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1.
Adv Sci (Weinh) ; : e2309976, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973256

ABSTRACT

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

2.
ACS Omega ; 9(23): 25223-25238, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38882102

ABSTRACT

After cochlear implant (CI) insertion, there is a possibility of postoperative inflammation, which may involve proinflammatory markers such as interleukin-6. Detecting this inflammation promptly is crucial for administering anti-inflammatory drugs, if required. One potential method for detecting inflammation is using molecular imprinted polymers (MIPs). These MIPs, which can be deposited on the CI electrode, provide readout employing impedance measurements, a feature already available on the CI circuit. MIPs designed for this purpose should possess biocompatibility, conductivity, and degradability. The degradability is crucial because there is a limitation on the number of electrodes available, and once the inflammation sensor degrades after the acute inflammation period, it should remain usable as a regular electrode. In this work, conductive poly(3,4-ethylenedioxythiophene) polystyrenesulfonate-based MIPs were synthesized against biotin as a surrogate target marker. Specific biotin binding with MIPs was determined before and after degradation using electrochemical impedance spectroscopy (EIS) and compared with the control nonimprinted polymers (NIPs). Subsequently, MIPs were electrochemically degraded by EIS with different potentials, wherein a potential dependence was observed. With decreasing potential, fewer dissolved polymers and more monomer molecules were detected in the solution in which degradation took place. At a potential of 0.205 V a negligible amount of dissolved polymer in addition to the dissolved monomer molecules was measured, which can be defined as the limiting potential. Below this potential, only dissolved monomer molecules are obtained, which enables renal clearance. Biocompatibility testing revealed that both the polymer and the solution with dissolved monomer molecules do not exceed the ISO 10993-5 cytotoxicity threshold. Based on these findings, we have developed conductive, biocompatible, and controllably degradable MIPs capable of detecting biotin. This research work paves the way for the advancement of CIs, where inflammation can be detected using molecular imprinting technology without compromising the stability and biosafety of the product.

3.
ACS Sens ; 8(10): 3643-3658, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37830899

ABSTRACT

Prostate cancer (PCa) is the second most common male cancer and is attributable to over 375,000 deaths annually. Prostate specific antigen (PSA) is a key biomarker for PCa and therefore measuring patient PSA levels is an important aspect of the diagnostic pathway. Automated immunoassays are currently utilized for PSA analysis, but they require a laboratory setting with specialized equipment and trained personnel. This results in high diagnostic costs, extended therapeutic turnaround times, and restrictions on testing capabilities in resource-limited settings. Consequently, there is a strong drive to develop point-of-care (PoC) PSA tests that can offer accurate, low-cost, and rapid results at the time and place of the patient. However, many emerging PoC tests experience a trade-off between accuracy, affordability, and accessibility which distinctly limits their translational potential. This review comprehensively assesses the translational advantages and limitations of emerging laboratory-level and commercial PoC tests for PSA determination. Electrochemical and optical PSA sensors from 2013 to 2023 are systematically examined. Furthermore, we suggest how the translational potential of emerging tests can be optimized to achieve clinical implementation and thus improve PCa diagnosis globally.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Point-of-Care Systems , Prostatic Neoplasms/diagnosis , Point-of-Care Testing , Biomarkers
4.
Anal Bioanal Chem ; 415(18): 4467-4478, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36905407

ABSTRACT

Lysozyme (LYZ) is a small cationic protein which is widely used for medical treatment and in the food industry to act as an anti-bacterial agent; however, it can trigger allergic reactions. In this study, high-affinity molecularly imprinted nanoparticles (nanoMIPs) were synthesized for LYZ using a solid-phase approach. The produced nanoMIPs were electrografted to screen-printed electrodes (SPEs), disposable electrodes with high commercial potential, to enable electrochemical and thermal sensing. Electrochemical impedance spectroscopy (EIS) facilitated fast measurement (5-10 min) and is able to determine trace levels of LYZ (pM) and can discriminate between LYZ and structurally similar proteins (bovine serum albumin, troponin-I). In tandem, thermal analysis was conducted with the heat transfer method (HTM), which is based on monitoring the heat transfer resistance at the solid-liquid interface of the functionalized SPE. HTM as detection technique guaranteed trace-level (fM) detection of LYZ but needed longer analysis time compared to EIS measurement (30 min vs 5-10 min). Considering the versatility of the nanoMIPs which can be adapted to virtually any target of interest, these low-cost point-of-care sensors hold great potential to improve food safety.


