Superlative and Selective Sensing of Serotonin in Undiluted Human Serum Using Novel Polystyrene Sulfonate Conductive Polymer.

In the past 5 years, real-time health monitoring has become ubiquitous with the development of watches and rings that can measure and report on the physiological state. As an extension, real-time biomarker sensors, such as the continuous glucose monitor, are becoming popular for both health and performance monitoring. However, few real-time sensors for biomarkers have been made commercially available; this is primarily due to problems with cost, stability, sensitivity, selectivity, and reproducibility of biosensors. Therefore, simple, robust sensors are needed to expand the number of analytes that can be detected in emerging and existing wearable platforms. To address this need, we present a simple but novel sensing material. In short, we have modified the already popular PEDOT/PSS conductive polymer by completely removing the PEDOT component and thus have fabricated a polystyrene sulfonate (PSS) sensor electrodeposited on a glassy carbon (GC) base (GC-PSS). We demonstrate that coupling the GC-PSS sensor with differential pulse voltammetry creates a sensor capable of the selective and sensitive detection of serotonin. Notably, the GC-PSS sensor has a sensitivity of 179 µA µM-1 cm-2 which is 36x that of unmodified GC and an interferent-free detection limit of 10 nM, which is below the concentrations typically found in saliva, urine, and plasma. Notably, the redox potential of serotonin interfacing with the GC-PSS sensor is at -0.188 V versus Ag/AgCl, which is significantly distanced from peaks produced by common interferants found in biofluids, including serum. Therefore, this paper reports a novel, simple sensor and polymeric interface that is compatible with emerging wearable sensor platforms.

Gastric Cancer Survivorship: Multidisciplinary Management, Best Practices and Opportunities.

PURPOSE: Gastric cancer is the 5th most common malignancy worldwide. As early detection increases and treatments for gastric cancer improve, the number of gastric cancer survivors grows. METHODS: Here, we review the diagnosis and management of gastric cancer and discuss important considerations for gastric cancer survivorship including cancer surveillance, weight loss, malnutrition, fatigue, specific complications related to surgery and radiation, quality of life in gastric cancer survivorship, health behavior, and models of survivorship. RESULTS: Multimodality therapy with chemotherapy and surgery can result in chronic toxicities in multiple organ systems. This emphasizes the need for a multidisciplinary survivorship care model including cancer surveillance, management of chronic toxicities, and optimization of modifiable risk factors with long-term involvement of appropriate providers. CONCLUSION: Adequately caring for gastric cancer survivors requires a coordinated, multidisciplinary approach.

Molecular analysis of XPO1 inhibitor and gemcitabine-nab-paclitaxel combination in KPC pancreatic cancer mouse model.

BACKGROUND: The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin-bound (nab)-paclitaxel (GemPac) necessitating the need for a more effective treatment strategy for this refractory disease. Previously, we have demonstrated that nuclear exporter protein exportin 1 (XPO1) is a valid therapeutic target in PDAC, and the selective inhibitor of nuclear export selinexor (Sel) synergistically enhances the efficacy of GemPac in pancreatic cancer cells, spheroids and patient-derived tumours, and had promising activity in a phase I study. METHODS: Here, we investigated the impact of selinexor-gemcitabine-nab-paclitaxel (Sel-GemPac) combination on LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx1-Cre (KPC) mouse model utilising digital spatial profiling (DSP) and single nuclear RNA sequencing (snRNAseq). RESULTS: Sel-GemPac synergistically inhibited the growth of the KPC tumour-derived cell line. The Sel-GemPac combination reduced the 2D colony formation and 3D spheroid formation. In the KPC mouse model, at a sub-maximum tolerated dose (sub-MTD) , Sel-GemPac enhanced the survival of treated mice compared to controls (p < .05). Immunohistochemical analysis of residual KPC tumours showed re-organisation of tumour stromal architecture, suppression of proliferation and nuclear retention of tumour suppressors, such as Forkhead Box O3a (FOXO3a). DSP revealed the downregulation of tumour promoting genes such as chitinase-like protein 3 (CHIL3/CHI3L3/YM1) and multiple pathways including phosphatidylinositol 3'-kinase-Akt (PI3K-AKT) signalling. The snRNAseq demonstrated a significant loss of cellular clusters in the Sel-GemPac-treated mice tumours including the CD44+ stem cell population. CONCLUSION: Taken together, these results demonstrate that the Sel-GemPac treatment caused broad perturbation of PDAC-supporting signalling networks in the KPC mouse model. HIGHLIGHTS: The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin-bound (nab)-paclitaxel (GemPac). Exporter protein exportin 1 (XPO1) inhibitor selinexor (Sel) with GemPac synergistically inhibited the growth of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mouse derived cell line and enhanced the survival of mice. Digital spatial profiling shows that Sel-GemPac causes broad perturbation of PDAC-supporting signalling in the KPC model.

