Comparison between conventional-dose and high-dose rocuronium use in general anesthesia for Cesarean section.

Background: There have been few studies comparing the effects of high- and low-dose rocuronium during cesarean section by directly measuring the concentration. Therefore, we conducted a study to examine the blood concentrations and clinical effects of both doses of rocuronium on mothers and fetuses. Methods: Eighteen patients were randomly assigned to two groups: C Group (0.6 mg/kg), and H Group, (1.0 mg/kg). The primary outcome was the comparison of umbilical vein rocuronium concentration between two groups. We assessed ease of intubation, time from rocuronium administration to some TOF points, post-anesthesia care unit (PACU) stay time, infused remifentanil dose, maternal rocuronium concentration, and Apgar scores. Results: No differences were observed in demographic data, ease of intubation, PACU stay time, 1 min Apgar scores, umbilical venous blood gas analysis between both groups. However, the time from rocuronium administration to T3 disappearance was shorter (p=0.009) and time to T1 and T2 reappearance were longer (p=0.003, p=0.009) in H group than that in C group. The administered remifentanil dose (p=0.042) was lower in the H group than in the C group. Rocuronium concentrations in the umbilical vein (p=0.004) and maternal vein before cord clamping (p=0.002) and at discharge (p<0.001) were also found to be higher in the H group than in the C group. Conclusions: We observed no prolongation of PACU stay, and no differences in Apgar scores in H group compared to C group. It suggests that 1.0 mg/kg of rocuronium has no negative effects on the fetus and mother in cesarean section.

Point-of-care human milk testing for maternal secretor status.

We present an electrochemical impedimetric-based biosensor for monitoring the variation in human milk oligosaccharide (HMO) composition. 2'-Fucosyllactose (2'FL) is an HMO associated with infant growth, cognitive development, and protection from infectious diarrhea, one of the major causes of infant death worldwide. Due to genetic variation, the milk of some women (non-secretors) contains no or very little 2'FL with potential implications for infant health and development. However, there is currently no technology to analyze the presence and concentration of HMOs in human milk at the point-of-care (POC). The lack of such technology represents a major impediment to advancing human milk research and improving maternal-infant health. Towards this unmet need, we report an impedimetric assay for HMOs with an α-1,2 linkage, the most abundant of which is 2'FL. The sensor uses a lectin for affinity, specifically Ulex europaeus agglutinin I (UEA), with electrochemical readout. In spiked studies, the sensor exhibited a high degree of linearity (R2 = 0.991) over 0.5 to 3.0 µM with a 330-nM detection limit. The sensor performance was clinically validated using banked human milk samples and correctly identified all secretor vs. non-secretor samples. Furthermore, despite the short 35-min assay time and low sample volume (25 µL), the assay was highly correlated with HPLC measurements. This bedside human milk testing assay enables POC, "sample-to-answer" quantitative HMO measurement, and will be a valuable tool to assess milk composition.

Fast Aptamer Generation Method Based on the Electrodynamic Microfluidic Channel and Evaluation of Aptamer Sensor Performance.

We demonstrate for the first time a fast aptamer generation method based on the screen-printed electrodynamic microfluidic channel device, where a specific aptamer selectively binds to a target protein on channel walls, following recovery and separation. A malaria protein as a model target, Plasmodium vivax lactate dehydrogenase (PvLDH) was covalently bonded to the conductive polymer layer formed on the carbon channel walls to react with the DNA library in a fluid. Then, the AC electric field was symmetrically applied on the channel walls for inducing the specific binding of the target protein to DNA library molecules. In this case, the partitioning efficiency between PvLDH and DNA library in the channel was attained to be 1.67 × 107 with the background of 5.56 × 10-6, which was confirmed using the quantitative polymerase chain reaction (qPCR). The selectively captured DNAs were isolated from the protein and separated in situ to give five aptamers with different sequences by one round cycle. The dissociation constants (Kd) of the selected aptamers were determined employing both electrochemical impedance spectroscopy (EIS) and the fluorescence method. The sensing performance of each aptamer was evaluated for the PvLDH detection after individual immobilization on the screen-printed array electrodes. The most sensitive aptamer revealed a detection limit of 7.8 ± 0.4 fM. The sensor reliability was evaluated by comparing it with other malaria sensors.

