METAL-ORGANIC FRAMEWORK AS PROTECTIVE COATING FOR CANCER BIOSPECIMEN PRESERVATION

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Summary Cancer research and clinical diagnostics for early detection of cancer rely on the availability of high-quality biofluids such as blood, urine, and saliva. Within these biofluids, the integrity of molecular biomarkers and the quality of information obtained from their analysis is highly dependent on the storage conditions during pre- analytical phase. Unfortunately, due to the poor stability of biomolecules (especially proteins) at ambient temperatures, they are prone to lose their structure and biofunctionality before analysis. Hence, an extensive distribution network of refrigeration, the “cold chain”, is necessary to maintain an optimal temperature during transport, storage, and handling of these biospecimens. Apart from causing a huge financial and environmental burden, the cold chain system is simply not feasible in pre-hospital and resource-limited settings such as urban and rural clinics, as well as developing countries with low and moderate incomes, where refrigeration and electricity are not guaranteed. Moreover, when the biofluids are frozen, decrease in thermodynamic free energy and unfavorable ice crystal-protein interactions can occur during subsequent thawing, which can further compromise analyte integrity. The above considerations clearly suggest the need for an alternate approach for preserving molecular biomarkers in biofluids during the pre-analytical stage, preferably, without the need for refrigeration. In this exploratory project, we propose a novel approach that involves the use of metal-organic frameworks (MOFs) as encapsulants for preserving the integrity of biomarkers in biofluids under normal (non-refrigerated) storage conditions. The approach suggested here is transformative in that it completely eliminates the need for refrigeration and avoids unwanted freeze-thaw cycles and overcomes a huge economic and environmental burden. This energy-efficient and environmentally- friendly approach not only represents a novel technique to eliminate the cold chain and temperature-controlled handling of cancer-related biospecimens, but also allows interruptible, storable, and restorable on-demand detection at a later time in a centralized manner/location to improve the reliability of clinical diagnostics. Towards this ultimate goal, we will (i) Develop and assess the MOF-based preservation of kidney cancer- related protein biomarkers in patient urine under fluctuating (unregulated) ambient temperature and humidity conditions; and (ii) Develop and assess the MOF-based preservation of prostate cancer-related biomarkers in patient serum/plasma under fluctuating temperature and humidity. Once this early, innovative and exploratory project is completed, we will have laid the groundwork and partially developed MOF-based interruptible, storable, and restorable biopreservation approach for cancer-related molecular biomarkers in clinical biospecimens, which overcomes the refrigeration requirement and enables on-demand bioanalytics in a centralized/distributed manner. The stage would be set for the next step, developing a facile, versatile and low-cost MOF-based technique for the preservation of different environmentally sensitive biomolecules, whole cells and bulk tissues for cancer research and clinical bioanalytics.