Implementing risk-based approaches to improve drinking water quality in small water supplies in the Nordic region - barriers and solutions.

Small water supplies face similar problems worldwide, regardless of ownership or management type. Non-compliance with water quality regulations is more frequent in small supplies than in large ones, as are waterborne disease outbreaks. The new European Union Drinking Water Directive requires risk-based approach (RBA) to secure water safety as is recommended in the World Health Organization's Guidelines for drinking water quality through 'water safety plans'. This is already in regulation in the Nordic countries, although less used in small supplies. In this research, we explore the challenges, barriers and possible solutions to implementing RBA and improving compliance in small supplies. This was achieved by conducting and analysing interviews with 53 stakeholders from all eight Nordic countries to produce recommendations for action by the different implicated actors. Our findings suggest the centrality of governmental policy, including support for continuous training, provision of simple RBA guidelines and increasing cooperation in the water sector. The Nordic experience reflects global challenges with small water supplies and the trend towards systematic preventive management epitomized in the framework for drinking water safety advocated by the World Health Organization since 2004.

Peptide-Functionalized Carbon Nanotube Chemiresistors: The Effect of Nanotube Density on Gas Sensing.

Biorecognition element (BRE)-based carbon nanotube (CNT) chemiresistors have tremendous potential to serve as highly sensitive, selective, and power-efficient volatile organic compound (VOC) sensors. While many research groups have studied BRE-functionalized CNTs in material science and device development, little attention has been paid to optimizing CNT density to improve chemiresistor performance. To probe the effect of CNT density on VOC detection, we present the chemiresistor-based sensing results from two peptide-based CNT devices counting more than 60 different individual measurements. We find that a lower CNT density shows a significantly higher noise level and device-to-device variation while exhibiting mildly better sensitivity. Further investigation with SEM images suggests that moderately high CNT density with a stable connection of the nanotube network is desirable to achieve the best signal-to-noise ratio. Our results show an essential design guideline for tuning the nanotube density to provide sensitive and stable chemiresistors.

Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.

KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we evaluated the combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We found that cancer cells resistant to KRASG12C inhibitor were sensitive to KPT9274-induced growth inhibition. Furthermore, KPT9274 synergized with sotorasib and adagrasib to inhibit the growth of KRASG12C-mutant cancer cells and reduce their clonogenic potential. Mechanistically, this combination suppressed cell growth signaling and downregulated cell-cycle markers. In a PDAC cell line-derived xenograft (CDX) model, the combination of a suboptimal dose of KPT9274 with sotorasib significantly reduced the tumor burden (P= 0.002). Similarly, potent antitumor efficacy was observed in an NSCLC CDX model, in which KPT9274, given as maintenance therapy, prevented tumor relapse following the discontinuation of sotorasib treatment (P= 0.0001). Moreover, the combination of KPT9274 and sotorasib enhances survival. In conclusion, this is the first study to demonstrate that KRASG12C inhibitors can synergize with the PAK4 inhibitor KPT9274 and combining KRASG12C inhibitors with KPT9274 can lead to remarkably enhanced antitumor activity and survival benefits, providing a novel combination therapy for patients with cancer who do not respond or develop resistance to KRASG12C inhibitor treatment.

