Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development We believe this review will promote communications among biology, chemistry, physics, and materials science

Emerging Droplet Microfluidics

The early detection of cancer can significantly reduce cancer mortality and saves lives. Thus, a great deal of effort has been devoted to the exploration of new technologies to detect early signs of the disease. Cancer biomarkers cover a broad range of biochemical entities, such as nucleic acids, proteins, sugars, small metabolites, and cytogenetic and cytokinetic parameters, as well as entire tumour cells found in the body fluid. They can be used for risk assessment, diagnosis, prognosis, and for the prediction of treatment efficacy and toxicity and recurrence. In this review, we provide an overview of recent advances in cancer biomarker detection. Several representative examples using different approaches for each biomarker have been reviewed, and all these cases demonstrate that the multidisciplinary technology-based cancer diagnostics are becoming an increasingly relevant alternative to traditional techniques. In addition, we also discuss the unsolved problems and future challenges in the evaluation of cancer biomarkers. Clearly, solving these hurdles requires great effort and collaboration from different communities of chemists, physicists, biologists, clinicians, material-scientists, and engineering and technical researchers. A successful outcome will result in the realization of point-of-care diagnosis and individualized treatment of cancers by non-invasive and convenient tests in the future.

Cancer biomarker detection: recent achievements and challenges

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell–microenvironment interactions continue to overturn much earl...

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Owing to their excellent multiplexing ability, high sensitivity, and large dynamic range, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal have found prosperous applications in fields such as disease diagnosis, environmental surveillance, and food safety supervision. Various ever-increasing demands have promoted SERS-based immunoassays from the classical sandwich-type ones to those integrated with fascinating automatic platforms (e.g., test strips and microfluidic chips). As recent years have witnessed impressive progress in SERS immunoassays, we try to comprehensively cover SERS-based immunoassays from their basic working principles to specific applications. Focusing on several basic elements in SERS immunoassays, typical structures of SERS nanoprobes, productive optical spectral encoding strategies, and popular immunoassay platforms are highlighted, followed by their representative biological applications in the last 5 years. Moreover, despite the vast advances achieved ...

SERS-Activated Platforms for Immunoassay: Probes, Encoding Methods, and Applications

Droplet microfluidics offers exquisite control over the flows of multiple fluids in microscale, enabling fabrication of advanced microparticles with precisely tunable structures and compositions in a high throughput manner The combination of these remarkable features with proper materials and fabrication methods has enabled high efficiency, direct encapsulation of actives in microparticles whose features and functionalities can be well controlled These microparticles have great potential in a wide range of bio-related applications including drug delivery, cell-laden matrices, biosensors and even as artificial cells In this review, we briefly summarize the materials, fabrication methods, and microparticle structures produced with droplet microfluidics We also provide a comprehensive overview of their recent uses in biomedical applications Finally, we discuss the existing challenges and perspectives to promote the future development of these engineered microparticles

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Microfluidic fabrication of microparticles for biomedical applications

Bioinspired multicompartmental microfibers are generated by novel capillary microfluidics. The resultant microfibers possess multicompartment body-and-shell compositions with specifically designed geometries. Potential use of these microfibers for tissue-engineering applications is demonstrated by creating multifunctional fibers with a spatially controlled encapsulation of cells.

Bioinspired Multicompartmental Microfibers from Microfluidics

Aptamer-functionalized barcode particles are employed to capture and detect various types of circulating tumor cells (CTCs). The particles are spherical colloidal crystal clusters, and the reflection properties that arise from their structures are how their codes are evaluated. Aptamer functionalization (with TD05, Sgc8, and Sgd5) make the particles interact with specific CTC types; dendrimers are used to amplify the effect of the aptamers, allowing for increased sensitivity, reliability, and specificity in CTC capture, detection, and subsequent release.

Aptamer-functionalized barcode particles for the capture and detection of multiple types of circulating tumor cells.

Janus particles with features of an anisotropic photonic band gap (PBG) structure and magnetic property have been achieved by phase separation and self-assembly of nanoparticles in microfluidic droplets. The resultant particles enable optical encoding and magnetically controllable motion, making them excellent functional encoded particles in biomedical applications.

Microfluidic generation of magnetoresponsive Janus photonic crystal particles

Photonic crystal encoded biomaterials microcarriers made from silica-hybrid photonic crystal beads are reported. The characteristic reflection peak originating from the physical periodic structure is used as the code of the microcarriers. They are stable during cell adhesion and culture on their surface. Based on this method, Different biomaterials are incorporated into different PCBs and used as encoded microcarriers for the multiplex evaluation of the interaction of cells and materials in a single culture experiment. These encoded microcarriers are ideal for multiplex bioevaluation of biomaterials or drug applications.

Photonic Crystal Encoded Microcarriers for Biomaterial Evaluation

The generation of cell gradients is critical for understanding many biological systems and realizing the unique functionality of many implanted biomaterials. However, most previous work can only control the gradient of cell density and this has no effect on the gradient of cell orientation, which has an important role in regulating the functions of many connecting tissues. Here, we report on a simple stretched inverse opal substrate for establishing desired cell orientation gradients. It was demonstrated that tendon fibroblasts on the stretched inverse opal gradient showed a corresponding alignment along with the elongation gradient of the substrate. This “random-to-aligned” cell gradient reproduces the insertion part of many connecting tissues, and thus, will have important applications in tissue engineering.

Jie Lu

Papers

Bioinspired Multicompartmental Microfibers from Microfluidics

Aptamer-functionalized barcode particles for the capture and detection of multiple types of circulating tumor cells.

Microfluidic generation of magnetoresponsive Janus photonic crystal particles

Photonic Crystal Encoded Microcarriers for Biomaterial Evaluation

Cell orientation gradients on an inverse opal substrate.