Doxorubicin Conjugated γ-Globulin Functionalised Gold Nanoparticles: A pH-Responsive Bioinspired Nanoconjugate Approach for Advanced Chemotherapeutics.

Developing successful nanomedicine hinges on regulating nanoparticle surface interactions within biological systems, particularly in intravenous nanotherapeutics. We harnessed the surface interactions of gold nanoparticles (AuNPs) with serum proteins, incorporating a γ-globulin (γG) hard surface corona and chemically conjugating Doxorubicin to create an innovative hybrid anticancer nanobioconjugate, Dox-γG-AuNPs. γG (with an isoelectric point of ~7.2) enhances cellular uptake and exhibits pH-sensitive behaviour, favouring targeted cancer cell drug delivery. In cell line studies, Dox-γG-AuNPs demonstrated a 10-fold higher cytotoxic potency compared to equivalent doxorubicin concentrations, with drug release favoured at pH 5.5 due to the γ-globulin corona's inherent pH sensitivity. This bioinspired approach presents a novel strategy for designing hybrid anticancer therapeutics. Our study also explored the intricacies of the p53-mediated ROS pathway's role in regulating cell fate, including apoptosis and necrosis, in response to these treatments. The pathway's delicate balance of ROS emerged as a critical determinant, warranting further investigation to elucidate its mechanisms and implications. Overall, leveraging the robust γ-globulin protein corona on AuNPs enhances biostability in harsh serum conditions, augments anticancer potential within pH-sensitive environments, and opens promising avenues for bioinspired drug delivery and the design of novel anticancer hybrids with precise targeting capabilities.

Theoretical analysis of immunochromatographic assay and consideration of its operating parameters for efficient designing of high-sensitivity cardiac troponin I (hs-cTnI) detection.

Troponin is the American College of Cardiology and American Heart Association preferred biomarker for diagnosing acute myocardial infarction (MI). We provide a modeling framework for high sensitivity cardiac Troponin I (hs-cTnI) detection in chromatographic immunoassays (flow displacement mode) with an analytical limit of detection, i.e., LOD < 10 ng/L. We show that each of the various control parameters exert a significant influence over the design requirements to reach the desired LOD. Additionally, the design implications in a multiplexed fluidic network, as in the case of Simple Plex™ Ella instrument, are significantly affected by the choice of the number of channels or partitions in the network. We also provide an upgrade on the existing LOD equation to evaluate the necessary minimum volume to detect a particular concentration by considering the effects of stochastics and directly incorporating the target number of copies in each of the partitions in case of multiplexed networks. Even though a special case of cTnI has been considered in this study, the model and analysis are analyte agnostic and may be applied to a wide class of chromatographic immunoassays. We believe that this contribution will lead to more efficient designing of the immunochromatographic assays.

Characterization of Fluidic-Barrier-Based Particle Generation in Centrifugal Microfluidics.

The fluidic barrier in centrifugal microfluidic platforms is a newly introduced concept for making multiple emulsions and microparticles. In this study, we focused on particle generation application to better characterize this method. Because the phenomenon is too fast to be captured experimentally, we employ theoretical models to show how liquid polymeric droplets pass a fluidic barrier before crosslinking. We explain how secondary flows evolve and mix the fluids within the droplets. From an experimental point of view, the effect of different parameters, such as the barrier length, source channel width, and rotational speed, on the particles' size and aspect ratio are investigated. It is demonstrated that the barrier length does not affect the particle's ultimate velocity. Unlike conventional air gaps, the barrier length does not significantly affect the aspect ratio of the produced microparticles. Eventually, we broaden this concept to two source fluids and study the importance of source channel geometry, barrier length, and rotational speed in generating two-fluid droplets.

Synthesis, Purification, and Characterization of Carbon Dots from Non-Activated and Activated Pyrolytic Carbon Black.

In this work, carbon dots were created from activated and non-activated pyrolytic carbon black obtained from waste tires, which were then chemically oxidized with HNO3. The effects caused to the carbon dot properties were analyzed in detail through characterization techniques such as ion chromatography; UV-visible, Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy; ζ potential; transmission electron microscopy (TEM); and spectrofluorometry. The presence of functional groups on the surface of all carbon dots was revealed by UV-visible, FTIR, XPS, and Raman spectra. The higher oxidation degrees of carbon dots from activated precursors compared to those from nonactivated precursors resulted in differences in photoluminescence (PL) properties such as bathochromic shift, lower intensity, and excitation-dependent behavior. The results demonstrate that the use of an activating agent in the recovery of pyrolytic carbon black resulted in carbon dots with different PL properties. In addition, a dialysis methodology is proposed to overcome purification obstacles, finding that 360 h were required to obtain pure carbon dots synthesized by a chemical oxidation method.

Fabrication of Multilayered Composite Nanofibers Using Continuous Chaotic Printing and Electrospinning: Chaotic Electrospinning.

Multi-material and multilayered micro- and nanostructures are prominently featured in nature and engineering and are recognized by their remarkable properties. Unfortunately, the fabrication of micro- and nanostructured materials through conventional processes is challenging and costly. Herein, we introduce a high-throughput, continuous, and versatile strategy for the fabrication of polymer fibers with complex multilayered nanostructures. Chaotic electrospinning (ChE) is based on the coupling of continuous chaotic printing (CCP) and electrospinning, which produces fibers with an internal multi-material microstructure. When a CCP printhead is used as an electrospinning nozzle, the diameter of the fibers is further scaled down by 3 orders of magnitude while preserving their internal structure. ChE enables the use of various polymer inks for the creation of nanofibers with a customizable number of internal nanolayers. Our results showcase the versatility and tunability of ChE to fabricate multilayered structures at the nanoscale at high throughput. We apply ChE to the synthesis of unique carbon textile electrodes composed of nanofibers with striations carved into their surface at regular intervals. These striated carbon electrodes with high surface areas exhibit 3- to 4-fold increases in specific capacitance compared to regular carbon nanofibers; ChE holds great promise for the cost-effective fabrication of electrodes for supercapacitors and other applications.

Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection.

The coronavirus disease 2019 (COVID-19) pandemic has crudely demonstrated the need for massive and rapid diagnostics. By the first week of July, more than 10,000,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization (WHO) for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of ~625 to 2×105 DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-QPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics.

Emerging microfluidic devices for cancer cells/biomarkers manipulation and detection.

Circulating tumour cells (CTCs) are active participants in the metastasis process and account for ∼90% of all cancer deaths. As CTCs are admixed with a very large amount of erythrocytes, leukocytes, and platelets in blood, CTCs are very rare, making their isolation, capture, and detection a major technological challenge. Microfluidic technologies have opened-up new opportunities for the screening of blood samples and the detection of CTCs or other important cancer biomarker-proteins. In this study, the authors have reviewed the most recent developments in microfluidic devices for cells/biomarkers manipulation and detection, focusing their attention on immunomagnetic-affinity-based devices, dielectrophoresis-based devices, surface-plasmon-resonance microfluidic sensors, and quantum-dots-based sensors.