An integrated multi-molecular sensor for simultaneous BRAFV600E protein and DNA single point mutation detection in circulating tumour cells

The analysis of circulating cancer biomarkers in the form of liquid biopsies confers several potential benefits as compared to traditional surgical tissue sampling. As a common key anomaly strongly implicated across several cancer types, the BRAFV600E mutation is one of the most valuable oncogenic biomarkers available in liquid biopsies. Crucially, BRAFV600E is also an actionable mutation which could be arrested by clinically beneficial drug inhibitors. Yet, as is true for most single base disease mutations, current BRAFV600E detection in either its DNA or protein molecular state is still liable to false positive/negative outcomes, thus impacting patient treatment benefit. Here we present an integrated multi-molecular sensor (IMMS) for an entire sample-to-answer workflow from melanoma cell capture to simultaneous quantification of both intracellular BRAFV600E DNA and protein levels on a single platform. The IMMS combines (i) specific capture and release of circulating melanoma cells; (ii) electric field-induced cell lysis; (iii) simultaneous quantification of BRAFV600E DNA and protein levels. We investigated the IMMS system's analytical performance in cell capture, release and lysis, and intracellular BRAFV600E detection by ligase-mediated DNA amplification and antibody-based protein hybridization. As a proof-of-concept, we successfully demonstrated circulating BRAFV600E detection at both DNA and protein molecular levels in simulated melanoma plasma samples. With its capabilities in integrated and miniaturized analysis, the IMMS could lead the emergence of a new generation of multi-molecular lab-on-chip biosensors for enabling more accurate and extensive analysis of powerful circulating biomarkers in patient liquid biopsies

A microfluidic-SERSplatform for isolation and immuno-phenotyping of antigen specific T-cells

T-cells play a major role in host defense mechanisms against many diseases. With the current growth of immunotherapy approaches, there is a strong need for advanced technologies to detect and characterize these immune cells. Herein, we present a simple approach for the isolation of antigen specific T-cells from the complex biological sample based on T-cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interaction. Subsequently, we characterize those antigen specific T-cells by profiling TCR expression heterogeneity. Our approach utilizes an alternating current electrohydrodynamic (ac-EHD) based microfluidic platform for isolation and surface enhanced Raman scattering (SERS) for TCR expression profiling. The use of ac-EHD enables specific isolation of T-cells by generating a nanoscopic shear force at the double layer of the sensing surface which enhances the frequency of pMHC and TCR interactions and consequently shears off the nonspecific targets. TCR expression profiling of the isolated T-cells was performed by encoding them with SERS-labelled pMHCs followed by SERS detection in bulk as well as in single T-Cell. In proof-of-concept experiments, 56.93 ± 7.31% of the total CD4+T-cells were captured from an excess amount of nonspecific cells (e.g., PBMCs) with high specificity and sensitivity (0.005%). Moreover, TCR analysis data using SERS shows the heterogeneity in the T-cell receptor expression which can inform on the activation status of T-cells and the patient’s response to immunotherapy. We believe that this approach may hold potential for numerous applications towards monitoring immune status, understanding therapeutic responses,and effective vaccine development

Adaptive elliptical patch antenna array for WLAN: A Smart approach to beam switching through phase shifting in feed network using elliptical patch array for Dual Band

The WLAN is operated in some high traffic area where the radiation beam produced by the elliptical  patch antenna is to be utilized with optimum efficiency. The aim of the antenna array is to produce some directive and switched beams rather than producing omni-directional pattern which cover 360°, can be considered to be wastage in some non-used or low traffic areas. Hence, directive beam and switching it without actually changing the direction of the elliptical patch array is a smart way for WLAN application . A smart antenna array system performs the adaptive beam forming by focusing the beam in the desired direction and creating nulls in other directions to avoid the interference and the wasting of the beams. This is performed by the operating the phase shifting in its feed network and different ports. This paper investigates the performance of the elliptical patch array patterns operating in dual bands with different phase shifting for the optimum performance of the WLAN applications

