Stephanie Oyola-Reynoso

Reprint of 'Draw your assay: Fabrication of low-cost paper-based diagnostic and multi-well test zones by drawing on a paper'.

Interest in low-cost diagnostic devices has recently gained attention, in part due to the rising cost of healthcare and the need to serve populations in resource-limited settings. A major challenge in the development of such devices is the need for hydrophobic barriers to contain polar bio-fluid analytes. Key approaches in lowering the cost in diagnostics have centered on (i) development of low-cost fabrication techniques/processes, (ii) use of affordable materials, or, (iii) minimizing the need for high-tech tools. This communication describes a simple, low-cost, adaptable, and portable method for patterning paper and subsequent use of the patterned paper in diagnostic tests. Our approach generates hydrophobic regions using a ball-point pen filled with a hydrophobizing molecule suspended in a solvent carrier. An empty ball-point pen was filled with a solution of trichloro perfluoroalkyl silane in hexanes (or hexadecane), and the pen used to draw lines on Whatman® chromatography 1 paper. The drawn regions defined the test zones since the trichloro silane reacts with the paper to give a hydrophobic barrier. The formation of the hydrophobic barriers is reaction kinetic and diffusion-limited, ensuring well defined narrow barriers. We performed colorimetric glucose assays and enzyme-linked immuno-sorbent assay (ELISA) using the created test zones. To demonstrate the versatility of this approach, we fabricated multiple devices on a single piece of paper and demonstrated the reproducibility of assays on these devices. The overall cost of devices fabricated by drawing are relatively lower (

Limits to the Effect of Substrate Roughness or Smoothness on the Odd–Even Effect in Wetting Properties of n-Alkanethiolate Monolayers

This study investigates the effect of roughness on interfacial properties of an n-alkanethiolate self-assembled monolayer (SAM) and uses hydrophobicity to demonstrate the existence of upper and lower limits. This article also sheds light on the origin of the previously unexplained gradual increase in contact angles with increases in the size of the molecule making the SAM. We prepared Au surfaces with a root-mean-square (RMS) roughness of ∼0.2-0.5 nm and compared the wetting properties of n-alkanethiolate (C10-C16) SAMs fabricated on these surfaces. Static contact angles, θ(s), formed between the SAM and water, diethylene glycol, and hexadecane showed an odd-even effect irrespective of the solvent properties. The average differences in subsequent SAM(E) and SAM(O) are Δθ(s|n  – (n+1)|) ≈ 1.7° (n = even) and Δθ(s|n – (n+1)|) ≈ 3.1° (n = odd). A gradual increase in θ(s) with increasing length of the molecule was observed, with values ranging from water 104.7-110.7° (overall Δθ(s) = 6.0° while for the evens Δθ(s)(E) = 4.4° and odds Δθ(s)(O) = 3.5°) to diethylene glycol 72.9-80.4° (overall Δθ(s) = 7.5° while for the evens Δθ(s)(E) = 2.9° and odds Δθ(s)(O) = 2.4°) and hexadecane 40.4–49.4° (overall Δθ(s) = 9.0° while for the evens Δθ(s)(E) = 3.7° and odds Δθ(s)(O) = 2.1°). This article establishes that the gradual increase in θ(s) with increasing molecular size in SAMs is due to asymmetry in the zigzag oscillation in the odd-even effect. Comparison of the magnitude and proportion differences in this asymmetry allows us to establish the reduction in interfacial dispersive forces, due to increasing SAM crystallinity with increasing molecular size, as the origin of this asymmetry. By comparing the dependence of θ(s) on surface roughness we infer that (i) RMS roughness ≈ 1 nm is a theoretical limit beyond which the odd-even effect cannot be observed and (ii) on a hypothetically flat surface the maximum difference in hydrophobicity, as expressed in θ(s), is ∼3°.

Empirical Evidence for Roughness-Dependent Limit in Observation of Odd–Even Effect in Wetting Properties of Polar Liquids on n-Alkanethiolate Self-Assembled Monolayers

Substrate roughness influences the wetting properties of self-assembled monolayers (SAMs), but details on this dependency at the sub-nanometer level are still lacking. This study investigates the effect of surface roughness on interfacial properties of n-alkanethiolate SAMs, specifically wetting, and confirms the predicted limit to the observation of the odd-even effect in hydrophobicity. This article studies static contact angles of polar and nonpolar probe liquids on a series of n-alkanethiolate SAMs on surfaces with tunable roughness. We prepared Ag surfaces with root-mean-square roughness (Rrms) of ∼0.6-2.2 nm and compared the wetting properties of n-alkanethiolate SAMs fabricated on these surfaces. We measured the static contact angles, θs, formed between SAM and probe liquids [water, glycerol, and hexadecane]. Hexadecane showed an odd-even effect on all surfaces irrespective of the degree of roughness. Polar liquids (water and glycerol), however, showed a dependency on the roughness of the substrate with an odd-even effect observable only on smooth, but not rougher (Rrms ≥ 1.15 nm), surfaces. These results confirm that the previously predicted limit to observation of the odd-even effect in hydrophobicity (here extended to polar liquids) is real. From the results with glycerol, we infer that this limit is not limited just to hydrophobicity but may extend to other polar liquids. Results from hexadecane, however, suggest that this limit may not be a universal property of the SAM.

