Detection of nuclear biomarkers, such as nucleic acids and nuclear proteins, is critical for early-stage cancer diagnosis and prognosis. Conventional methods relying on morphological assessment of cell nuclei in histopathology slides may be subjective, whereas colorimetric immunohistochemical and fluorescence-based imaging are limited by strong light absorption, broad emission bands and low contrast. Here, we describe the development and use of a scanning laser-emission-based microscope that maps lasing emissions from nuclear biomarkers in human tissues. Forty-one tissue samples from 35 patients labelled with site-specific and biomarker-specific antibody-conjugated dyes were sandwiched in a Fabry–Pérot microcavity while an excitation laser beam built a laser-emission image. We observed multiple subcellular lasing emissions from cancer cell nuclei, with a threshold of tens of μJ mm⁻², submicrometre resolution (<700 nm), and a lasing band in the few-nanometre range. Different lasing thresholds of nuclei in cancer and normal tissues enabled the identification and multiplexed detection of nuclear proteomic biomarkers, with high sensitivity for early-stage cancer diagnosis. Laser-emission-based cancer screening and immunodiagnosis might find use in precision medicine and facilitate research in cell biology.

Optofluidic lasers (OFLs) are an emerging technological platform for biochemical sensing, and their good performance especially high sensitivity has been demonstrated. However, high-throughput detection with an OFL remains a major challenge due to the lack of reproducible optical microcavities. Here, we introduce the concept of a distributed fibre optofluidic laser (DFOFL) and demonstrate its potential for high-throughput sensing applications. Due to the precise fibre geometry control via fibre drawing, a series of identical optical microcavities uniformly distributed along a hollow optical fibre (HOF) can be achieved to obtain a one-dimensional (1D) DFOFL. An enzymatic reaction catalysed by horseradish peroxidase (HRP) can be monitored over time, and the HRP concentration is detected by DFOFL-based arrayed colorimetric detection. Experimentally, five-channel detection in parallel with imaging has been demonstrated. Theoretically, spatial multiplexing of hundreds of channels is achievable with DFOFL-based detection. The DFOFL wavelength is tuned over hundreds of nanometers by optimizing the dye concentration or reconfiguring the liquid gain materials. Extending this concept to a two-dimensional (2D) chip through wavelength multiplexing can further enhance its multi-functionality, including multi-sample detection and spectral analysis. This work opens the door to high-throughput biochemical sensing.

A glass capillary array system for rapid ELISA with low sample/reagent volumes.

Rapid and sensitive detection of drugs of abuse plays an important role in monitoring of drug use and treatment compliance. Sweat based drug analysis shows great advantages due to its non-invasive nature. However, most of the related methods developed to date are qualitative, slow, or costly, which significantly hinders their application in field use. Here we report rapid, sensitive, quantitative detection of drugs of abuse in sweat based on capillary arrays combined with competitive enzyme-linked immunosorbent assay. Using four common drugs of abuse, methadone, methamphetamine, amphetamine, and tetrahydrocannabinol, spiked in artificial sweat as a model system, we demonstrate rapid, quantitative, and multiplexed detection of the four drugs in ∼16 minutes with a low sweat volume (∼4 μL per analyte) and a large dynamic range (methadone: 0.0016 ng mL⁻¹–1 ng mL⁻¹; METH: 0.016 ng mL⁻¹–25 ng mL⁻¹; amphetamine: 0.005 ng mL⁻¹–10 ng mL⁻¹; THC: 0.02 ng mL⁻¹–1000 ng mL⁻¹). In addition, we show that the detection range can be tuned for different applications by adjusting the competitors’ concentrations. Our work paves a way to develop an autonomous, portable, and cost-effective device for hospital testing, workplace drug-use screening, roadside testing, and patient monitoring in drug rehabilitation centers.

Laser emission-based detection and imaging technology has attracted significant interest in biomedical research due to its high sensitivity, narrow linewidth, and superior spectral and spatial resolution.

Lasing particles are emerging tools for amplifying light–matter interactions at the biointerface by exploiting its strong intensity and miniaturized size. Recent advances in implementing laser particles into living cells and tissues have opened a new frontier in biological imaging, monitoring, and tracking. Despite remarkable progress in micro- and nanolasers, lasing particles with surface functionality remain challenging due to the low mode-volume while maintaining a high Q-factor. Herein, we report the novel concept of bioresponsive microlasers by exploiting interfacial energy transfer based on whispering-gallery-mode (WGM) microdroplet cavities. Lasing wavelengths were manipulated by energy transfer-induced changes of a gain spectrum resulting from the binding molecular concentrations at the cavity surface. Both protein-based and enzymatic-based interactions were demonstrated, shedding light on the development of functional microlasers. Finally, tunable lasing wavelengths over a broad spectral range were achieved by selecting different donor/acceptor pairs. This study not only opens new avenues for biodetection, but also provides deep insights into how molecules modulate laser light at the biointerface, laying the foundation for the development of smart bio-photonic devices at the molecular level.