Point-of-care therapeutic drug monitoring of adalimumab by integrating a FO-SPR biosensor in a self-powered microfluidic cartridge.

Disease treatment with advanced biological therapies such as adalimumab (ADM), although largely beneficial, is still costly and suffers from loss of response. To tackle these aspects, therapeutic drug monitoring (TDM) is proposed to improve treatment dosing and efficacy, but is often associated with long sampling-to-result workflows. Here, we present an in-house constructed ADM-sensor, allowing TDM of ADM at the doctor's office. This biosensor brings fiber optic surface plasmon resonance (FO-SPR), combined with self-powered microfluidics, to a point of care (POC) setting for the first time. After developing a rapid FO-SPR sandwich bioassay for ADM detection on a commercial FO-SPR device, this bioassay was implemented on the fully-integrated ADM-sensor. For the latter, we combined (I) a gold coated fiber optic (FO) probe for bioassay implementation and (II) an FO-SPR readout system with (III) the self-powered iSIMPLE microfluidic technology empowering plasma sample and reagent mixing on the-cartridge as well as connection to the FO-SPR readout system. With a calculated limit of detection (LOD) of 0.35 µg/mL in undiluted plasma, and a total time-to-result (TTR) within 12 min, this innovative biosensor demonstrated a comparable performance to existing POC biosensors for ADM quantification in patient plasma samples, while requiring only 1 µL of plasma. Whereas this study demonstrates great potential for FO-SPR biosensing at the POC using ADM as a model case, it also shows huge potential for bedside TDM of other drugs (e.g. other immunosuppressants, anti-epileptics and antibiotics), as the bioassay is highly amenable to adaptation.

Nanodiamond for Sample Preparation in Proteomics.

Protein analysis of potential disease markers in blood is complicated by the fact that proteins in plasma show very different abundances. As a result, high-abundance proteins dominate the analysis, which often render the analysis of low-abundance proteins impossible. Depleting high-abundance proteins is one strategy to solve this problem. Here, we present, for the first time, a very simple approach based on selective binding of serum proteins to the surface of nanodiamonds. In our first proof-of-principle experiments, we were able to detect, on average, eight proteins that are present at a concentration of 1 ng/mL (instead of 0.5 ng/mL in the control without sample preparation). Remarkably, we detect proteins down to a concentration of 400 pg/mL after only one simple depletion step. Among the proteins we could analyze are also numerous disease biomarkers, including markers for multiple cancer forms, cardiovascular diseases, or Alzheimer's disease. Remarkably, many of the biomarkers we find also could not be detected with a state-of-the-art ultrahigh-performance liquid chromatography column (which depletes the 64 most-abundant serum proteins).