A persistent challenge in developing personalized treatments for hematologic cancers is the lack of patient specific, physiologically relevant disease models to test investigational drugs in clinical trials and to select therapies in a clinical setting. Biomicrofluidic systems and organ-on-a-chip technologies have the potential to change how researchers approach the fundamental study of hematologic cancers and select clinical treatment for individual patient. Here, we review microfluidics cell-based technology with application toward studying hematologic tumor microenvironments (TMEs) for the purpose of drug discovery and clinical treatment selection. We provide an overview of state-of-the-art microfluidic systems designed to address questions related to hematologic TMEs and drug development. Given the need to develop personalized treatment platforms involving this technology, we review pharmaceutical drugs and different modes of immunotherapy for hematologic cancers, followed by key considerations for developing a physiologically relevant microfluidic companion diagnostic tool for mimicking different hematologic TMEs for testing with different drugs in clinical trials. Opportunities lie ahead for engineers to revolutionize conventional drug discovery strategies of hematologic cancers, including integrating cell-based microfluidics technology with machine learning and automation techniques, which may stimulate pharma and regulatory bodies to promote research and applications of microfluidics technology for drug development.
Abstract:In this paper, we present a microfluidic paper-based analytical device (µPAD) with a gold nanosensor functionalized with α-lipoic acid and thioguanine (Au-TA-TG) to detect whether the arsenic level of groundwater from hand tubewells in Bangladesh is above or below the World Health Organization (WHO) guideline level of 10 µg/L. We analyzed the naturally occurring metals present in Bangladesh groundwater and assessed the interference with the gold nanosensor. A method was developed to prevent interference from alkaline metals found in Bangladesh groundwater (Ca, Mg, K and Na) by increasing the pH level on the µPADs to 12.1. Most of the heavy metals present in the groundwater (Ni, Mn, Cd, Pb, and Fe II) did not interfere with the µPAD arsenic tests; however, Fe III was found to interfere, which was also prevented by increasing the pH level on the µPADs to 12.1.The µPAD arsenic tests were tested with 24 groundwater samples collected from hand tubewells in three different districts in Bangladesh: Shirajganj, Manikganj, and Munshiganj, and the predictions for whether the arsenic levels were above or below the WHO guideline level agreed with the results obtained from laboratory testing. The µPAD arsenic test is the first paper-based test validated using Bangladesh groundwater samples and capable of detecting whether the arsenic level in groundwater is above or below the WHO guideline level of 10 µg/L, which is a step towards enabling the villagers who collect and consume the groundwater to test their own sources and make decisions about where to obtain the safest water.
Coronavirus disease has spread all across the world. Low-and medium-income countries are more affected economically and socially compared to developed countries due to the lack of a rapid, robust, and affordable testing infrastructure. Furthermore, the high cost of real-time polymerase chain reaction (PCR) system, sophisticated user-handling procedure, and high expense of the conventional clinical tests are the root causes of the less accessibility of the testing systems to the users. In this study, a COVID-19 Point-of-Care (POC) ecosystem model is proposed for the low-and medium-income countries (or energy deprived countries) that will facilitate the technological development with locally available fabrication components. In addition, the nontechnological development phases have also been discussed, which encompasses the collaboration among academia, local as well as government bodies, and entrepreneurial ventures. In addition, a hypothetical design of a microfluidic paper-based analytical (μPADs) POC platform is proposed to detect COVID-19 analyte using unprocessed patient-derived saliva, which is a miniaturized form-factor of conventional real-time polymerase chain reaction (PCR) technique. The device contains four major reaction zones, which are sample zone, buffer zone, loop-mediated isothermal amplification (LAMP) Master Mix zone, Ethylenediamine tetraacetic acid (EDTA) zone, and sensor zone. To obtain quicker test results and easier operation, a handheld image acquisition technique is introduced in this study. It is hypothesized that in a remote setting, the proposed design could be used as an initial guideline to develop a POC COVID-19 testing system, which may be simple, easy-to-use, and costeffective.
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