Development of paper-based microfluidic devices began in the early 21st century to meet a need for inexpensive and portable medical diagnostic systems.
Paper-based microfluidic devices feature the following regions:[2] The movement of fluid through a porous medium such as paper is governed by permeability (earth sciences), geometry and evaporation effects.
[19] This technique has relatively low equipment costs and utilizes readily available materials making it a promising candidate for mass production of point of care diagnostic devices.
The technique, first described by Graham Cooks group at Purdue,[23] involves applying a voltage to a triangular sheet of wet paper near the inlet of a mass spectrometer.
Wax printing hydrophobic barriers is a common method for creating distinct flow channels within paper devices, and this has been extended to μPAD-MS to enhance ionization efficiency (by enabling focusing of the analyte stream) and enable reaction mixing by wax printing on the triangular paper surface.
However, in 2009, screen-printed electrodes were integrated into a paper-based microfluidic device to create a biosensor for glucose, lactate, and uric acid.
[39] Screen-printed electrodes on paper-based microfluidic devices have been used not only to develop biosensors for metabolites,[39][41][42] but also to detect bacteria[43] and heavy metals[44] in food and water.
The scalabile nature of this process make it promising to create electrochemical devices at ultra-low cost suitable for field testing.
[38][46] As a proof-of-concept, Ko et al. developed a paper-based electrical chip using a home office printer, an ink made of carbon nanotubes, and magazine paper.
[47] Similarly, silver nanoparticles were printed into microfluidic channels to sense changes in the permittivity of fluids, revealing information about concentration and mixing ratios.
[48] Research groups have found, however, that these nanoparticle containing inks can self-aggregate on the paper due to uneven drying, which leads to non-uniform coverage and non-linear responses.
As the seeds clusters grow and interconnect inside of the paper fibers, there properties and structure of the final material can be controlled through the process and chemical conditions.
[52] Inkjet printing is compatible with a wide variety of materials, and is a promising technology to not only fabricate conductive traces, but also incorporate advanced electronic components such as transistors into paper-based devices.
This approach has been adapted to sputter gold electrode onto paper-based microfluidic devices and demonstrated excellent performances DNA detection using quantum dots labels.
The pencil-on-paper technique is arguibly the simplest and most accessible way of creating electrodes on paper-based microfluidics as it uses inexpensive, common office supplies.
[58] The electrodes are created in situ, and retain the porous and wicking propertie of the paper substrate, whilst demonstrating large electroactive surface area for sensing.
[60] Other physical integration methods (spray or spin coating, blending, and vacuum filtration) have been developed for paper electronics,[46] but have yet to be implemented in paper-based microfluidic devices.
[61] These characteristics of paper-based microfluidics make it ideal for point-of-care testing, particularly in countries that lack advanced medical diagnostic tools.
[67][68][69][70] The main issues in the application of this technology are the lack of research into the flow control techniques, accuracy, and precision, the need for simpler operator procedures in the field, and the scaling of production to meet the volume requirements of a global market.
[37] This is largely due to the focus in the industry on utilizing the current silicon based manufacturing channels to commercialized LOC technologies more efficiently and economically.
[71] The original goal for paper-based microfluidics (μPAD) was to make low-cost and user-friendly point-of-care (POC) devices that can be operated without the assistance of medical personnel or any other qualified specialist in resource-limited and rural areas.
[72] To achieve this goal, μPAD should fit the "Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, Deliver" criteria, provided by the World Health Organization (WHO), which are the requirements for diagnostic testing for resource-constrained settings.
[77] The concept was exhibited with a paper-based microfluidic device prototype, made from a filter paper shaped to a central zone with three extending channels.
[77] Since μPADs were purposely created for use in resource-shortage conditions, it is highly important to provide the capability to analyze real samples like non-pretreated human blood and urine.
[78] This device is constructed to analyze whole-blood samples, which is an important step to increase the user acceptance of paper-based microfluidic diagnostics.
Simultaneously, separation doesn’t happen on hands soaked in non-specific antibody and the blood sample is weakened as a uniform and stable solution.
The PAD is fabricated using a combination of wax dipping technologies to join Whatman chromatography paper and blood separation membrane.
[85] Whitesides' group also developed a 3D paper-based microfluidic device for glucose detection that can produce calibration curves on-chip because of the improved fluid flow design.
[69] This device is distinguished by its use of bioactive paper instead of compartments with pre-stored reagents, and it was demonstrated to have good long-term stability, making it ideal for field use.
[69] A more recent paper-based microfluidic design utilized a sensor, consisting of fluorescently labeled single-stranded DNA (ssDNA) coupled with graphene oxide, on its surface to simultaneously detect heavy metals and antibiotics in food products.