Open AccessAn Immuno-Biochip Selectively Captures Tumor-Derived Exosomes and Detects Exosomal RNAs for Cancer Diagnosis
Author(s) -
Yunchen Yang,
Eric Kannisto,
Yu Guan,
Mary E. Reid,
Santosh K. Patnaik,
Yun Wu
Publication year - 2018
Publication title -
acs applied materials and interfaces
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.535
H-Index - 228
eISSN - 1944-8252
pISSN - 1944-8244
DOI - 10.1021/acsami.8b13971
Subject(s) - biochip , microvesicles , lung cancer , microrna , cancer research , biology , microbiology and biotechnology , metastasis , multiplex , rna , cancer biomarkers , exosome , angiogenesis , cancer , bioinformatics , pathology , medicine , biochemistry , gene , genetics
Tumor-derived exosomes (TEXs) play instrumental roles in tumor growth, angiogenesis, immune modulation, metastasis, and drug resistance. TEX RNAs are a new class of noninvasive biomarkers for cancer. Neither current techniques, such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and next-generation sequencing, nor new ones, such as electrochemical or surface plasmon resonance-based biosensors, are able to selectively capture and separate TEXs from normal cell-derived exosomes, making TEX RNAs potentially less sensitive biomarkers. We developed an immuno-biochip that selectively captures TEXs using antibodies against tumor-associated proteins and quantifies in situ TEX RNAs using cationic lipoplexes containing molecular beacons. We used the immuno-biochip to measure the expression of miR-21 microRNA and TTF-1 mRNA in EGFR- or PD-L1-bearing exosomes from human sera and achieved absolute sensitivity and specificity in distinguishing normal controls from non-small cell lung cancer patients. Our results demonstrated that the effective separation of TEXs from other exosomes greatly improved the detection sensitivity and specificity. Compared with the traditional immunomagnetic separation-RNA isolation-qRT-PCR workflow, the immuno-biochip showed superior lung cancer diagnostic performance, consumed less samples (∼30 μL), and shortened assay time from ∼24 to 4 h.