Machine learning-assisted exploration of multidrug-drug administration regimens for organoid arrays.

Combination therapies enhance the therapeutic effect of cancer treatment; however, identifying effective interdependent doses, durations, and sequences of multidrug administration regimens is a time- and labor-intensive task. Here, we integrated machine learning, automation, and large microfluidic arrays of cancer spheroids or patient-derived organoids formed in a tissue-mimetic hydrogel to achieve notable acceleration of the discovery of effective multidrug administration regimens. For the clinically approved drug combination, we found a sequential administration regimen leading to a substantial reduction in the total drug dose, in comparison with concurrent drug supply, both at comparable drug efficacy.

Spheroid-based skin-on-a-chip platform for the evaluation of the toxicity of small molecules and nanoparticles.

Exposure of human skin to chemical agents may lead to skin sensitization, irritation, and corrosion. Time-efficient toxicity screening is currently achieved using skin-on-a-chip models; however, these either lack a multilayer structure characteristic of the skin, or require long fabrication time. Here, we report the development and proof-of-concept application of the microfluidic spheroid-based skin-on-a-chip platform utilizing gravity-driven flow and large arrays of multilayer skin spheroids (MSSs).

Self-driving lab for the photochemical synthesis of plasmonic nanoparticles with targeted structural and optical properties.

Many applications of plasmonic nanoparticles require precise control of their optical properties that are governed by nanoparticle dimensions, shape, morphology and composition. Finding reaction conditions for the synthesis of nanoparticles with targeted characteristics is a time-consuming and resource-intensive trial-and-error process, however closed-loop nanoparticle synthesis enables the accelerated exploration of large chemical spaces without human intervention. Here, we introduce the Autonomous Fluidic Identification and Optimization Nanochemistry (AFION) self-driving lab that integrates a microfluidic reactor, in-flow spectroscopic nanoparticle characterization, and machine learning for the exploration and optimization of the multidimensional chemical space for the photochemical synthesis of plasmonic nanoparticles.

Microfluidic Platform for Generating and Releasing Patient-Derived Cancer Organoids with Diverse Shapes: Insight into Shape-Dependent Tumor Growth.

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation.

A Microfluidic Platform for Evaluating the Internalization of Liposome Drug Carriers in Tumor Spheroids.

The development of in vitro models recapitulating nanoparticle transport under physiological flow conditions is of great importance for predicting the efficacy of nanoparticle drug carriers. Liposomes are extensively used for drug delivery owing to their biocompatibility and biodegradability and the ability to carry both hydrophilic and hydrophobic compounds. Here, we used a library of liposomes with various dimensions and a microfluidic platform comprising a large array of uniformly sized breast cancer spheroids to explore size-dependent liposome internalization and retention in the spheroids under close-to-physiological interstitial conditions.

Integrating spheroid-on-a-chip with tubeless rocker platform: A high-throughput biological screening platform.

Spheroid-on-a-chip platforms are emerging as promising in vitro models that enable screening of the efficacy of biologically active ingredients. Generally, the supply of liquids to spheroids occurs in the steady flow mode with the use of syringe pumps; however, the utilization of tubing and connections, especially for multiplexing and high-throughput screening applications, makes spheroid-on-a-chip platforms labor- and cost-intensive. Gravity-induced flow using rocker platforms overcomes these challenges.

Printing Structurally Anisotropic Biocompatible Fibrillar Hydrogel for Guided Cell Alignment.

Many fibrous biological tissues exhibit structural anisotropy due to the alignment of fibers in the extracellular matrix. To study the impact of such anisotropy on cell proliferation, orientation, and mobility, it is important to recapitulate and achieve control over the structure of man-made hydrogel scaffolds for cell culture. Here, we report a chemically crosslinked fibrous hydrogel due to the reaction between aldehyde-modified cellulose nanofibers and gelatin.

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications.

Over the past decade, droplet microfluidics has attracted growing interest in biology, medicine, and engineering. In this feature article, we review the advances in droplet microfluidics, primarily focusing on the research conducted by our group. Starting from the introduction to the mechanisms of microfluidic droplet formation and the strategies for cell encapsulation in droplets, we then focus on droplet transformation into microgels.

Nanostructured Temperature Indicator for Cold Chain Logistics.

