Dielectric Characterization of Interstitial Fluid Phantoms for Hypoxia Monitoring at Microwave Frequencies

Hypoxia-induced metabolic acidosis resulting in a pH below 7 is a significant contributor to neonatal morbidity and mortality worldwide, affecting approximately four million neonates. This condition causes an estimated one million neonatal deaths annually. Early detection of hypoxia can result in prompt intervention and management, which can the risk of adverse outcomes. Arterial blood gas (ABG) analysis is an accurate method used to evaluate the condition of neonates and assess hypoxia-induced metabolic acidosis. However, ABG analysis requires the invasive sampling of arterial blood carrying the risk of complications including arterial occlusion, severe ischaemia and extreme necrosis. Recently, the development of biosensing devices for the detection of biomarkers from the interstitial fluid (ISF) hasreceived increasing attention due to the development of minimally invasive microneedle-based ISF sampling methods. Unlike blood, ISF, which surrounds cells in the body, can be accessed relatively easily using microneedles. Early testing and validation of novel biosensors require ISF-mimicking phantomsin absence of commercially available ISF-sampling microneedles. Therefore, in this study, we aimed to develop an ISF-mimicking buffer phantom for monitoring dielectric changes in ISFat microwave frequencies due to changes in pH during the hypoxic episode.Three types of buffers, including carbonate bicarbonate (CBC) buffer, sodium phosphate (SP) buffer and artificial ISF were developed. The CBC buffer was developed using anhydrous sodium carbonate (Na2CO3) and sodium bicarbonate (NaHCO3), whereas the SP buffer was made using monosodium phosphate (NaH 2 PO 4 ) and disodium phosphate (Na2HPO4). The artificial ISF was prepared by combining calcium chloride (CaCl 2 ), potassium chloride (KCl), sodium chloride (NaCl), magnesium sulphate (MgSO 4 ), NaH 2 PO 4 , glucose, Hepes and saccharose. The buffers were prepared at room temperature with a concentration of 0.1 M in deionized water. To mimic the hypoxiamodel, acidosis was induced in all buffers by introducing hydrochloric acid. The collection of a sufficient amount of ISF to detect specific biomarkers is still difficult and studies have reported that plasma and ISF have similar dielectric properties due to their high-water content and similar concentrations of dissolved electrolytes. In this study, to assess buffer properties, plasma samples were obtained by collecting blood from a healthy volunteer and subsequently separating it through centrifugation. The dielectric properties of these liquid phantoms were measured by employing an open-ended coaxial probe technique for a frequency range of 0.5-8.5 GHz over 101 linearly spaced frequency points. The effects of hypoxiaon the dielectric properties of the solutions were also investigated. The results showed that CBC buffer and plasma have similar dielectric properties, indicating its potential as a substitute buffer for ISF. Moreover, the dielectric properties of the SP and CBC buffers were found to be influenced by the varying pH levels of these buffers, thus enabling the detection of comparable changes in an asphyxia model. The dielectric characterization of ISF liquid phantoms can offer a relatively affordable, repeatable, and reliable way to examine the dielectric response of tissues across many research and training platforms and more specifically dielectric applications for hypoxia monitoring.