Differential densimetry: A method for determining ultra-low fluid flux and tissue permeability

Christopher S Hale,Heran C Bhakta,Carrie R Jonak,William H Grover,V G J Rodgers,Jennifer M Yonan,Devin K Binder

doi:10.1063/1.5122953

Abstract

Osmotic transport devices (OTDs) are forward osmosis membrane devices that we recently developed to remove accumulated fluid from swollen tissue, in-vivo, under severe conditions. As such, the relative volume of the fluid required to be removed and the volumetric flowrate may be two orders of magnitude less than the operating volume and tangential flowrate of the device. This makes it challenging to measure the rate of fluid flow from the swollen tissue. Here, we introduce a differential densimetry method for determining ultra-low volumetric flux through tissue samples. This technique uses two vibrating tube density sensors, one placed upstream of the membrane in contact with the tissue sample, and one placed downstream. Any flow of biological fluid withdrawn through the tissue will combine with the OTD operating fluid resulting in an observed density shift in the second density sensor. By measuring the difference in density between the upstream and downstream fluids, one can calculate the amount of fluid flowing across the tissue with a relatively high level of sensitivity. This method is also relatively insensitive to drift from temperature fluctuations and capable of continuously monitoring tissue permeability in real time. As a proof of concept, we used this technique to measure fluid flow across ex-vivo rat spinal tissue for an appropriately scaled OTD. The repeatability error had a maximum of only 12%. This implies that this method can provide highly acceptable flux measurements with reasonable reproducibility in real-time applications of fluid removal in-vivo.

Highlights

Forward osmosis membrane processes termed osmotic transport devices (OTD) have been shown to have tremendous success in removing fluid from biological tissue with edema associated with traumatic brain injury (TBI) and spinal cord injury (SCI)
The OTD is based on standard tangential ultrafiltration technology where the flux, Jv, normal through the membrane is given by the Kedem-Katchalsky model
After each switch of the fluid path, we observed that the density sensors took roughly 1.5 h to reach steady state values

Summary

Introduction

Forward osmosis membrane processes termed osmotic transport devices (OTD) have been shown to have tremendous success in removing fluid from biological tissue with edema associated with traumatic brain injury (TBI) and spinal cord injury (SCI). The general operation of the device consists of placing a semipermeable membrane process across a hydrogel that is applied directly on the swollen tissue (Figure 1). Forward osmosis membrane processes termed osmotic transport devices (OTD) have been shown to have tremendous success in removing fluid from biological tissue with edema associated with traumatic brain injury (TBI) and spinal cord injury (SCI).. The general operation of the device consists of placing a semipermeable membrane process across a hydrogel that is applied directly on the swollen tissue (Figure 1). The hydrogel acts as a medium for continuous fluid contact between the device and the tissue. The process contains an impermeable osmolyte such as a protein that passes tangentially across the membrane. The resulting osmotic pressure provides a driving force to expel permeable fluid in the tissue from the body into the OTD. The OTD is based on standard tangential ultrafiltration technology where the flux, Jv, normal through the membrane is given by the Kedem-Katchalsky model:

Methods

Results

Discussion

Conclusion