Food, chemicals, agricultural products, drugs, and vaccines should be transported and stored within an appropriate low-temperature range, following cold chain logistics. Violations of the required temperature regime are generally reported by time-temperature indicators; however, current sensors do not cover a sufficiently broad low-temperature range and may lack thermal and photostability. Here, we report a nanostructured solvatochromic temperature indicator formed from cellulose nanocrystals decorated with carbon dots (C-dots).

Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study.

Microfluidic tumour spheroid-on-a-chip platforms enable control of spheroid size and their microenvironment and offer the capability of high-throughput drug screening, but drug supply to spheroids is a complex process that depends on a combination of mechanical, biochemical, and biophysical factors. To account for these coupled effects, many microfluidic device designs and operating conditions must be considered and optimized in a time- and labour-intensive trial-and-error process. Computational modelling facilitates a systematic exploration of a large design parameter space in silico simulations, but the majority of in silico models apply only a small set of conditions or parametric levels.

Angiogenic Sprouting Dynamics Mediated by Endothelial-Fibroblast Interactions in Microfluidic Systems.

Angiogenesis, the development of new blood vessels from existing vasculature, is a key process in normal development and pathophysiology. In vitro models are necessary for investigating mechanisms of angiogenesis and developing antiangiogenic therapies. Microfluidic cell culture models of angiogenesis are favored for their ability to recapitulate 3D tissue structures and control spatiotemporal aspects of the microenvironments.

Microfluidic arrays of dermal spheroids: a screening platform for active ingredients of skincare products.

Organotypic micrometre-size 3D aggregates of skin cells (multicellular spheroids) have emerged as a promising model that can be utilized as an alternative of animal models to test active ingredients (AIs) of skincare products; however, a reliable dermal spheroid-based microfluidic (MF) model with a goal of AI screening is yet to be developed. Here, we report a MF platform for the growth of massive arrays of dermal fibroblast spheroids (DFSs) in a biomimetic hydrogel under close-to-physiological flow conditions and with the capability of screening AIs for skincare products. The DFSs formed after two days of on-chip culture and, in a case study, were used in a time-efficient manner for screening the effect of vitamin C on the synthesis of collagen type I and fibronectin.

Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies.

One of the obstacles limiting progress in the development of effective cancer therapies is the shortage of preclinical models that capture the dynamic nature of tumor microenvironments. Interstitial flow strongly impacts tumor response to chemotherapy; however, conventional in vitro cancer models largely disregard this key feature. Here, a proof of principle microfluidic platform for the generation of large arrays of breast tumor spheroids that are grown under close-to-physiological flow in a biomimetic hydrogel is reported.

Toward a living soft microrobot through optogenetic locomotion control of .

Learning from the locomotion of natural organisms is one of the most effective strategies for designing microrobots. However, the development of bioinspired microrobots is still challenging because of technical bottlenecks such as design and seamless integration of high-performance actuation mechanism and high-density energy source for untethered locomotion. Directly harnessing the activation energy and intelligence of living tissues in synthetic micromachines provides an alternative route to developing biohybrid microrobots.

Antibacterial efficiency assessment of polymer-nanoparticle composites using a high-throughput microfluidic platform.

Over the past decades, inorganic nanoparticles (NPs), particularly metal oxide NPs, have attracted great attention due to their strong bactericidal effects. Researchers have used NPs to fabricate nanocomposite materials which have innate antibacterial capability. Herein, we present a straightforward method to fabricate antibacterial nanocomposites.

Nanoparticles at biointerfaces: Antibacterial activity and nanotoxicology.

Development of a biomaterial that is resistant to the adhesion and consequential proliferation of bacteria, represents a significant challenge in terms of application of such materials in various aspects of health care. Over recent years a large number of synthetic methods have appeared with the overall goal of the prevention of bacterial adhesion to surfaces. In contrast to these artificial techniques, living organisms over millions of years have developed different systems to prevent the colonization of microorganisms.

An integrated microfluidic flow-focusing platform for on-chip fabrication and filtration of cell-laden microgels.

We present the development of a stable continuous, and integrated microfluidic platform for the high-throughput fabrication of monodisperse cell-laden microgel droplets with high and maintained cellular viability. This is through combining onto one chip all the required processes from the droplet generation in a flow focusing microfluidic junction passing through on-chip photocrosslinking to the separation of the droplets from the continuous oil phase. To avoid cellular aggregation during the droplet generation process, cells were treated with bovine serum albumin (BSA) before mixing with gelatin methacrylate (GelMA).