Challenges in blood fractionation for cancer liquid biopsy: how can microfluidics assist?

Liquid biopsy provides a minimally invasive approach to characterise the molecular and phenotypic characteristics of a patient's individual tumour by detecting evidence of cancerous change in readily available body fluids, usually the blood. When applied at multiple points during the disease journey, it can be used to monitor a patient's response to treatment and to personalise clinical management based on changes in disease burden and molecular findings. Traditional liquid biopsy approaches such as quantitative PCR, have tended to look at only a few biomarkers, and are aimed at early detection of disease or disease relapse using predefined markers.

Syringable Microcapsules for Sustained, Localized, and Controllable siRNA Delivery.

The clinical use of small interfering RNA (siRNA) and antisense oligonucleotides often requires invasive routes of administration, including intrathecal or intraocular injection. Additionally, these treatments often necessitate repeated injections. While nanoparticle formulation and chemical modifications have extended siRNA therapeutic durability, challenges persist, such as the side effects of bolus injections with high toxicity and maximum exposure in the acute phase.

Interfacial Engineering of Biocompatible Nanocapsules for Near-Infrared-Triggered Drug Release and Photothermal Therapy.

Chemotherapy is an effective option for cancer treatment. However, its clinical application is often limited by the severe side effects of chemical drugs. To overcome these limitations, a novel drug-loaded phase-change nanocapsule system is developed.

Stiff Hydrogel Encapsulation Retains Mesenchymal Stem Cell Stemness for Regenerative Medicine.

Mesenchymal stem cell (MSC) stands as a prominent choice in regenerative medicine, yet their therapeutic potential remains controversial due to challenges in maintaining lineage and viability. As directly injected MSCs are quickly cleared by the host immune system, entrapping viable cells in a 3D semi-permeable hydrogel matrix extends cell retention, showing great promise in enhancing therapeutic effect. However, the effects of hydrogel encapsulation on MSC subpopulations are not fully understood.

Jammed Pickering Emulsion Gels.

Emulsion gels with specific rheological properties have widespread applications in foods, cosmetics, and biomedicines. However, the constructions of water-in-oil emulsion gels are still challenging, due to the limited interactions available in the continuous oil phase. Here, a versatile strategy is developed to prepare a new type of emulsion gels, called Jammed Pickering emulsion gels (JPEGs).

Corrigendum: An orally available small molecule that targets soluble TNF to deliver anti-TNF biologic-like efficacy in rheumatoid arthritis.

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Tuning porosity of macroporous hydrogels enables rapid rates of stress relaxation and promotes cell expansion and migration.

Extracellular matrix (ECM) viscoelasticity broadly regulates cell behavior. While hydrogels can approximate the viscoelasticity of native ECM, it remains challenging to recapitulate the rapid stress relaxation observed in many tissues without limiting the mechanical stability of the hydrogel. Here, we develop macroporous alginate hydrogels that have an order of magnitude increase in the rate of stress relaxation as compared to bulk hydrogels.

Epigenetic adaptation drives monocyte differentiation into microglia-like cells upon engraftment into the retina.

The identification of specific markers for microglia has been a long-standing challenge. Recently, markers such as P2ry12, TMEM119, and Fcrls have been proposed as microglia-specific and widely used to explore microglial functions within various central nervous system (CNS) contexts. The specificity of these markers was based on the assumption that circulating monocytes retain their distinct signatures even after infiltrating the CNS.

Mechanical testing of colloidal solids with millipascal stress and single-particle strain resolution.

We introduce a technique, traction rheoscopy, to carry out mechanical testing of colloidal solids. A confocal microscope is used to directly measure stress and strain during externally applied deformation. The stress is measured, with single-mPa resolution, by determining the strain in a compliant polymer gel in mechanical contact with the colloidal solid.

Digital droplet RT-LAMP increases speed of SARS-CoV-2 viral RNA detection.

Nucleic acid amplification testing (NAAT) remains one of the most reliable methods for pathogen identification. However, conventional bulk NAATs may not be sufficiently fast or sensitive enough for the detection of clinically-relevant pathogens in point-of-care testing. Here, we have developed a digital droplet RT-LAMP (ddRT-LAMP) assay that rapidly and quantitatively detects the SARS-CoV-2 viral E gene in microfluidic drops.

Targeted whole-genome recovery of single viral species in a complex environmental sample.

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. We present an experimental method for reliably recovering complete viral genomes from complex environmental samples.