Subject(s)
Molecular Imprinting , Nanoparticles , Muramidase/analysis , Allergens , Molecular Imprinting/methods , Nanoparticles/chemistry , Electrodes , Serum Albumin, Bovine , Electrochemical Techniques/methods , Limit of Detection
5.
Foods ; 11(18)2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36141032

ABSTRACT

In recent years, melamine-sensing technologies have increasingly gained attention, mainly due to the misuse of the molecule as an adulterant in milk and other foods. Molecularly imprinted polymers (MIPs) are ideal candidates for the recognition of melamine in real-life samples. The prepared MIP particles were incorporated into a thermally conductive layer via micro-contact deposition and its response towards melamine was analyzed using the heat-transfer method (HTM). The sensor displayed an excellent selectivity when analyzing the thermal response to other chemicals commonly found in foods, and its applicability in food safety was demonstrated after evaluation in untreated milk samples, demonstrating a limit of detection of 6.02 µM. As the EU/US melamine legal limit in milk of 2.5 mg/kg falls within the linear range of the sensor, it can offer an innovative solution for routine screening of milk samples in order to detect adulteration with melamine. The results shown in this work thus demonstrate the great potential of a low-cost thermal platform for the detection of food adulteration in complex matrices.

6.
ACS Sens ; 7(4): 1122-1131, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35416035

ABSTRACT

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivity and utilize antibodies as receptors, which can only function in narrow temperature and pH ranges. Consequently, molecularly imprinted polymer nanoparticles (nanoMIPs) are synthetized with a fast (2 h) and scalable process using merely a tiny SARS-CoV-2 fragment (∼10 amino acids). The nanoMIPs rival the affinity of SARS-CoV-2 antibodies under standard testing conditions and surpass them at elevated temperatures or in acidic media. Therefore, nanoMIP sensors possess clear advantages over antibody-based assays as they can function in various challenging media. A thermal assay is developed with nanoMIPs electrografted onto screen-printed electrodes to accurately quantify SARS-CoV-2 antigens. Heat transfer-based measurements demonstrate superior detection limits compared to commercial rapid antigen tests and most antigen tests from the literature for both the alpha (∼9.9 fg mL-1) and delta (∼6.1 fg mL-1) variants of the spike protein. A prototype assay is developed, which can rapidly (∼15 min) validate clinical patient samples with excellent sensitivity and specificity. The straightforward epitope imprinting method and high robustness of nanoMIPs produce a SARS-CoV-2 sensor with significant commercial potential for population screening, in addition to the possibility of measurements in diagnostically challenging environments.


Subject(s)
COVID-19 , Molecular Imprinting , Nanoparticles , Antibodies , COVID-19/diagnosis , Humans , Molecularly Imprinted Polymers , Nanoparticles/chemistry , Point-of-Care Systems , SARS-CoV-2
7.
Mikrochim Acta ; 189(2): 73, 2022 01 24.
Article in English | MEDLINE | ID: mdl-35075499

ABSTRACT

Redesigning 3D-printed flow cells is reported used for heat transfer based detection of biomolecules from a flow-through system to an addition-type measurement cell. The aim of this study is to assess the performance of this new measurement design and critically analyse the influence of material properties and 3D printing approach on thermal analysis. Particular attention is paid to reduce the time to stabilisation, the sample volume in order to make the technique suitable for clinical applications, and improving the sensitivity of the platform by decreasing the noise and interference of air bubbles. The three different approaches that were studied included a filament polylactic acid cell using only fused filament fabrication (FFF), a resin cell printed using stereolitography (SLA), and finally a design made of copper, which was manufactured by combining metal injection moulding (MIM) with fused filament fabrication (FFF). Computational fluid dynamic (CFD) modelling was undertaken using ANSYS Fluent V18.1 to provide insight into the flow of heat within the measurement cell, facilitating optimisation of the system and theoretical response speed.It was shown that the measurement cells using SLA had the lowest noise (~ 0.6%) and shortest measurement time (15 min), whereas measurement cells produced using other approaches had lower specificity or suffered from voiding issues. Finally, we assessed the potential of these new designs for detection of biomolecules and amoxicillin, a commonly used beta lactam antibiotic, to demonstrate the proof of concept. It can be concluded that the resin addition-type measurement cells produced with SLA are an interesting affordable alternative, which were able to detect amoxicillin with high sensitivity and have great promise for clinical applications due to the disposable nature of the measurement cells in addition to small sample volumes.