Properties of Self-Assembled Monolayers Revealed via Inverse Tensiometry

Self-assembled monolayers (SAMs) have emerged as a simple platform technology and hence have been broadly studied. With advances in state-of-the-art fabrication and characterization methods, new insights into SAM structure and related properties have been delineated, albeit with some discrepancies and/or incoherencies. Some discrepancies, especially between experimental and theoretical work, are in part due to the misunderstanding of subtle structural features such as phase evolution and SAM quality. Recent work has, however, shown that simple techniques, such as the measurement of static contact angles, can be used to delineate otherwise complex properties of the SAM, especially when complemented by other more advanced techniques. In this article, we highlight the effect of nanoscale substrate asperities and molecular chain length on the SAM structure and associated properties. First, surfaces with tunable roughness are prepared on both Au and Ag, and their corresponding n-alkanethiolate SAMs are characterized through wetting and spectroscopy. From these data, chain-length- and substrate-morphology-dependent limits to the odd-even effect (structure and properties vary with the number of carbons in the molecules and the nature of the substrate), parametrization of gauche defect densities, and structural phase evolution (liquidlike, waxy, crystalline interfaces) are deduced. An evaluation of the correlation between the effect of roughness and the components of surface tension (polar-γp and dispersive-γd) reveals that wetting, at nanoscale rough surfaces, evolves proportionally with the ratio of the two components of surface tension. The evolution of conformational order is captured over a range of molecular lengths and parametrized through a dimensionless number, χc. By deploying a well-known tensiometry technique (herein the liquid is used to characterize the solid, hence the term inverse tensiometry) to characterize SAMs, we demonstrate that complex molecular-level phenomena in SAMs can be understood through simplicity.

Quantifying Gauche Defects and Phase Evolution in Self-Assembled Monolayers through Sessile Drops

Self-assembled monolayers (SAMs) are widely used in surface modifications, specifically in tuning the surface chemistry of materials. The structure and properties of SAMs have been extensively studied often with sophisticated tools, even for the simplest n-alkanethiolate SAMs. In SAMs, especially in linear n-alkanethiolates, the properties are dependent on the chain length, which is best manifested in the so-called odd–even effect, a simple yet not fully understood phenomenon. One main challenge is fully delineating the origin of length-dependent properties, which can be due to the structure (ideal SAMs), defect evolution, or substrate-molecule effects. This study demonstrates that utilizing the wetting behavior of polar (water) and nonpolar (hexadecane (HD)) solvents on n-alkanethiolate SAMs formed on ultraflat gold and silver surfaces, the evolution of chain-length-dependent gauche defects can be revealed and parameterized through a newly defined dimensionless number (χ). The observation of the odd–even effect in hydrophobicity, however, depends on the thiol chain length, and it was only observed on longer-chain (>C8) molecules. The trend in this odd–even effect demonstrates that there are three main transitions in the nature of wetting, hence structure, across n-alkanethiols. From wetting with HD, the role of dispersive components in wetting reveal that the SAMs are dynamic, which we attribute to rotations associated with previously reported evolution in gauche defects and changes in packing density. Therefore, from re-expression of the Young–Dupre equation, we define a new dimensionless number associated with molecular conformations, whose periodicity mirrors the energetics of Goodman’s conformations of n-alkanes in unbound states and associated four- or two-twist turns. Therefore, we infer that the evolution in surface energy is largely due to molecular conformations and associated relaxations of the bound thiolates.

Recruiting physisorbed water in surface polymerization for bio-inspired materials of tunable hydrophobicity

