Title:
Microneedle based device to sample interstitial fluid through skin

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Samant, Pradnya P.
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Prausnitz, Mark R.
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Abstract
Diagnosis of diseased state and regular monitoring during treatment is essential to effective management of diseases. Detection of biomarkers in body fluids such as blood, urine, saliva, and sweat is the basis for diagnosis. In addition to these body fluids, interstitial fluid (ISF) is a major body fluid that contains valuable information. However ISF is not widely used for diagnosis because of limitations in ISF sampling technologies - limited sample volumes and patient discomfort. In this study, we have developed a simple, reliable method that can sample multiple microliters of ISF through skin using a microneedle (MN) based system. MNs are microscopic needles that can penetrate past the upper skin layers and reach the lower dermis and access the ISF in the lower skin layer. Based on experimental studies and theoretical evaluation of different mechanisms and driving forces to push the ISF from within skin to the skin surface, we optimized use of pressure driven convection in conjunction with MN technology to achieve high flow rates. To evaluate the composition of ISF, we investigated the metabolomic profile of suction blister ISF and compared it with plasma in 10 human participants. We discovered several clinically relevant metabolites common to ISF and plasma as well as several that are elevated in ISF, indicating the utility of ISF for diagnostics. Finally, we evaluated the performance of MNs in-vivo in human volunteers. Several clinically relevant molecules were detected using MN derived ISF and plasma, indicating the utility of this method.We also detected several local and exogenous biomarkers uniquely in the MN derived ISF. The MN treatment was well-tolerated by participants that shows potential acceptability of this method. This MN-based technique is a significant improvement over other ISF sampling techniques because of its minimally-invasive nature and ease of use and could become a platform technology that can be used by researchers and clinicians to access ISF for diagnostic purposes in the future
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Date Issued
2018-01-22
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Dissertation
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