Subject(s)
Amoxicillin/chemistry , Hot Temperature , Printing, Three-Dimensional , Computer Simulation , Hydrodynamics , Materials Testing , Models, Chemical , Molecularly Imprinted Polymers
8.
Adv Colloid Interface Sci ; 299: 102563, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34826745

ABSTRACT

Pluronic (PEO-PPO-PEO) block copolymers can form nano-sized micelles with a structure composed of a hydrophobic PPO core and hydrophilic PEO shell layer. Pluronics are U.S. Food and Drug Administration approved polymers, which are widely used for solubilization of drugs and their delivery, gene/therapeutic delivery, diagnostics, and tissue engineering applications due to their non-ionic properties, non-toxicity, micelle forming ability, excellent biocompatibility and biodegradability. Although Pluronics have been employed as drug carrier systems for several decades, numerous issues such as rapid dissolution, shorter residence time in biological media, fast clearance and weak mechanical strength have hindered their efficacy. Pluronics have been functionalized with pH-sensitive, biological-responsive moieties, antibodies, aptamers, folic acid, drugs, different nanoparticles, and photo/thermo-responsive hydrogels. These functionalization strategies enable Pluronics to act as stimuli responsive and targeted drug delivery vehicles. Moreover, Pluronics have emerged in nano-emulsion formulations and have been utilized to improve the properties of cubosomes, dendrimers and nano-sheets, including their biocompatibility and aqueous solubility. Functionalization of Pluronics results in the significant improvement of target specificity, loading capacity, biocompatibility of nanoparticles and stimuli responsive hydrogels for the promising delivery of a range of drugs. Therefore, this review presents an overview of all advancements (from the last 15 years) in functionalized Pluronics, providing a valuable tool for industry and academia in order to optimize their use in drug or therapeutic delivery, in addition to several other biomedical applications.


Subject(s)
Poloxamer , United States
9.
Anal Chem ; 93(39): 13235-13241, 2021 10 05.
Article in English | MEDLINE | ID: mdl-34549586

ABSTRACT

Electrospun nylon 6,6 fibers incorporating polypyrrole (PPy) molecular-imprinted polymers (MIPs) were produced for the selective detection of d-glucose using a thermal detection methodology. PPy MIPs were produced using a facile bulk synthesis approach and electrospun into intricate fibrous scaffolds giving a highly mass-producible sensing interface. The maximum incorporation of MIPs and greatest sensing performance was found to be 12.1 wt % in conjunction with the heat-transfer method (HTM), a low-cost and simple thermal detection method that measures changes in the thermal resistance at the solid-liquid interface. It is demonstrated that a 12.1% incorporation of MIPs into electrospun fibers produces the widest working linear range with a limit of detection of 0.10 ± 0.01 mM. There were no observed changes in the measured thermal resistance response to incubation with a series of structurally similar compounds, providing evidence toward the selectivity of the platform. Additionally, the sensing platform exhibited a linear working response to glucose samples in artificial sweat solutions in the biologically relevant range. This is the first report of the incorporation of MIPs into nylon 6,6 fibers for the detection of glucose and points toward the possibility of developing mass-producible electrospun fibers embedded with low-cost recognition elements of improved thermal and chemical stability for the application of wearable sensor technology.


