Natural and synthetic affinity agents as microdialysis sampling mass transport enhancers: Current progress and future perspectives

Microdialysis sampling is a diffusion-based separation method that allows analytes to freely diffuse across a hollow fiber semi-permeable dialysis membrane. This sampling technique has been widely used for in vivo chemical collection. The inclusion of affinity-based trapping agents into the microdialysis perfusion fluid serves to improve the relative recovery via the binding reaction of low molecular weight hydrophobic analytes and larger analytes such as peptides and proteins. Here, we briefly review our past studies using different compounds (native cyclodextrins and antibodies) to improve microdialysis sampling recovery. A brief compilation of our studies using antibody-immobilized beads as a means to improve cytokine collection during microdialysis sampling is also described. We present new work focused on the use of antibody-immobilized bead microdialysis sampling enhancement for various endocrine hormones (amylin, GLP-1, glucagon, insulin, and leptin). The antibody-bead enhancement approach allowed for recovery enhancements that ranged between 3 and 20-fold for these peptides. Using the enhanced recovery approach, endocrine peptides at pM concentrations can be quantified. Finally, our initial work focused on developing non-antibody based enhancement agents using bovine serum albumin–heparin conjugates covalently bound to polystyrene microspheres is presented for the cytokine, tumor necrosis factor-alpha (TNF-α). Unlike antibodies, heparin provides the advantage of being reusable as an enhancement agent and served to improve the relative recovery of TNF-α by three-fold.