A dual-functional microfluidic chip for guiding personalized lung cancer medicine : combining EGFR mutation detection and organoid-based drug response test

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Lab on a chip - 24(2024), 6 vom: 12. März, Seite 1762-1774

Sprache:

Englisch

Beteiligte Personen:

Zhang, Kexin [VerfasserIn]
Xi, Jiyu [VerfasserIn]
Zhao, Huiting [VerfasserIn]
Wang, Yadong [VerfasserIn]
Xue, Jianchao [VerfasserIn]
Liang, Naixin [VerfasserIn]
Wei, Zewen [VerfasserIn]

Links:

Volltext

Themen:

9007-49-2
Antineoplastic Agents
DNA
EC 2.7.10.1
EGFR protein, human
ErbB Receptors
Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 13.03.2024

Date Revised 26.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1039/d3lc00974b

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368430936