BioTrojans: viscoelastic microvalve-based attacks in flow-based microfluidic biochips and their countermeasures.

Flow-based microfluidic biochips (FMBs) are widely used in biomedical research and diagnostics. However, their security against potential material-level cyber-physical attacks remains inadequately explored, posing a significant future challenge. One of the main components, polydimethylsiloxane (PDMS) microvalves, is pivotal to FMBs' functionality.

Material-level countermeasures for securing microfluidic biochips.

Flow-based microfluidic biochips (FMBs) have been rapidly commercialized and deployed in recent years for biological computing, clinical diagnostics, and point-of-care-tests (POCTs). However, outsourcing FMBs makes them susceptible to material-level attacks by malicious actors for illegitimate monetary gain. The attacks involve deliberate material degradation of an FMB's polydimethylsiloxane (PDMS) components by either doping with reactive solvents or altering the PDMS curing ratio during fabrication.

Structural Attacks and Defenses for Flow-Based Microfluidic Biochips.

Flow-based microfluidic biochips (FMBs) have seen rapid commercialization and deployment in recent years for point-of-care and clinical diagnostics. However, the outsourcing of FMB design and manufacturing makes them susceptible to susceptible to malicious physical level and intellectual property (IP)-theft attacks. This work demonstrates the first structure-based (SB) attack on representative commercial FMBs.

Biomimetic fracture model of lizard tail autotomy.

Lizard tail autotomy is an antipredator strategy consisting of sturdy attachment at regular times but quick detachment during need. We propose a biomimetic fracture model of lizard tail autotomy using multiscale hierarchical structures. The structures consist of uniformly distributed micropillars with nanoporous tops, which recapitulate the high-density mushroom-shaped microstructures found on the lizard tail's muscle fracture plane.

Biomimicking interfacial fracture behavior of lizard tail autotomy with soft microinterlocking structures.

Biological soft interfaces often exhibit complex microscale interlocking geometries to ensure sturdy and flexible connections. If needed, the interlocking can rapidly be released on demand leading to an abrupt decrease of interfacial adhesion. Here, inspired by lizard tail autotomy where such apparently tunable interfacial fracture behavior can be observed, we hypothesized an interlocking mechanism between the tail and body based on the muscle-actuated mushroom-shaped microinterlocks along the fracture planes.

Biophysical analysis of drug efficacy on C. elegans models for neurodegenerative and neuromuscular diseases.

Caenorhabditis elegans has emerged as a powerful model organism for drug screening due to its cellular simplicity, genetic amenability and homology to humans combined with its small size and low cost. Currently, high-throughput drug screening assays are mostly based on image-based phenotyping with the focus on morphological-descriptive traits not exploiting key locomotory parameters of this multicellular model with muscles such as its thrashing force, a critical biophysical parameter when screening drugs for muscle-related diseases. In this study, we demonstrated the use of a micropillar-based force assay chip in combination with a fluorescence assay to evaluate the efficacy of various drugs currently used in treatment of neurodegenerative and neuromuscular diseases.

Understanding interfacial fracture behavior between microinterlocked soft layers using physics-based cohesive zone modeling.

We examine the underlying fracture mechanics of the human skin dermal-epidermal layer's microinterlocks using a physics-based cohesive zone finite-element model. Using microfabrication techniques, we fabricated highly dense arrays of spherical microstructures of radius ≈50μm without and with undercuts, which occur in an open spherical cavity whose centroid lies below the microstructure surface to create microinterlocks in polydimethylsiloxane layers. From experimental peel tests, we find that the maximum density microinterlocks without and with undercuts enable the respective ≈4-fold and ≈5-fold increase in adhesion strength as compared to the plain layers.

Quantitative fluorescence imaging of mitochondria in body wall muscles of Caenorhabditis elegans under hyperglycemic conditions using a microfluidic chip.

