A microneedle patch measured a kidney injury biomarker in dermal interstitial fluid and remained functional following exposure to high temperatures, according to a study published in Advanced Materials.
The patch detects neutrophil gelatinase-associated lipocalin, a protein that increases following renal tubular injury. Neutrophil gelatinase-associated lipocalin may rise before conventional kidney function markers such as serum creatinine and blood urea nitrogen, although its concentration can also be affected by inflammation and other conditions.
Researchers developed a patch containing 121 antibody-coated microneedles. The needles enter the upper layers of the skin and capture neutrophil gelatinase-associated lipocalin from interstitial fluid without reaching blood vessels. After removal, the patch undergoes additional antibody-labeling and fluorescence-imaging steps to quantify the captured protein.
The assay had a detection limit of 16 pg/mL in mouse samples and produced linear measurements from 0.1 to 2,000 ng/mL. In human testing, the detection limit was 9 pg/mL.
The researchers first evaluated the patch in mice with lipopolysaccharide-induced acute kidney injury. Neutrophil gelatinase-associated lipocalin increased within four hours, including at lipopolysaccharide doses that did not produce detectable changes in serum creatinine. Interstitial fluid measurements followed the same dose-dependent pattern as serum results and corresponded with histopathologic evidence of tubular injury.
Testing in healthy volunteers produced 11 paired interstitial fluid and plasma measurements. Absolute concentrations were lower in interstitial fluid, but the two sample types were strongly correlated. Application left small skin openings without bleeding, and the skin recovered within 30 minutes. The study did not test the patch in patients with kidney disease.
To improve storage stability, the researchers covered the antibody-coated needles with a thin layer of zeolitic imidazolate framework-8, a metal-organic framework. This protective coating was removed before the patch was used.
Protected patches retained 94 percent of their fluorescence signal following 4 weeks of repeated temperature cycling between 23 and 50 degrees Celsius. Unprotected patches retained 7 percent. The protected patches also maintained assay sensitivity after three days at 50 degrees Celsius followed by seven days of unrefrigerated transport between Missouri and Texas.
Following transport, the patches detected increased interstitial fluid neutrophil gelatinase-associated lipocalin in the mouse kidney injury model. However, concentrations measured by the patch were lower than those obtained from serum or extracted interstitial fluid, highlighting the need for sample-specific reference ranges.
The study shows how interstitial fluid could provide an alternative matrix for minimally invasive kidney biomarker testing. The current system is not a fully self-contained test because labeling, washing, imaging, and calibration are performed after patch removal.
Further studies are needed to define clinically actionable interstitial fluid thresholds, assess diagnostic performance in patients, and determine how inflammation and other confounders affect results. Multiplexed measurement of additional kidney biomarkers may also be needed to improve specificity.
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