Subject(s)
Polymers , Pyrroles , Glucose , Molecularly Imprinted Polymers , Nylons
10.
ACS Appl Mater Interfaces ; 13(24): 27868-27879, 2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34110781

ABSTRACT

We demonstrate that a novel functionalized interface, where molecularly imprinted polymer nanoparticles (nanoMIPs) are attached to screen-printed graphite electrodes (SPEs), can be utilized for the thermal detection of the cardiac biomarker troponin I (cTnI). The ultrasensitive detection of the unique protein cTnI can be utilized for the early diagnosis of myocardial infraction (i.e., heart attacks), resulting in considerably lower patient mortality and morbidity. Our developed platform presents an innovative route to develop accurate, low-cost, and disposable sensors for the diagnosis of cardiovascular diseases, specifically myocardial infraction. A reproducible and advantageous solid-phase approach was utilized to synthesize high-affinity nanoMIPs (average size = 71 nm) for cTnI, which served as synthetic receptors in a thermal sensing platform. To assess the performance and commercial potential of the sensor platform, various approaches were used to immobilize nanoMIPs onto thermocouples or SPEs: dip coating, drop casting, and a covalent approach relying on electrografting with an organic coupling reaction. Characterization of the nanoMIP-functionalized surfaces was performed with electrochemical impedance spectroscopy, atomic force microscopy, and scanning electron microscopy. Measurements from an in-house designed thermal setup revealed that covalent functionalization of nanoMIPs onto SPEs led to the most reproducible sensing capabilities. The proof of application was provided by measuring buffered solutions spiked with cTnI, which demonstrated that through monitoring changes in heat transfer at the solid-liquid interface, we can measure concentrations as low as 10 pg L-1, resulting in the most sensitive test of this type. Furthermore, preliminary data are presented for a prototype platform, which can detect cTnI with shorter measurement times and smaller sample volumes. The excellent sensor performance, versatility of the nanoMIPs, and reproducible and low-cost nature of the SPEs demonstrate that this sensor platform technology has a clear commercial route with high potential to contribute to sustainable healthcare.


Subject(s)
Molecularly Imprinted Polymers/chemistry , Nanoparticles/chemistry , Troponin I/analysis , Biomarkers/analysis , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Electrodes , Graphite/chemistry , Temperature
11.
Langmuir ; 37(27): 8177-8189, 2021 07 13.
Article in English | MEDLINE | ID: mdl-34184901

ABSTRACT

It is well established that many leaf surfaces display self-cleaning properties. However, an understanding of how the surface properties interact is still not achieved. Consequently, 12 different leaf types were selected for analysis due to their water repellency and self-cleaning properties. The most hydrophobic surfaces demonstrated splitting of the νs CH2 and ν CH2 bands, ordered platelet-like structures, crystalline waxes, high-surface-roughness values, high-total-surface-free energy and apolar components of surface energy, and low polar and Lewis base components of surface energy. The surfaces that exhibited the least roughness and high polar and Lewis base components of surface energy had intracuticular waxes, yet they still demonstrated the self-cleaning action. Principal component analysis demonstrated that the most hydrophobic species shared common surface chemistry traits with low intra-class variability, while the less hydrophobic leaves had highly variable surface-chemistry characteristics. Despite this, we have shown through partial least squares regression that the leaf water contact angle (i.e., hydrophobicity) can be predicted using attenuated total reflectance Fourier transform infrared spectroscopy surface chemistry data with excellent ability. This is the first time that such a statistical analysis has been performed on a complex biological system. This model could be utilized to investigate and predict the water contact angles of a range of biological surfaces. An understanding of the interplay of properties is extremely important to produce optimized biomimetic surfaces.


Subject(s)
Plant Leaves , Waxes , Hydrophobic and Hydrophilic Interactions , Principal Component Analysis , Surface Properties
12.
Anal Chem ; 93(14): 5931-5938, 2021 04 13.
Article in English | MEDLINE | ID: mdl-33793190