Mitigating Medication Tampering and Diversion via Real-Time Intravenous Opioid Quantification.

Opioid tampering and diversion pose a serious problem for hospital patients with potentially life-threatening consequences. The ongoing opioid crisis has resulted in medications used for pain management and anesthesia, such as fentanyl and morphine, being stolen, substituted with a different substance, and abused. This work aims to mitigate tampering and diversion through analytical verification of the administered drug before it enters the patient. We present an electrochemical-based sensor and miniaturized wireless potentiostat that enable real-time intravenous (IV) monitoring of opioids, specifically fentanyl and morphine. The proposed system is connected to an IV drip system during surgery or post-operation recovery. Measurement results of two opioids are presented, including calibration curves and data on the sensor performance concerning pH, temperature, interference, reproducibility, and long-term stability. Finally, we demonstrate real-time fluidic measurements connected to a flow cell to simulate IV administration and a blind study classified using a machine-learning algorithm. The system achieves limits of detection (LODs) of 1.26 µg/mL and 2.75 µg/mL for fentanyl and morphine, respectively, while operating with >1-month battery lifetime due to an optimized ultra-low power 36 µA sleep mode.

An Electrochemical CMOS Biosensor Array Using Phase-Only Modulation With 0.035% Phase Error And In-Pixel Averaging.

This paper presents a 16×20 CMOS biosensor array based on electrochemical impedance spectroscopy (EIS), a highly sensitive label-free technique for rapid disease detection at point-of-care. This high-density system implements a polar-mode detection with phase-only EIS measurement over a 5 kHz - 1 MHz frequency range. The design features predominantly digital readout circuitry, ensuring scalability with technology, along with a load-compensated transimpedance amplifier at the front, all within a 140×140 µm2; pixel. The architecture enables in-pixel digitization and accumulation, which increases the SNR by 10 dB for each 10× increase in readout time. Implemented in a 180 nm CMOS process, the 3×4 mm2 chip achieves state-of-the-art performance with an rms phase error of 0.035% at 100 kHz through a duty-cycle insensitive phase detector and one of the smallest per pixel areas with in-pixel quantization.

A non-invasive wearable stress patch for real-time cortisol monitoring using a pseudoknot-assisted aptamer.

Stress is part of everyone's life and is exacerbated by traumatic events such as pandemics, disasters, violence, lifestyle changes, and health disorders. Chronic stress has many detrimental health effects and can even be life-threatening. Long-term stress monitoring outside of a hospital is often accomplished by measuring heart rate variability. While easy to measure, this digital biomarker has low specificity, greatly limiting its utility. To address this shortcoming, we report a non-invasive, wearable biomolecular sensor to monitor cortisol levels in sweat. Cortisol is a neuroendocrine hormone that regulates homeostasis as part of the stress pathway. Cortisol is detected using an electrochemical sensor functionalized with a pseudoknot-assisted aptamer and a flexible microfluidic sweat sampling system. The skin-worn microfluidic sampler provides rapid sweat collection while separating old and new sweat. The conformation-switching aptamer provides high specificity towards cortisol while being regenerable, allowing it to monitor temporal changes continuously. The aptamer was engineered to add a pseudoknot, restricting it to only two states, thus minimizing the background signal and enabling high sensitivity. An electrochemical pH sensor allows pH-corrected amperometric measurements. Device operation was demonstrated invitro with a broad linear dynamic range (1 pM - 1 µM) covering the physiological range and a sub-picomolar (0.2 pM) limit of detection in sweat. Real-time, on-body measurements were collected from human subjects using an induced stress protocol, demonstrating in-situ signal regeneration and the ability to detect dynamic cortisol fluctuations continuously for up to 90 min. The reported device has the potential to improve prognosis and enable personalized treatments.

