High Throughput Screening (HTS) is a high-efficiency analytical method that enables the simultaneous testing of a large number of compounds, genetic targets, or biological conditions in modern biomedical research and drug discovery processes. Particularly in cell-based screenings, enzyme activity assays, protein–protein interactions, and phenotypic change studies, HTS technology accelerates and systematizes research processes thanks to its capacity to generate large datasets in a short time. These screenings, conducted in 96-, 384-, or 1,536-well microplate formats, operate in integration with automation systems, robotic liquid handling units, and imaging technologies, providing highly reproducible, low-cost, and time-efficient solutions. Today, HTS has become an indispensable tool not only in drug development but also in many core scientific research areas such as cancer biology, immunology, neuroscience, and genetics.

Fields such as cancer biology, protein–protein interactions, genetic screening systems, drug discovery, and toxicity analyses prefer HTS-compatible plate systems to obtain comprehensive data. This technology allows multiple compounds or conditions to be analyzed in small volumes, reproducibly and quickly.

- Cancer Biology

Cancer biology is a field that requires high-resolution and systematic analyses due to the complexity of cellular signaling pathways, the diversity of genetic mutations, and the dynamic effects of the tumor microenvironment. In this context, High Throughput Screening (HTS) technology offers the opportunity to simultaneously evaluate the effects of different drug compounds, genetic targets, or environmental conditions on cancer cells under multiple conditions. In particular, in studies investigating the tumor microenvironment–genomic instability relationship, cancer stem cell sensitivity, apoptosis, and proliferation responses, HTS-compatible plate systems provide researchers with speed, accuracy, and scalability. Today, most drug screenings, genetic intervention screenings (CRISPR, RNAi), and phenotypic analyses for cancer therapy are carried out in HTS format.

In cancer research, the limited physiological relevance of traditional 2D cell culture systems has driven researchers toward more realistic and meaningful 3D cell-based test systems. In recent years, the integration of these three-dimensional models into high-throughput screening (HTS) formats has gained significant momentum, especially in early-stage drug discovery processes.

This integration has been made possible through critical innovations such as microplate surface modifications, spheroid culture techniques, and nanotechnology-assisted cell manipulations. In particular, labeling cells with nanoparticles like NanoShuttle-PL and inducing rapid 3D structure formation under a magnetic field enables consistent spheroid production suitable for HTS systems.

Studies have shown that transferring these systems from manual applications to robotic HTS platforms significantly increases efficiency. However, this transition also required special transport systems, magnetic incubators, and automation-assisted solutions. Platforms developed in this scope, integrated with 3D bioprinting systems, make it possible to recreate the realistic microarchitecture of cancer cells and to test multiple drug candidates in parallel on these models.

HTS-compatible plate systems are the cornerstone of such innovative approaches. The 384- or 1,536-well formats offer the ability to culture in low volumes per spheroid while working in full harmony with automation systems. The combination of 3D systems with HTS in cancer biology provides researchers with both physiological relevance and experimental speed.

In modern cancer therapy, rather than one-size-fits-all solutions, personalized approaches shaped according to the patient’s genetic profile have come to the forefront. However, the main obstacles researchers face in implementing these strategies include tumor heterogeneity, the difficulty of obtaining primary cells, the lack of pharmacogenomic data, and the limitations of rapid drug screening systems linked to clinical data.

New-generation technologies developed to overcome these challenges allow the culture of primary cancer cells in micro-volume systems and the simultaneous testing of multiple drugs. For example, in a recent study, researchers encapsulated primary cells obtained from brain tumors into 30 nL alginate-based microdroplets on a chip and performed dose–response analyses against 24 different anticancer drugs. This system clearly revealed the drug sensitivity profile specific to the patient’s cells and showed a high correlation between in vitro data and previous in vivo xenograft model results.

The strongest complement to such micro-volume test systems is HTS-compatible plate designs. Whether in 96-, 384-, or 1,536-well formats, or integrated with microfluidic platforms, special plate systems accelerate primary cell-based drug efficacy screenings and bring them one step closer to clinical applicability.

- Targeting Protein–Protein Interactions

Protein–protein interactions (PPIs) are becoming increasingly important in next-generation therapeutic development strategies, especially in cases where traditional enzyme inhibition approaches are limited. One striking example in this area is the interaction between p38 kinases, which play a critical role in neurological diseases, particularly Alzheimer’s disease (AD), and one of their most important substrates, MAPK-activated protein kinase 2 (MK2). The p38/MK2 interaction plays a key role in neuronal damage, neuroinflammation, and disease progression.

In a recent study, an innovative approach was developed targeting isoform-specific p38/MK2 protein–protein interaction rather than p38’s kinase activity. Researchers optimized a Time-Resolved Fluorescence Energy Transfer (TR-FRET)-based assay system and miniaturized it into 384-well and ultra-HTS 1,536-well formats. This enabled the screening of more than 10,000 pharmacologically active compounds with structural diversity, resulting in the identification of new molecules that inhibit the p38/MK2 interaction at low micromolar levels.

