Instrument-free quantitative detection of alkaline phosphatase using paper-based devices

Almost all the existing assay methods for alkaline phosphatase (ALP) require expensive analytical instruments and well-trained users to achieve quantitative results. This work initially describes a quantitative ALP assay that integrates low-cost microfluidic paper-based analytical devices (μPADs) with an instrument-free length-measuring readout. The detection motif of length measurement is based on the starch-mediated wettability change of the μPAD from hydrophilic to hydrophobic. Under optimal conditions, this new method is quantitatively sensitive to ALP levels in buffer samples ranging from ∼0.075 to 5 U mL−1, with a visual detection limit of 0.075 U mL−1. The satisfactory recovery results of assaying several human serum samples additionally prove its practicability. The proposed method needs only a ubiquitous cheap ruler to realize quantitative analysis, thus making it a simple, cost-efficient, and promising alternative tool for potential broad applications in the diagnosis of ALP-relevant diseases or assessment of ALP functions in biological systems especially in resource-poor settings.

[1]  Jinfang Nie,et al.  One-step patterning of hollow microstructures in paper by laser cutting to create microfluidic analytical devices. , 2013, The Analyst.

[2]  Dianyang Lin,et al.  Rapid and sensitive SERS method for determination of Rhodamine B in chili powder with paper-based substrates , 2015 .

[3]  Yun Zhang,et al.  Fabrication of paper devices via laser-heating-wax-printing for high-tech enzyme-linked immunosorbent assays with low-tech pen-type pH meter readout. , 2017, The Analyst.

[4]  Rajendra Prasad,et al.  Alkaline Phosphatase: An Overview , 2013, Indian Journal of Clinical Biochemistry.

[5]  Wenying Li,et al.  Nucleic acid-regulated perylene probe-induced gold nanoparticle aggregation: a new strategy for colorimetric sensing of alkaline phosphatase activity and inhibitor screening. , 2014, ACS applied materials & interfaces.

[6]  Eka Noviana,et al.  Paper-Based Microfluidic Devices: Emerging Themes and Applications. , 2017, Analytical chemistry.

[7]  Yun Zhang,et al.  Timing readout in paper device for quantitative point-of-use hemin/G-quadruplex DNAzyme-based bioassays. , 2015, Biosensors & bioelectronics.

[8]  G. Whitesides,et al.  Measuring markers of liver function using a micropatterned paper device designed for blood from a fingerstick. , 2012, Analytical chemistry.

[9]  Gregory G. Lewis,et al.  Quantifying analytes in paper-based microfluidic devices without using external electronic readers. , 2012, Angewandte Chemie.

[10]  Charles S Henry,et al.  Simple, distance-based measurement for paper analytical devices. , 2013, Lab on a chip.

[11]  M. Brunetto,et al.  Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease , 1996 .

[12]  Peter Kauffman,et al.  Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks. , 2010, Lab on a chip.

[13]  Bingcheng Lin,et al.  Chemiluminescence diminishment on a paper-based analytical device: high throughput determination of β-agonists in swine hair , 2014 .

[14]  J. Morote,et al.  Serum bone alkaline phosphatase levels enhance the clinical utility of prostate specific antigen in the staging of newly diagnosed prostate cancer patients , 1999, European Journal of Nuclear Medicine.

[15]  Ning Zhang,et al.  Lab-on-a-drop: biocompatible fluorescent nanoprobes of gold nanoclusters for label-free evaluation of phosphorylation-induced inhibition of acetylcholinesterase activity towards the ultrasensitive detection of pesticide residues. , 2014, The Analyst.

[16]  Fei Li,et al.  Advances in paper-based point-of-care diagnostics. , 2014, Biosensors & bioelectronics.

[17]  Yun Zhang,et al.  Equipment-free quantitative measurement for microfluidic paper-based analytical devices fabricated using the principles of movable-type printing. , 2014, Analytical chemistry.

[18]  Jianhui Jiang,et al.  Inhibition of dsDNA-templated copper nanoparticles by pyrophosphate as a label-free fluorescent strategy for alkaline phosphatase assay. , 2013, Analytical chemistry.

