Lipidic Cubic Phases as a Versatile Platform for the Rapid Detection of Biomarkers, Viruses, Bacteria, and Parasites

Abstract

Rapid and affordable detection of analytes is critical in diagnostic technologies, but current methods are typically expensive and unsuitable for field detection. Lipidic cubic phases are optically isotropic, transparent lyotropic liquid crystals (LC), containing highly confined water nanochannels in‐between percolating lipid bilayers following defined space groups. Due to this nanoconfinement, the water in these systems provides a unique environment for chemical and enzymatic reactions. Here, it is shown that during the in meso peroxidase enzymatic reaction, the converted product crystallizes within the mesophase domains, generating a detectable birefringence signal and a new general assay principle is presented for the detection of an unprecedented vast class of analytes using such birefringence as sole optical output signal. By exploiting bienzymatic cascade reactions or introducing an enzyme‐linked immunosorbent assay based on birefringence (Birefringent‐ELISA), this approach is used for real‐time detection of exemplary analytes, such as glucose and cholesterol, model pathogenic microorganisms, Escherichia coli, and viruses such as Ebola and HIV. It is also shown how the same technology enables the rapid, naked‐eye screening of malaria infection via in meso detection of hemozoin crystallites. This new technology is general and readily adaptable to the rapid detection of virtually any type of analyte, such as disease biomarkers, viruses, bacteria, and parasites.

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

“…Precisely in the same way as innovation frequently stems from exploiting boundaries between different fields, interfacing between the various disciplines related to the study of lipid‐based lyotropic liquid crystals offers immense opportunities for designing materials and technologies based on lyotropic liquid crystals. For example, learning how the unique water environment in lipidic cubic phases allowed improved yield of the Maillard reaction, led to the design of precisely controlled in meso enzymatic reactions and new technologies for the detection of viruses, parasites, bacteria, and biomarkers . Similarly, the unconventional single gyroid and single diamond bicontinuous cubic structures observed in some species of butterflies and beetles, respectively, not only offer new fundamental structure formation paradigms calling for deeper understanding, but may also trigger new strategies in materials templating, protein crystallization, and drug delivery.…”

Cubosomes: The Next Generation of Smart Lipid Nanoparticles?

“…These systems have been used to demonstrate detection systems for viruses including HIV and Ebola and to create a naked eye test for malaria infected blood. [96] The pathogens are detected via an enzymatic cascade that results in products that crystallize within the lipid bilayer causing birefringence. All of these studies imply that at least from a structural perspective there is access to the lipid cubic phase in bulk samples.…”

Effect of Lipid-Based Nanostructure on Protein Encapsulation within the Membrane Bilayer Mimetic Lipidic Cubic Phase Using Transmembrane and Lipo-proteins from the Beta-Barrel Assembly Machinery

“…6,7 The flexible cubic phase nanostructure can also accommodate soluble and peripheral proteins with a range of molecular weights. 8,9 The applications of encapsulated proteins in cubic phases include the in meso crystallization of membrane proteins, 10 as well as use as biosensors 11 The nanostructure of cubic phases can be significantly impacted by the incorporation of amphiphilic proteins and peptides, and can induce phase transitions to non-cubic phases. 8 The retention of the cubic phase is essential, however, for current and prospective applications of such systems.…”