ABSTRACT

This paper reports the detection of the inflammatory and sepsis-related biomarker, interleukin-6 (IL-6), in human blood plasma using functionalized screen-printed electrodes (SPEs) in conjunction with a thermal detection methodology, termed heat-transfer method (HTM). SPEs are functionalized with antibodies specific for IL-6 through electrodeposition of a diazonium linking group and N'-ethylcarbodiimide hydrochloride (EDC) coupling, which was tracked through the use of cyclic voltammetry and Raman spectroscopy. The functionalized SPEs are mounted inside an additively manufactured flow cell and connected to the HTM device. We demonstrate the ability to detect IL-6 at clinically relevant concentrations in PBS buffer (pH = 7.4) with no significant interference from the similarly sized sepsis-related biomarker procalcitonin (PCT). The limit of detection (3σ) of the system is calculated to correspond to 3.4 ± 0.2 pg mL-1 with a working range spanning the physiologically relevant concentration levels in both healthy individuals and patients with sepsis, indicating the sensitivity of the sensor is suitable for the application. Further experiments helped provide a proof-of-application through the detection of IL-6 in blood plasma with no significant interference observed from PCT or the constituents of the medium. Due to the selectivity, sensitivity, straightforward operation, and low cost of production, this sensor platform has the potential for use as a traffic light sensor for the multidetection of inflammatory biomarkers for the diagnosis of sepsis and other conditions in which the rapid testing of blood biomarkers has vital clinical application.


Subject(s)
Interleukin-6/blood , Sepsis , Electrodes , Humans , Plasma , Procalcitonin , Sepsis/diagnosis
13.
ACS Sens ; 6(1): 100-110, 2021 01 22.
Article in English | MEDLINE | ID: mdl-33337133

ABSTRACT

In this article, we report on the development of a catheter-based, biomimetic sensor as a step toward a minimally invasive diagnostic instrument in the context of functional bowel disorders. Histamine is a key mediator in allergic and inflammatory processes in the small intestines; however, it is a challenge to determine histamine levels at the duodenal mucosa, and classical bioreceptors are unsuitable for use in the digestive medium of bowel fluid. Therefore, we have developed molecularly imprinted polypyrrole coatings for impedimetric sensing electrodes, which enable the quantification of histamine in nondiluted, human bowel fluid in a broad concentration range from 25 nM to 1 µM. The electrodes show negligible cross-sensitivity to histidine as a competitor molecule and, for comparison, we also evaluated the response of nonimprinted and taurine-imprinted polypyrrole to histamine. Furthermore, using equivalent-circuit modeling, we found that the molecular recognition of histamine by polypyrrole primarily increases the resistive component of the electrode-liquid interface while capacitive effects are negligible. The sensor, integrated into a catheter, measures differentially to correct for nonspecific adsorption effects in the complex matrix of bowel fluids, and a single triggering frequency is sufficient to determine histamine concentrations. Together, these features are beneficial for real-time diagnostic tests.


Subject(s)
Molecular Imprinting , Polymers , Catheters , Histamine , Humans , Pyrroles
14.
Sens Actuators B Chem ; 325: 128973, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33012991

ABSTRACT

Molecularly imprinted polymers (MIPs) have emerged over the past few decades as interesting synthetic alternatives due to their long-term chemical and physical stability and low-cost synthesis procedure. They have been integrated into many sensing platforms and assay formats for the detection of various targets, ranging from small molecules to macromolecular entities such as pathogens and whole cells. Despite the advantages MIPs have over natural receptors in terms of commercialization, the striking success stories of biosensor applications such as the glucose meter or the self-test for pregnancy have not been matched by MIP-based sensor or detection kits yet. In this review, we zoom in on the commercial potential of MIP technology and aim to summarize the latest developments in their commercialization and integration into sensors and assays with high commercial potential. We will also analyze which bottlenecks are inflicting with commercialization and how recent advances in commercial MIP synthesis could overcome these obstacles in order for MIPs to truly achieve their commercial potential in the near future.

