Background
Immunosuppressive drugs (ISD) are an essential tool in the treatment of transplant rejection and immune-mediated diseases. Therapeutic drug monitoring (TDM) for determination of ISD concentrations in biological samples is an important instrument for dose personalization for improving efficacy while reducing side effects. While currently ISD concentration measurements are performed at specialized, centralized facilities, making the process complex and laborious for the patient, various innovative technical solutions have recently been proposed for bringing TDM to the point-of-care (POC).
Content
In this review, we evaluate current ISD-TDM and its value, limitations, and proposed implementations. Then, we discuss the potential of POC-TDM in the era of personalized medicine, and provide an updated review on the unmet needs and available technological solutions for the development of POC-TDM devices for ISD monitoring. Finally, we provide concrete suggestions for the generation of a meaningful and more patient-centric process for ISD monitoring.
Summary
POC-based ISD monitoring may improve clinical care by reducing turnaround time, by enabling more frequent measurements in order to obtain meaningful pharmacokinetic data (i.e., area under the curve) faster reaction in case of problems and by increasing patient convenience and compliance. The analysis of the ISD-TDM field prompts the evolution of POC testing toward the development of fully integrated platforms able to support clinical decision-making. We identify 4 major areas requiring careful combined implementation: patient usability, data meaningfulness, clinicians’ acceptance, and cost-effectiveness.
Several azide-derivatized and fluorescently-labeled peptides were immobilized on azadibenzocyclooctyne (ADIBO)-activated slide surfaces via a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction revealing excellent immobilization kinetics, good spot homogeneities and reproducible fluorescence signal intensities. A myc-peptide micro-array immunoassay showed an antibody limit-of-detection (LOD) superior to a microtiter plate-based ELISA. Bovine serum albumin (BSA) and dextran covalently attached via "click" chemistry more efficiently reduced non-specific binding (NSB) of fluorescently-labeled IgG to the microarray surface in comparison to immobilized hexanoic acid and various types of polyethylene glycol (PEG) derivatives. Confirmation of these findings via further studies with other proteins and serum components could open up new possibilities for human sample and microarray platform-based molecular diagnostic tests.
The profile of phenolic compounds in strawberry fruits varies significantly among cultivars. High performance liquid chromatography with diode array detection coupled to electrospray ionization mass spectrometric detection with positive and negative modes of ionization was employed to identify phenolic compounds in extract of strawberries from Charlotte cultivar. This is the first time phenolic profile of Charlotte cultivar has been characterized. The fruits contained phenolics belonging to six groups: anthocyanins, ellagic acid and its conjugates, gallotannins, flavonols, flavanols and hydroxycinnamic acid derivatives. The presence of pentagalloyl glucose in strawberries fruits was reported for the first time.
Peptide and protein microarrays provide a multiplex approach to identification and quantification of protein-protein interactions (PPI), useful to study for instance antigen-antibody properties. Multivariate serology assays detecting multiple tumor auto-antibodies (TAA) is an emerging class of blood tests for cancer detection. Here we describe the efficient coupling of peptide baits derived from the BRCA1-associated RING domain protein 1 (BARD1) to a solid surface and detection of a commercially available anti-BARD1 antibody with this newly designed peptide microarray. Analytical sensitivity and specificity were shown to be comparable to a microtiter plate based enzyme-linked immunosorbent assay (ELISA).
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