Rapid and Simple Buffer Exchange Using Cation-Exchange Chromatography to Improve Point-of-Care Detection of Pharmacological Agents.

The current COVID-19 pandemic has highlighted the power, speed, and simplicity of point-of-care (POC) diagnostics. POC diagnostics are available for a wide range of targets, including both drugs of abuse as well as performance-enhancing drugs. For pharmacological monitoring, minimally invasive fluids such as urine and saliva are commonly sampled. However, false positives or negatives caused by interfering agents excreted in these matrices may confound results. For example, false positives have, in most cases, prevented the use of POC diagnostics for pharmacological agent detection; the consequence is that centralized labs are instead tasked to perform these screenings, resulting in significant delays between sampling and testing. Thus, a rapid, simple, and inexpensive methodology for sample purification is required for the POC to reach a field-deployable tool for the pharmacological human health and performance assessments. Buffer exchange is a simple, rapid approach to remove interfering agents, but has traditionally been difficult to perform on small pharmacological molecules. Therefore, in this communication, we use salbutamol, a performance-enhancing drug, as a case example to demonstrate the efficacy of ion-exchange chromatography as a technique to perform buffer exchange for charged pharmacological agents. This manuscript demonstrates the efficacy of this technique leveraging a commercial spin column to remove interfering agents found in simulant urines, such as proteins, creatinine, and urea, while retaining salbutamol. The utility and efficacy of the method was then confirmed in actual saliva samples. The eluent was then collected and run on the lateral flow assays (LFAs), improving the reported limit of detection by over 5× (new lower limit of detection of 10 ppb compared to reported 60 ppb by the manufacturer) while simultaneously removing noise due to background interfering agents.

Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers.

KRASG12C inhibitors have revolutionized the treatment landscape for cancer patients harboring the G12C mutant isoform of KRAS. With the recent FDA approval of sotorasib and adagrasib, patients now have access to more promising treatment options. However, patients who receive these agents as a monotherapy usually develop drug resistance. Thus, there is a need to develop logical combination strategies that can delay or prevent the onset of resistance and simultaneously enhance the antitumor effectiveness of the treatment regimen. In this study, we aimed at pharmacologically targeting PAK4 by KPT9274 in combination with KRASG12C inhibitors in KRASG12C mutant pancreatic ductal adenocarcinoma (PDAC) and nonâ€"small cell lung cancer (NSCLC) preclinical models. PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We assessed the cytotoxicity of PAK4 and KRASG12C inhibitors combination in KRASG12C mutant 2D and 3D cellular models. KPT9274 synergized with both sotorasib and adagrasib in inhibiting the growth of KRASG12C mutant cancer cells. The combination was able to reduce the clonogenic potential of KRASG12C mutant PDAC cells. We also evaluated the antitumor activity of the combination in a KRASG12C mutant PDAC cell line-derived xenograft (CDX) model. Oral administration of a sub-optimal dose of KPT9274 in combination with sotorasib (at one-fourth of MTD) demonstrated significant inhibition of the tumor burden ( p = 0.002). Similarly, potent antitumor efficacy was observed in an NSCLC CDX model where KPT9274, acting as an adjuvant, prevented tumor relapse following the discontinuation of sotorasib treatment ( p = 0.0001). KPT9274 and sotorasib combination also resulted in enhanced survival. This is the first study showing that KRASG12C inhibitors can synergize with PAK4 inhibitor KPT9274 both in vitro and in vivo resulting in remarkably enhanced antitumor activity and survival outcomes. Significance: KRASG12C inhibitors demonstrate limited durable response in patients with KRASG12C mutations. In this study, combining PAK4 inhibitor KPT9274 with KRASG12C inhibitors has resulted in potent antitumor effects in preclinical cancer models of PDAC and NSCLC. Our results bring forward a novel combination therapy for cancer patients that do not respond or develop resistance to KRASG12C inhibitor treatment.

