TY - JOUR
T1 - A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors
AU - Genco, Enrico
AU - Modena, Francesco
AU - Sarcina, Lucia
AU - Björkström, Kim
AU - Brunetti, Celestino
AU - Caironi, Mario
AU - Caputo, Mariapia
AU - Demartis, Virginia Maria
AU - Di Franco, Cinzia
AU - Frusconi, Giulia
AU - Haeberle, Lena
AU - Larizza, Piero
AU - Mancini, Maria Teresa
AU - Österbacka, Ronald
AU - Reeves, William
AU - Scamarcio, Gaetano
AU - Scandurra, Cecilia
AU - Wheeler, May
AU - Cantatore, Eugenio
AU - Esposito, Irene
AU - Macchia, Eleonora
AU - Torricelli, Fabrizio
AU - Viola, Fabrizio Antonio
AU - Torsi, Luisa
PY - 2023/10/19
Y1 - 2023/10/19
N2 - A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.
AB - A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma.
KW - bioelectronics
KW - biomarkers
KW - early detection
KW - pancreatic cancer precursors
KW - printed-electronics
KW - single molecules
KW - single-molecule-with-a-large-transistor
KW - Early Detection of Cancer
KW - Humans
KW - Proto-Oncogene Proteins p21(ras)/genetics
KW - Cysts
KW - Pancreatic Neoplasms/diagnosis
KW - Pancreatic Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85169443659&partnerID=8YFLogxK
U2 - 10.1002/adma.202304102
DO - 10.1002/adma.202304102
M3 - Article
C2 - 37452695
AN - SCOPUS:85169443659
SN - 0935-9648
VL - 35
JO - Advanced Materials
JF - Advanced Materials
IS - 42
M1 - 2304102
ER -