PMID- 27853258 OWN - NLM STAT- MEDLINE DCOM- 20180517 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Nov 17 TI - Digital Detection of Exosomes by Interferometric Imaging. PG - 37246 LID - 10.1038/srep37246 [doi] LID - 37246 AB - Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30-100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip. We demonstrate these characterization concepts using purified exosomes from a HEK 293 cell culture. As a demonstration of clinical utility, we characterize exosomes directly from human cerebrospinal fluid (hCSF). Our interferometric imaging method could capture, from a very small hCSF volume (20 uL), nanoparticles that have a size compatible with exosomes, using antibodies directed against tetraspanins. With this unprecedented capability, we foresee revolutionary implications in the clinical field with improvements in diagnosis and stratification of patients affected by different disorders. FAU - Daaboul, George G AU - Daaboul GG AD - Nexgen Arrays, Boston, Massachusetts 02215, USA. FAU - Gagni, Paola AU - Gagni P AD - Consiglio Nazionale delle Ricerche, Istituto di Chimica del Riconoscimento Molecolare (ICRM), Milano, Italy. FAU - Benussi, Luisa AU - Benussi L AD - Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. FAU - Bettotti, Paolo AU - Bettotti P AD - Nanoscience Laboratory, Department of Physics, University of Trento, Povo (TN) Italy. FAU - Ciani, Miriam AU - Ciani M AD - Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. FAU - Cretich, Marina AU - Cretich M AD - Consiglio Nazionale delle Ricerche, Istituto di Chimica del Riconoscimento Molecolare (ICRM), Milano, Italy. FAU - Freedman, David S AU - Freedman DS AD - Nexgen Arrays, Boston, Massachusetts 02215, USA. FAU - Ghidoni, Roberta AU - Ghidoni R AD - Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. FAU - Ozkumur, Ayca Yalcin AU - Ozkumur AY AD - Department of Electrical and Electronics Engineering, Bahcesehir University, Istanbul, Turkey. FAU - Piotto, Chiara AU - Piotto C AD - Nanoscience Laboratory, Department of Physics, University of Trento, Povo (TN) Italy. FAU - Prosperi, Davide AU - Prosperi D AD - Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, Milano, Italy. FAU - Santini, Benedetta AU - Santini B AD - Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, Milano, Italy. FAU - Unlu, M Selim AU - Unlu MS AD - Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts 02215, USA. FAU - Chiari, Marcella AU - Chiari M AD - Consiglio Nazionale delle Ricerche, Istituto di Chimica del Riconoscimento Molecolare (ICRM), Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161117 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Cerebrospinal Fluid/*chemistry MH - Exosomes/*chemistry MH - HEK293 Cells MH - Humans MH - Interferometry/methods MH - Microarray Analysis/instrumentation/*methods PMC - PMC5112555 COIS- The authors declare the following competing financial interest(s): George G. Daaboul is the chief scientific officer of Nexgenarrays LLC. David Freedman is the chief executive officer of NexgenArrays LLC. All remaining contributing authors declare no competing financial interests. EDAT- 2016/11/18 06:00 MHDA- 2018/05/18 06:00 PMCR- 2016/11/17 CRDT- 2016/11/18 06:00 PHST- 2016/06/20 00:00 [received] PHST- 2016/10/26 00:00 [accepted] PHST- 2016/11/18 06:00 [entrez] PHST- 2016/11/18 06:00 [pubmed] PHST- 2018/05/18 06:00 [medline] PHST- 2016/11/17 00:00 [pmc-release] AID - srep37246 [pii] AID - 10.1038/srep37246 [doi] PST - epublish SO - Sci Rep. 2016 Nov 17;6:37246. doi: 10.1038/srep37246.