Sequence-defined oligourethane probe libraries for high-resolution surface characterization

Background

Understanding the chemical landscape of material and biological surfaces at the molecular level is critical for advancing applications in materials science, biotechnology, and environmental monitoring. Surface-bound functional groups govern key interactions relevant to contamination detection, catalyst performance, biosensing, and drug discovery. However, many surfaces present heterogeneous and complex chemistries that traditional analysis tools struggle to profile with high specificity and throughput.

Current techniques—such as X-ray photoelectron spectroscopy (XPS), secondary ion mass spectrometry (SIMS), fluorescence labeling, and antibody-based assays—face limitations including low chemical specificity, poor multiplexing capacity, and sample preparation requirements that can disrupt native surface states. Conventional affinity probes like peptides and antibodies offer limited combinatorial diversity and often fail to capture subtle stereo­chemical nuances. These shortcomings constrain efforts to generate comprehensive, quantitative molecular fingerprints of complex surfaces.

Technology overview

This technology introduces sequence-defined oligourethane probe libraries synthesized by solid-phase chemistry to achieve precise control over monomer sequence, functional group presentation, and stereochemistry. High-throughput automated protocols generate hundreds to thousands of probes, including chiral variants characterized by circular dichroism to assess stereochemical properties.

Surface interaction profiling is performed by passing the probe library through a chromatographic column where the substrate of interest serves as the stationary phase. Binding affinities manifest as distinct elution profiles, and probe identities are determined using LC-MS/MS. Unknown probes can be sequenced through selective chain-end degradation and reanalysis, enabling label-free, high-sensitivity detection with minimal material consumption.

Unlike traditional methods requiring surface modification or indirect labeling, this approach preserves the native chemistry of the substrate and supports broad functional group exploration. The combination of automated synthesis, surface chromatography, and mass-spectrometric decoding delivers compre­hensive, high-throughput surface interaction maps with greater chemical resolution and versatility than existing techniques.

Benefits

• Enables precise, label-free profiling of surface chemistry under native conditions
• Supports large combinatorial libraries with controlled functional group and stereochemical diversity
• Reduces sample preparation and preserves native surface states
• High-throughput, automated synthesis and analysis enable rapid screening of complex surfaces.
• Sensitive mass-spectrometric detection minimizes required material quantities.

Applications

• Biosensor development and optimization
• Surface contamination detection and environmental monitoring
• Catalyst surface interaction studies
• Drug candidate surface-binding profiling
• Extraterrestrial material surface analysis for astrobiology

Opportunity

• Replaces conventional surface analysis methods with a more sensitive, versatile, and high-throughput platform.
• Unlocks detailed molecular interaction mapping for advanced material, biological, and environmental applications.
• Available for licensing to partners in surface science, biotechnology, environmental monitoring, and pharmaceutical development.

Intellectual property

PCT/US2025/018365 filed 03/04/2025