Urinary tract infection (UTI) diagnosis based on urine
culture
for bacteriuria analysis is time-consuming and often leads to wastage
of hospital resources due to false-positive UTI cases. Direct cellular
phenotyping (e.g., RBCs, neutrophils, epithelial cells) of urine samples
remains a technical challenge as low cell concentrations, and urine
characteristics (conductivities, pH, microbes) can affect the accuracy
of cell measurements. In this work, we report a microfluidic inertial-impedance
cytometry technique for label-free rapid (<5 min) neutrophil sorting
and impedance profiling from urine directly. Based on size-based inertial
focusing effects, neutrophils are isolated, concentrated, and resuspended
in saline (buffer exchange) to improve consistency in impedance-based
single-cell analysis. We first observed that both urine pH and the
presence of bacteria can affect neutrophil high-frequency impedance
measurements possibly due to changes in nucleus morphology as neutrophils
undergo NETosis and phagocytosis, respectively. As a proof-of-concept
for clinical testing, we report for the first time, rapid UTI testing
based on multiparametric impedance profiling of putative neutrophils
(electrical size, membrane properties, and distribution) in urine
samples from non-UTI (n = 20) and UTI patients (n = 20). A significant increase in cell count was observed
in UTI samples, and biophysical parameters were used to develop a
UTI classifier with an area under the receiver operating characteristic
curve of 0.84. Overall, the developed platform facilitates rapid culture-free
urine screening which can be further developed to assess disease severity
in UTI and other urologic diseases based on neutrophil electrical
signatures.