Characterizing asthma from a drop of blood using neutrophil chemotaxis.
Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements.
Materials Science Program, Department of Biomedical Engineering, Wisconsin Institute for Medical Research, Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and Departments of Biostatistics and Medical Informatics and Pediatrics, University of Wisconsin-Madison, Madison, WI 53705.
Eric Karl-Heinz
EK
Sackmann
Erwin
E
Berthier
Elizabeth A
EA
Schwantes
Paul S
PS
Fichtinger
Michael D
MD
Evans
Laura L
LL
Dziadzio
Anna
A
Huttenlocher
Sameer K
SK
Mathur
David J
DJ
Beebe
D000328:Adult; D001249:Asthma / Q000097:blood* / Q000473:pathology*; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D044085:Microfluidics; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D055815:Young Adult
D009569:Nitric Oxide
KOALA; diagnostics; microfluidics; passive pumping