Detection of Asthma Inhaler Use via Terahertz Spectroscopy.

Inhaled medications are commonplace for administering bronchodilators, anticholinergics, and corticosteroids. While they have a defined legitimate use, they are also used in sporting events as performance-enhancing drugs. These performance enhancers can be acquired via both legal (i.e., at a pharmacy through over-the-counter medications or through a prescription) and illicit (i.e., black market and foreign pharmacies) means, thus making monitoring procurement impossible. While urine tests can detect these pharmacological agents hours after they have been inhaled, there is a significant lag time before they are observed in urine. Direct detection of these inhaled agents is complicated and requires a multiplexed approach due to the sheer number of inhaled pharmacological agents. Therefore, detection of propellants, which carry the drug into the lungs, provides a simpler path forward toward detection of broad pharmacological agents. In this paper, we demonstrate the first use of terahertz spectroscopy (THz) to detect inhaled medications in human subjects. Notably, we were able to detect and quantitate the propellant, HFA-134a, in breath up to 30 min after using an asthma inhaler, enabling the use of a point-of-care device to monitor exhaled breath for the presence of propellants. We also demonstrate via simulations that the same approach can be leveraged to detect and identify next-generation propellants, specifically HFA-152a. As a result, we provide evidence that a single point-of-care THz sensor can detect when individuals have used pressure-mediated dose inhalers (pMDIs) without further modification of the hardware.

Terahertz Spectroscopic Molecular Sensor for Rapid and Highly Specific Quantitative Analytical Gas Sensing.

Quantitative analytical gas sampling is of great importance in a range of environmental, safety, and scientific applications. In this article, we present the design, operation, and performance of a recently developed tabletop terahertz (THz) spectroscopic molecular sensor capable of rapid (minutes) and sensitive detection of polar gaseous analytes with near "absolute" specificity. A novel double-coil absorption cell design and an array of room-temperature sorbent-based preconcentration modules facilitate quantitative THz detection of light polar volatile compounds, which often challenge the capabilities of established gas sensing techniques. Acetone, ethanol, methanol, acetaldehyde, formaldehyde, and isoprene are detected at low parts-per-billion to high parts-per-trillion levels. This work evaluates performance-limiting factors for THz spectroscopy-based chemical identification: (1) spectral signal to noise and (2) preconcentrator efficiency.

Potentially curative resection of an abdominal wall metastasis from pancreatic adenocarcinoma: a case report.

Pancreatic cancer has a low survival rate even after ostensible complete resection, and treatment for recurrence is usually only palliative. However, rare solitary metastasis can occur and may be operable. In this report, we describe such a case and review the literature on metastasectomy for pancreatic adenocarcinoma. A 66-year-old female underwent Whipple procedure at our institution in 2014 for a pT3N0 pancreatic adenocarcinoma. A slowly growing umbilical mass was noted 6 years later with concomitant rise in her CA 19-9 levels. CT-guided biopsy of her abdominal wall mass confirmed a well-differentiated adenocarcinoma consistent with her primary pancreatic cancer. The patient underwent metastasectomy of the isolated abdominal wall mass, with negative margins. She received no further postoperative treatment. The patient remains disease and symptom-free over 18 months after resection of the metastasis. In highly selected cases of pancreatic adenocarcinoma, resection of solitary metastasis may be therapeutic.

Inhibitor of the Nuclear Transport Protein XPO1 Enhances the Anticancer Efficacy of KRAS G12C Inhibitors in Preclinical Models of KRAS G12C-Mutant Cancers.

