Biosensors are powerful diagnostic tools defined as having a biorecognition element for analyte specificity and a transducer for a quantifiable signal. There are a variety of different biorecognition elements, each with unique characteristics. Understanding the advantages and disadvantages of each biorecognition element and their influence on overall biosensor performance is crucial in the planning stages to promote the success of novel biosensor development. Therefore, this review will focus on selecting the optimal biorecognition element in the preliminary design phase for novel biosensors. Included is a review of the typical characteristics and binding mechanisms of various biorecognition elements, and how they relate to biosensor performance characteristics, specifically sensitivity, selectivity, reproducibility, and reusability. The goal is to point toward language needed to improve the design and development of biosensors toward clinical success.
A new biomaterial, a degradable thermoset polymer, was made from simple, economical, biocompatable monomers without the need for a catalyst. Glycerol and citric acid, non-toxic and renewable reagents, were crosslinked by a melt polymerization reaction at temperatures from 90-150°C. Consistent with a condensation reaction, water was determined to be the primary byproduct. The amount of crosslinking was controlled by the reaction conditions, including temperature, reaction time, and ratio between glycerol and citric acid. Also, the amount of crosslinking was inversely proportional to the rate of degradation. As a proof-of-principle for drug delivery applications, gentamicin, an antibiotic, was incorporated into the polymer with preliminary evaluations of antimicrobial activity. The polymers incorporating gentamicin had significantly better bacteria clearing of Staphylococcus aureus compared to non-gentamicin gels for up to nine days.
Mapping molecular sub-types in breast cancer (BC) tumours is a rapidly evolving area due to growing interest in, for example, targeted therapy and screening high-risk populations for early diagnosis. We report a new concept for profiling BC molecular sub-types based on volatile organic compounds (VOCs). For this purpose, breath samples were collected from 276 female volunteers, including healthy, benign conditions, ductal carcinoma in situ (DCIS) and malignant lesions. Breath samples were analysed by gas chromatography mass spectrometry (GC-MS) and artificially intelligent nanoarray technology. Applying the non-parametric Wilcoxon/Kruskal-Wallis test, GC-MS analysis found 23 compounds that were significantly different (p < 0.05) in breath samples of BC patients with different molecular sub-types. Discriminant function analysis (DFA) of the nanoarray identified unique volatolomic signatures between cancer and non-cancer cases (83% accuracy in blind testing), and for the different molecular sub-types with accuracies ranging from 82 to 87%, sensitivities of 81 to 88% and specificities of 76 to 96% in leave-one-out cross-validation. These results demonstrate the presence of detectable breath VOC patterns for accurately profiling molecular sub-types in BC, either through specific compound identification by GC-MS or by volatolomic signatures obtained through statistical analysis of the artificially intelligent nanoarray responses.
Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin-hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p<0.0001) compared to non-sterilized polymers . In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p<0.05) and a prolonged therapeutic effect (p<0.05) but less drug loading (p<0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials.
The use of highly cross-linked molecularly imprinted polymers as a synthetic target receptor has the limitations of restricted accessibility to the binding sites, resulting in a slow response time. Moreover, such artificial receptors often require additional transduction mechanisms to translate target binding events into measurable signals. Here, we propose the development of a single-chain stimuli-responsive templated polymer, without using any covalent interchain cross-linkers, as a target recognition element. The synthesized polymer chain exhibits preferential binding with the target molecule with which the polymer is templated. Moreover, upon specific target recognition, the polymer undergoes conformation change induced by its particular stimuli responsiveness, namely, the target binding event. Such templated single-chain polymers can be attached to the electrode surface to implement a label-free electrochemical sensing platform. A target analyte, 4-nitrophenol (4-NP), was used as a template to synthesize a poly(N-isopropylacrylamide) (PNIPAM)based copolymer chain which was anchored to the electrode to be used as a selective receptor for 4-NP. The electrode surface chemistry analysis and the electrochemical impedance study reveal that the polymer concentration, the interchain interactions, and the Hofmeister effect play a major role in influencing the rate of polymer grafting as well as the morphology of the polymers grafted to the electrode. We also show that the specific binding between 4-NP and the copolymer results in a substantial change in the charge transfer kinetics at the electrode signifying the polymer conformation change.
Controlling the sensing properties of a silicon nanowire field effect transistor is dependent on the surface chemistry of the silicon nanowire. A standard silicon nanowire has a passive oxide layer (native oxide), which has trap states that cause sensing inaccuracies and desensitize the surface to nonpolar molecules. In this paper, we successfully modified the silicon nanowire surface with different nonoxide C3 alkyl groups, specifically, propyl (Si-CH2-CH2-CH3), propenyl (Si-CH═CH-CH3), and propynyl (Si-C≡C-CH3) modifications. The effect of the near surface bond on the sensor sensitivity and stability was explored by comparing three C3 surface modifications. A reduction of trap-states led to greater sensor stability and accuracy. The propenyl-modified sensor was consistently the most stable and sensitive sensor, among the applied sensors. The propenyl- and propynyl-modified sensors consistently performed with the best accuracy in identifying specific analytes with similar polarity or similar molecular weights. A combination of features from different sensing surfaces led to the best rubric for specific analytes identification. These results indicate that nonoxide sensor surfaces are useful in identifying specific analytes and that a combination of sensors with different surfaces in a cross-reactive array can lead to specific analytes detection.
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