Wettability-based ultrasensitive detection of amphiphiles through directed concentration at disordered regions in self-assembled monolayers

Abstract

Various forms of ecological monitoring and disease diagnosis rely upon the detection of amphiphiles, including lipids, lipopolysaccharides, and lipoproteins, at ultralow concentrations in small droplets. Although assays based on droplets' wettability provide promising options in some cases, their reliance on the measurements of surface and bulk properties of whole droplets (e.g., contact angles, surface tensions) makes it difficult to monitor trace amounts of these amphiphiles within small-volume samples. Here, we report a design principle in which self-assembled monolayer-functionalized microstructured surfaces coated with silicone oil create locally disordered regions within a droplet's contact lines to effectively concentrate amphiphiles within the areas that dominate the droplet static friction. Remarkably, such surfaces enable the ultrasensitive, naked-eye detection of amphiphiles through changes in the droplets' sliding angles, even when the concentration is four to five orders of magnitude below their critical micelle concentration. We develop a thermodynamic model to explain the partitioning of amphiphiles at the contact line by their cooperative association within the disordered, loosely packed regions of the self-assembled monolayer. Based on this local analyte concentrating effect, we showcase laboratory-on-a-chip surfaces with positionally dependent pinning forces capable of both detecting industrially and biologically relevant amphiphiles (e.g., bacterial endotoxins), as well as sorting aqueous droplets into discrete groups based on their amphiphile concentrations. Furthermore, we demonstrate that the sliding behavior of amphiphile-laden aqueous droplets provides insight into the amphiphile's effective length, thereby allowing these surfaces to discriminate between analytes with highly disparate molecular sizes.

Keywords: amphiphiles; lubricated surfaces; self-assembly; sensors; wettability.

Scheme 1.

Comparison between mechanisms involved in amphiphile detection using wettability-based sensors. (A) Traditional wettability-based sensors rely on the partitioning of analytes between the bulk phase and on the surface of water droplets to induce changes in the droplets’ surface tension. At low concentrations of analytes, the surface tension of aqueous droplets is indistinguishable from that of pure water. (B) Proposed contact line–based sensors take advantage of the local concentration of analyte molecules via their preferential partition within a contact line region, which may lead to different sliding behaviors from those of pure water even at trace amounts of analytes in water droplets. Red boxes indicate the contact line region. The distribution of analyte molecules is schematic.

Fig. 1.

Design of DMOAP SAM-functionalized, silicone oil–infused Si micropillar arrays that enable cooperative self-assembly of amphiphiles in disordered regions of the SAM at the top edge of the micropillars. (A) Schematic illustration of a DMOAP SAM-functionalized Si micropillar array. Disordered DMOAP assembly regions are located at the edge of micropillars. Pillar height, radius, and pitch are fixed at 30 μm, 5 μm, and 25 μm, respectively. Inset shows a representative scanning electron microscopy (SEM) image of micropillar structures on a Si wafer. The length of the DMOAP molecule was calculated from Chem3D. Note that the structure of the SAM is schematic. (B) Left: A representative goniometer image of a water droplet resting on a DMOAP SAM-functionalized, silicone oil–infused Si micropillar array. Right: The friction force experienced by a 2-μL aqueous droplet as a function of time on a DMOAP SAM-functionalized, silicone oil–infused Si micropillar array (red), a flat DMOAP SAM-functionalized, silicone oil–infused flat Si surface (blue), and a conventional SLIPS system with poly(C₄F₈)-functionalized glass coated with Krytox 103 perfluoropolyether lubricant (black). The maximum friction force is defined as the static pinning force, F_pinning. Scale bar, 500 μm. (C) Fluorescence micrograph showing BODIPY-labeled amphiphiles becoming locally concentrated by self-assembling with DMOAP in disordered regions of the SAM at the top edge of the micropillars lubricated with silicone oil. Scale bar, 10 μm.

Fig. 2.

Effect of amphiphiles’ molecular structure on static friction of aqueous droplets on a lubricated DMOAP SAM-functionalized Si micropillar array. (A) Molecular structure of SDS. The length of SDS was calculated from Chem3D. (B) F_pinning of aqueous droplets as a function of SDS concentration on a DMOAP-functionalized Si micropillar array lubricated with silicone oil (red), a DMOAP-functionalized, silicone oil–coated flat Si surface (blue), and a conventional SLIPS system with poly(C₄F₈)-functionalized glass coated with Krytox 103 perfluoropolyether lubricant (black). The volume of aqueous droplets is 2 μL. (C, D) Dependence of the concentration of (C) individually dispersed SDS within water droplets (X_monomeric) and (D) self-assembled SDS within the disordered region of the SAM (X_assembly) on the total concentration of SDS (X_total), as calculated by Eq. 2. The right y axis of (D) shows the F_pinning of aqueous droplets as a function of total concentration of SDS. Regions (i), (ii), and (iii) correspond to stages depicted in (E). (E) Schematic illustration of the three stages of cooperative self-assembly of amphiphiles within disordered DMOAP SAM at the top edge of the micropillars as a function of amphiphile concentration. Note that the structure of the SAM is schematic.

Fig. 3.

(A) Molecular structure of a nonionic amphiphile, Brij 97, and a scheme of coassembly of Brij 97 at the disordered DMOAP SAM region. Note that Brij 97 is nearly twice as long as the length of DMOAP. The length of Brij was calculated from Chem3D. The structure of the SAM is schematic. (B) F_pinning of aqueous droplets on a DMOAP-functionalized Si micropillar array lubricated with silicone oil as a function of Brij 97 concentration. (C) Molecular structure of an endotoxin molecule, which consists of a lipid A covalently bound to a polysaccharide head group. The polysaccharide is composed of O-antigen, outer core, and inner core segments, which are linearly and covalently bound. Note that endotoxin is much larger than DMOAP, the scheme in (C) is not to scale, and the structure of the SAM is schematic. (D) F_pinning of aqueous droplets on a DMOAP SAM-functionalized silicon micropillar array lubricated with silicone oil as a function of concentrations of endotoxin, lipid A, and polysaccharide. The volume of aqueous droplets is kept at 2 μL.

Fig. 4.

Sorting SDS-laden aqueous droplets into discrete groups using a patterned lubricated DMOAP-functionalized Si micropillar array. Plot showing F_pinning of aqueous droplets as a function of (A) total circumference (C_tot) and (B) total surface area (A_tot) of the total micropillars under water droplets. (C) Sequential photographs showing pinning of SDS-laden aqueous droplets on a DMOAP SAM-functionalized Si micropillar array lubricated with silicone oil with a gradient in micropillar dimensions. P was varied from 35 to 15 μm (from top to bottom), while R remained constant at 5 μm in each region. Threshold SDS concentrations for aqueous droplets to pass different regions are listed next to the photographs. The volume of SDS aqueous droplets was 2 μL. Scale bar, 1 cm.