The identification of molecules that can bind covalently to KRAS G12C and lock it in an inactive GDP-bound conformation has opened the door to targeting KRAS G12C selectively. These agents have shown promise in preclinical tumor models and clinical trials. FDA has recently granted approval to sotorasib for KRAS G12C mutated non-small cell lung cancer (NSCLC). However, patients receiving these agents as monotherapy generally develop drug resistance over time. This necessitates the development of multi-targeted approaches that can potentially sensitize tumors to KRAS inhibitors. We generated KRAS G12C inhibitor-resistant cell lines and observed that they exhibit sensitivity toward selinexor, a selective inhibitor of nuclear export protein exportin1 (XPO1), as a single agent. KRAS G12C inhibitors in combination with selinexor suppressed the proliferation of KRAS G12C mutant cancer cell lines in a synergistic manner. Moreover, combined treatment of selinexor with KRAS G12C inhibitors resulted in enhanced spheroid disintegration, reduction in the number and size of colonies formed by G12C mutant cancer cells. Mechanistically, the combination of selinexor with KRAS G12C inhibitors suppressed cell growth signaling and downregulated the expression of cell cycle markers, KRAS and NF-kB as well as increased nuclear accumulation of tumor suppressor protein Rb. In an in vivo KRAS G12C cell-derived xenograft model, oral administration of a combination of selinexor and sotorasib was demonstrated to reduce tumor burden and enhance survival. In conclusion, we have shown that the nuclear transport protein XPO1 inhibitor can enhance the anticancer activity of KRAS G12C inhibitors in preclinical cancer models. Significance: In this study, combining nuclear transport inhibitor selinexor with KRAS G12C inhibitors has resulted in potent antitumor effects in preclinical cancer models. This can be an effective combination therapy for cancer patients that do not respond or develop resistance to KRAS G12C inhibitor treatment.

Microfluidic Thermal Flowmeters for Drug Injection Monitoring.

This paper presents a microfluidic thermal flowmeter for monitoring injection pumps, which is essential to ensure proper patient treatment and reduce medication errors that can lead to severe injury or death. The standard gravimetric method for flow-rate monitoring requires a great deal of preparation and laboratory equipment and is impractical in clinics. Therefore, an alternative to the standard method suitable for remote, small-scale, and frequent infusion-pump monitoring is in great demand. Here, we propose a miniaturized thermal flowmeter consisting of a silicon substrate, a platinum heater layer on a silicon dioxide thin-membrane, and a polymer microchannel to provide accurate flow-rate measurement. The present thermal flowmeter is fabricated by the micromachining and micromolding process and exhibits sensitivity, linearity, and uncertainty of 0.722 mW/(g/h), 98.7%, and (2.36 ± 0.80)%, respectively, in the flow-rate range of 0.5-2.5 g/h when the flowmeter is operated in the constant temperature mode with the channel width of 0.5 mm. The measurement range of flow rate can be easily adjusted by changing the cross-sectional microchannel dimension. The present miniaturized thermal flowmeter shows a high potential for infusion-pump calibration in clinical settings.

Axillary Needle Biopsy in the Era of American College of Surgeons Oncology Group (ACOSOG) Z0011: Institutional Experience With a Largely Urban Minority Population and Review of the Literature.

BACKGROUND:  The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that sentinel lymph node biopsy (SLNB) alone is adequate for axillary control in patients with one to two positive axillary lymph nodes. However, axillary lymph node dissection (ALND) is required in patients with N1 disease diagnosed with a preoperative needle biopsy. In this report, we determined how many patients could potentially have had SNB alone based on finding only one to two positive nodes in the axilla. METHODS:  A retrospective review of patients with positive preoperative axillary needle biopsy undergoing ALND was used to identify rates of high volume axillary disease (>2 positive nodes). Wilcoxon's rank-sum and Fisher's exact test were used for statistical analysis. A review of the literature is included for comparison. RESULTS:  73% of 51 total patients with a positive needle biopsy had >2 positive nodes on axillary dissection. The high-volume axillary disease was significantly more likely with the presence of lymphovascular invasion and extranodal extension. CONCLUSIONS:  Patients with positive preoperative axillary needle biopsies have a significantly higher rate of high volume axillary disease. However, at least one-quarter of these patients will have <3 positive nodes and potentially could have been treated with SNB alone.

