Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers.

Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, high-efficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3-fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

Printed On-Chip Perovskite Heterostructure Arrays for Optical Switchable Logic Gates.

The use of optoelectronic devices for high-speed and low-power data transmission and computing is considered in the next-generation logic circuits. Heterostructures, which can generate and transmit photoresponse signals dealing with different input lights, are highly desirable for optoelectronic logic gates. Here, the printed on-chip perovskite heterostructures are demonstrated to achieve optical-controlled "AND" and "OR" optoelectronic logic gates. Perovskite heterostructures are printed with a high degree of control over composition, site, and crystallization. Different regions of the printed perovskite heterostructures exhibit distinguishable photoresponse to varied wavelengths of input lights, which can be utilized to achieve optical-controlled logic functions. Correspondingly, parallel operations of the two logic gates ("AND" and "OR") by way of choosing the output electrodes under the single perovskite heterostructure. Benefiting from the uniform crystallization and strict alignment of the printed perovskite heterostructures, the integrated 3 × 3 pixels all exhibit 100% logic operation accuracy. Finally, optical-controlled logic gates responding to multiwavelength light can be printed on the predesigned microelectrodes as the on-chip integrated circuits. This printing strategy allows for integrating heterostructure-based optical and electronic devices from a unit-scale device to a system-scale device.

Printed Divisional Optical Biochip for Multiplex Visualizable Exosome Analysis at Point-of-Care.

Rapid detection of various exosomes is of great significance in early diagnosis and postoperative monitoring of cancers. Here, a divisional optical biochip is reported for multiplex exosome analysis via combining the self-assembly of nanochains and precise surface patterning. Arising from resonance-induced near-field enhancement, the nanochains show distinct color changes after capturing target exosomes for direct visual detection. Then, a series of divisional nanochain-based biochips conjugated with several specific antibodies are fabricated through designed hydrophilic and hydrophobic patterns. Because of the significant wettability difference, one sample droplet is precisely self-splitting into several microdroplets enabling simultaneous identification of multiple target exosomes in 30 min with a sensitivity of 6 × 107 particles mL-1 , which is about two orders lower than enzyme-linked immunosorbent assay. Apart from the trace amount detection, excellent semiquantitative capability is demonstrated to distinguish clinical exosomes from glioblastoma patients and healthy people. This method is simple, versatile, and highly efficient that can be extended as a diagnostic tool for many diseases, promoting the development of liquid biopsy.

Molecular Recognition-Modulated Hetero-Assembly of Nanostructures for Visualizable and Portable Detection of Circulating miRNAs.

Biomolecular markers, particularly circulating microRNAs (miRNAs) play an important role in diagnosis, monitoring, and therapeutic intervention of cancers. However, existing detection strategies remain intricate, laborious, and far from being developed for point-of-care testing. Here, we report a portable colorimetric sensor that utilizes the hetero-assembly of nanostructures driven by base pairing and recognition for direct detection of miRNAs. Following hybridization, two sizes of nanoparticles modified with single-strand DNA can be robustly assembled into heterostructures with strong optical resonance, exhibiting distinct structure colors. Particularly, the large nanoparticles are first arranged into nanochains to enhance scattering signals of small nanoparticles, which allows for sensitive detection and quantification of miRNAs without the requirement of target extraction, amplification, and fluorescent labels. Furthermore, we demonstrate the high specificity and single-base selectivity of testing different miRNA samples, which shows great potential in the diagnosis, staging, and monitoring of cancers. These heterogeneous assembled nanostructures provide an opportunity to develop simple, fast, and convenient tools for miRNAs detection, which is suitable for many scenarios, especially in low-resource setting.

Wearable perovskite solar cells by aligned liquid crystal elastomers.

In a flexible perovskite solar cell, the bottom interface between perovskite and the electron-transporting layer is critical in determining its efficiency and reliability. High defect concentrations and crystalline film fracturing at the bottom interface substantially reduce the efficiency and operational stability. In this work, a liquid crystal elastomer interlayer is intercalated into a flexible device with the charge transfer channel toughened by the aligned mesogenic assembly. The molecular ordering is instantly locked upon photopolymerization of liquid crystalline diacrylate monomers and dithiol-terminated oligomers. The optimized charge collection and the minimized charge recombination at the interface boost the efficiency up to 23.26% and 22.10% for rigid and flexible devices, respectively. The liquid crystal elastomer-induced suppression of phase segregation endows the unencapsulated device maintaining >80% of the initial efficiency for 1570 h. Moreover, the aligned elastomer interlayer preserves the configuration integrity with remarkable repeatability and mechanical robustness, which enables the flexible device to retain 86% of its original efficiency after 5000 bending cycles. The flexible solar cell chips are further integrated into a wearable haptic device with microneedle-based arrays of sensors to demonstrate a pain sensation system in virtual reality.

At-Home COVID-19 Rapid Antigen Test Down to 0.03 pg mL-1 of Nucleocapsid Protein.

