| 1. |
- Winkler, Thomas, Ph.D., et al.
(författare)
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Molecular processes in an electrochemical clozapine sensor
- 2017
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Ingår i: Biointerphases. - : American Institute of Physics (AIP). - 1934-8630 .- 1559-4106. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Selectivity presents a crucial challenge in direct electrochemical sensing. One example is schizophrenia treatment monitoring of the redox-active antipsychotic clozapine. To accurately assess efficacy, differentiation from its metabolite norclozapine-similar in structure and redox potentialis critical. Here, the authors leverage biomaterials integration to study, and effect changes in, diffusion and electron transfer kinetics of these compounds. Specifically, the authors employ a catechol-modified chitosan film, which the authors have previously presented as the first electrochemical detection mechanism capable of quantifying clozapine directly in clinical serum. A key finding in our present work is differing dynamics between clozapine and norclozapine once the authors interface the electrodes with chitosan-based biomaterial films. These additional dimensions of redox information can thus enable selective sensing of largely analogous small molecules.
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| 2. |
- Winkler, Thomas, Ph.D., et al.
(författare)
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The interplay of electrode- and bio-materials in a redox-cycling-based clozapine sensor
- 2017
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Ingår i: Electrochemistry communications. - : Elsevier. - 1388-2481 .- 1873-1902. ; 79, s. 33-36
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Tidskriftsartikel (refereegranskat)abstract
- We investigate gold, TiN, and platinum in combination with a chitosan catechol-based redox-cycling system (RCS) for electrochemical detection of the antipsychotic clozapine. We have previously demonstrated the RCS for detection of clozapine in serum, but challenges remain regarding low signal-to-noise ratios. This can be mitigated by selection of electrode materials with beneficial surface morphologies and/or compositions. We employ cyclic voltammetry to assess the redox current generated by clozapine, and differentiate solely surface area-based effects from clozapine-specific ones using a standard redox couple. We find that nano- and microstructured platinum greatly amplifies the clozapine signal compared to gold (up to 1490-fold for platinum black). However, the material performs poorly in the presence of chloride ions, and RCS modification provides no further amplification. The RCS combined with atomic-layer-deposited (ALD) TiN, on the other hand, increases the signal by 7.54 times, versus 2.86 times for RCS on gold, with a 9.2-fold lower variability, indicating that the homogenous and chemically inert properties of ALD-TiN may make it an ideal electrode material.
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| 3. |
- Winkler, Thomas, Ph.D., et al.
(författare)
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The Role of Microsystems Integration Towards Point-of-Care Clozapine Treatment Monitoring in Schizophrenia.
- 2018
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Ingår i: IEEE sensors letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 2475-1472. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a perspective on microsystems integration aspects for concurrent cellular and molecular sensing in a lab-on-a-chip device. While of interest for a range of applications, very few - narrowly focused - examples of such devices can be found in the literature. Here, we approach the challenge from a systems level, considering sensor integration both in parallel and in series. Our study is specifically geared toward schizophrenia treatment, where concurrent blood monitoring of the antipsychotic clozapine and white blood cells could lead to improved treatment outcomes. We evaluate the critical system components for either design, namely plasma skimming (parallel) and in-blood clozapine detection (series). We find that plasma skimming is infeasible, but for the first time demonstrate direct detection of clozapine in whole blood. With a corresponding series-integrated microsystem, we finally demonstrate downstream white blood cell analysis on the same samples using impedance cytometry. We thus present the first lab-on-a-chip device capable of label- and reagent-free concurrent sensing of cellular and molecular markers.
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