METAL-ORGANIC FRAMEWORK AS PROTECTIVE COATING FOR CANCER BIOSPECIMEN PRESERVATION


Year of Award:
2019
Status:
Active
Award Type:
R21
Project Number:
CA236652
RFA Number:
RFA-CA-18-004
Technology Track:
Biospecimen Science Technologies
PI/Project Leader:
SINGAMANENI, SRIKANTH
Other PI or Project Leader:
MORRISSEY, JEREMIAH J
Institution:
WASHINGTON UNIVERSITY
SummaryCancer research and clinical diagnostics for early detection of cancer rely on the availability of high-qualitybiofluids such as blood, urine, and saliva. Within these biofluids, the integrity of molecular biomarkers and thequality 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 ambienttemperatures, they are prone to lose their structure and biofunctionality before analysis. Hence, an extensivedistribution network of refrigeration, the ?cold chain?, is necessary to maintain an optimal temperature duringtransport, storage, and handling of these biospecimens. Apart from causing a huge financial andenvironmental burden, the cold chain system is simply not feasible in pre-hospital and resource-limited settingssuch as urban and rural clinics, as well as developing countries with low and moderate incomes, whererefrigeration and electricity are not guaranteed. Moreover, when the biofluids are frozen, decrease inthermodynamic free energy and unfavorable ice crystal-protein interactions can occur during subsequentthawing, which can further compromise analyte integrity. The above considerations clearly suggest the needfor 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 thatinvolves the use of metal-organic frameworks (MOFs) as encapsulants for preserving the integrity ofbiomarkers in biofluids under normal (non-refrigerated) storage conditions. The approach suggested here istransformative in that it completely eliminates the need for refrigeration and avoids unwanted freeze-thawcycles 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-controlledhandling of cancer-related biospecimens, but also allows interruptible, storable, and restorable on-demanddetection 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 humidityconditions; and (ii) Develop and assess the MOF-based preservation of prostate cancer-related biomarkers inpatient serum/plasma under fluctuating temperature and humidity. Once this early, innovative and exploratoryproject 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 clinicalbiospecimens, which overcomes the refrigeration requirement and enables on-demand bioanalytics in acentralized/distributed manner. The stage would be set for the next step, developing a facile, versatile andlow-cost MOF-based technique for the preservation of different environmentally sensitive biomolecules, wholecells and bulk tissues for cancer research and clinical bioanalytics.