We detect short oligonucleotides and distinguish between sequences that differ by a single base, using label-free, electronic field-effect transistors (FETs). Our sensing platform utilizes ultrathin-film indium oxide FETs chemically functionalized with single-stranded DNA (ssDNA). The ssDNA-functionalized semiconducting channels in FETs detect fully complementary DNA sequences and differentiate these sequences from those having different types and locations of single base-pair mismatches. Changes in charge associated with surface-bound ssDNA vs double-stranded DNA (dsDNA) alter FET channel conductance to enable detection due to differences in DNA duplex stability. We illustrate the capability of ssDNA-FETs to detect complementary RNA sequences and to distinguish from RNA sequences with single nucleotide variations. The development and implementation of electronic biosensors that rapidly and sensitively detect and differentiate oligonucleotides present new opportunities in the fields of disease diagnostics and precision medicine.
Supported lipid membranes are versatile biomimetic coatings for the chemical functionalization of inorganic surfaces. Developing simple and effective fabrication strategies to form supported lipid membranes with micropatterned geometries is a long-standing challenge. Herein, we demonstrate how the combination of chemical lift-off lithography (CLL) and easily prepared lipid bicelle nanostructures can yield micropatterned, supported lipid membranes on gold surfaces with high pattern resolution, conformal character, and biofunctionality. Using CLL, we functionalized gold surfaces with patterned arrays of hydrophilic and hydrophobic self-assembled monolayers (SAMs). Time-lapse fluorescence microscopy imaging revealed that lipid bicelles adsorbed preferentially onto the hydrophilic SAM regions, while there was negligible lipid adsorption onto the hydrophobic SAM regions. Functional receptors could be embedded within the lipid bicelles, which facilitated selective detection of receptor–ligand binding interactions in a model streptavidin–biotin system. Quartz crystal microbalance-dissipation measurements further identified that lipid bicelles adsorb irreversibly and remain intact on top of the hydrophilic SAM regions. Taken together, our findings indicate that lipid bicelles are useful lipid nanostructures for reproducibly assembling micropatterned, supported lipid membranes with precise pattern fidelity.
Spin-dependent and enantioselective electron–molecule scattering occurs in photoelectron transmission through chiral molecular films. This spin selectivity leads to electron spin filtering by molecular helices, with increasing magnitude concomitant with increasing numbers of helical turns. Using ultraviolet photoelectron spectroscopy, we measured spin-selective surface charging accompanying photoemission from ferromagnetic substrates functionalized with monolayers of mercurated DNA hairpins that constitute only one helical turn. Mercury ions bind specifically at thymine–thymine mismatches within self-hybridized single-stranded DNA, enabling precise control over the number and position of Hg2+ along the helical axis. Differential charging of the organic layers, manifested as substrate-magnetization-dependent photoionization energies, was observed for DNA hairpins containing Hg2+; no differences were measured for hairpin monolayers in the absence of Hg2+. Inversion of the DNA helical secondary structure at increased metal loading led to complementary inversion in spin selectivity. We attribute these results to increased scattering probabilities from relativistic enhancement of spin–orbit interactions in mercurated DNA.
Chemical lift-off lithography (CLL) is a subtractive soft-lithographic technique that uses polydimethylsiloxane (PDMS) stamps to pattern self-assembled monolayers of functional molecules for applications ranging from biomolecule patterning to transistor fabrication. A hallmark of CLL is preferential cleavage of Au–Au bonds, as opposed to bonds connecting the molecular layer to the substrate, i.e., Au–S bonds. Herein, we show that CLL can be used more broadly as a technique to pattern a variety of substrates composed of coinage metals (Pt, Pd, Ag, Cu), transition and reactive metals (Ni, Ti, Al), and a semiconductor (Ge) using straightforward alkanethiolate self-assembly chemistry. We demonstrate high-fidelity patterning in terms of precise features over large areas on all surfaces investigated. We use patterned monolayers as chemical resists for wet etching to generate metal microstructures. Substrate atoms, along with alkanethiolates, were removed as a result of lift-off, as previously observed for Au. We demonstrate the formation of PDMS-stamp-supported bimetallic monolayers by performing CLL on two different metal surfaces using the same PDMS stamp. By expanding the scope of the surfaces compatible with CLL, we advance and generalize CLL as a method to pattern a wide range of substrates, as well as to produce supported metal monolayers, both with broad applications in surface and materials science.