15.
ACS Omega ; 5(33): 21054-21066, 2020 Aug 25.
Article in English | MEDLINE | ID: mdl-32875242

ABSTRACT

A charge-transfer (CT) interaction between 1,3,5-trinitro-2,4-dimethylbenzene (TNX) and anionic phosphate is evaluated, yielding a high band electronic transfer interaction that can be observed as a distinct color change when phosphate is present in solution. The induced interaction was studied using 1H NMR, UV-visible, and Fourier transform infrared spectroscopies. The stoichiometric determination of the interaction was divined by means of continuous variation, applying the Schaeppi-Treadwell method to calculate the binding constant (k). Furthermore, the effect of the polarity of solvents toward the generation of the CT interaction was examined, with multiple solvents considered. Complex deconstruction studies were undertaken, examining the effects of water on complex destruction and understanding the volumes needed to hinder the CT interaction potency. Specificity and selectivity of the CT interaction were also studied against other biologically relevant species (CH3CH2OH, Na+, K+, Ca2+, Cl-, HCO3 -, F-, CH3COO-, and SO4 2-), assessing the capabilities of the assay to differentiate anionic species and counter cations that could act as interferences. The role of TNX concentration in CT formation was also analyzed, aiming to optimize the phosphate-sensing assay and improve its limit of detection. The sensing platform was subsequently used to study phosphate concentrations in urine samples to further understand its potential application in biomedical research. To validate the developed technique, urine samples were analyzed for their phosphate content with both the developed sensor and a validated vanadate-molybdate reagent. The results indicate that the sensing method is capable of accurately reporting elevated phosphate levels in urine samples in a rapid and sensitive manner, illustrating that the colorimetric test could be used as a prescreening test for conditions such as hyperphosphatemia or chronic kidney disease.

16.
Biosens Bioelectron ; 158: 112152, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-32275205

ABSTRACT

In this work, we report on the development of a catheter-based sensor designed for measuring the concentration of histamine in the human duodenum. Certain gut disorders, such as the irritable bowel syndrome (IBS), are associated with elevated levels of intestinal histamine due to chronic immune activation. As it is still impossible to determine histamine concentrations in vivo, a nasointestinal catheter with histamine-sensing capabilities has the potential to become a valuable diagnostic instrument. Regarding the sensing principle, we selected impedance spectroscopy using voltages that are compatible with intra-body applications with molecularly imprinted polymers (MIPs) as recognition elements. MIPs are synthetic receptors that offer the advantages of robustness, high specificity and selectivity for histamine as a target. In this specific case, the MIPs were synthesized from acryclic acid monomers, which guarantees a uniform binding capacity within the pH range of intestinal fluid. We have validated the catheter sensor on human intestinal liquids spiked with histamine in a testing setup that mimics the environment inside the duodenum. The dose-response curves show an analytical range between 5 and 200 nM of histamine, corresponding to physiologically normal conditions while higher concentrations correlate with disease. The key output signal of the sensor is the resistive component of the MIP-functionalized titanium electrodes as derived from the equivalent-circuit modelling of full-range impedance spectra. Future applications could be catheters tailored to cardiovascular, urological, gastrointestinal, and neurovascular applications. This, in combination with the versatility of the MIPs, will make this sensor platform a versatile diagnostic tool.


Subject(s)
Biosensing Techniques , Catheters , Electric Impedance , Histamine/metabolism , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/metabolism , Biomimetics/instrumentation , Biomimetics/methods , Dielectric Spectroscopy , Electrodes , Equipment Design , Humans , Hydrogen-Ion Concentration , Irritable Bowel Syndrome/etiology , Molecularly Imprinted Polymers
17.
ACS Sens ; 4(10): 2838-2845, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31571480

ABSTRACT

This manuscript describes the production of molecularly imprinted polymer nanoparticles (nanoMIPs) for the cardiac biomarkers heart-fatty acid binding protein (H-FABP) and ST2 by solid-phase synthesis, and their use as synthetic antibodies in a multiplexed sensing platform. Analysis by surface plasmon resonance (SPR) shows that the affinity of the nanoMIPs is similar to that of commercially available antibodies. The particles are coated onto the surface of thermocouples and inserted into 3D-printed flow cells of different multiplexed designs. We demonstrate that it is possible to selectively detect both cardiac biomarkers within the physiologically relevant range. Furthermore, the developed sensor platform is the first example of a multiplex format of this thermal analysis technique which enables simultaneous measurements of two different compounds with minimal cross selectivity. The format where three thermocouples are positioned in parallel exhibits the highest sensitivity, which is explained by modeling the heat flow distribution within the flow cell. This design is used in further experiments and proof-of-application of the sensor platform is provided by measuring spiked fetal bovine serum samples. Because of the high selectivity, short measurement time, and low cost of this array format, it provides an interesting alternative to traditional immunoassays. The use of nanoMIPs enables a multimarker strategy, which has the potential to contribute to sustainable healthcare by improving the reliability of cardiac biomarker testing.


