A Cell‐Resolved Ultrastable Biosensor Enables One‐Step Detection of Gene‐Fusion Transcripts in Unprocessed Whole Blood
Abstract
ABSTRACT Cell‐specific detection of aberrant mRNA in blood is essential for diagnosing and treating hematological malignancies. However, current sensors are unable to function in unprocessed whole blood due to limitations in chemical stability and cell‐targeting capability. Here, we engineer a cell‐resolved ultrastable sensor for hematology (CRUSH) via spherical‐nucleic‐acid (SNA) technology, which enables live‐cell detection of leukemia fusion transcripts in unprocessed whole blood. CRUSH employs stoichiometrically controlled thiol protector to achieve a defect‐free thiol monolayer on AuNPs. This design feature endows CRUSH with a record‐breaking stability, withstanding 0.1 M dithiothreitol, a 10,000‐fold improvement over conventional SNAs. We also demonstrate that the phagocytic bias of myeloid cells over lymphoid cells drives selective internalization of CRUSH in myeloid lineages in whole blood. Leveraging cellular selectivity and engineered stability, CRUSH offers a mixed‐and‐read diagnostic test, where lyophilized sensors are directly mixed with whole blood samples, followed by standard flow cytometry analysis. This one‐step test detects BCR‐ABL1 fusions in living myeloid cells with high specificity and robustness, enabling accurate discrimination of multilineage acute lymphoblastic leukemia within 1 h. Our study bridges biosensing innovation with urgent diagnostic needs, offering a rapid, specific, and robust tool for accurate diagnosis and treatment of hematologic malignancies.
Article Details
Authors (15)
Chuipeng Kong
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Analytical & Testing Centre Sichuan University Chengdu Sichuan P. R. China
Xin Zhang
Yuanyuan Chen
Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo and Biosensing, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, College of Chemistry and Chemical Engineering
Cuizheng Peng
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Analytical & Testing Centre Sichuan University Chengdu Sichuan P. R. China
Guoying Yao
MOELaboratory of Bioinorganic and Synthetic Chemistry Lehn Institute of Functional Materials School of Chemistry Sun Yat‐sen University Guangzhou, Guang Dong P.R. China
Nenggang Jiang
Department of Laboratory Medicine Department of Hematology Urology Department West China Hospital Sichuan University Chengdu Sichuan P. R. China
Dan Huang
School of Chemistry and Chemical Engineering, State Key Laboratory of Luminescent Materials and Devices
Lijie Du
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Analytical & Testing Centre Sichuan University Chengdu Sichuan P. R. China
Junbo Chen
School of Chemistry and Chemical Engineering Guizhou University Guiyang China
Tao Zeng
Jie Wang
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Turun Song
Hang Xing
State Key Laboratory of Chemo-/Bio-Sensing and Chemometrics, School of Chemistry and Chemical Engineering
Hongyan Liao
Department of Laboratory Medicine Department of Hematology Urology Department West China Hospital Sichuan University Chengdu Sichuan P. R. China
Feng Li