Towards sustainable and humane dairy farming: A low-cost electrochemical sensor for on-site diagnosis of milk fever.

Milk fever is a metabolic disorder that predominantly affects dairy animals during the periparturient period and within four weeks of calving. Milk fever is primarily attributed to a decrease in the animal's serum Ca2+ levels. Clinical milk fever occurs when Ca2+ concentration drops below 1.5 mM (6 mg/dL). Without prompt intervention, clinical milk fever leads to noticeable physical symptoms and health complications including coma and fatality. Subclinical milk fever is characterized by Ca2+ levels between 1.5 and 2.12 mM (6-8.48 mg/dL). Approximately 50% of multiparous dairy cows suffer from subclinical milk fever during the transition to lactation. The economic impact of milk fever, both direct and indirect, is substantial, posing challenges for farmers. To address this issue, we developed a low-cost electrochemical sensor that can measure bovine serum calcium levels on-site, providing an opportunity for early detection of subclinical and clinical milk fever and early intervention. This calcium sensor is a scalable solid contact ion sensing platform that incorporates a polymeric calcium-selective membrane and ionic liquid-based reference membrane into laser-induced graphene (LIG) electrodes. Our sensing platform demonstrates a sensitivity close to the theoretical Nernstian value (29.6 mV/dec) with a limit of detection of 15.6 µM and selectivity against the species in bovine serum. Moreover, our sensor can detect Ca2+ in bovine serum with 91% recovery.

LiFT (a Lithium Fiber-Based Test): An At-Home Companion Diagnostics for a Safer Lithium Therapy in Bipolar Disorder.

This work presents LiFT (a lithium fiber-based test), a low-cost electrochemical sensor that can measure lithium in human saliva and urine with FDA-required accuracy. Lithium is used for the treatment of bipolar disorder, and has a narrow therapeutic window. Close monitoring of lithium concentration in biofluids and adjustment of drug dosage can minimize the devastating side effects. LiFT is an inexpensive, yet accurate and simple-to-operate lithium sensor for frequent at-home testing for early identification of lithium toxicity. The low cost and high accuracy of LiFT are enabled through an innovative design and the use of ubiquitous materials such as yarn and carbon black for fabrication. LiFT measures Li+ through potentiometric recognition using a lithium selective sensing membrane that is deposited on the ink-coated yarn. A detection limit of 0.97 µM is obtained with a sensitivity of 59.07±1.25 mV/decade for the Li+ sensor in deionized water. Moreover, the sodium correction extended LiFT's linear range in urine and saliva to 0.5 mM. The LiFT platform sends the test results to the patient's smartphone, which subsequently can be shared with the patient's healthcare provider to expedite diagnosis and prevention of acute lithium toxicity.

SPOOC (Sensor for Periodic Observation of Choline): An Integrated Lab-on-a-Spoon Platform for At-Home Quantification of Choline in Infant Formula.

Choline is an essential micronutrient for infants' brain development and health. To ensure that infants receive the needed daily dose of choline, the U.S. Food and Drug Administration (FDA) has set requirements for choline levels in commercialized infant formulas. Unfortunately, not all families can access well-regulated formulas, leading to potential inadequacies in choline intake. Economic constraints or difficulties in obtaining formulas, exacerbated by situations like COVID-19, prompt families to stretch formulas. Accurate measurement of choline in infant formulas becomes imperative to guarantee that infants receive the necessary nutritional support. Yet, accessible tools for this purpose are lacking. An innovative integrated sensor for the periodic observation of choline (SPOOC) designed for at-home quantification of choline in infants' formulas and milk powders is reported. This system is composed of a choline potentiometric sensor and ionic-liquid reference electrode developed on laser-induced graphene (LIG) and integrated into a spoon-like device. SPOOC includes a micro-potentiometer that conducts the measurements and transmits results wirelessly to parents' mobile devices. SPOOC demonstrated rapid and accurate assessment of choline levels directly in pre-consuming infant formulas without any sample treatment. This work empowers parents with a user-friendly tool for choline monitoring promoting informed nutritional decision-making in the care of infants.

Toward Personalized Treatment of Depression: An Affordable Citalopram Test based on a Solid-Contact Potentiometric Electrode for at-Home Monitoring of the Antidepressant Dosage.

Citalopram (CTLP) is one of the most common antidepressants prescribed worldwide. It has a narrow therapeutic window and can cause severe toxicity and mortality if the dosage exceeds the safe level. Reports indicated that at-home monitoring of citalopram dosage considerably benefits the patients, yet there are no devices capable of such measurement of citalopram in biofluids. This work presents an affordable citalopram test for at-home and point-of-care monitoring of citalopram levels in urine, ensuring a safe and effective drug compliance. Our platform consists of a citalopram-selective yarn-based electrode (CTLP-SYE) that uses polymeric sensing membranes to provide valuable information about drug concentration in urine. CTLP-SYE is noninvasive and has a response time of fewer than 10 s. The fabricated electrode showed near-Nernstian behavior with a 52.3 mV/decade slope in citalopram hydrobromide solutions ranging from 0.5 µM to 1.0 mM, with a detection limit of 0.2 µM. Results also indicated that neither interfering ions nor pH affects electrode performance. We showed that CTLP-SYE could accurately and reproducibly measure citalopram in human urine (RSD 2.0 to 3.2%, error <12%) at clinically relevant concentrations. This work paves the way for the personalized treatment of depression and accessible companion diagnostics to improve treatment efficacy and safety.

FAST (Flexible Acetylcholine Sensing Thread): Real-Time Detection of Acetylcholine with a Flexible Solid-Contact Potentiometric Sensor.

