High-Throughput Screening Reagents:

Essential Consumables for Scalable Drug Discovery

High-throughput screening (HTS)

High-throughput screening (HTS) has transformed drug discovery by enabling researchers to test vast compound libraries in parallel, dramatically speeding up the hunt for new therapeutics. Instead of evaluating one compound at a time, modern HTS platforms can assess thousands – even millions – of compounds simultaneously for activity against a target. This leap in scale is powered by advanced automation, miniaturized assay formats, and sensitive detection methods, which together compress months of experimental work into days. Just as importantly, emerging HTS technologies like CRISPR-based genetic screens, high-content imaging, and mass spectrometry (MS)-based assays are expanding what can be screened, from gene functions to complex cellular phenotypes. These cutting-edge approaches introduce new requirements for reagents and consumables, making the choice of HTS consumables a critical factor in scaling up drug discovery campaigns effectively.

Diverse HTS Assay Formats and Their Consumable Needs

Modern HTS encompasses a variety of assay formats – from biochemical enzyme assays to live-cell phenotypic screens. Each format comes with distinct consumable needs to ensure robust, scalable performance. Below, we outline key HTS assay types and the essential consumables that enable them:

Biochemical HTS Assays (In Vitro Target-Based Screens)

Biochemical assays involve purified proteins or other targets tested in solution with candidate compounds. They are a staple of early drug discovery and typically rely on straightforward mix-and-read protocols.

Assay Plates (96, 384, 1536 wells): Multi-well plates are the backbone of HTS. Higher-density formats (384-well and especially 1536-well plates) allow more tests per run, boosting throughput and reducing reagent use. Many biochemical assays can be miniaturized into 384- or 1536-well volumes relatively easily. These plates must meet ANSI/SBS standards for automation and may be made of polystyrene or cyclic olefin with clear, white, or black walls depending on detection mode.
Detection Reagents and Kits: Biochemical screens often use colorimetric, fluorescent, or luminescent readouts. Common examples include fluorescent substrates for enzyme activity, FRET/TR-FRET reagents, or luciferase-based HTS assay kits for measuring ATP or second messengers. In fact, fluorescence-, luminescence-, and absorbance-based assays remain among the most widely used HTS technologies. Selecting high-quality, sensitive detection reagents ensures signal can be detected even in tiny reaction volumes.
Buffer and Compound Handling Consumables: These assays require reliable source plates for compound libraries (e.g. deep-well plates), reservoir plates for bulk reagents, and automation-friendly pipette tips for liquid handling. Low-retention, sterile robotic tips help accurately dispense microliter volumes and prevent cross-contamination. Proper plate seals or lids are also needed to prevent evaporation when working with miniaturized volumes.

Because biochemical assays don’t involve living cells, they can be readily scaled down in volume. Researchers often leverage this to cut costs – assay miniaturization is a smart strategy to reduce consumption of expensive reagents and samples without compromising data quality. The result is faster, more economical screens that still reliably identify hits.

Cell-Based HTS Assays (Phenotypic and Targeted Cellular Screens)

Cell-based assays bring biological context into HTS by screening compounds on living cells. These can reveal effects on cell viability, signaling pathways, gene expression, or other phenotypes that wouldn’t be evident in a cell-free system. Key consumables for cell-based HTS include:

Cell Lines and Culture Media: Robust cell lines (often engineered with reporter genes or disease-relevant mutations) are the foundation of these assays. Cells must be maintained in consistent growth medium and conditions to ensure uniform responses. Avantor offers a range of cell culture media, serum, and supplements to support healthy cell growth at scale. Using the same lot of serum or media across a screen can minimize variability – for example, scientists often purchase bulk cell culture reagents from a single lot to ensure consistency.
Tissue Culture-Treated Assay Plates: Unlike biochemical assays, cell-based screens require plates that support cell attachment and growth. Sterile, tissue culture-treated multiwell plates (commonly 96- or 384-well) with lids are used. Surface coatings can be critical: plates pre-coated with extracellular matrix proteins or poly-D-lysine promote even cell attachment for sensitive cell types.

