A time-of-flight flow sensor for the volume measurement of trace amount of interstitial fluid

Abstract

Transdermal extraction of interstitial fluid (ISF) offers an attractive method for noninvasive blood glucose monitoring. The existing macroscale systems are not suitable for ISF collection, mainly because of the minute volume of the transdermally extracted ISF which scatters on the skin surface. Human skin's low permeability to glucose and its varying permeability exemplify the crucial need to make precise ISF volume measurements in order to calculate blood glucose concentrations accurately. In this paper, we present a novel time-of-flight flow sensor consisting of four electrode pairs fabricated directly into the channel of a polydimethylsiloxane (PDMS) microfluidic device designed to accurately measure the volume of transdermally extracted ISF. As fluid traverses the channel, it bridges each electrode pair and changes its resistance. By measuring the time difference in resistance change between each electrode pair, a precise fluid volume can be measured. In order to verify the suitability of the sensor for biological applications, experiments were conducted using a normal saline solution which is similar to ISF. The stability of the sensor was tested using a fixed volume, and the coefficient of variation for 20 tests was determined to be 0.0041. The consistency of the sensor for varied volume measurements was shown by the high correlation coefficient (R2 = 0.9992) between the tested volume and the volume measured by a commercial micro syringe. The excellent functionality of the flow sensor can be extended toward the measurement of conductive chemical and biochemical buffers and reagents.