TY - JOUR
T1 - A dual-functional microfluidic chip for guiding personalized lung cancer medicine
T2 - combining EGFR mutation detection and organoid-based drug response test
AU - Zhang, Kexin
AU - Xi, Jiyu
AU - Zhao, Huiting
AU - Wang, Yadong
AU - Xue, Jianchao
AU - Liang, Naixin
AU - Wei, Zewen
N1 - Publisher Copyright:
© 2024 The Royal Society of Chemistry.
PY - 2024/2/14
Y1 - 2024/2/14
N2 - Many efforts have been paid to advance the effectiveness of personalized medicine for lung cancer patients. Sequencing-based molecular diagnosis of EGFR mutations has been widely used to guide the selection of anti-lung-cancer drugs. Organoid-based assays have also been developed to ex vivo test individual responses to anti-lung-cancer drugs. After addressing several technical difficulties, a new combined strategy, in which anti-cancer medicines are first selected based on molecular diagnosis and then ex vivo tested on organoids, has been realized in a single dual-functional microfluidic chip. A DNA-based nanoruler has been developed to detect the existence of EGFR mutations and shrink the detection period from weeks to hours, compared with sequencing. The employment of the DNA-based nanoruler creates a possibility to purposively test anti-cancer drugs, either EGFR-TKIs or chemotherapy drugs, not both, on limited amounts of organoids. Moreover, a DNA-based nanosensor has been developed to recognize intracellular ATP variation without harming cell viability, realizing in situ monitoring of the whole course growth status of organoids for on-chip drug response test. The dual-functional microfluidic chip was validated by both cell lines and clinical samples from lung cancer patients. Furthermore, based on the dual-functional microfluidic chip, a fully automated system has been developed to span the divide between experimental procedures and therapeutic approaches. This study constitutes a novel way of combining EGFR mutation detection and organoid-based drug response test on an individual patient for guiding personalized lung cancer medicine.
AB - Many efforts have been paid to advance the effectiveness of personalized medicine for lung cancer patients. Sequencing-based molecular diagnosis of EGFR mutations has been widely used to guide the selection of anti-lung-cancer drugs. Organoid-based assays have also been developed to ex vivo test individual responses to anti-lung-cancer drugs. After addressing several technical difficulties, a new combined strategy, in which anti-cancer medicines are first selected based on molecular diagnosis and then ex vivo tested on organoids, has been realized in a single dual-functional microfluidic chip. A DNA-based nanoruler has been developed to detect the existence of EGFR mutations and shrink the detection period from weeks to hours, compared with sequencing. The employment of the DNA-based nanoruler creates a possibility to purposively test anti-cancer drugs, either EGFR-TKIs or chemotherapy drugs, not both, on limited amounts of organoids. Moreover, a DNA-based nanosensor has been developed to recognize intracellular ATP variation without harming cell viability, realizing in situ monitoring of the whole course growth status of organoids for on-chip drug response test. The dual-functional microfluidic chip was validated by both cell lines and clinical samples from lung cancer patients. Furthermore, based on the dual-functional microfluidic chip, a fully automated system has been developed to span the divide between experimental procedures and therapeutic approaches. This study constitutes a novel way of combining EGFR mutation detection and organoid-based drug response test on an individual patient for guiding personalized lung cancer medicine.
UR - http://www.scopus.com/inward/record.url?scp=85185316705&partnerID=8YFLogxK
U2 - 10.1039/d3lc00974b
DO - 10.1039/d3lc00974b
M3 - Article
C2 - 38352981
AN - SCOPUS:85185316705
SN - 1473-0197
VL - 24
SP - 1762
EP - 1774
JO - Lab on a Chip
JF - Lab on a Chip
IS - 6
ER -