Type 2 diabetes is the most common metabolic disease, and insulin resistance plays a role in the pathogenesis of the disease. Because completely functional mitochondria are necessary to obtain glucose-stimulated insulin from pancreatic beta cells, dysfunction of mitochondrial oxidative pathway could be involved in the development of diabetes. As a simple animal model, Caenorhabditis elegans renders itself to investigate such metabolic mechanisms because it possesses insulin/insulin-like growth factor-1 signaling pathway similar to that in humans.

Phenotyping of the thrashing forces exerted by partially immobilized C. elegans using elastomeric micropillar arrays.

As a simple model organism, C. elegans plays an important role in gaining insight into the relationship between bodily thrashing forces and biological effects, such as disease and aging, or physical stimuli, like touch and light. Due to their similar length scale, microfluidic chips have been extensively explored for use in various biological studies involving C.

Rapid Detection and Trapping of Extracellular Vesicles by Electrokinetic Concentration for Liquid Biopsy on Chip.

Exosomes have gained immense importance since their proteomic and genetic contents could potentially be used for disease diagnostics, monitoring of cancer progression, metastasis, and drug efficacy. However, establishing the clinical utility of exosomes has been restricted due to small sizes and high sample loss from extensive sample preparation. Sample loss is particularly critical for body fluids limited in volume and difficult to access, e.

Author Correction: A Multiwell-Based Detection Platform with Integrated PDMS Concentrators for Rapid Multiplexed Enzymatic Assays.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A Multiwell-Based Detection Platform with Integrated PDMS Concentrators for Rapid Multiplexed Enzymatic Assays.

We report an integrated system for accelerating assays with concentrators in a standard 12-well plate (ISAAC-12) and demonstrate its versatility for rapid detection of matrix metalloproteinase (MMP)-9 expression in the cell culture supernatant of breast cancer cell line MDA-MB-231 by accelerating the enzymatic reaction and end-point signal intensity via electrokinetic preconcentration. Using direct printing of a conductive ion-permselective polymer on a polydimethylsiloxane (PDMS) channel, the new microfluidic concentrator chip can be built without modifying the underlying substrate. Through this decoupling fabrication strategy, our microfluidic concentrator chip can easily be integrated with a standard multiwell plate, the de facto laboratory standard platform for high-throughput assays, simply by reversible bonding on the bottom of each well.

High-throughput sorting of eggs for synchronization of C. elegans in a microfluidic spiral chip.

In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs from a mixed age nematode population, which can subsequently be cultured to a desired developmental stage. For the sorting of a mixture containing three different developmental stages, eggs, L1 and L4, we utilized a microfluidic spiral chip with a trapezoidal channel to obtain a sorting efficiency of above 97% and a sample purity (SP) of above 80% for eggs at different flow rates up to 10 mL min. The result demonstrated a cost-effective, simple, and highly efficient method for synchronizing C.

Rapid detection of exosomal microRNA biomarkers by electrokinetic concentration for liquid biopsy on chip.

An ion concentration polarization (ICP)-based electrokinetic concentration device is used for accelerating the surface hybridization reaction between exosomal microRNAs (miRNAs) and morpholinos (MOs) as a synthetic oligo capture probe in the nanomolar concentration range in a microfluidic channel. Compared with standard hybridization at the same concentration, the hybridization time of the miRNA target on MO capture probes could be reduced from ∼24 h to 30 min, with an increase in detection speed by 48 times. This ICP-enhanced hybridization method not only significantly decreases the detection time but also makes workflow simple to use, circumventing use of quantitative reverse transcription polymerase chain reaction or other conventional enzyme-based amplification methods that can cause artifacts.

Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing.

Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology.

Creating Sub-50 Nm Nanofluidic Junctions in PDMS Microfluidic Chip via Self-Assembly Process of Colloidal Particles.