Chemical grafting has been widely used to modify the surface properties of materials, especially surface energy for controlled wetting, because of the resilience of such coatings/modifications. Reagents with multiple reactive sites have been used with the expectation that a monolayer will form. The step-growth polymerization mechanism, however, suggests the possibility of gel formation for hydrolyzable moieties in the presence of physisorbed water. In this report, we demonstrated that using alkyltrichlorosilanes (trivalent [i.e., 3 reactive sites]) in the surface modification of a cellulosic material (paper) does not yield a monolayer but rather gives surface-bound particles. We infer that the presence of physisorbed (surface-bound) water allows for polymerization (or oligomerization) of the silane prior to its attachment on the surface. Surface energy mismatch between the hydrophobic tails of the growing polymer and any unreacted bound water leads to the assembly of the polymerizing material into spherical particles to minimize surface tension. By varying paper grammage (16.2–201.4 g m−2), we varied the accessible surface area and thus the amount of surface-adsorbed water, allowing us to control the ratio of the silane to the bound water. Using this approach, polymeric particles were formed on the surface of cellulose fibers ranging from ∼70 nm to a film. The hydrophobicity of the surface, as determined by water contact angles, correlates with particle sizes (p < 0.001, Students t-test), and, hence, the hydrophobicity can be tuned (contact angle between 94° and 149°). Using a model structure of a house, we demonstrated that as a result of this modification, paper-based houses can be rendered self-cleaning or tolerant to surface running water. In another application, we demonstrated that the felicitous choice of architectural design allows for the hydrophobic paper to be used for water harvesting.

Pot-in-pot reactions: a simple and green approach to efficient organic synthesis

Incompatible organic reactions impede efficient green synthesis by making multi-component or cascade reactions a big challenge. This review highlights pot-in-pot reactions (multiple reactions carried out in one pot by separating key reactions with a thin polymeric membrane) as an efficient, green synthetic alternative to conventional synthesis. We discuss the advantages of homogeneous processes to develop new cascade reaction sequences by reviewing the use of polymeric thimbles as selective semi-permeable walls. These thimbles allow small organic molecules to diffuse through while retaining polar reagents, polar solvents, and/or organometallic catalysts. The dynamic and versatile nature of this technique is demonstrated by performing 2- and 3-step cascade reactions in one glass pot. A pot-in-pot reaction approach to synthesis circumvents the need to isolate intermediates, or handling of toxic/unpleasant by-products, therefore enabling synthesis of otherwise challenging molecules, improving the efficiency, or enabling greener approaches to modular synthesis.

Surface polymerization of perfluorosilane treatments on paper mitigates HF production upon incineration

Hydrophobic paper has inspired advances in low-cost technologies. Of importance is the use of perfluorinated reagents, due to suspected release of HF. Surprisingly, by using a coupled TGA-IR-MS, we demonstrate that polymerization of a perfluorinated silane on paper, leads to rapid degradation, low-ash residue, and no toxic HF gas is produced under thermolysis.

Paper-based microfluidic devices by asymmetric calendaring

We report a simple, efficient, one-step, affordable method to produce open-channel paper-based microfluidic channels. One surface of a sheet of paper is selectively calendared, with concomitant hydrophobization, to create the microfluidic channel. Our method involves asymmetric mechanical modification of a paper surface using a rolling ball (ball-point pen) under a controlled amount of applied stress (σz) to ascertain that only one side is modified. A lubricating solvent (hexane) aids in the selective deformation. The lubricant also serves as a carrier for a perfluoroalkyl trichlorosilane allowing the channel to be made hydrophobic as it is formed. For brevity and clarity, we abbreviated this method as TACH (Targeted Asymmetric Calendaring and Hydrophobization). We demonstrate that TACH can be used to reliably produce channels of variable widths (size of the ball) and depths (number of passes), without affecting the nonworking surface of the paper. Using tomography, we demonstrate that these channels can vary from 10s to 100s of microns in diameter. The created hydrophobic barrier extends around the channel through wicking to ensure no leakages. We demonstrate, through modeling and fabrication, that flow properties of the resulting channels are analogous to conventional devices and are tunable based on associated dimensionless numbers.

Melt-and-mold fabrication (MnM-Fab) of reconfigurable low-cost devices for use in resource-limited settings.

Interest in low-cost analytical devices (especially for diagnostics) has recently increased; however, concomitant translation to the field has been slow, in part due to personnel and supply-chain challenges in resource-limited settings. Overcoming some of these challenges require the development of a method that takes advantage of locally available resources and/or skills. We report a Melt-and-mold fabrication (MnM Fab) approach to low-cost and simple devices that has the potential to be adapted locally since it requires a single material that is recyclable and simple skills to access multiple devices. We demonstrated this potential by fabricating entry level bio-analytical devices using an affordable low-melting metal alloy, Fields metal, with molds produced from known materials such as plastic (acrylonitrile-butadiene-styrene (ABS)), glass, and paper. We fabricated optical gratings then 4×4 well plates using the same recycled piece of metal. We then reconfigured the well plates into rapid prototype microfluidic devices with which we demonstrated laminar flow, droplet generation, and bubble formation from T-shaped channels. We conclude that this MnM-Fab method is capable of addressing some challenges typically encountered with device translation, such as technical know-how or material supply, and that it can be applied to other devices, as needed in the field, using a single moldable material.