Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

Abstract

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential for their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. The biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review.

Keywords: amphiphile; biomarkers; biosensors; diagnostics; lipid.

Figure 1

Examples of biosensor techniques incorporating lipids for the detection of analytes include (a) optical (b) electrical and (c) mechanical.

Figure 2

Immunoassay strategies to detect lipid and amphiphilic biomarkers using (a) membrane insertion or (b) lipoprotein capture.

Figure 3

A comparison of the sensitivity of membrane insertion and lipoprotein capture technologies for the measurement of amphiphilic biomarkers based on the medium of presentation (serum vs. buffer). Biomarkers that are readily detected in (a) phosphate buffered saline (PBS) can be poorly observed in (b) serum when utilizing a membrane insertion assay strategy, because of the uptake of these signatures by host serum carrier molecules. This signal can be recovered if (c) lipoproteins are incorporated in the assay format, exploiting the host pathogen interaction for maximal sensitivity of detection.