For suspension cell assays or advanced 3D cultures (spheroids, organoids), ultra-low attachment plates or specialized microcavity plates are used to prevent cells from sticking to the plastic and to foster uniform spheroid formation.

Detection Reagents for Live Cells: Many cell HTS readouts rely on reagents that measure cell health or reporter activity. The most common approach in high-throughput labs is to measure cell viability via an ATP-dependent luminescent assay – when cells die, they rapidly lose ATP, so luminescence from an ATP-based kit correlates with live cell number. Other assays use fluorescence to detect markers of cytotoxicity (e.g. enzyme release or membrane integrity dyes) or reporter gene readouts (fluorescent or luminescent signals indicating pathway activation). These reagents must be non-toxic (for live-cell assays), reproducible, and compatible with plate readers or imaging systems.
Automation-Friendly Liquid Handling Tools: High-density cell assays often require multiple dispense steps (seeding cells, adding compounds, then adding detection reagents). Automation is crucial for throughput and consistency. Sterile robotic pipette tips, reagent reservoirs, and plate washers that are compatible with cell assays (gentle dispensing, minimal perturbation) help maintain uniform cell conditions across all wells. Consistent handling reduces well-to-well variability in cell responses.

Cell-based HTS comes with additional challenges – cells are sensitive to their environment. Edge wells of plates can evaporate and skew results, and slight differences in cell numbers can affect assay readouts. By using high-quality plates and reagents and controlling environmental factors, researchers can mitigate these issues and obtain reliable, biologically relevant hits from phenotypic screens.

High-Content Screening (HCS) and Imaging-Based Assays

High-content screening is a powerful variant of HTS that uses automated microscopy and image analysis to extract multi-parameter data from cells or organisms in each well. Instead of a single readout (like total fluorescence), HCS might quantify changes in cell morphology, subcellular marker expression, or organelle structure – effectively performing dozens of measurements per well. To enable these information-rich assays, specialized consumables are essential:

Imaging-Compatible Microplates: HCS typically employs plates with black walls and clear bottoms, designed for microscopy. The black sidewalls minimize fluorescent crosstalk between wells, while the optically clear bottoms (made of glass or high-quality polymer) allow high-resolution imaging. An ideal imaging plate has a uniform bottom thickness of ~0.17 mm (equivalent to a #1.5 coverslip) to match the focal length of high numerical aperture microscope objectives. These plates may also be tissue-culture treated if live cells are to be imaged. Using the proper plate ensures that microscope autofocus and image clarity are consistent across the entire screen.
Fluorescent Probes and Stains: HCS assays often rely on multiple fluorescent reagents to label different cellular components (DNA dyes for nuclei, antibody conjugates for proteins, reporter gene constructs for pathways, etc.). Bulk packs of validated fluorophores, cell stains, and antibody detection kits are key consumables. It’s important that these reagents are highly specific and produce bright signals with minimal background to enable automated image analysis. For example, cell painting assays use a cocktail of dyes to stain many organelles at once, requiring a reliable supply of these imaging reagents.
Plate Handling Accessories: Because imaging assays may involve live-cell incubation, fixation, and washing steps, additional consumables come into play. Robotic friendly plate lids or sealers help maintain humidity (preventing edge-well drying) during long incubations. Plate washers or automated liquid handlers with gentle aspiration are used to wash cells without disrupting them. Again, low-volume pipette tips and reservoirs that can handle small wash buffers are useful when miniaturizing imaging assays in 384-well or higher formats.
3D Culture and Advanced Models: When imaging 3D cell cultures like spheroids or organoids, consumable needs can include specialized plates with U-bottom or ultra-low attachment surfaces that encourage spheroid formation.. These newer formats (e.g. 384-well spheroid plates) allow high-throughput imaging of 3D microtissues, but they demand consistent plate manufacturing so that each well’s geometry and optical properties are identical for reliable image capture.

High-content screening produces rich data but is technologically demanding. By investing in high-quality imaging plates and reagents, labs ensure that data quality (image resolution, signal-to-noise) is high across all wells. As noted by industry experts, HCS and other multi-parametric methods are becoming more widespread as HTS formats – having the right consumables is what makes this possible at scale.

