Paper-Based Distance Sensor for the Detection of Lipase via a Phase Separation-Induced Viscosity Change

Abstract

Human pancreatic lipase is a symbolic biomarker for the diagnosis of acute pancreatitis, which has profound significance for clinical detection and disease treatment. Herein, we first demonstrate a paper-based lipase sensor via a phase separation-induced viscosity change. Lipase catalyzes triolein to produce oleic acid and glycerol. Adding an excess of Ca2+ produces calcium oleate. The remaining Ca2+ binds with sodium alginate, triggering hydrogelation with an “egg-box” structure. The viscosity change of the aqueous solution induced by the phase separation process can be quantified by measuring the solution flow distance on a pH test paper. The paper-based lipase sensor has high sensitivity with a detection limit of 0.052 U/mL and also shows excellent specificity. Additionally, it is also utilized for quantitative lipase analysis in human serum samples to exhibit its potency in acute pancreatitis detection. This method overcomes the drawbacks of low sensitivity, slow response, and poor reproducibility caused by the nonuniform distribution of the highly viscous hydrogel on the sensing interface in existing approaches. In conclusion, thanks to the prominent characteristics of high portability, low cost, and easy operation, it is prospective for simple quantitative detection of lipase and has great potential for commercialization.

Sensing of Digestive Enzymes—Diagnosis and Monitoring of Pancreatitis

“…Xia et al investigated the application of a pH-test-paper-based viscosity assay for lipase measurement. The addition of lipase causes phase separation of the substrate which in turn flows over different lengths of the pH test paper due to viscosity changes It catalyzes the formation of oleic acid and glycerol from the trioleic acid in the substrate The oleic acid will form calcium oleate particles with Ca 2+ ions, while the unreacted Ca 2+ will form a hydrogel with alginate [242].…”

“…It catalyzes the formation of oleic acid and glycerol from the trioleic acid in the substrate. The oleic acid will form calcium oleate particles with Ca 2+ ions, while the unreacted Ca 2+ will form a hydrogel with alginate [242].…”

A Simple and Effective Visual Fluorescent Sensing Paper-Based Chip for the Ultrasensitive Detection of Mercury Ions in Environmental Water

“…Normally, sample storage, transportation and pretreatment are necessary when using traditional instrumentation methods for the detection of mercury ions at trace levels, which are not adaptable to the needs of rapid on-site environmental analysis [ 4 , 5 , 6 ]. In contrast, paper-based visual analytical methods have been developed for rapid on-site environmental analysis due to their being user-friendly, disposable and low-cost [ 7 , 8 , 9 ]. To date, molecular and nano-materials have been widely developed for the construction of visual sensing methods on paper-based devices for the rapid detection of mercury ions, such as organic chromophores/fluorophores [ 10 ], plasma nanoparticles [ 11 ], quantum dots [ 12 ], carbon dots [ 13 ] and so on.…”

Slippery Viscosity-Sensing Platform with Time Readout for the Detection of Hyaluronidase and Its Inhibitor

“…20,27−29 Unfortunately, these methods usually suffer from slow response, low sensitivity, and poor reproducibility due to the slow substance transport on the biphase interface between the hydrogel matrix and external environment, 30−32 and inhomogeneous coating of substrate surface due to the high viscosity of hydrogel. 33 Therefore, the development of novel methods that can overcome these disadvantages is critical.…”

“…Stimuli-responsive polymers undergo physicochemical changes responding to appropriate external stimuli and have been widely applied for biosensing applications. − In particular, polymeric hydrogels with designed functional cross-linking units have attracted considerable attention for the construction of biosensors. − Conventionally, the sensing mechanism is based on the principle of analyte-triggered volume change or gel-to-sol transition. ,− Unfortunately, these methods usually suffer from slow response, low sensitivity, and poor reproducibility due to the slow substance transport on the biphase interface between the hydrogel matrix and external environment, − and inhomogeneous coating of substrate surface due to the high viscosity of hydrogel . Therefore, the development of novel methods that can overcome these disadvantages is critical.…”