Single B Cell Platforms

Our automated single B cell antibody discovery platforms

Beacon^® Optofluidic platform
Genovac is a proud user of the Beacon Optofluidic platform, which enables vastly superior high-throughput screening of the natural antibody repertoire of an immunized animal. This state-of-the-art approach significantly increases the chances for the discovery of rare functional antibodies against challenging targets like GPCRs and ion channels and reduces the total development timeline by six to ten weeks.

The Beacon platform, created by Bruker Cellular Analysis, is uniquely designed to carefully and specifically isolate, monitor and assay cells derived from lymph nodes, bone marrow, and PBMCs. The Beacon can isolate and identify functional antibody-producing plasma cells or plasmablasts (APCs) in less than one day, eliminating weeks of work.

Once individual antibody-producing cells are identified, they can be exported for cDNA generation through single cell RT PCR and subsequent cloning and sequencing of the immunoglobulin heavy- and light-chain variable-region (VH and VL) genes of single B cells is performed on our high-throughput Tecan Fluent system. Each cell is tracked so that the phenotype can be linked to the genotype. We operate three Beacon instruments and can screen up to 160,000 individual B cells for target-specificity, cross-reactivity, bead and cell-based assays, or certain functional assays utilizing our fully automated Beacon platform.

Features of the Beacon platform:

• Unique combination of genetic immunization and Beacon maximizes chance of the discovery of specific, functional, and high-affinity therapeutic antibodies
• Cell-based assays allow native conformation recognition for many target types, including multi-transmembrane proteins
• Sequential assays enable parallel screening of cross-reactive antibodies
• Ability to screen multiple host species, including:
  • Wild type mice and rats (plasma cells)
  • Transgenic mice and rats (plasma cells)
  • Rabbit (activated memory B cells)
  • Human PBMC (activated memory B and plasma cells)
  • Llama (activated memory B cells)
  • Transgenic llama mouse (plasma cells)

Genovac Nano^™
Genovac Nano is a gravity-based, high-throughput technology that Genovac developed as either a complementary or independent screening platform. Genovac Nano is a robust and economical single B cell screening platform that can screen up to 1 million single plasma cells or plasmablasts per project. In contrast to the Beacon instrument, Genovac Nano can only be used for screening with bead-based assays. However, genetic immunization can still be paired with Genovac Nano if recombinant protein production is feasible.

On the Genovac Nano, clones are retrieved using a robotic picking system that transfers specific APCs to a 96-well plate. Once individual APCs are identified, they can be exported for cDNA generation through single cell RT PCR. From there, subsequent cloning of the immunoglobulin heavy- and light-chain variable-region (VH and VL) genes of single B cells is performed on our high-throughput Tecan Fluent system. Finally, high-throughput Sanger sequencing is performed. Each cell is tracked so that the phenotype can be linked to the genotype.

Features of the Genovac Nano platform:

• Very high-throughput, bead-based screening
• Economical single B cell approach
• Ability to screen multiple host species, including:
  • Wild type mouse and rat (plasma cells)
  • Transgenic mouse (plasma cells)
  • Rabbit (activated memory B cells)
  • Human PBMC (activated memory B and plasma cells)

10X Genomics Chromium X^® + NGS
Genovac also offers single B cell services utilizing the Chromium X® from 10X Genomics. This instrument, in combination with NGS sequencing (Illumina instrument), offers a high-throughput screening technology with the potential of screening up to 240,000 cells per day. We can analyze full-length V(D)J sequences for paired B cell receptors.

This platform can be used as a primary screening method or in combination with our Beacon^® or Genovac Nano™ platforms. When combined with a different primary single B cell platform, the Chromium X instrument can support repertoire sequencing, allowing Genovac to take unused single cell pools and compare sequences of known hits to find better and more diverse candidates.