CRISPR-Based and Functional Genomics Screens

One of the most exciting developments in drug discovery is the rise of CRISPR-based screening. Instead of testing compounds, these screens introduce genome edits (knockouts, knockdowns, or activations of genes) across a population of cells to identify which genes are involved in a disease phenotype or drug response. CRISPR screens can be pooled (many genes tested at once, with readout by DNA sequencing) or arrayed (each well targeted for a specific gene, similar to classical HTS). In both cases, they merge the worlds of genomics and screening, and require specialized consumables:

CRISPR Reagents (Libraries and Tools): At the heart of these screens are libraries of guide RNAs (gRNAs) or CRISPR plasmids targeting hundreds or thousands of genes. These libraries are costly and precious reagents. Many researchers obtain whole-genome or custom gRNA libraries in multiwell plates or lentiviral formats – maintaining their quality (avoid freeze-thaw cycles, ensure correct concentrations) is critical. Avantor supplies genomic research reagents that can include gRNA libraries, CRISPR nucleases (Cas9 protein, mRNA, or high-quality plasmid DNA), and necessary enzymes for vector production or analysis.
Transfection and Viral Delivery Consumables: Delivering CRISPR components into cells at scale requires optimized reagents. High-throughput transfection reagents (lipid-based or polymer reagents compatible with automation) are used for arrayed CRISPR screens to introduce gRNAs and Cas9 into cells efficiently in each well. For pooled screens, viral delivery (lentiviruses) is common – large batches of cell culture plates, filters, and viral titering kits are needed to infect cells with the library. Products like specialized HTS transfection reagents (e.g. PEI derivatives) are formulated for consistency and compatibility with 96- or 384-well formats.
Cell Pools and Selection Media: In pooled CRISPR knockout screens, a single culture may contain a mix of many edited cells. Consumables here include large tissue culture flasks or multiwell plates to maintain these pools, and selective media or antibiotics (if using selectable markers). For example, after delivering a library, cells might be cultured in 384-well plates under puromycin selection to ensure only those with CRISPR vectors grow. Avantor’s portfolio of cell culture reagents and antibiotics comes into play to support these genome-scale experiments.
Assay Reagents for Phenotyping: Whether arrayed or pooled, CRISPR screens ultimately need a readout. Arrayed CRISPR screens often use the same detection reagents as other cell-based assays (viability assays, reporter gene assays, imaging, etc.) to measure the effect of each gene knockout on the cells. Pooled screens might require DNA extraction kits and next-generation sequencing reagents to read out which gRNA sequences became enriched or depleted. In both cases, having high-purity reagents (PCR reagents, sequencing library prep kits, etc.) ensures that the “hits” – genes of interest – are identified accurately.

CRISPR-based HTS is a powerful complement to small-molecule screening, revealing the biology behind drug responses. It has greatly advanced assay designs for cell-based phenotypic screening, enabling researchers to pinpoint drug targets via loss-of-function or gain-of-function genetics. By stocking the right mix of genomic reagents and traditional assay consumables, screening facilities can tackle these complex, information-rich experiments at scale.

Overcoming Common HTS Scaling Challenges

Scaling up high-throughput screening isn’t as simple as running more assays – it introduces technical challenges that must be managed through careful planning and the right consumable choices. Here are some common pain points in modern HTS and how thoughtful selection of reagents and consumables can address them:

Assay Miniaturization and Volume Reduction: As labs push to screen larger libraries, miniaturization is essential to save on reagent costs and increase throughput. Moving from 96-well to 384-well plates cuts per-test volumes ~4-fold; going to 1536-well plates cuts them even further. This can yield substantial cost savings (e.g. millions of cells or reagents saved per screen). However, working with low volumes means even tiny errors matter – pipetting must be extremely precise and evaporation can distort results. Solutions include using acoustic liquid handling (tip-less dispensing) or low-volume validated pipette tips, and choosing plate materials that minimize evaporation (lids, well designs). SBS/ANSI-standard plates ensure that even in high density, plates remain compatible with automation decks. By miniaturizing intelligently (often starting with 384- well formats which are broadly accessible), labs can scale up screens without sacrificing data quality or blowing through their budgets.
Assay Variability and Edge Effects: When running thousands of wells, variability can creep in from multiple sources – slight differences in liquid dispensing, incubation conditions (like edge vs. center of a plate), or inconsistent reagent mixing. To combat this, researchers use high-quality consumables with tight manufacturing tolerances. For instance, premium assay plates have uniform well volumes and flat bottoms, reducing well-to-well differences. Surface treatments (like blocking proteins or specialized coatings) can prevent nonspecific binding that would cause variability.