Polydimethylsiloxane (PDMS) is the prevailing building material to make microfluidic devices due to its ease of molding and bonding as well as its transparency. Due to the softness of the PDMS material, however, it is challenging to use PDMS for building nanochannels. The channels tend to collapse easily during plasma bonding.

Integration of Multiplexed Microfluidic Electrokinetic Concentrators with a Morpholino Microarray via Reversible Surface Bonding for Enhanced DNA Hybridization.

Unlabelled: We describe a microfluidic concentration device to accelerate the surface hybridization reaction between DNA and morpholinos (MOs) for enhanced detection. The microfluidic concentrator comprises a single polydimethylsiloxane (PDMS) microchannel onto which an ion-selective layer of conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (

Pedot: PSS) was directly printed and then reversibly surface bonded onto a morpholino microarray for hybridization. Using this electrokinetic trapping concentrator, we could achieve a maximum concentration factor of ∼800 for DNA and a limit of detection of 10 nM within 15 min.

Enhancing the speed of morpholino-DNA biosensor by electrokinetic concentration of DNA in a microfluidic chip.

Unlabelled: Electrokinetic methods that conveniently concentrate charged analytes by orders of magnitude are highly attractive for nucleic acid assays where they can bypass the complexity and costs of enzyme-based amplification. The present study demonstrates an electrokinetic concentration device incorporating charge-neutral morpholino (MO) probes: as DNA analyte is concentrated in a microfluidic channel using ion concentration polarization (ICP) it is simultaneously hybridized to spots of complementary MO probes immobilized on the channel floor. This approach is uniquely favored by the match between the optimum buffer ionic strength of approximately 10mM for both MO-DNA surface hybridization and electrokinetic concentration.

Microfabricated nerve-electrode interfaces in neural prosthetics and neural engineering.

Neural interfaces and implants are finding more clinical applications and there are rapid technological advances for more efficient and safe design, fabrication and materials to establish high-fidelity neural interfaces. In this review paper, we highlight new developments of the microfabricated electrodes and substrates with regard to the design, materials, fabrication and their clinical applications. There is a noticeable trend towards integration of microfluidic modules on a single neural platform.

Tunable membranes for free-flow zone electrophoresis in PDMS microchip using guided self-assembly of silica microbeads.

In this paper, we evaluate the strategy of using self-assembled microbeads to build a robust and tunable membrane for free-flow zone electrophoresis in a PDMS microfluidic chip. To fabricate a porous membrane as a salt bridge for free-flow zone electrophoresis, we used silica or polystyrene microbeads between 3-6 μm in diameter and packed them inside a microchannel. After complete evaporation, we infiltrated the porous microbead structure with a positively or negatively charged hydrogel to modify its surface charge polarity.

Nanofluidic preconcentration device in a straight microchannel using ion concentration polarization.

In this paper, we introduce a simple, straight microchannel design for a nanofluidic protein concentration device. Compared with concentration devices previously developed, the anode channel and cathode channel in this new concentration scheme are both integrated into a straight microchannel, with one inlet and one outlet. Most of the functions of a conventional two-channel concentration device can be achieved by this concentration device, and the efficiency of sample accumulation can be controlled by the dimension of the Nafion membrane.

Nanotechnology in plastic surgery.

Background: Nanotechnology has made inroads over time within surgery and medicine. Translational medical devices and therapies based on nanotechnology are being developed and put into practice. In plastic surgery, it is anticipated that this new technology may be instrumental in the future.

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes.

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve.

Enhancing protease activity assay in droplet-based microfluidics using a biomolecule concentrator.

We introduce an integrated microfluidic device consisting of a biomolecule concentrator and a microdroplet generator, which enhances the limited sensitivity of low-abundance enzyme assays by concentrating biomolecules before encapsulating them into droplet microreactors. We used this platform to detect ultralow levels of matrix metalloproteinases (MMPs) from diluted cellular supernatant and showed that it significantly (~10-fold) reduced the time required to complete the assay and the sample volume used.