Cancer has become a leading cause of morbidity and mortality, and there is an increasing need for versatile tools to enable sensitive, simple and early cancer monitoring. Here, we report platinum supernanoparticles as an exogenous nanosensor which can dissociate into ultrasmall platinum nanoclusters (PtNCs) under tumor-specific hypoxia conditions. The resulting PtNCs can be filtered through the kidney as urinary reporters to be quantified by a companion volumetric bar-chart chip (V-Chip) for point-of-care analysis. The V-Chip signals of triple-negative breast cancer and its lung metastasis mouse model showed a significant increase compared to healthy mice. Our nanosensor can also noninvasively monitor the course of treatment, which is significant for screening tumor recurrence and individualized evaluation of pharmacological and follow-up efficacy. Importantly, this strategy could be adapted for various diseases to form a common diagnostic platform by changing responsive linkers.
CRISPR/Cas12a
has shown great potential in molecular diagnostics,
but its application in sensing of microRNAs (miRNAs) was limited by
sensitivity and complexity. Here, we have sensitively and conveniently
detected microRNAs by reasonably integrating metal–organic
frameworks (MOFs) based biobarcodes with CRISPR/Cas12a assay (designated as MBCA). In this work, DNA-functionalized Zr-MOFs
were designed as the converter to convert and amplify each miRNA target
into activators that can initiate the trans-cleavage
activity of CRISPR/Cas12a to further amplify the signal. Such integration
provides a universal strategy for sensitive detection of miRNAs. By
tuning the complementary sequences modified on nanoprobes, this assay
achieves subattomolar sensitivity for different miRNAs and was selective
to single-based mismatches. With the proposed method, the expression
of miR-21 in different cancer cells can be assessed, and breast cancer
patients and healthy individuals can be differentiated by analyzing
the target miRNAs extracted from serum samples, holding great potential
in clinical diagnosis.
CRISPR/Cas12a
shows excellent potential in disease diagnostics.
However, insensitive signal conversion strategies hindered its application
in detecting protein biomarkers. Here, we report a metal–organic
framework (MOF)-based DNA bio-barcode integrated with the CRISPR/Cas12a
system for ultrasensitive detection of protein biomarkers. In this
work, zirconium-based MOF nanoparticles were comodified with antibodies
and bio-barcode phosphorylated DNA as an efficient signal converter,
which not only recognized the protein biomarker to form the sandwich
complex but also released the bio-barcode DNA activators after MOF
dissociation to activate the trans-cleavage activity of Cas12a. Due
to the obvious advantages, including numerous loaded oligonucleotides,
a convenient release process, and the nontoxic release reagent, this
MOF-DNA bio-barcode strategy could amplify the CRISPR/Cas12a system
to achieve simple and highly sensitive detection of tumor protein
biomarkers with detection limits of 0.03 pg/mL (PSA) and 0.1 pg/mL
(CEA), respectively. Furthermore, this platform could detect PSA directly
in clinical serum samples, offering a powerful tool for early disease
diagnosis.
A simple aptazymes-induced cascade signal amplification (denoted as ACSA) was integrated with a triple-channel volumetric bar-chart chip (TV-Chip) to visually quantitate aflatoxin B1 (AFB1) and adenosine triphosphate (ATP). Bifunctional aptazymes...
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