Abstract:Highlights Comparative analysis of current blood microsampling devices is reviewed. Intrinsic and extrinsic factors affecting blood flow in porous materials are presented. Current advances in the design and development of micro devices and materials for development of blood microsamplers are presented. Major clinical and preclinical applications of dried blood spot created by a blood microsampler device are discussed.
“…In 2002, Sch€ utz and colleagues [52] combined DBS sampling with gas chromatography (GC)-MS detection to show its utility in forensic cases where only small sample volumes or bloodstains were available. Since the initial DBS report, there have been significant advances in DBS technology, which is reflected in the increase in the number of publications, although there still remain many challenges in its implementation [53].…”
Urine drug testing is one of the objective tools available to assess adherence. To monitor adherence, quantitative urinary results can assist in differentiating "new" drug use from "previous" (historical) drug use. "Spikes" in urinary concentration can assist in identifying patterns of drug use. Coupled chromatographic-mass spectrometric methods are capable of identifying very small amounts of analyte and can make clinical interpretation rather challenging, specifically for drugs that have a longer half-life. Polypharmacy is common in treatment and rehabilitation programs because of co-morbidities. Medications prescribed for comorbidities can cause drug-drug interaction and phenoconversion of genotypic extensive metabolizers into phenotypic poor metabolizers of the treatment drug. This can have significant impact on both pharmacokinetic (PK) and pharmacodynamic properties of the treatment drug. Therapeutic drug monitoring (TDM) coupled with PKs can assist in interpreting the effects of phenoconversion. TDM-PKs reflects the cumulative effects of pathophysiological changes in the patient as well as drug-drug interactions and should be considered for treatment medications/drugs used to manage pain and treat substance abuse. Since only a few enzyme immunoassays for TDM are available, this is a unique opportunity for clinical laboratory scientists to develop TDM-PK protocols that can have a significant impact on patient care and personalized medicine. Interpretation of drug screening results should be done with caution while considering pharmacological properties and the presence or absence of the parent drug and its metabolites. The objective of this manuscript is to review and address the variables that influence interpretation of different drugs analyzed from a rehabilitation and treatment programs perspective.
“…In 2002, Sch€ utz and colleagues [52] combined DBS sampling with gas chromatography (GC)-MS detection to show its utility in forensic cases where only small sample volumes or bloodstains were available. Since the initial DBS report, there have been significant advances in DBS technology, which is reflected in the increase in the number of publications, although there still remain many challenges in its implementation [53].…”
Urine drug testing is one of the objective tools available to assess adherence. To monitor adherence, quantitative urinary results can assist in differentiating "new" drug use from "previous" (historical) drug use. "Spikes" in urinary concentration can assist in identifying patterns of drug use. Coupled chromatographic-mass spectrometric methods are capable of identifying very small amounts of analyte and can make clinical interpretation rather challenging, specifically for drugs that have a longer half-life. Polypharmacy is common in treatment and rehabilitation programs because of co-morbidities. Medications prescribed for comorbidities can cause drug-drug interaction and phenoconversion of genotypic extensive metabolizers into phenotypic poor metabolizers of the treatment drug. This can have significant impact on both pharmacokinetic (PK) and pharmacodynamic properties of the treatment drug. Therapeutic drug monitoring (TDM) coupled with PKs can assist in interpreting the effects of phenoconversion. TDM-PKs reflects the cumulative effects of pathophysiological changes in the patient as well as drug-drug interactions and should be considered for treatment medications/drugs used to manage pain and treat substance abuse. Since only a few enzyme immunoassays for TDM are available, this is a unique opportunity for clinical laboratory scientists to develop TDM-PK protocols that can have a significant impact on patient care and personalized medicine. Interpretation of drug screening results should be done with caution while considering pharmacological properties and the presence or absence of the parent drug and its metabolites. The objective of this manuscript is to review and address the variables that influence interpretation of different drugs analyzed from a rehabilitation and treatment programs perspective.
“…Contact angle hysteresis, and consequent pinning of a liquid on the surface of a solid or a porous substrate are important for a large variety of engineering and scientific applications, for example, paint flow on a surface, enhanced oil recovery, wetting of a particle surface in a froth flotation cell, adhesive bonding on a rough surface, fabrication of porous polymer films by use of pinned water droplets, blood microsampling using porous substrate, generation of robust and high-fidelity patterns for making photonic crystals, and spray coating on urea pellets for controlled release of urea . In all these examples, the substrate is characterized by topographical roughness coupled with heterogeneous energy landscape because of which the spreading front of a liquid drop gets trapped into a metastable state and stops moving.…”
Spreading or pinning of a liquid drop on a solid substrate is determined by the surface energy of solid and liquid, topography of substrate surface, and different external forces like electric field, magnetic field, and vibration. Here we present a novel mechanism of depinning, driven by in situ generation of a species following reaction between a constituent of the droplet and one in the substrate. In particular, fluoro-carbon (FC) functionalized agarose and pHEMA gels are used as the substrates; the substrate is soaked with chloroauric acid. A drop of poly(dimethylsiloxane) (PDMS) mixed with the cross-linking agent is dispensed on it. The drop does not spread in absence of the salt, but as the salt concentration increases, the spreading diameter increases with decrease in the contact angle. The Si−H group, present as a constituent in the cross-linking agent, reduces the salt, leading to in situ generation of gold nanoparticles, that mitigates the pinning effect of the drop and the drop spreads.
“…Especially in blood sampling applications, like Dried Blood Spot analysis, the general variability in hematocrit volume (volume percentage of red blood cells) of blood amongst individuals poses challenge during formation of consistent size and uniformity of blood spots. This leads to poor adoption of the dried blood spot technique for any quantitative analysis in pharmaceutical and diagnostic field 37 . Hence, a qualitative blood flow characterization provides sufficient utility than an accurate quantitative flow characterization for diagnostic applications as such accuracy is very difficult to achieve.…”
Rapid and even spreading of complex fluids over a large area on substrates like paper is required for chemical and biological sensing applications. Non-Newtonian flow behaviour and presence of multi-phase components poses a significant challenge to uniform flow in porous media. Specially in case of blood, for bio-sensing applications, fast spread on a large area is required to avoid coagulation and non-uniform component spread. In this work we have developed a filter paper based device to resolve this spreading challenge. We sandwich the filter paper between a matrix of nanofibrous membrane backed by polyethylene terephatalate (PET) sheets, forming a multi-scale pore network: one within the filter paper and the other between the PET sheet and the filter paper. By doing so, we decrease the overall resistance to flow while maintaining the same capillary suction pressure to obtain a quick, uniform spread of dyed liquids, milk solutions and whole blood. The device design and concepts used here can be used in paper microfluidic applications and to develop devices for Dried Blood Spot analysis that utilize this fast flow while maintaining even spreading over a large area.
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