Manipulating the duration of picoinjection controls the injected volume of individual droplets.

The ability to add reagents into droplets is required in many microfluidic workflows. Picoinjection can address this need; however, it is unable to control the injection volume for each individual droplet. Here, we present an improved picoinjection method that can inject controlled volumes into individual droplets.

Ultrasoft silicone gels with tunable refractive index for traction force microscopy.

We formulate and characterize silicone gels near the gelation threshold with tunable refractive index, 1.4 < < 1.49, and small viscoelastic moduli, '∼1 Pa, for use in traction force microscopy.

Work hardening in colloidal crystals.

Colloidal crystals exhibit interesting properties that are in many ways analogous to their atomic counterparts. They have the same crystal structures, undergo the same phase transitions, and possess the same crystallographic defects. In contrast to these structural properties, the mechanical properties of colloidal crystals are quite different from those of atomic systems.

Systems and Methods for Continuous Evolution of Enzymes.

Directed evolution generates novel biomolecules with desired functions by iteratively diversifying the genetic sequence of wildtype biomolecules, relaying the genetic information to the molecule with function, and selecting the variants that progresses towards the properties of interest. While traditional directed evolution consumes significant labor and time for each step, continuous evolution seeks to automate all steps so directed evolution can proceed with minimum human intervention and dramatically shortened time. A major application of continuous evolution is the generation of novel enzymes, which catalyze reactions under conditions that are not favorable to their wildtype counterparts, or on altered substrates.

Polysaccharide functionalization reduces lipid vesicle stiffness.

The biophysical properties of lipid vesicles are important for their stability and integrity, key parameters that control the performance when these vesicles are used for drug delivery. The vesicle properties are determined by the composition of lipids used to form the vesicle. However, for a given lipid composition, they can also be tailored by tethering polymers to the membrane.

Propagation of extended fractures by local nucleation and rapid transverse expansion of crack-front distortion.

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex.

Surface-Functionalized Microgels as Artificial Antigen-Presenting Cells to Regulate Expansion of T Cells.

Artificial antigen-presenting cells (aAPCs) are currently used to manufacture T cells for adoptive therapy in cancer treatment, but a readily tunable and modular system can enable both rapid T cell expansion and control over T cell phenotype. Here, it is shown that microgels with tailored surface biochemical properties can serve as aAPCs to mediate T cell activation and expansion. Surface functionalization of microgels is achieved via layer-by-layer coating using oppositely charged polymers, forming a thin but dense polymer layer on the surface.

Thin adhesive oil films lead to anomalously stable mixtures of water in oil.

Oil and water can only be mixed by dispersing droplets of one fluid in the other. When two droplets approach one another, the thin film that separates them invariably becomes unstable, causing the droplets to coalesce. The only known way to avoid this instability is through addition of a third component, typically a surfactant, which stabilizes the thin film at its equilibrium thickness.

Shell buckling for programmable metafluids.

The pursuit of materials with enhanced functionality has led to the emergence of metamaterials-artificially engineered materials whose properties are determined by their structure rather than composition. Traditionally, the building blocks of metamaterials are arranged in fixed positions within a lattice structure. However, recent research has revealed the potential of mixing disconnected building blocks in a fluidic medium.

Reading Room Interruptions are Less Disruptive When Using Asynchronous Communication Methods.

Radiologist interruptions, though often necessary, can be disruptive. Prior literature has shown interruptions to be frequent, occurring during cases, and predominantly through synchronous communication methods such as phone or in person causing significant disengagement from the study being read. Asynchronous communication methods are now more widely available in hospital systems such as ours.

Toward the quantification of α-synuclein aggregates with digital seed amplification assays.

The quantification and characterization of aggregated α-synuclein in clinical samples offer immense potential toward diagnosing, treating, and better understanding neurodegenerative synucleinopathies. Here, we developed digital seed amplification assays to detect single α-synuclein aggregates by partitioning the reaction into microcompartments. Using pre-formed α-synuclein fibrils as reaction seeds, we measured aggregate concentrations as low as 4 pg/mL.

Development and future of droplet microfluidics.

Over the past two decades, advances in droplet-based microfluidics have facilitated new approaches to process and analyze samples with unprecedented levels of precision and throughput. A wide variety of applications has been inspired across multiple disciplines ranging from materials science to biology. Understanding the dynamics of droplets enables optimization of microfluidic operations and design of new techniques tailored to emerging demands.