Combining Acoustic Bioprinting with AI-Assisted Raman Spectroscopy for High-Throughput Identification of Bacteria in Blood.
Identifying pathogens in complex samples such as blood, urine, and wastewater is critical to detect infection and inform optimal treatment. Surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) can distinguish among multiple pathogen species, but processing complex fluid samples to sensitively and specifically detect pathogens remains an outstanding challenge. Here, we develop an acoustic bioprinter to digitize samples into millions of droplets, each containing just a few cells, which are identified with SERS and ML. We demonstrate rapid printing of 2 pL droplets from solutions containing S. epidermidis, E. coli, and blood; when they are mixed with gold nanorods (GNRs), SERS enhancements of up to 1500× are achieved.We then train a ML model and achieve ≥99% classification accuracy from cellularly pure samples and ≥87% accuracy from cellularly mixed samples. We also obtain ≥90% accuracy from droplets with pathogen:blood cell ratios <1. Our combined bioprinting and SERS platform could accelerate rapid, sensitive pathogen detection in clinical, environmental, and industrial settings.
View details for DOI 10.1021/acs.nanolett.2c03015
View details for PubMedID 36856600
Toward rapid infectious disease diagnosis with advances in surface-enhanced Raman spectroscopy.
The Journal of chemical physics
2020; 152 (24): 240902
In a pandemic era, rapid infectious disease diagnosis is essential. Surface-enhanced Raman spectroscopy (SERS) promises sensitive and specific diagnosis including rapid point-of-care detection and drug susceptibility testing. SERS utilizes inelastic light scattering arising from the interaction of incident photons with molecular vibrations, enhanced by orders of magnitude with resonant metallic or dielectric nanostructures. While SERS provides a spectral fingerprint of the sample, clinical translation is lagged due to challenges in consistency of spectral enhancement, complexity in spectral interpretation, insufficient specificity and sensitivity, and inefficient workflow from patient sample collection to spectral acquisition. Here, we highlight the recent, complementary advances that address these shortcomings, including (1) design of label-free SERS substrates and data processing algorithms that improve spectral signal and interpretability, essential for broad pathogen screening assays; (2) development of new capture and affinity agents, such as aptamers and polymers, critical for determining the presence or absence of particular pathogens; and (3) microfluidic and bioprinting platforms for efficient clinical sample processing. We also describe the development of low-cost, point-of-care, optical SERS hardware. Our paper focuses on SERS for viral and bacterial detection, in hopes of accelerating infectious disease diagnosis, monitoring, and vaccine development. With advances in SERS substrates, machine learning, and microfluidics and bioprinting, the specificity, sensitivity, and speed of SERS can be readily translated from laboratory bench to patient bedside, accelerating point-of-care diagnosis, personalized medicine, and precision health.
View details for DOI 10.1063/1.5142767
View details for PubMedID 32610995