Electrochemical biosensor for rapid detection of fungal contamination in fuel systems.

There is an increased demand for real-time monitoring of biological and biochemical processes. While most sensor research focuses on physiological conditions, less has been done towards developing real-time biosensors that can operate in and survive exposure to extreme environments and harsh chemicals such as fuel. One interesting application is monitoring microbial load in fuel tanks to prevent both fuel spoilage and biocorrosion. We developed a comprehensive method to enable the first reagentless, real-time, microbial sensor platform that is also fuel resistant. We first identified an extracellular protein epitope conserved in fuel-degrading fungi then used this epitope to develop a suitable biorecognition element (BRE) through biopanning of a 7-mer phage displayed peptide library. After demonstrating the BRE's affinity to fungi using molecular and fluorescence assays, we incorporated the BRE into a reagentless, real-time electrochemical sensing platform based on a self-assembled monolayer of peptide BREs and redox reporters. Finally, we incorporated this real-time electrochemical sensing platform into a microfluidic device. We demonstrated detection of Yarrowia lipolytica as low as 1 × 104 CFU/mL in a bath cell, and demonstrate a microfluidic cell that functions even after exposure to jet fuel. In summary, this work describes development of a fuel-resistant biosensor for monitoring microbial growth in extreme environments.

Laser-Fabricated 2D Molybdenum Disulfide Electronic Sensor Arrays for Rapid, Low-Cost, Ultrasensitive Detection of Influenza A and SARS-Cov-2.

Multiplex electronic antigen sensors for detection of SARS-Cov-2 spike glycoproteins and hemagglutinin from influenza A are fabricated using scalable processes for straightforward transition to economical mass-production. The sensors utilize the sensitivity and surface chemistry of a 2D MoS2 transducer for attachment of antibody fragments in a conformation favorable for antigen binding with no need for additional linker molecules. To make the devices, ultra-thin layers (3 nm) of amorphous MoS2 are sputtered over pre-patterned metal electrical contacts on a glass chip at room temperature. The amorphous MoS2 is then laser annealed to create an array of semiconducting 2H-MoS2 transducer regions between metal contacts. The semiconducting crystalline MoS2 region is functionalized with monoclonal antibody fragments complementary to either SARS-CoV-2 S1 spike protein or influenza A hemagglutinin. Quartz crystal microbalance experiments indicate strong binding and maintenance of antigen avidity for antibody fragments bound to MoS2. Electrical resistance measurements of sensors exposed to antigen concentrations ranging from 2-20 000 pg mL-1 reveal selective responses. Sensor architecture is adjusted to produce an array of sensors on a single chip suited for detection of analyte concentrations spanning six orders of magnitude from pg mL-1 to µg mL-1.

Biomarkers and Detection Platforms for Human Health and Performance Monitoring: A Review.

Human health and performance monitoring (HHPM) is imperative to provide information necessary for protecting, sustaining, evaluating, and improving personnel in various occupational sectors, such as industry, academy, sports, recreation, and military. While various commercially wearable sensors are on the market with their capability of "quantitative assessments" on human health, physical, and psychological states, their sensing is mostly based on physical traits, and thus lacks precision in HHPM. Minimally or noninvasive biomarkers detectable from the human body, such as body fluid (e.g., sweat, tear, urine, and interstitial fluid), exhaled breath, and skin surface, can provide abundant additional information to the HHPM. Detecting these biomarkers with novel or existing sensor technologies is emerging as critical human monitoring research. This review provides a broad perspective on the state of the art biosensor technologies for HHPM, including the list of biomarkers and their physiochemical/physical characteristics, fundamental sensing principles, and high-performance sensing transducers. Further, this paper expands to the additional scope on the key technical challenges in applying the current HHPM system to the real field.

Micromagnetic and morphological characterization of heteropolymer human ferritin cores.

