Capacitive sensing of triglyceride film reactions: a proof-of-concept demonstration for sensing in simulated duodenal contents with gastrointestinal targeting capsule system.

Ingestible capsule systems continue to evolve to overcome drawbacks associated with traditional gastrointestinal (GI) diagnostic and therapeutic processes, such as limitations on which sections of the GI tract can be accessed or the inability to measure local biomarker concentrations. We report an integrated capsule sensing system, utilizing a hybrid packaging scheme coupled with triglyceride film-coated capacitive sensors, for measuring biochemical species present in the duodenum, such as pancreatic lipase and bile acids. The system uses microfabricated capacitive sensors interfaced with a Bluetooth low-energy (BLE)-microcontroller, allowing wireless connectivity to a mobile app. The triglyceride films insulate the sensor surface and react either with 0.01-1 mM lipase via hydrolysis or 0.07-7% w/v bile acids via emulsification in simulated fluids, leading to measurable changes in capacitance. Cross reactivity of the triglyceride films is evaluated in both phosphate buffered saline (PBS) as well as pancreatic trypsin solutions. The film morphology is observed after exposure to each stimulus to better understand how these changes alter the sensor capacitance. The capsule utilizes a 3D-printed package coated with polymers that remain intact in acid solution (mimicking gastric conditions), then dissolve at a duodenum-mimicking neutral pH for triggered opening of the sensing chamber from which we can subsequently detect the presence of pancreatic lipase. This device strategy represents a significant step towards using embedded packaging and triglyceride-based materials to target specific regions of the GI tract and sensing biochemical contents for evaluating gastrointestinal health.

A Study on Magnetic Removal of Hexavalent Chromium from Aqueous Solutions Using Magnetite/Zeolite-X Composite Particles as Adsorbing Material.

Toxic and heavy metals are considered harmful derivatives of industrial activities; they are not biodegradable and their accumulation in living organisms can become lethal. Among other heavy and toxic metals, chromium is considered hazardous, especially in the hexavalent (Cr6+) form. Numerous established studies show that exposure to Cr6+ via drinking water leads to elevated chromium levels in tissues, which may result in various forms of cancer. The purpose of this research is to synthesize magnetite/zeolite-X composite particles for the adsorption and magnetic removal of Cr6+ ions from aqueous solutions. Synthesis and characterization of such composite nanomaterials, along with an initial experimental evaluation of Cr6+ removal from water-based solution, are presented. Results show that zeolite-X is a very promising zeolite form, that when bound to magnetic nanoparticles can be used to trap and magnetically remove toxic ions from aqueous solutions.

Ingestible Sensors and Sensing Systems for Minimally Invasive Diagnosis and Monitoring: The Next Frontier in Minimally Invasive Screening.

Ingestible electronic systems that are capable of embedded sensing, particularly within the gastrointestinal (GI) tract and its accessory organs, have the potential to screen for diseases that are difficult if not impossible to detect at an early stage using other means. Furthermore, these devices have the potential to (1) reduce labor and facility costs for a variety of procedures, (2) promote research for discovering new biomarker targets for associated pathologies, (3) promote the development of autonomous or semiautonomous diagnostic aids for consumers, and (4) provide a foundation for epithelially targeted therapeutic interventions. These technological advances have the potential to make disease surveillance and treatment far more effective for a variety of conditions, allowing patients to lead longer and more productive lives. This review will examine the conventional techniques, as well as ingestible sensors and sensing systems that are currently under development for use in disease screening and diagnosis for GI disorders. Design considerations, fabrication, and applications will be discussed.

The Binding Effect of Proteins on Medications and Its Impact on Electrochemical Sensing: Antipsychotic Clozapine as a Case Study.

Clozapine (CLZ), a dibenzodiazepine, is demonstrated as the optimal antipsychotic for patients suffering from treatment-resistant schizophrenia. Like many other drugs, understanding the concentration of CLZ in a patient's blood is critical for managing the patients' symptoms, side effects, and overall treatment efficacy. To that end, various electrochemical techniques have been adapted due to their capabilities in concentration-dependent sensing. An open question associated with electrochemical CLZ monitoring is whether drug-protein complexes (i.e., CLZ bound to native blood proteins, such as serum albumin (SA) or alpha-1 acid-glycoprotein (AAG)) contribute to electrochemical redox signals. Here, we investigate CLZ-sensing performance using fundamental electrochemical methods with respect to the impact of protein binding. Specifically, we test the activity of bound and free fractions of a mixture of CLZ and either bovine SA or human AAG. Results suggest that bound complexes do not significantly contribute to the electrochemical signal for mixtures of CLZ with AAG or SA. Moreover, the fraction of CLZ bound to protein is relatively constant at 31% (AAG) and 73% (SA) in isolation with varying concentrations of CLZ. Thus, electrochemical sensing can enable direct monitoring of only the unbound CLZ, previously only accessible via equilibrium dialysis. The methods utilized in this work offer potential as a blueprint in developing electrochemical sensors for application to other redox-active medications with high protein binding more generally. This demonstrates that electrochemical sensing can be a new tool in accessing information not easily available previously, useful toward optimizing treatment regimens.

Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine.

Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1-3µM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine. Our electrochemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correlated to centralized laboratory analysis for the readily detected uric acid and for the clozapine which is present at 100-fold lower concentration. The benefits of our electrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement (≈20min) without serum pretreatment; (ii) appropriate selectivity and sensitivity (limit of detection 0.7µM); (iii) reusability of an electrode over several weeks; and (iv) rapid reliability testing to detect common error-causing problems. This simple and rapid electrochemical approach for serum clozapine measurements should provide clinicians with the timely point-of-care information required to adjust dosages and personalize the management of schizophrenia.

A stochastic and integrative model of breathing.

Human breathing patterns contain both temporal scaling characteristics, and an innately random component. A stochastic and mathematically integrative model of breathing (SIMB) that simulated the natural random and fractal-like pattern of human breathing was designed using breath-to-breath interval (BBI) data recorded from 14 healthy subjects. Respiratory system memory was estimated with autocorrelation, and a probability density function (PDF) was created by fitting a polynomial curve to each normalized BBI sequence histogram. SIMB sequences were produced by randomly selecting BBI values using a PDF and imparting memory with an autocorrelation-based function. Temporal scaling was quantified with detrended fluctuation analysis. The SIMB BBI sequences were embedded with significant fractal scaling (p<0.001) that was similar to the human data (p>0.05), and increasing SIMB output length did not alter the temporal scaling (p>0.05). This study demonstrated a new computational model that can reproduce the inherent stochastic and time scaling characteristics of human breathing.

Redox Probing for Chemical Information of Oxidative Stress.

Oxidative stress is implicated in many diseases yet no simple, rapid, and robust measurement is available at the point-of-care to assist clinicians in detecting oxidative stress. Here, we report results from a discovery-based research approach in which a redox mediator is used to probe serum samples for chemical information relevant to oxidative stress. Specifically, we use an iridium salt (K2IrCl6) to probe serum for reducing activities that can transfer electrons to iridium and thus generate detectable optical and electrochemical signals. We show that this Ir-reducing assay can detect various biological reductants and is especially sensitive to glutathione (GSH) compared to alternative assays. We performed an initial clinical evaluation using serum from 10 people diagnosed with schizophrenia, a mental health disorder that is increasingly linked to oxidative stress. The measured Ir-reducing capacity was able to discriminate people with schizophrenia from healthy controls (p < 0.005), and correlations were observed between Ir-reducing capacity and independent measures of symptom severity.