Rapid and ultra-sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for early screening and management of COVID-19. Currently, the real-time reverse transcription polymerase chain reaction (rRT-PCR) is the primary laboratory method for diagnosing SARS-CoV-2. It is not suitable for at-home COVID-19 diagnostic test due to the long operating time, specific equipment, and professional procedures. Here an all-printed photonic crystal (PC) microarray with portable device for at-home COVID-19 rapid antigen test is reported. The fluorescence-enhanced effect of PC amplifies the fluorescence intensity of the labeled probe, achieving detection of nucleocapsid (N-) protein down to 0.03 pg mL-1 . A portable fluorescence intensity measurement instrument gives the result (negative or positive) by the color of the indicator within 5 s after inserting the reacted PC microarray test card. The N protein in inactivated virus samples (with cycle threshold values of 26.6-40.0) can be detected. The PC microarray provides a general and easy-to-use method for the timely monitoring and eventual control of the global coronavirus pandemic.

Fast and Sensitive Detection of Protein Markers Using an All-Printing Photonic Crystal Microarray via Fingertip Blood.

With the demand for point-of-care testing (POCT) in cardiovascular diseases, the detection of biomarkers in trace blood samples is of great significance in emergency medicine settings. Here, we demonstrated an all-printed photonic crystal microarray for POCT of protein markers (named "P4 microarray"). The paired nanobodies were printed as probes to target the soluble suppression of tumorigenicity 2 (sST2) as a certified cardiovascular protein marker. Benefiting from photonic crystal-enhanced fluorescence and integrated microarrays, quantitative detection of sST2 is 2 orders of magnitude lower than that of a traditional fluorescent immunoassay. The limit of detection is down to 10 pg/mL with the coefficient of variation being less than 8%. Detection of sST2 via fingertip blood is achieved in 10 min. Moreover, the P4 microarray after 180 days of storage at room temperature showed excellent stability for detection. This P4 microarray, as a convenient and reliable immunoassay for rapid and quantitative detection of protein markers in trace blood samples, has high sensitivity and strong storage stability, which hold great potential to advance cardiovascular precision medicine.

Rapid Identification and Monitoring of Multiple Bacterial Infections Using Printed Nanoarrays.

Fast and accurate detection of microbial cells in clinical samples is highly valuable but remains a challenge. Here, a simple, culture-free diagnostic system is developed for direct detection of pathogenic bacteria in water, urine, and serum samples using an optical colorimetric biosensor. It consists of printed nanoarrays chemically conjugated with specific antibodies that exhibits distinct color changes after capturing target pathogens. By utilizing the internal capillarity inside an evaporating droplet, target preconcentration is achieved within a few minutes to enable rapid identification and more efficient detection of bacterial pathogens. More importantly, the scattering signals of bacteria are significantly amplified by the nanoarrays due to strong near-field localization, which supports a visualizable analysis of the growth, reproduction, and cell activity of bacteria at the single-cell level. Finally, in addition to high selectivity, this nanoarray-based biosensor is also capable of accurate quantification and continuous monitoring of bacterial load on food over a broad linear range, with a detection limit of 10 CFU mL-1 . This work provides an accessible and user-friendly tool for point-of-care testing of pathogens in many clinical and environmental applications, and possibly enables a breakthrough in early prevention and treatment.

Lateral Heterostructured Vis-NIR Photodetectors with Multimodal Detection for Rapid and Precise Classification of Glioma.

Precise diagnosis of the boundary and grade of tumors is especially important for surgical dissection. Recently, visible and near-infrared (Vis-NIR) absorption differences of tumors are demonstrated for a precise tumor diagnosis. Here, a template-assisted sequential printing strategy is investigated to construct lateral heterostructured Vis-NIR photodetectors, relying on the up-conversion nanoparticles (UCNPs)/perovskite arrays. Under the sequential printing process, the synergistic effect and co-confinement are demonstrated to induce the UCNPs to cover both sides of the perovskite microwire. The side-wrapped lateral heterogeneous UCNPs/perovskite structure exhibits more satisfactory responsiveness to Vis-NIR light than the common fully wrapped structure, due to sufficient visible-light-harvesting ability. The Vis-NIR photodetectors with R reaching 150 mA W-1 at 980 nm and 1084 A W-1 at 450 nm are employed for the rapid classification of glioma. The detection accuracy rate of 99.3% is achieved through a multimodal analysis covering the Vis-NIR light, which provides a reliable basis for glioma grade diagnosis. This work provides a concrete example for the application of photodetectors in tumor detection and surgical diagnosis.

All-printed point-of-care immunosensing biochip for one drop blood diagnostics.

Designing and preparing a fast and easy-to-use immunosensing biochip are of great significance for clinical diagnosis and biomedical research. In particular, sensitive, specific, and early detection of biomarkers in trace samples promotes the application of point-of-care testing (POCT). Here, we demonstrate an all-printed immunosensing biochip with the characteristics of hydrodynamic enrichment and photonic crystal-enhanced fluorescence. Direct quantitative detection of cardiac biomarkers via one drop of blood is achieved in 10 min. After simulating the hydrodynamic behavior of one droplet serum on the printed assay, creatine kinase-MB (CK-MB) has been recognized and located on the photonic crystal arrays. Benefiting from the fluorescence enhancement effect, quantitative detection of CK-MB has been demonstrated from 0.01 ng ml-1 to 100 ng ml-1, which is superior to the conventional enzyme-linked immunosorbent assay (ELISA). This strategy provides a general and easy-to-use approach for fast quantitative detection of biomarkers, which would be improved further for portable clinical diagnostics and home medical monitoring.