Health monitoring of mining conveyor belts

The paper presents a new methodology for monitoring health conditions of mining conveyor belts using Radio Frequency Identification (RFID) based sensors. The existing monitoring technique is based on simple visual inspections which is quite labor intensive and do not provide accurate health condition of the conveyor belt. The new methodology based on UHF chipped and chipless RFID sensors provides highly sophisticated real-time monitoring schemes for different conveyor belt health parameters such as cracks. When combined with machine learning algorithm-based approach, the proposed technique can detect and predict wear and tear over the entire belt. Simulation results show that the proposed methodology offers high accuracy in detecting cracks with width of 0.5 mm and demonstrates the efficiency of RFID sensors to track the crack orientation in the belt

Electromagnetic Transduction Based Chipless RFID Sensors for Internet of Things (IoT)

This thesis provides low cost chipless RFID based sensing solutions for a number of specified Internet of Things (IoT) application areas, namely- Precision Agriculture, smart buildings, and retail and supply chain. These areas have a burning requirement of low cost sensing and item tagging devices. However, due to the absence of such devices, these applications areas do not receive enough traction in terms of industrial applications. This thesis involves the development of such inexpensive devices to monitor soil moisture and salinity contents, leaf moisture contents, temperature in perishable food items and environment as well as crack in public infrastructure

Smart Antenna Arrays for Advanced WLAN: Performance analysis of Linear and square array approach for adaptivity through phase shifting in antenna feed

The WLAN is operated in some high traffic area where the radiation beam produced by the antenna is to be utilized with optimum efficiency. The aim of those antennas is to produce some directive and switched beams rather than producing Omni-directional pattern since these beam patterns are considered to be wastage in some non-used or low traffic areas. Hence, the antenna systems producing the directive and switched beams should be highly preferred for the WLAN application. A smart antenna array system performs the adaptive beam forming by focusing the beam in the desired direction and creating nulls in other directions to avoid the interference and the wasting of the beams. This is performed by operating the phase shifting in its feed network and different ports. This paper investigates the performance of the different array patterns with different phase shifting for the optimum performance of the WLAN applications in a highly congested indoor environment

Surface-enhanced Raman spectroscopy for cancer immunotherapy applications: opportunities, challenges, and current progress in nanomaterial strategies

Cancer immunotherapy encompasses a variety of approaches which target or use a patient's immune system components to eliminate cancer. Notably, the current use of immune checkpoint inhibitors to target immune checkpoint receptors such as CTLA-4 or PD-1 has led to remarkable treatment responses in a variety of cancers. To predict cancer patients' immunotherapy responses effectively and efficiently, multiplexed immunoassays have been shown to be advantageous in sensing multiple immunomarkers of the tumor microenvironment simultaneously for patient stratification. Surface-enhanced Raman spectroscopy (SERS) is well-regarded for its capabilities in multiplexed bioassays and has been increasingly demonstrated in cancer immunotherapy applications in recent years. This review focuses on SERS-active nanomaterials in the modern literature which have shown promise for enabling cancer patient-tailored immunotherapies, including multiplexed in vitro and in vivo immunomarker sensing and imaging, as well as immunotherapy drug screening and delivery

Amplification-free multi-RNA-type profiling for cancer risk stratification via alternating current electrohydrodynamic nanomixing

Simultaneous analysis of messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA)-multi-RNA-type profiling-is increasingly crucial in cancer diagnostics. Yet, rapid multi-RNA-type profiling is challenging due to enzymatic amplification reliance and RNA-type-dependent characteristics. Here, a nanodevice is reported to uniquely use alterable alternating current electrohydrodynamic (ac-EHD) forces to enhance probe-target hybridization prior to direct native RNA target detection, without target amplification or surface functionalization. To exemplify clinical applicability, noninvasive screening of next-generation prostate cancer (PCa) RNA biomarkers (of different types) in patient urine samples is performed. A strong correlation between multi-RNA-type expression and aggressive PCa is found, and the nanodevice performance is statistically evaluated. It is believed that this miniaturized system exhibits great potential for cancer risk stratification via multi-RNA-type profiling