It’s also wise to obtain large batches of critical reagents and plastics from a single lot or manufacturer, so that every plate in the screen performs similarly.

Additionally, many labs include control wells and reference standards across the plate to monitor and correct for any drift in the data.

Automation Compatibility: High-throughput screening is practically synonymous with automation – robotic systems handle plate movements, liquid transfers, and readouts far faster and more consistently than humans. But to fully leverage this, all consumables must be automation-friendly. That means plates built to standard dimensions (to fit stackers, handlers and readers), tip boxes and reservoirs that integrate into robotic platforms, and barcodes on plates for tracking. Robotic arms and plate handlers can precisely repeat tasks 24/7, but only if plates and tips are built to not jam or vary. When selecting consumables, it’s crucial to stick to well-established brands and standards known to work with your automation hardware. The payoff is huge: seamless integration leads to higher throughput and consistent data from run to run. (For example, the image below shows an automated plate handler loading microplates into an HTS instrument, illustrating how integral standardized plates and robotics are in modern screening.)

Automated robotic systems load assay plates in high-throughput screening laboratories, enabling rapid, reproducible testing at scale. All HTS consumables – from microplates to pipette tips – must be compatible with such automation. By using plates that conform to industry standards and tips designed for robotic precision, laboratories ensure smooth operations without errors. Automation not only accelerates the screening process but also improves data consistency by eliminating manual variability.

Reagent Stability and Quality: Screening thousands of samples demands reagents that are stable and reliable over the course of large experiments. Enzyme-based detection reagents, antibodies, cell stains, or CRISPR libraries can lose potency if not stored or handled properly. Using high-purity reagents with proven shelf-life, and aliquoting or bulk-purchasing in a way that minimizes freeze-thaws, is key. Many vendors (including Avantor) perform quality control on HTS reagents to ensure lot-to-lot consistency. For critical assays, pilot testing a new lot of reagent before the main screen is a common practice to verify performance. In short, reagent quality directly impacts data quality –cutting corners on cheaper or unvalidated reagents can lead to noisy or irreproducible results down the line.
Data Reproducibility: Ultimately, a scalable HTS process must deliver data you can trust. Reproducibility issues can derail hit validation and lead to false conclusions. By addressing the above factors – uniform miniaturization, low variability, robust automation, and high-grade reagents – labs set themselves up for success. It’s also important to document and follow standardized protocols for every screen. Many screening groups create detailed SOPs (Standard Operating Procedures) for how plates are handled, how long incubations last, how readouts are done, etc., to ensure one screening campaign can be repeated or compared to another reliably. The right consumables support this effort by performing consistently every time. With the combination of careful process control and top-tier consumables, data from modern HTS assays can be highly reproducible, instilling confidence as “hits” move to the next phase of drug development.

Avantor: Your Partner in High-Throughput Screening Consumables

Scaling up HTS requires not only advanced instruments, but also a dependable supply of specialized consumables. This is where Avantor delivers unmatched value to screening labs and core facilities. As a leading global supplier of scientific products, Avantor (through its VWR® and other product lines) provides a one-stop portfolio of everything needed for high-throughput screening – all backed by quality manufacturing and expert support:

Comprehensive Microplate Selection: Avantor offers assay plates in all standard formats (96, 384, 1536 wells and beyond), including variants optimized for HTS. Whether you need white plates for luminescence, black clear-bottom plates for imaging, or ultra-low attachment plates for 3D cultures, you’ll find options that meet ANSI/SLAS dimensions and strict quality specs. These plates are manufactured from high-grade materials for optical clarity and minimal impurities. By using reliable plates, “HTS microplates facilitate numerous tests conducted simultaneously for faster identification” and consistent results.
Assay Detection Reagents and Kits: From enzyme substrates to complete high-throughput screening kits, Avantor’s catalog covers a broad range of detection chemistries. You can source fluorescence and luminescence assay kits for common readouts (ATP, cAMP, protease activity, etc.), stable chromogenic reagents for absorbance assays, and even multiplexed detection sets for dual-readout screens. All reagents are vetted for performance in microplate formats, helping you maximize Z’ factors and assay sensitivity.
Cell Culture Reagents and Cell Lines: Ensuring you have healthy, consistent cells for screening is made easier with Avantor’s cell culture solutions. We provide high-quality cell culture media (including specialty formulations for sensitive cell types), sera and growth supplements, and even authenticated cell lines or cell line development services through our partners. For labs performing CRISPR screens or high-content phenotypic assays, these cell culture products ensure your “assay system” (the cells) are as reliable as your instrumentation.
Liquid Handling Consumables: Avantor stocks all the consumables needed to outfit automated liquid handlers and multichannel pipettors. This includes filtered robotic pipette tips (in 96 or 384-tip formats) that fit popular platforms, reagent reservoirs and troughs for bulk dispensing, and sealers, films, and storage plates for managing compound libraries. Our automation-compatible tips and plates are engineered to stringent standards – they fit and function seamlessly, preventing costly interruptions during large screening runs.
Surface-Coated Plates and Advanced Formats: As screening assays evolve, Avantor keeps pace by supplying next-generation consumables. Need poly-D-lysine coated plates for neuron or stem cell assays? We have them sterile and ready to use. Working with organoids or spheroids? Check out our low-attachment and U-bottom plates designed for uniform 3D cell culture in high throughput. We even offer permeable support plates (Transwell inserts) suitable for ADMET and barrier function screens in 96-well HTS format, expanding the possibilities of what you can tackle in an automated workflow.
CRISPR and Genomic Screening Reagents: For groups embracing CRISPR in their screening pipeline, Avantor provides many of the needed reagents through our life science portfolio. This includes DNA oligonucleotides (for gRNA synthesis or PCR), transfection reagents optimized for high-throughput use, gene editing kits, and selection antibiotics. While your CRISPR libraries may be custom, we can support your downstream needs – from cell culture reagents to plates and detection kits – to execute the functional screens successfully. By having these tools available from one source, coordinating a large CRISPR screen becomes far more efficient.

Beyond the breadth of products, Avantor’s value lies in quality and support. Every item in our HTS consumables collection is sourced from trusted manufacturers or produced under our strict quality control, meaning you can count on lot-to-lot consistency. We understand that a screening campaign’s success can hinge on having enough plates or reagents from the same batch; our logistics network can help you forecast and secure inventory so you don’t run out mid-screen. With distribution centers worldwide, Avantor ensures rapid delivery and supply chain reliability – a crucial advantage when you’re scaling up to screen hundreds of thousands of compounds on tight timelines. Our technical specialists are also available to consult on product selection, helping you identify the best consumables for your specific assays and automation systems.

In summary, Avantor strives to be a trusted partner in your high-throughput endeavors. By providing a broad portfolio, quality assurance, and scalable supply of HTS consumables, we let you focus on the science of discovery while we handle the essentials that make it possible.

Accelerate Your Screening – Start Your HTS Scale-Up Today

High-throughput screening continues to accelerate the path to new drug candidates, especially when supported by the right infrastructure. The essential consumables – assay plates, reagents, cell models, and more – form the foundation of any successful HTS platform. Modern drug discovery teams must not only choose the proper assay format but also the best tools to run it at scale, from a single 384-well plate to an entire automated screening facility. By understanding the needs of biochemical vs. cell-based vs. high-content assays, anticipating challenges like miniaturization and variability, and partnering with a reliable supplier, scientists and lab managers can scale up HTS efficiently and confidently.

Avantor is here to help you every step of the way on this journey. Explore our high-throughput screening product collection to find the consumables and reagents tailored to your needs, or contact our HTS specialists for personalized guidance on scaling up your assays. With the right consumables in hand, you can maximize the power of HTS to drive discovery – accelerating the arrival of new therapies to the patients who need them. Let’s set your screening program up for success and throughput at an unprecedented scale.