Acetylcholine (ACh) is involved in memory and learning and has implications in neurodegenerative diseases; it is therefore important to study the dynamics of ACh in the brain. This work creates a flexible solid-contact potentiometric sensor for in vitro and in vivo recording of ACh in the brain and tissue homogenate. We fabricate this sensor using a 250 µm diameter cotton yarn coated with a flexible conductive ink and an ACh sensing membrane that contains a calix[4]arene ionophore. The exposed ion-to-electron transducer was sealed with a 2.5 µm thick Parylene C coating to maintain the flexibility of the sensor. The resulting diameter of the flexible ACh sensing thread (FAST) was 400 µm. The FAST showed a linear response range from 1.0 µM to 10.0 mM in deionized water, with a near-Nernstian slope of 56.11 mV/decade and a limit of detection of 2.6 µM. In artificial cerebrospinal fluid, the limit of detection increased to 20 µM due to the background signal of ionic content of the cerebrospinal fluid. The FAST showed a signal stability of 226 µV/h over 24 h. We show that FAST can measure ACh dynamics in sheep brain tissue and sheep brain homogenate after ACh spiking. FAST is the first flexible electrochemical sensor for monitoring ACh dynamics in the brain.

Impedimetric Sensing: An Emerging Tool for Combating the COVID-19 Pandemic.

The COVID-19 pandemic revealed a pressing need for the development of sensitive and low-cost point-of-care sensors for disease diagnosis. The current standard of care for COVID-19 is quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). This method is sensitive, but takes time, effort, and requires specialized equipment and reagents to be performed correctly. This make it unsuitable for widespread, rapid testing and causes poor individual and policy decision-making. Rapid antigen tests (RATs) are a widely used alternative that provide results quickly but have low sensitivity and are prone to false negatives, particularly in cases with lower viral burden. Electrochemical sensors have shown much promise in filling this technology gap, and impedance spectroscopy specifically has exciting potential in rapid screening of COVID-19. Due to the data-rich nature of impedance measurements performed at different frequencies, this method lends itself to machine-leaning (ML) algorithms for further data processing. This review summarizes the current state of impedance spectroscopy-based point-of-care sensors for the detection of the SARS-CoV-2 virus. This article also suggests future directions to address the technology's current limitations to move forward in this current pandemic and prepare for future outbreaks.

Home-Based Electrochemical Rapid Sensor (HERS): A Diagnostic Tool for Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most frequently occurring vaginal infection worldwide, yet it remains significantly underdiagnosed as a majority of patients are asymptomatic. Untreated BV poses a serious threat as it increases one's risk of STI acquisition, pregnancy complications, and infertility. We aim to minimize these risks by creating a low-cost disposable sensor for at-home BV diagnosis. A clinical diagnosis of BV is most commonly made according to the Amsel criteria. In this method, a fish-like odor, caused by increased levels of trimethylamine (TMA) in vaginal fluid, is used as a key diagnostic. This paper outlines the development of a Home-Based Electrochemical Rapid Sensor (HERS), capable of detecting TMA in simulated vaginal fluid (sVF). Instead of odor-based detection of volatilized TMA, we identify TMA in trimethylammonium form by utilizing HERS and a potentiometric readout. We fabricated the ion selective electrode using a carbon-black-coated cotton string and a TMA-selective membrane consisting of calix[4]arene and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. When paired with a standard reference electrode, our device was able to quantify TMA concentration in deionized (DI) water, as well as sVF samples at multiple pH levels with a clinically relevant limit of detection (8.66 µM, and theoretically expected Nernstian slope of 55.14 mV/decade).

Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers.

The burden of cancer continues to increase in society and negatively impacts the lives of numerous patients. Due to the high cost of current treatment strategies, there is a crucial unmet need to develop inexpensive preclinical platforms to accelerate the process of anti-cancer drug discovery to improve outcomes in cancer patients, most especially in female patients. Many current methods employ expensive animal models which not only present ethical concerns but also do not often accurately predict human physiology and the outcomes of anti-cancer drug responsiveness. Conventional treatment approaches for cancer generally include systemic therapy after a surgical procedure. Although this treatment technique is effective, the outcome is not always positive due to various complex factors such as intratumor heterogeneity and confounding factors within the tumor microenvironment (TME). Patients who develop metastatic disease still have poor prognosis. To that end, recent efforts have attempted to use 3D microengineered platforms to enhance the predictive power and efficacy of anti-cancer drug screening, ultimately to develop personalized therapies. Fascinating features of microengineered assays, such as microfluidics, have led to the advancement in the development of the tumor-on-chip technology platforms, which have shown tremendous potential for meaningful and physiologically relevant anti-cancer drug discovery and screening. Three dimensional microscale models provide unprecedented ability to unveil the biological complexities of cancer and shed light into the mechanism of anti-cancer drug resistance in a timely and resource efficient manner. In this review, we discuss recent advances in the development of microengineered tumor models for anti-cancer drug discovery and screening in female-related cancers. We specifically focus on female-related cancers to draw attention to the various approaches being taken to improve the survival rate of women diagnosed with cancers caused by sex disparities. We also briefly discuss other cancer types like colon adenocarcinomas and glioblastoma due to their high rate of occurrence in females, as well as the high likelihood of sex-biased mutations which complicate current treatment strategies for women. We highlight recent advances in the development of 3D microscale platforms including 3D tumor spheroids, microfluidic platforms as well as bioprinted models, and discuss how they have been utilized to address major challenges in the process of drug discovery, such as chemoresistance, intratumor heterogeneity, drug toxicity, etc. We also present the potential of these platform technologies for use in high-throughput drug screening approaches as a replacements of conventional assays. Within each section, we will provide our perspectives on advantages of the discussed platform technologies.