug discovery, bioassays, research and pharmaceutical industries for screening applications. Microplate loading can also be automated, with robotic microplate stackers to increase throughput. Find the best microplate readers in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Cell-Based AssaysCell-based assays are used to monitor the presence, quantity and activities of a desired cellular analyte including drug molecules or biomarkers. This can reveal information on cell health (apoptosis, cytotoxicity, viability and proliferation assays), cell metabolism, cell migration and cell signaling mechanisms. Find the best cell-based assay products, kits and equipment with our peer reviewed product directory: compare products, check customer reviews and receiving pricing direct from manufacturers.High-Content ScreeningHigh-content screening (HCS), also known as high-content analysis (HCA), is a high-throughput technique used in drug discovery to identify substances that alter the phenotype of cells. HCS uses fluorescent microscopic imaging and automated image analysis to investigate cellular events such as apoptosis, cell viability, GPCR activation, oxide production, neurite outgrowth, and cell signaling. Find the best fluorescent labeling reagents, cellular assays, and high-content imaging systems in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.BiomarkersBiomarkers are biological markers which can be measured and evaluated to indicate a biological state. The use of biomarkers in research and diagnosis can indicate a normal or disease state or drug response of cells / tissues. Biomarkers include genetic markers, cell surface markers such as antigens, antibodies or receptors and secreted molecules such as cytokines. An assay system is required for identification of biomarkers. :Automation Supplies / AccessoriesAutomated accessories and consumables make lab processes fast, efficient and reliable. Useful automation accessories include microplate sealers, label printers and reagent reservoirs.Plate ProcessingAutomated plate processing is used in microplate technologies for high-throughput, speed and efficiency. Plate processing systems include microplate handlers for moving plates, heat sealers, stackers and carousels for storage, retrieval and delivery, microplate washers and piercers. Useful features of plate processors include walk-away automation, compatibility and easy integration with microplate systems.AutomationAutomation in laboratories and manufacturing processes enhances efficiency, precision, and scalability by reducing the need for manual intervention. It plays a critical role in improving productivity, minimizing human error, and accelerating workflows in fields like diagnostics, drug development, and industrial testing. Automation technologies include robotic systems, automated liquid handlers, and process control systems that streamline complex tasks and ensure consistent, reproducible results. Explore our peer-reviewed product directory to discover the best automation solutions, compare options, read user reviews, and get prices directly from manufacturers.High ThroughputHigh throughput experiments allow the simultaneous processing of several samples. This parallelization reduces the cost per experiment and increases reproducibility and output volume of data.