Addressable nanoantennas with cleared hotspots for single-molecule detection on a portable smartphone microscope

• Published in: Nature communications 2021-02, Vol.12 (1), p.950-8, Article 950
• Main Authors: Trofymchuk, Kateryna, Glembockyte, Viktorija, Grabenhorst, Lennart, Steiner, Florian, Vietz, Carolin, Close, Cindy, Pfeiffer, Martina, Richter, Lars, Schütte, Max L., Selbach, Florian, Yaadav, Renukka, Zähringer, Jonas, Wei, Qingshan, Ozcan, Aydogan, Lalkens, Birka, Acuna, Guillermo P., Tinnefeld, Philip
• Format: Article
• Language: English
• Subjects: 631/61/350/59; 639/624/399/354; 639/925/926/1049; 639/925/927/1021; 639/925/930/2735; 9/10; Antibiotic resistance; Antibiotics; Bioassays; Deoxyribonucleic acid; Diagnostic software; Diagnostic systems; DNA; DNA - chemistry; Drug Resistance, Bacterial; Emitters; Fluorescence; Humanities and Social Sciences; Humans; Klebsiella; Klebsiella pneumoniae - drug effects; Male; Microscopy; multidisciplinary; Nanoantennas; Nanostructures; Nanotechnology; Optical instruments; Point-of-Care Testing; Science; Science (multidisciplinary); Serum - chemistry; Signal processing; Smartphone; Smartphones
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21238-9

The advent of highly sensitive photodetectors and the development of photostabilization strategies made detecting the fluorescence of single molecules a routine task in many labs around the world. However, to this day, this process requires cost-intensive optical instruments due to the truly nanoscopic signal of a single emitter. Simplifying single-molecule detection would enable many exciting applications, e.g., in point-of-care diagnostic settings, where costly equipment would be prohibitive. Here, we introduce addressable NanoAntennas with Cleared HOtSpots (NACHOS) that are scaffolded by DNA origami nanostructures and can be specifically tailored for the incorporation of bioassays. Single emitters placed in NACHOS emit up to 461-fold (average of 89 ± 7-fold) brighter enabling their detection with a customary smartphone camera and an 8-US-dollar objective lens. To prove the applicability of our system, we built a portable, battery-powered smartphone microscope and successfully carried out an exemplary single-molecule detection assay for DNA specific to antibiotic-resistant Klebsiella pneumonia on the road. Single-molecule fluorescence currently requires specialized imaging equipment due to the low signal of a single emitter. Here the authors introduce NanoAntennas with Cleared HOtSpots (NACHOS) to boost the signal sufficient for detection of a single emitter by a smartphone, opening the door to point-of-care applications.