Chemical painting for high-throughput single-cell drug response analysis

This technology is a multiplexed vibrational imaging platform for large-scale single-cell analysis of drug responses, enabling the identification of mechanisms of action, drug resistance, and the effects of combination therapies.

Unmet Need: High-content, scalable single-cell drug profiling

Single-cell drug response measurements are crucial for drug discovery, as cellular phenotype, gene expression, and metabolic activity can vary significantly between individual cells and across different disease contexts. Single-cell measurements also provide valuable insights into drug mechanism of action, drug-induced molecular changes, and drug resistance. Current methods for drug response measurements utilize electrical, optical, mass spectrometry, or singling approaches. However, these methods have several limitations, including low throughput and sensitivity, as well as complexity and high cost. There is a clear need for a scalable, high-content, and minimally invasive method that captures cellular heterogeneity and accurately characterizes the effects of drugs at the single-cell level.

The Technology: Multiplexed infrared imaging for quantitative single-cell drug profiling

This technology is a method that examines single-cell drug responses by integrating mid-infrared imaging, multiplexed vibrational microspectrometry, and a data analysis pipeline for large-scale measurements. This technology includes three infrared-active vibrational probes that can measure distinct metabolic activities in drug-perturbed cell phenotypes. The data analysis pipeline incorporates machine learning to predict drug mechanisms of action with high accuracy, minimal batch effects, and in a high-throughput manner. Thus, this technology has the potential to advance translational drug research and drug discovery.

This technology has been validated on human cancer cell lines, profiling over 10,000 single-cell drug responses across 15 different drugs.

Applications:

• Single-cell drug response profiling for drug discovery
• Mechanism-of-action classification and prediction
• Identification of resistant cell subpopulations
• Screening of genetic function
• Research tool for elucidating drug mechanisms
• Research tool for understanding drug resistance
• Research tool for optimizing drug therapy
• Combination therapy optimization and evaluation
• Translational research in precision medicine

Advantages:

• High-throughput platform for drug screening and high-content single-cell analysis
• Sensitive to subtle drug-perturbed phenotypes
• Machine learning integration enables robust mechanism-of-action predictions
• High content for multiple cell feature detection
• Non-invasive measurement from intact or live cells
• Cost-effective compared to existing single-cell platforms
• Sufficient signal-to-noise ratio on single-cell

Lead Inventor:

Wei Min, Ph.D.

Patent Information:

Patent Pending (WO/2024249409)

Related Publications:

• Shou J, Oda R, Hu F, Karasawa K, Nuriya M, Yasui M, Shiramizu B, Min W, Ozeki Y. “Super-multiplex imaging of cellular dynamics and heterogeneity by integrated stimulated Raman and fluorescence microscopy.” Iscience. 20 Aug; 24(8): 102832.

• Chen C, Zhao Z Qian N, Wei S, Hu F, Min W. “Multiplexed live-cell profiling with Raman probes.” Nat Commun. 2021 Jun; 12(1): 3405.

• Shi L, Liu X, Shi L, Stinson HT, Rowlette J, Kahl LJ, Evans CR, Zheng C, Dietrich LEP, Min W. “Mid-infrared metabolic imaging with vibrational probes.” Nat Methods. 2020 Aug; 17(8): pp. 844-851.

• Shi L, Xiong H, Shen Y, Long R, Wei L, Min W. “Electronic resonant stimulated Raman scattering microspectroscopy.” J Phys Chem B. 2018 Oct; 122(39): pp. 9218-9224.

Tech Ventures Reference:

• IR CU23332

• Licensing Contact: Dovina Qu