Rapid, precise, and reproducible deposition of a broad variety of functional materials, including analytical assay reagents and biomolecules, has made inkjet printing an effective tool for the fabrication of microanalytical devices. A ubiquitous office device as simple as a standard desktop printer with its multiple ink cartridges can be used for this purpose. This Review discusses the combination of inkjet printing technology with paper as a printing substrate for the fabrication of microfluidic paper-based analytical devices (μPADs), which have developed into a fast-growing new field in analytical chemistry. After introducing the fundamentals of μPADs and inkjet printing, it touches on topics such as the microfluidic patterning of paper, tailored arrangement of materials, and functionalities achievable exclusively by the inkjet deposition of analytical assay components, before concluding with an outlook on future perspectives.

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"Distance-based" detection motifs on microfluidic paper-based analytical devices (μPADs) allow quantitative analysis without using signal readout instruments in a similar manner to classical analogue thermometers. To realize a cost-effective and calibration-free distance-based assay of lactoferrin in human tear fluid on a μPAD not relying on antibodies or enzymes, we investigated the fluidic mobilities of the target protein and Tb(3+) cations used as the fluorescent detection reagent on surface-modified cellulosic filter papers. Chromatographic elution experiments in a tear-like sample matrix containing electrolytes and proteins revealed a collapse of attractive electrostatic interactions between lactoferrin or Tb(3+) and the cellulosic substrate, which was overcome by the modification of the paper surface with the sulfated polysaccharide ι-carrageenan. The resulting μPAD based on the fluorescence emission distance successfully analyzed 0-4 mg mL(-1) of lactoferrin in complex human tear matrix with a lower limit of detection of 0.1 mg mL(-1) by simple visual inspection. Assay results of 18 human tear samples including ocular disease patients and healthy volunteers showed good correlation to the reference ELISA method with a slope of 0.997 and a regression coefficient of 0.948. The distance-based quantitative signal and the good batch-to-batch fabrication reproducibility relying on printing methods enable quantitative analysis by simply reading out "concentration scale marks" printed on the μPAD without performing any calibration and using any signal readout instrument.

This work demonstrates the fabrication of microfluidic paper-based analytical devices (µPADs) suitable for the analysis of sub-microliter sample volumes. The wax-printing approach widely used for the patterning of paper substrates has been adapted to obtain high-resolution microfluidic structures patterned in filter paper. This has been achieved by replacing the hot plate heating method conventionally used to melt printed wax features into paper by simple hot lamination. This patterning technique, in combination with the consideration of device geometry and the influence of cellulose fiber direction in filter paper, led to a model µPAD design with four microfluidic channels that can be filled with as low as 0.5 µL of liquid. Finally, the application to a colorimetric model assay targeting total protein concentrations is shown. Calibration curves for human serum albumin (HSA) were recorded from sub-microliter samples (0.8 µL), with tolerance against ±0.1 µL variations in the applied liquid volume.

A general and simple implementation of simultaneous multiparametric sensing in a single microchip is presented by using a capillary-assembled microchip (CAs-CHIP) integrated with the plural different reagent-release capillaries (RRCs), acting as various biochemical sensors. A novel "drop-and-sip" technique of fluid handling is performed with a microliter droplet of a model sample solution containing proteases (trypsin, chymotrypsin, thrombin, elastase) and divalent cations (Ca2+, Zn2+, Mg2+) that passes through the microchannel with the aid of a micropipette as a vacuum pump, concurrently filling each RRC via capillary force. To avert the evaporation of the nanoliter sample volume in each capillary, PDMS oil is dropped on the outlet hole of the CAs-CHIP exploiting the capillary force that results in spontaneous sealing of all the RRCs. In addition, this high-speed sample introduction alleviates the possibility of protein adsorption and capillary cross-contamination, allowing a reliable and multianalyte determination of a sample containing many different proteases and divalent cations by using the fluorescence image analysis. Presented results suggested the possible application of this microchip in the field of drug discovery and systems biology.