HTS-compatible plate systems, providing high signal-to-noise ratio, long-term signal stability, and DMSO tolerance, increase the reliability of these screenings and allow a smooth transition to both biochemical and cellular validation stages. This approach represents an important model for PPI-targeted therapeutic development studies not only in Alzheimer’s but also in cancer biology.

High-throughput screening (HTS) technology offers a wide range of applications for protein-based studies in biology, biotechnology, and medicine. Widely used in fields such as yield optimization, drug or biomarker discovery, and protein engineering, these methods critically depend on the expression yield, solubility, stability, purity, and biological activity of the target proteins. However, obtaining sufficient amounts and purity of protein usually requires large culture volumes and time-consuming manual extraction and purification steps. This limits the number of protein variants that can be tested simultaneously and the types of assays that can be used.

The recently developed Vesicle Nucleating peptide (VNp) technology offers an innovative solution to overcome these limitations. This method promotes high-yield vesicular export of functional proteins from E. coli cells into the culture medium. As a result, proteins reach sufficient purity and yield to be directly used in enzymatic tests in multi-well plate format without additional purification steps.

-Microbiology

Candida species are among the most common nosocomial infection agents, especially in immunocompromised patients. Existing antifungal treatment options are limited and often fail to achieve the desired efficacy. One of the most important factors complicating treatment is biofilm formation. Biofilms not only worsen the course of infection but also increase drug resistance, reducing treatment success.

Therefore, research on new therapeutic agents, especially those with anti-biofilm activity, is of great importance. A recently developed, simple, fast, economical, and highly reproducible 384-well microplate model can model biofilm formation of both Candida albicans and Candida auris in vitro. This system, when combined with high-throughput screening (HTS) techniques, allows large compound libraries to be tested in a short time.

HTS-compatible microplate models contribute to accelerating drug discovery processes in microbiology and to identifying promising new candidate molecules for combating resistant fungal infections.

From cancer biology to protein–protein interactions, from microbiological studies to drug discovery research, one of the most critical steps in achieving reliable and reproducible results in high-throughput screenings is selecting the right microplate. Greiner Bio-One’s HTS-compatible microplate series offers formats from 96 to 1,536 wells, various surface coatings, and designs fully compatible with automation systems to bring speed and confidence to your research.

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The Greiner Bio-One HTS microplate series offers a wide range of formats to meet different experimental needs: 96 well, 96 well half area, 384 well SV hibase, 384 well SV lobase, and 1,536 well lobase formats to suit every scale of screening. Bottom options include solid bottom, clear bottom, foil bottom, and glass bottom.

• F-bottom design provides maximum light transmission for precise optical camera measurements. Since the well geometry does not deflect the light beam, it prevents spherical aberrations. This feature is especially ideal for cell culture applications.

• U-bottom format is suitable for suspension cultures where cell adhesion is not required. In washing applications, it enables easy centrifugation to obtain cell pellets and quick removal of the supernatant. It also ensures automatic centering of the sample in homogeneous cell-based assays.

• V-bottom format has a very low dead volume, facilitating residue-free pipetting of valuable compounds, and is typically used for storage plates.

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     Contact us to learn more about Greiner Bio-One HTS plate products.

     

                                                              info@novagentek.com

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References:

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Baillargeon P, Shumate J, Hou S, et al. Automating a Magnetic 3D Spheroid Model Technology for High-Throughput Screening. SLAS TECHNOLOGY: Translating Life Sciences Innovation. 2019;24(4):420-428. doi:10.1177/2472630319854337

Lee, D. W., Choi, Y.-S., Seo, Y. J., Lee, M.-Y., Jeon, S. Y., Ku, B., Kim, S.-j., Yi, S. H., & Nam, D.-H. (2014). High-throughput screening (HTS) of anticancer drug efficacy on a micropillar/microwell chip platform. Analytical Chemistry, 86(1), 535–542. https://doi.org/10.1021/ac402546b

Baker, K., & Mulvihill, D. P. (2025). A high-throughput multiwell-plate based approach for the combined expression, export and assay of recombinant proteins (Preprint). bioRxiv. https://doi.org/10.1101/2025.07.29.667353

Ajetunmobi, O.H., Wall, G., Bonifacio, B.V., Montelongo-Jauregui, D., Lopez-Ribot, J.L. (2023). A 384-Well Microtiter Plate Model for Candida Biofilm Formation and Its Application to High-Throughput Screening. In: Krysan, D.J., Moye-Rowley, W.S. (eds) Antifungal Drug Resistance. Methods in Molecular Biology, vol 2658. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3155-3_5

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