Breast cancer (BC) is the most common malignancy in women and ranks second among all cancer types worldwide. The escalating demand for early and precise diagnosis has intensified the quest for ultrasensitive and highly specific biosensors. Here we present a self-referencing photoelectrochemical (PEC) strategy based on a nanopipette that enables the direct quantification of the BC biomarker miRNA-21 in single living cells. The nanopipette's ultrafine tip minimizes membrane disruption, while an integrated self-referencing electrode cancels out trans-membrane potential fluctuations, yielding a linear dynamic range of 1–7 nM and a detection limit of 0.328 nM without cell lysis or amplification. The platform markedly enhances the accuracy of single-cell heterogeneity analyses and offers a new paradigm for intracellular trace-nucleic-acid quantification. Moreover, the modular self-referencing architecture creates a methodological foundation for extending nanopipette-based sensors to broader single-cell omics applications.
Dual emission quantum dots (QDs) have attracted considerable interest as a novel phosphor for constructing ratiometric optical thermometry because of its self-referencing capability. In this work, the exploration of codoped Zn–In–S QDs with dual emissions at ≈512 and ≈612 nm from intrinsic Cu and Mn dopants for ratiometric temperature sensing is reported. It is found that the dopant emissions can be tailored by adjusting the Mn-to-Cu concentration ratios, enabling the dual emissions in a tunable manner. The energy difference between the conduction band of the host and Cu dopant states is considered as the key for the occurrence of Mn ion emission. The as-constructed QD ratiometric temperature sensor exhibits a totally robust stability with a fluctuation of ≈ I Cu / I tot versus times lower than 1% and almost no hysteresis in cycles over a broad window of 100–320 K. This discovery represents that the present cadmium-free, intrinsic dual-emitting codoped QDs can open a new door for the synthesis of novel QDs with stable dual emissions, which poise them well for challenging applications in optical nanothermometry.
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