Singular Genomics Systems, Inc. unveiled the G4X Spatial Sequencer. The G4X is designed to offer high-throughput in situ direct sequencing of RNA (Direct-Seq?), targeted transcriptomics, and proteomics profiling from formalin-fixed, paraffin-embedded (FFPE) tissues. The G4X will share the same platform as the existing G4® sequencer and is expected to be the industry?s first dual-purpose instrument offering both traditional NGS and tissue-based spatial sequencing capabilities.

With the addition of high-throughput multiomics and novel Direct-Seq technology to its portfolio with the G4X, Singular is positioned to become the only company worldwide to offer in situ spatial sequencing of tissues and NGS on the same instrument. The G4X Spatial Sequencer is designed to offer novel capabilities, stackable data streams, and unprecedented throughput for spatial profiling of tissue. Its novel capabilities will include Direct-Seq, which is the sequencing of RNA molecules in situ and has the potential to open new areas of scientific discovery.

In addition, the G4X will offer readouts of targeted transcripts, targeted proteins, and a fluorescent H&E stain, all in the same tissue sample. And lastly, this combination of readout modalities will be offered at an unprecedented scale. With 40 cm2 of flexible imaging area and single-day run times, the G4X system will enable labs to process 20 times more samples per week than existing technologies.

Initial kits on the G4X will support transcription, proteomics, and offer a fluorescent H&E stain. The system is designed to accommodate a large number of samples and will read out hundreds of gene targets and dozens of proteins in the same tissue section. Content will be available in fixed panels or customizable for the customer.

Future kits on the G4X will also support Direct-Seq, which is designed to directly read variable regions of RNA, such as cancer hotspot mutations, guide RNAs in CRISPR screens, or B- and T-cell receptor sequences. The capability to perform direct sequencing of RNA within cells and tissues is expected to bring a powerful new readout modality for in situ molecular pathology. Direct-Seq will be initially available as a service, with plans for broader release shortly thereafter.

Singular previously announced a technology access program for the PX, the learnings from which have been applied to the development of the G4X. Through its technology access program, Singular has been actively collaborating with leading institutions to generate data on the G4X and demonstrate its applicability in critical research areas. Expected Key Features of the G4X?

Spatial Sequencer: Industry-leading Throughput: An imaging area of 40 cm2 per run across four spatial flow cells is expected to dramatically increase sample throughput while retaining flexibility for smaller runs. Direct-Seq:In situ sequencing of RNA, designed to sequence variable gene regions directly within cells and tissues, with potential applications in immunology, immuno-oncology, cancer research, and gene editing. Transcripts: Hundreds of gene transcripts, which will be available in curated panels and custom gene target selection.

Proteins: Dozens of proteins, which will be available in curated panels and custom protein target selection. Fluorescent H&E: Fluorescent H&E stain overlayed with transcripts and proteins on the same tissue sample. Rapid Turn-around-time: With a specialized tissue transfer process, streamlined sample preparation workflow, and high-speed single-day sequencing, users will have the ability to go from sample-to-discovery in just three days.

Cost-Effective: With its unprecedented throughput, the G4X will significantly reduce the cost per sample to less than half that of alternative approaches, making spatial multiomics more accessible. The system is listed at $495,000, G4X upgrades are expected to be available to G4 customers by the end of 2024, along with an initial immuno-oncology panel of approximately 300 gene transcripts, 10-15 proteins, and the ability to customize content. Direct-Seq and additional panels are expected to be released at a later date.

Singular also plans to provide G4X Spatial Sequencing Technology Access Services starting in the second quarter of 2024. The company plans to share more information and data at the upcoming annual AGBT General Meeting in Orlando, Florida (February 5?8, 2024).