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Hyperdoma™: A High-Throughput Hybridoma Generation Platform

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With the great progress in high-throughput screening technology, Creative Biolabs has developed the novel Hyperdoma™ platform, which is a high-throughput hybridoma generation and screening platform based on the advanced ClonePix system. We offer first-class customized monoclonal antibody development services for research, diagnostic, as well as therapeutic antibody developments. The powerful ClonePix system significantly increases the success rate of obtaining antibodies for challenging tasks, such as neutralization, blocking, as well as anti-idiotypic antibodies.

Unique Electrofusion System in Hyperdoma™ Platform

Conventional hybridoma preparation uses a polyethylene glycol (PEG)-mediated cell fusion procedure to merge spleen cells with myeloma cell fusion partners to form hybridoma. PEG-mediated fusion methods often yield a decent pool of positive hybridoma cells. However, the fusion efficiency with PEG-mediated methods is often inadequate for the development of challenging antibodies such as therapeutic antibodies and anti-idiotypic antibodies. To increase the fusion efficiency and generate a larger pool of positive clones for antibody screening, Creative Biolabs has adopted the electrofusion method in the Hyperdoma™ platform.

Electrofusion is a method that fuses spleen cells and myeloma cell via electric shocks. This fast-growing technique has been widely applied in the field of life science research, biotechnology and medicine. Using this method, a high fusion efficiency and success rate can be achieved, with as many as 103~104 positive clones per fusion. The exponentially expanded positive clone pool significantly increases the success of obtaining the functional clones.

High-Throughput Screening Systems

Hyperdoma™: A High-Throughput Hybridoma Generation Platform

Hybridoma screening, during which positive hybridoma clones secreting functional antibodies are identified, is a crucial step in antibody discovery. Conventional screening methods include ELISA and flow cytometry-based cell sorting (FACS). They are not suitable for high-throughput applications since the conventional methods usually lack the sensitivity and accuracy and require a significant amount of time and resources, which can sometimes pose a challenge (low expression level antigens, membrane proteins, multi-chain protein complexes…). Creative Biolabs has adopted several innovative high-throughput screening methods that are compatible with the electrofusion system to exploit the vast positive clone pool in a highly efficient and fully automated fashion.

ClonePix 2 is a highly automated system that accurately picks out and deposits positive hybridoma colonies for screening. This system uses a gel-like matrix to minimize colony movements and with the robotic design, it considerably reduces the risk of colony disturbance and physical damage and in the meantime, increases workflow efficiency with fewer plate handling steps.

With a fluorescence scanning laser reader and a unique image analysis software package, FMAT is a high-throughput analytical system that is suitable for homogeneous formats of both cell- or bead-based assays. The powerful red laser used by the FMAT® 8200 exerts unique excitation and emission wavelengths that minimizes the interferences of colored substances (e.g. color of the culture media in hybridoma cultures) in FMAT analysis. This technique provides a high-throughput homogeneous assay for antigen binding on hybridoma cell surface to provide indications regarding the activity of antibody secreted by corresponding hybridoma cells.

Schematic representation of FMAT for high-throughput screening of soluble scFv recombinant antibodies.Fig 1. Schematic representation of FMAT for high-throughput screening of soluble scFv recombinant antibodies. (Bradley, C., 2007)

Creative Biolabs has adopted and developed high-throughput cell-based assays using Celigo Image Cytometer, which enables the direct imagery and analysis of live cells bound with antibodies. Using Celigo Image Cytometer, researchers are allowed to directly characterize antibodies that interact with the targeted cell surface antigen. The build-in high-throughput analysis platform in a Celigo Image Cytometer enables fast examination of cell plates at a speed of approximately 9 min/plate (one bright-field and two fluorescence channel analysis).

Overlay of fluorescence images of AF594, PE, and Hoechst at selected antibody concentrations for purified and commercial antibodies by the Celigo Image Cytometer method.Fig 2. Overlay of fluorescence images of AF594, PE, and Hoechst at selected antibody concentrations for purified and commercial antibodies by the Celigo Image Cytometer method. (Lu, M., 2017)

Advantages of the Hyperdoma™ Platform

Over 80% of the current therapeutic antibodies were derived from hybridoma. Comparing to other antibody development techniques such as phage display, the antibodies secreted from hybridoma harness the power of natural hyper-mutation and sequence optimization that often exert high affinity and excellent stability. However, the limited size of the positive clone pool is often considered a caveat in the hybridoma approach.

The high-throughput Hyperdoma™ production platform fully utilizes the machinery of hybridoma to screen for the best antibodies for any research project and in the meantime, its electrofusion and the high-throughput screening methods generate an expanded positive clone pool to greatly increase the chance of obtaining the most suitable clone. Hyperdoma™ is by far the most comprehensive and advanced hybridoma generation and screening system that drives hybridoma-based antibody discovery into a brand-new era.

Summarized Features of the Hyperdoma™ Platform


Creative Biolabs has extensive experience in antibody generation using the high-throughput Hyperdoma™ platform. Our scientists are confident in offering the best services and products in a timely and cost-effective manner. Meanwhile, we also provide other various services regarding antibody development. Please feel free to contact us for more information.

References
1. Bradley, C., (2007). “Carcinogen-induced histone alteration in normal human mammary epithelial cells.” Carcinogenesis, 28(10), 2184-2192.
2. Lu, M., (2017). “High-throughput screening of hybridoma supernatants using multiplexed fluorescent cell barcoding on live cells.” Journal of immunological methods.




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