The document discusses the history and fundamentals of paper-based diagnostic devices. It describes key developments like the invention of litmus paper in the 17th century to detect pH, the first use of patterned fluidic channels on paper in 1949, and the introduction of lateral flow assays in the 1980s using colloidal gold or silver for colorimetric detection. It also provides equations that model liquid wicking in paper and the effect of evaporation and humidity on wicking speed.

1. • Effect of relative humidity on wicking speed [9]
• By considering the evaporation effect, imbibition distance of the liquid front
(Fries et al.)
• 𝑦𝑓 =
𝑎−𝑎 exp(−2𝑏𝑡)
𝑏
1
2
• where 𝑎 =
4𝛾cos(𝜃)
𝐷𝑒𝜇
and 𝑏 =
𝐹(𝑊+𝑇)
𝜌𝑊𝑇
• 𝐷𝑒,  , and  are the effective pore diameter, the effective permeability, and the
porosity of the material, respectively.
• F is the evaporation flux, W is the width of the channel, ρ is the liquid density,
and T is the paper thickness
Fundamentals of paper microfluidics - Flow Equations

2. • Effect of relative humidity on wicking speed [10]
• Castro et al. developed a modified version of the Fries et al. model.
(considering relative humidity)
• 𝑦𝑓 =
𝑎−𝑎 exp(−2𝑏𝑡)
𝑏
1
2
• where 𝑎 =

2
1
2 𝛾cos(𝜃)
𝜇
and 𝑏 =
𝐹(𝑊+𝑇)
𝜌(1−𝑆𝑤)𝑊𝑇
• Sw being the degree of water saturation
• 𝑆𝑤 =
𝑚𝑟𝑤
𝜌𝑉𝑇
• 𝑚𝑟𝑤 is mass of the retained water and 𝑉𝑇 is the total volume of the paper
Fundamentals of paper microfluidics - Flow Equations

3. History of Paper Based Diagnostics
• 17th century - the invention of litmus paper
• a pH indicator paper treated with a natural water-soluble dye [11], [12].
• In 1945, West developed a spot test paper for metal ion detection [13]
• In 1949, Müller and Clegg - patterned a flow channel on filter paper using hydrophobic paraffin wax [14]
• Advantages of patterning:
i. transportation of the sample to specific regions
ii. accessibility to small sample volumes
iii. distribution of a liquid sample into multiple regions to enable multiplexing
• In 1956 - first paper-based dipstick tests to measure urinary glucose levels - by Comer [15] and Free et al [16]
• In 1956 - Plotz and Singer [17] - diagnosed rheumatoid arthritis using the latex agglutination test.
• Latex-made of amorphous polymer (usually polystyrene) - latex coated with specific antigens/Abs in serial
dilutions–sample Ag/Ab->agglutination/clumping->positive result
• In 1980 - Leuvering et al. developed a colloidal gold or silver particle-based colorimetric LFA [18], [19].
They demonstrated sandwich immunoassays in the LFA format to detect human placental lactogen and
chorionic gonadotrophin.
• In 2007, the Whitesides Group [20] reported a simple method for patterning a chromatographic paper with
hydrophobic photoresist via conventional photolithography to create millimeter-scale channels and reaction
zones.

4. History of Paper Based Diagnostics
Spot test paper
for metal ion
detection
Fluidic channel
patterning on a
filter paper with
paraffin
Lateral flow
assay to
diagnose
rheumatoid
arthritis
Paper based
dipstick to
measure urinary
glucose level
Colloidal gold or
silver particles
based LFA (SPIA)
Introduction of
microfluidic
paper-based
analytical
devices (PADs)
1945 1949 1956 1980 2007 & 2008
Timeline of paper-based diagnostic devices

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[8] Z. Liu, J. Hu, Y. Zhao, Z. Qu, and F. Xu, “Experimental and numerical studies on liquid wicking into filter papers for paper-based diagnostics,” Appl. Therm.
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[9] N. Fries, K. Odic, M. Conrath, and M. Dreyer, “The effect of evaporation on the wicking of liquids into a metallic weave,” J. Colloid Interface Sci., vol. 321,
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[10] C. Castro, C. Rosillo, and H. Tsutsui, “Characterizing effects of humidity and channel size on imbibition in paper-based microfluidic channels,” Microfluid.
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[11] C. Carrell et al., “Beyond the lateral flow assay: A review of paper-based microfluidics,” Microelectron. Eng., vol. 206, no. January, pp. 45–54, 2019, doi:
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References