Journal
BIOSENSORS & BIOELECTRONICS
Volume 169, Issue -, Pages -Publisher
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2020.112622
Keywords
Cancerous exosome; Electrochemical aptasensor; Microfluidic vortexer; 3D printed magnetic housing; Minimally invasive diagnostic
Categories
Funding
- Bio-Medical Technology Development Program of the National Research Foundation (NRF) of Korea [NRF-2018R1A2A2A15019814, NRF-2018R1C1B6002499, 2020R1A5A1018052]
- Ministry of Trade, Industry, and Energy (MOTIE) of Korea [20008829]
- Korea Evaluation Institute of Industrial Technology (KEIT) [20008829] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2020R1A5A1018052, 4199990314094] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The quantification of cancer-derived exosomes has a strong potential for minimally invasive diagnosis of cancer during its initial stage. As cancerous exosomes form a small fraction of all the exosomes present in blood, ultrasensitive detection is a prerequisite for the development of exosome-based cancer diagnostics. Herein, a detachable microfluidic device implemented with an electrochemical aptasensor (DeMEA) is introduced for highly sensitive and in-situ quantification of cancerous exosomes. To fabricate the aptasensor, a nanocomposite was applied on the electrode surface followed by electroplating of gold nanostructures. Subsequently, an aptamer against an epithelial cell adhesion molecule is immobilized on the electrode surface to specifically detect cancerspecific exosomes. A micmfluidic vortexer is then constructed and implemented in the sensing system to increase the collision between the exosomes and sensing surface using hydrodynamically generated transverse flow. The microfluidic vortexer was integrated with the aptasensor via a 3D printed magnetic housing. The detachable clamping of the two different devices provides an opportunity to subsequently harvest the exosomes for downstream analysis. The DeMEA has high sensitivity and specificity with an ultra-low limit of detection of 17 exosomes/4 over a wide dynamic range (1 x 10(2) to 1 x 10(9)) exosomes/mu L in a short period. As proof of the concept, the aptasensor can be separated from the 3D printed housing to harvest and analyze the exosomes by real-time polymerase chain reaction. Moreover, the DeMEA quantifies the exosomes from plasma samples of patients with breast cancer at different stages of the disease. The DeMEA provides a bright horizon for the application of micmfluidic integrated biosensors for the early detection of cancerous biomarkers.
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