High-throughput microfluidic systems accelerated by artificial intelligence for biomedical applications.

High-throughput microfluidic systems are widely used in biomedical fields for tasks like disease detection, drug testing, and material discovery. Despite the great advances in automation and throughput, the large amounts of data generated by the high-throughput microfluidic systems generally outpace the abilities of manual analysis. Recently, the convergence of microfluidic systems and artificial intelligence (AI) has been promising in solving the issue by significantly accelerating the process of data analysis as well as improving the capability of intelligent decision. This review offers a comprehensive introduction on AI methods and outlines the current advances of high-throughput microfluidic systems accelerated by AI, covering biomedical detection, drug screening, and automated system control and design. Furthermore, the challenges and opportunities in this field are critically discussed as well.

A tough and bioadhesive injectable hydrogel formed with maleimidyl alginate and pristine gelatin.

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare.

Multi-biomarker combination detection system for diagnosis and classification of dry eye disease by imaging of a multi-channel metasurface.

Dry eye disease (DED) is one of the most common ocular surface diseases, characterized by unstable tear film and ocular inflammation, affecting hundreds of millions of people worldwide. Currently, the clinical diagnosis of DED mainly relies on physical methods such as optical microscopy and ocular surface interferometric imaging, but classifying DED is still difficult. Here, we propose a compact and portable immune detection system based on the direct imaging of a nanophotonic metasurface with gradient geometry, for fast and ultra-sensitive detection of multiple biomarkers (i.e. Matrix metalloproteinase-9 (MMP-9), Lipocalin-1 (LCN-1), Lactoferrin (LTF)) in tears for the diagnosis and classification of DED. This centimeter-scale concentric nanophotonic metasurface, which consists of millions of unique metallic nanostructures, was fabricated through a cost-effective nanoimprint lithography (NIL) process. The immune detection system based on the antibody-modified metasurface shows favorable detection selectivity, an ultra-high sensitivity (3350 pixels/Refractive Index Unit (RIU)) and low limit of detection (LOD) (0.3 ng/mL for MMP-9, 1 ng/mL for LTF, and 0.5 ng/mL for LCN-1). Further clinical sampling and detection results demonstrated that this multi-biomarker detection system enabled accurate determination and symptom classification of DED, manifesting high correlation and consistency with clinical diagnosis results. The advantages such as low sample consumption, one-step detection, simple operation, and simultaneous detection of multiple biomarkers make the platform promising for screening and detecting a broader range of biomarker combinations in clinical practice.

Laser-guided programmable construction of cell-laden hydrogel microstructures forin vitrodrug evaluation.

Cell-laden hydrogel microstructures have been used in broad applications in tissue engineering, translational medicine, and cell-based assays for pharmaceutical research. However, the construction of cell-laden hydrogel microstructuresin vitroremains challenging. The technologies permitting generation of multicellular structures with different cellular compositions and spatial distributions are needed. Herein, we propose a laser-guided programmable hydrogel-microstructures-construction platform, allowing controllable and heterogeneous assembly of multiple cellular spheroids into spatially organized multicellular structures with good bioactivity. And the cell-laden hydrogel microstructures could be further leveraged forin vitrodrug evaluation. We demonstrate that cells within hydrogels exhibit significantly higher half-maximal inhibitory concentration values against doxorubicin compared with traditional 2D plate culture. Moreover, we reveal the differences in drug responses between heterogeneous and homogeneous cell-laden hydrogel microstructures, providing valuable insight intoin vitrodrug evaluation.

Superiorly Stable Three-Layer Air Microbubbles Generated by Versatile Ethanol-Water Exchange for Contrast-Enhanced Ultrasound Theranostics.

Microbubbles have been widely used as ultrasound contrast agents in clinical diagnosis. Moreover, most current preparation methods for microbubbles are uncontrollable, and the as-obtained microbubbles are unstable in aqueous solution or under ultrasound. Here, we report a strategy to prepare superiorly stable microbubbles with three-layer structures by the ethanol-water exchange. This versatile method can also be applied to prepare different kinds of protein microbubbles with various sizes for advanced biomedical applications. To demonstrate this, the protein air microbubbles are created, which is stable in water for several days with intact structures and exhibits excellent contrast-enhanced ultrasound imaging. Moreover, the protein air microbubbles can also deliver a mass of drugs while maintaining their stable structures, making them a platform for ultrasound imaging-guided drug delivery. The versatile protein air microbubbles have great potential for the design and application of theranostic platforms.