Recent advances in microfluidic methods in cancer liquid biopsy.

Early cancer detection, its monitoring, and therapeutical prediction are highly valuable, though extremely challenging targets in oncology. Significant progress has been made recently, resulting in a group of devices and techniques that are now capable of successfully detecting, interpreting, and monitoring cancer biomarkers in body fluids. Precise information about malignancies can be obtained from liquid biopsies by isolating and analyzing circulating tumor cells (CTCs) or nucleic acids, tumor-derived vesicles or proteins, and metabolites. The current work provides a general overview of the latest on-chip technological developments for cancer liquid biopsy. Current challenges for their translation and their application in various clinical settings are discussed. Microfluidic solutions for each set of biomarkers are compared, and a global overview of the major trends and ongoing research challenges is given. A detailed analysis of the microfluidic isolation of CTCs with recent efforts that aimed at increasing purity and capture efficiency is provided as well. Although CTCs have been the focus of a vast microfluidic research effort as the key element for obtaining relevant information, important clinical insights can also be achieved from alternative biomarkers, such as classical protein biomarkers, exosomes, or circulating-free nucleic acids. Finally, while most work has been devoted to the analysis of blood-based biomarkers, we highlight the less explored potential of urine as an ideal source of molecular cancer biomarkers for point-of-care lab-on-chip devices.

Label-free virus identification and characterization using electrochemical impedance spectroscopy.

We demonstrate here the application of electrochemical impedance spectroscopy (EIS) in microfluidic devices for label-free virus identification by means of their specific "signature" and also investigate its feasibility for titer quantitation using two basic approaches. The first one is a method based on identifying so-called "resonance" frequencies manifesting in our microdevices and monitoring their variation as a function of the virus concentration, whereas the second one relies on measuring the relative impedance variation at these "resonance" frequencies. Best results have been obtained for the highest "resonance" frequency (∼80 MHz), which we attribute to be due to both the structure of the microdevice and the extremely small size of the viruses that make their effect significant only at such frequencies. This is a simpler method of determining virus concentration in diluted solutions of purified viruses than the well-established traditional plaque assay titer estimation method, and-since it is based on frequency measurement-could potentially be more accurate.

An integrated microfluidic platform for magnetic microbeads separation and confinement.

An innovative microfluidic platform for magnetic beads manipulation is introduced, consisting of novel microfabricated 3D magnetic devices positioned in a microfluidic chamber. Each magnetic device comprises of an embedded actuation micro-coil in various design versions, a ferromagnetic pillar, a magnetic backside plate and a sensing micro-coil. The various designs of the micro-coils enable efficient magnetic beads trapping and concentration in different patterns. The finite element analysis (FEA) results show a significant increase of the developed force on suspended magnetic beads when the magnetic pillar and backside plate were integrated into the device structure. These simulation results were confirmed experimentally by measuring the magnetic beads trapping ratios for the different designs and structures of the devices under continuous flow conditions. The trapping ratios and profiles were studied using beads counting, measuring the change of inductance with the sensing micro-coil and by image processing. The devices have efficiently demonstrated a controlled and localized magnetic beads trapping and concentration at small spatial locations for the first time. The new results shown in this study demonstrate the feasibility of efficiently using these original devices as key elements in complex bio-analysis systems.