[19]  Charles S Henry,et al.  Paper-based analytical devices for environmental analysis. , 2016, The Analyst.

[20]  Huan‐Tsung Chang,et al.  Detection of mercury(II) ions using colorimetric gold nanoparticles on paper-based analytical devices. , 2014, Analytical chemistry.

[21]  Yao Jiang,et al.  Fluorimetric Mercury Test Strips with Suppressed “Coffee Stains” by a Bio-inspired Fabrication Strategy , 2016, Scientific Reports.

[22]  Jinghua Yu,et al.  Facile and sensitive paper-based chemiluminescence DNA biosensor using carbon dots dotted nanoporous gold signal amplification label , 2013 .

[23]  K. Shiraki,et al.  High‐molecular intestinal alkaline phosphatase in chronic liver diseases , 2007, Journal of clinical laboratory analysis.

[24]  Xinggui Gu,et al.  A new fluorometric turn-on assay for alkaline phosphatase and inhibitor screening based on aggregation and deaggregation of tetraphenylethylene molecules. , 2013, The Analyst.

[25]  Yuming Dong,et al.  Versatile and Amplified Biosensing through Enzymatic Cascade Reaction by Coupling Alkaline Phosphatase in Situ Generation of Photoresponsive Nanozyme. , 2015, Analytical chemistry.

[26]  G. Whitesides,et al.  Patterned paper as a platform for inexpensive, low-volume, portable bioassays. , 2007, Angewandte Chemie.

[27]  G. M. Rao,et al.  Correlation between serum alkaline phosphatase activity and blood glucose levels. , 1986, Enzyme.

[28]  Yun Zhang,et al.  Naked-eye quantitative aptamer-based assay on paper device. , 2016, Biosensors & bioelectronics.

[29]  Wei Qi,et al.  Ultrasensitive electroanalysis of low-level free microRNAs in blood by maximum signal amplification of catalytic silver deposition using alkaline phosphatase-incorporated gold nanoclusters. , 2014, Analytical chemistry.

[30]  Elain Fu,et al.  Enabling robust quantitative readout in an equipment-free model of device development. , 2014, The Analyst.

[31]  Jingjing Deng,et al.  Real-time ratiometric fluorescent assay for alkaline phosphatase activity with stimulus responsive infinite coordination polymer nanoparticles. , 2015, Analytical chemistry.

[32]  Hui Feng,et al.  Carbon quantum dots-based recyclable real-time fluorescence assay for alkaline phosphatase with adenosine triphosphate as substrate. , 2015, Analytical chemistry.

[33]  W. Goodman,et al.  Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients , 1996 .

[34]  Wensheng Shi,et al.  Fluorescent biosensor for alkaline phosphatase based on fluorescein derivatives modified silicon nanowires , 2014 .

[35]  G. Whitesides,et al.  Diagnostics for the developing world: microfluidic paper-based analytical devices. , 2010, Analytical chemistry.

[36]  Terence G. Henares,et al.  Paper-based inkjet-printed microfluidic analytical devices. , 2015, Angewandte Chemie.

[37]  I. McKelvie,et al.  Development of a gas-diffusion microfluidic paper-based analytical device (μPAD) for the determination of ammonia in wastewater samples. , 2015, Analytical chemistry.

[38]  Jun Li,et al.  Ratiometric fluorescent probe for alkaline phosphatase based on betaine-modified polyethylenimine via excimer/monomer conversion. , 2014, Analytical chemistry.

[39]  Z. Song,et al.  Novel preparation and electrochemiluminescence application of luminol functional-Au nanoclusters for ALP determination , 2015 .

[40]  Zhi Zhu,et al.  Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets. , 2015, Analytical chemistry.

[41]  Lianming Zhang,et al.  Low-cost fabrication of paper-based microfluidic devices by one-step plotting. , 2012, Analytical chemistry.

[42]  A. Vlessidis,et al.  Programming fluid transport in paper-based microfluidic devices using razor-crafted open channels. , 2014, Analytical chemistry.

[43]  Gregory G. Lewis,et al.  A prototype point-of-use assay for measuring heavy metal contamination in water using time as a quantitative readout. , 2014, Chemical communications.