The physical properties of in vitro iron-reconstituted and genetically engineered human heteropolymer ferritins were investigated. High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), electron energy-loss spectroscopy (EELS), and 57Fe Mössbauer spectroscopy were employed to ascertain (1) the microstructural, electronic, and micromagnetic properties of the nanosized iron cores, and (2) the effect of the H and L ferritin subunit ratios on these properties. Mössbauer spectroscopic signatures indicate that all iron within the core is in the high spin ferric state. Variable temperature Mössbauer spectroscopy for H-rich (H21/L3) and L-rich (H2/L22) ferritins reconstituted at 1000 57Fe/protein indicates superparamagnetic behavior with blocking temperatures of 19 K and 28 K, while HAADF-STEM measurements give average core diameters of (3.7 ± 0.6) nm and (5.9 ± 1.0) nm, respectively. Most significantly, H-rich proteins reveal elongated, dumbbell, and crescent-shaped cores, while L-rich proteins present spherical cores, pointing to a correlation between core shape and protein shell composition. Assuming an attempt time for spin reversal of τ 0 = 10-11 s, the Néel-Brown formula for spin-relaxation time predicts effective magnetic anisotropy energy densities of 6.83 × 104 J m-3 and 2.75 × 104 J m-3 for H-rich and L-rich proteins, respectively, due to differences in surface and shape contributions to magnetic anisotropy in the two heteropolymers. The observed differences in shape, size, and effective magnetic anisotropies of the derived biomineral cores are discussed in terms of the iron nucleation sites within the interior surface of the heteropolymer shells for H-rich and L-rich proteins. Overall, our results imply that site-directed nucleation and core growth within the protein cavity play a determinant role in the resulting core morphology. Our findings have relevance to iron biomineralization processes in nature and the growth of designer's magnetic nanoparticles within recombinant apoferritin nano-templates for nanotechnology.

A Dual Approach of an Oil-Membrane Composite and Boron-Doped Diamond Electrode to Mitigate Biofluid Interferences.

Electrochemical biosensors promise a simple method to measure analytes for both point-of-care diagnostics and continuous, wearable biomarker monitors. In a liquid environment, detecting the analyte of interest must compete with other solutes that impact the background current, such as redox-active molecules, conductivity changes in the biofluid, water electrolysis, and electrode fouling. Multiple methods exist to overcome a few of these challenges, but not a comprehensive solution. Presented here is a combined boron-doped diamond electrode and oil-membrane protection approach that broadly mitigates the impact of biofluid interferents without a biorecognition element. The oil-membrane blocks the majority of interferents in biofluids that are hydrophilic while permitting passage of important hydrophobic analytes such as hormones and drugs. The boron-doped diamond then suppresses water electrolysis current and maintains peak electrochemical performance due to the foulant-mitigation benefits of the oil-membrane protection. Results show up to a 365-fold reduction in detection limits using the boron-doped diamond electrode material alone compared with traditional gold in the buffer. Combining the boron-doped diamond material with the oil-membrane protection scheme maintained these detection limits while exposed to human serum for 18 h.

Oil-Membrane Protection of Electrochemical Sensors for Fouling- and pH-Insensitive Detection of Lipophilic Analytes.

To take full advantage of the reagent- and label-free sensing capabilities of electrochemical sensors, a frequent and remaining challenge is interference and degradation of the sensors due to uncontrolled pH or salinity in the sample solution or foulants from the sample solution. Here, we present an oil-membrane sensor protection technique that allows for the permeation of hydrophobic (lipophilic) analytes into a sealed sensor compartment containing ideal salinity and pH conditions while simultaneously blocking common hydrophilic interferents (proteins, acids, bases, etc.) In this paper, we validate the oil-membrane sensor protection technique by demonstrating continuous cortisol detection via electrochemical aptamer-based (EAB) sensors. The encapsulated EAB cortisol sensor exhibits a 5 min concentration-on rise time and maintains a measurement signal of at least 7 h even in the extreme condition of an acidic solution of pH 3.