The potential application of phospholipids in biosensors

I. Structural and Characteristic Foundations of Phospholipids

Phospholipids are a class of lipids containing phosphate groups, with a typical structure including a glycerol backbone, fatty acid chains, and polar head groups (such as choline, ethanolamine, etc.). Their amphiphilic nature (hydrophilic heads and hydrophobic tails) allows them to spontaneously form phospholipid bilayers in aqueous solutions, mimicking the structure and function of biological membranes. This characteristic endows phospholipids with the following advantages:

Biocompatibility: Naturally compatible with biological systems (such as cells, enzymes, antibodies), reducing nonspecific adsorption;

Membrane-mimicking environment: Capable of constructing artificial lipid bilayers to provide a near-native microenvironment for biomolecules (such as receptors, enzymes), maintaining their activity;

Modifiability: Head groups or fatty acid chains can be chemically modified to connect recognition molecules (such as antibodies, nucleic acids) or signaling molecules, enhancing sensor functions.

II. Core Application Directions of Phospholipids in Biosensors

Biomolecular Recognition Elements Based on Phospholipid Membranes

Mimicking cell membrane receptor interfaces: Fix phospholipid bilayers on sensor substrates (such as quartz crystal microbalance, surface plasmon resonance chips), embed membrane proteins (such as receptors, ion channels), and use them to detect interactions between ligands (such as hormones, drugs) and membrane proteins. For example, reconstruct G protein-coupled receptors (GPCRs) through phospholipid membranes to monitor the binding kinetics of drugs and receptors in real time.

Liposome-encapsulated signal amplification systems: Prepare liposomes using phospholipids to encapsulate fluorescent molecules, enzymes, or nanoparticles. When liposomes interact with target molecules (such as bacteria, toxins) and rupture, signal molecules are released for detection. For instance, a fluorescence enhancement method based on liposome rupture for endotoxin detection.

Phospholipid-Modified Sensor Interfaces for Performance Enhancement

Antifouling coatings: The hydrophilic head groups of phospholipids reduce nonspecific adsorption of proteins, cells, etc., on the sensor surface, improving the detection signal-to-noise ratio. For example, graft phospholipid polymers (such as polyethylene glycol-phospholipid) on the surface of electrochemical sensors to reduce matrix interference from biological samples.

Interface charge regulation: Adjust sensor interface charges by selecting negatively charged (such as phosphatidic acid) or neutral (such as lecithin) phospholipids to optimize the adsorption efficiency and orientation of biomolecules (such as nucleic acids, proteins).

Phospholipid-Nanomaterial Composite Biosensors

Phospholipid-encapsulated nanoparticles as signal probes: Encase gold nanoparticles, quantum dots, etc., in phospholipid layers. Utilize the biocompatibility of phospholipids to enhance the binding capacity of probes to target molecules, while amplifying detection signals through the optical or electrical properties of nanomaterials. For example, phospholipid-modified gold nanoparticles are used in immunosensors to improve the sensitivity of antigen-antibody binding.

Phospholipid-carbon nanotube composite interfaces: Combine phospholipid bilayers with carbon nanotubes (CNT) to construct electrochemical sensor interfaces. The high conductivity of CNT and the biocompatibility of phospholipids enhance the electron transfer efficiency of enzyme electrodes, applied to detect metabolites such as glucose and lactate.

Biosensing Applications at the Cell/Tissue Level

Living cell interface sensors: Leverage the fusion property of phospholipid membranes with cell membranes to directly embed sensors on the cell membrane surface, real-time monitoring of dynamic changes in intracellular signaling molecules (such as calcium ions, second messengers). For example, phospholipid-modified nanoprobes enter cells through endocytosis, responding to intracellular pH or enzyme activity changes and releasing fluorescent signals.

Biosensing in tissue engineering: Phospholipids can serve as coatings for scaffold materials, combined with sensors to monitor biochemical indicators (such as inflammatory factors, growth factors) during tissue repair, providing real-time data for wound healing or organ regeneration.

III. Current Challenges and Future Trends

Stability issues: Phospholipid bilayers are prone to degradation under non-physiological conditions (such as high salt, high temperature), requiring the development of more stable phospholipid analogs (such as synthetic fluorinated phospholipids) or cross-linking technologies.

Large-scale preparation: The controlled synthesis of complex phospholipid membrane structures (such as multi-layer liposomes, nanovesicles) and sensor integration processes still need optimization to reduce costs and improve repeatability.

Multifunctional integration: Combine phospholipid-based sensors with portable detection devices by integrating artificial intelligence and microfluidic technologies, promoting their application in on-site diagnosis (such as pathogen detection, cancer marker screening).

Phospholipids, with their natural biological membrane-mimicking properties, are becoming key materials connecting biomolecular recognition and sensor functions, holding broad application prospects in disease diagnosis, environmental monitoring, and biomedical research in the future.