Subject(s)
Biosensing Techniques , Fatty Acid Binding Protein 3/blood , Interleukin-1 Receptor-Like 1 Protein/blood , Molecular Imprinting , Biomarkers/blood , Nanoparticles/chemistry , Surface Plasmon Resonance
18.
ACS Omega ; 4(6): 11251-11262, 2019 Jun 30.
Article in English | MEDLINE | ID: mdl-31460227

ABSTRACT

Pluronics (tri-block copolymers) have a significant role in the pharmaceutical industry and are being used to enhance the solubility and delivery of hydrophobic drugs in different marketed formulations. However, instability and unsatisfactory drug-loading capacity are the major weak spots of these pluronic micelles. The present research work is designed to solve the existing issues by the solubilization study of hydrophobic drugs in different pluronic micelles at variable temperatures. The solubilization of the hydrophobic antiepileptic drug lamotrigine (LAM) in five different pluronic micelles viz. P84, P85, F127, F108, and F68 was studied at different temperatures, 37, 47, and 57 °C, using UV-visible spectroscopy. The solubilization of LAM in pluronic micelles increased with the increase in temperature. Small-angle neutron scattering (SANS) measurements were used to observe the morphological and structural changes taking place in pluronics by increasing the temperature. The SANS results showed the morphological changes of spherical P84 micelles to prolate ellipsoidal micelles at 57 °C due to remarkable increase in the aggregation number. This morphological conversion was further confirmed by the heat transfer method (HTM) and dynamic light scattering (DLS) measurements. DLS measurements confirmed that LAM-loaded micelles showed a greater hydrodynamic diameter (D h) compared to unloaded micelles, assuring LAM solubilization in the pluronic micelles. The rate of controlled release of LAM from five different pluronic micelles was accessed by using different kinetic models to evaluate the in vitro release profile. This is the first report in which HTM measurements are established for the analysis of morphological changes in the thermoresponsive pluronic micelles in real time. The present work corroborates how we can control the drug-loading capacity, morphological structure of the drug carrier, as well as drug release by simply changing the temperature of pluronic micellar media.

19.
Biomimetics (Basel) ; 4(1)2019 Jan 14.
Article in English | MEDLINE | ID: mdl-31105190

ABSTRACT

The Bioinspired Materials conference 2018 was organized for the third time by a team of researchers from Manchester Metropolitan University. This international conference aims to bring together the scientific committee in the fields of biomimetic sensors, bioinspired materials, materials chemistry, three-dimensional (3D) printing, and tissue engineering. The 2018 edition was held at the John Dalton Building of Manchester Metropolitan University, Manchester, UK, and took place on the 10th of October 2018. There were over 60 national and international attendees, with the international attendees participating in a lab tour through the synthetic facilities and Fuel Cell Innovation Centre on the 9th of October. The three conference sessions encompassed a wide range of topics, varying from biomimetic sensors, hydrogels, and biofabrics and bioengineering.

20.
Biomimetics (Basel) ; 4(1)2019 Feb 20.
Article in English | MEDLINE | ID: mdl-31105203

ABSTRACT

Antidepressants such as amitryptiline and fluoxetine are on the list of modern essential medicines of the World Health Organization. However, there are growing concerns regarding the ecological impact of these pharmaceuticals, leading to a great need to improve current wastewater treatment procedures. In this contribution, we will report on the use of molecularly imprinted polymers (MIPs) for the extraction of antidepressants in water samples. MIPs were developed for fluoxetine and duloxetine, antidepressants belonging to the class of selective serotonin reuptake inhibitors (SSRIs). The binding capacity of these microparticles was evaluated using ultraviolet-visible (UV-Vis) spectroscopy. A new high-performance liquid chromatography (HPLC) procedure coupled to UV detection was developed, which enabled the study of mixtures of fluoxetine and duloxetine with other nitrogen-containing compounds. These results indicate that it is possible to selectively extract SSRIs from complex samples. Therefore, these versatile polymers are a promising analytical tool for the clean-up of water samples, which will benefit aquatic life and reduce the ecological impact of pharmaceuticals.

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