# Super-resolution single-molecule sequencing by observing the dynamic hybridization of a repertoire of oligonucleotides to DNA targets

> **NIH NIH R43** · XGENOMES CORP. · 2024 · $384,418

## Abstract

PROJECT SUMMARY/ABSTRACT
The genome is a critical factor in our health. However, the cost and performance of current sequencing
technologies are limiting genomics from realizing its full potential in healthcare, including monitoring of cancer
development and recurrence. The goal of the project is to develop a revolutionary sequencing platform that is
superior to existing technologies across a range of metrics. Rather than reading one base or letter at a time, the
proposed technology reads short segments of sequence or “words”, by measuring the kinetics of short
oligonucleotide probe binding to their complementary sequence in the target using super-resolution fluorescence
imaging. Each nucleotide is read multiple times during sequencing. Super-resolution imaging enables the
sequencing of a high molecular density of targets. Advanced statistical and machine learning algorithms are used
for image processing, base calling and sequence assembly. Once developed, this platform will surpass existing
sequencing technology by one or more orders of magnitude in factors including accuracy and sequencing
cost. XGenomes’ prior work has validated the fundamental approach. This Phase I project will develop a full-stack
proof-of-concept through three specific aims. In Aim 1, we will apply our experience to expand the probe set to the
96 we will require for demonstrating sequencing in Aim 3. In Aim 2, the bioinformatics pipeline will be fully
implemented and our prototype fluidics platform will be scaled up to deliver and image 96 probes. Finally, in Aim 3
we will construct the synthetic test targets and demonstrate Q50 sequencing of targeted variants of a clinically
relevant loci. The successful completion of these aims will prove the technology works and position XGenomes to
scale up to the complete platform.

## Key facts

- **NIH application ID:** 11008187
- **Project number:** 1R43HG013911-01
- **Recipient organization:** XGENOMES CORP.
- **Principal Investigator:** Kalim Ullah Mir
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $384,418
- **Award type:** 1
- **Project period:** 2024-09-25 → 2026-05-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008187

## Citation

> US National Institutes of Health, RePORTER application 11008187, Super-resolution single-molecule sequencing by observing the dynamic hybridization of a repertoire of oligonucleotides to DNA targets (1R43HG013911-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11008187. Licensed CC0.

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