Electrochemical Carbamazepine Aptasensor for Therapeutic Drug Monitoring at the Point of Care.

Monitoring the anti-epileptic drug carbamazepine (CBZ) is crucial for proper dosing, optimizing a patient's clinical outcome, and managing their medication regimen. Due to its narrow therapeutic window and concentration-related toxicity, CBZ is prescribed and monitored in a highly personalized manner. We report an electrochemical conformation-changing aptasensor with two assay formats: a 30 min assay for routine monitoring and a 5 min assay for rapid emergency testing. To enable "sample-to-answer" testing, a de novo CBZ aptamer (K d < 12 nM) with conformational switching due to a G-quadruplex motif was labeled with methylene blue and immobilized on a gold electrode. The electrode fabrication and detection conditions were optimized using electrochemical techniques and visualized by atomic force microscopy (AFM). The aptasensor performance, including reproducibility, stability, and interference, was characterized using electrochemical impedance spectroscopy and voltammetry techniques. The aptasensor exhibited a wide dynamic range in buffer (10 nM to 100 µM) with limits of detection of 1.25 and 1.82 nM for the 5 and 30 min assays, respectively. The clinical applicability is demonstrated by detecting CBZ in finger prick blood samples (<50 µL). The proposed assays provide a promising method to enable point-of-care monitoring for timely personalized CBZ dosing.

Development of a Soluble KIT Electrochemical Aptasensor for Cancer Theranostics.

An electrochemical sensor based on a conformation-changing aptamer is reported to detect soluble KIT, a cancer biomarker, in human serum. The sensor was fabricated with a ferrocene-labeled aptamer (Kd < 5 nM) conjugated to a gold electrode. Quantitative KIT detection was achieved using electrochemical impedance spectroscopy (EIS) and square-wave voltammetry (SWV). EIS was used to optimize experimental parameters such as the aptamer-to-spacer ratio, aptamer immobilization time, pH, and KIT incubation time, and the sensor surface was characterized using voltammetry. The assay specificity was demonstrated using interfering species and exhibited high specificity toward the target protein. The aptasensor showed a wide dynamic range, 10 pg/mL-100 ng/mL in buffer, with a 1.15 pg/mL limit of detection. The sensor also has a linear response to KIT spiked in human serum and successfully detected KIT in cancer-cell-conditioned media. The proposed aptasensor has applications as a continuous or intermittent approach for cancer therapy monitoring and diagnostics (theranostics).

Cortisol Detection in Undiluted Human Serum Using a Sensitive Electrochemical Structure-Switching Aptamer over an Antifouling Nanocomposite Layer.

There is a strong and growing need to monitor stress biomarkers in vivo for real-time emotional and wellness assessment. Toward this, we report a reagent-free electrochemical aptasensor with a nanocomposite antifouling layer for sensitive and continuous detection of cortisol in human serum. A thiolated, methylene blue (MB)-tagged conformation-switching aptamer was immobilized over a gold nanowire (AuNW) nanocomposite to capture cortisol and generate a signal proportional to the cortisol concentration. The signal is recorded through differential pulse voltammetry (DPV) and chronoamperometry. The aptasensor exhibited a sensitive response with 0.51 and 0.68 nM detection limits in spiked buffer and undiluted serum samples, respectively. Interference from other structurally similar analogs, namely, epinephrine and cholic acid, was negligible (<10%). The developed nanocomposite-based aptasensor showed excellent stability in undiluted human serum, outperforming several other nanocomposite materials even after prolonged exposure. This work lays the foundation for new biosensor formats such as implantable and wearable sensors.

Separation detection of different circulating tumor cells in the blood using an electrochemical microfluidic channel modified with a lipid-bonded conducting polymer.

Different circulating tumor cells (CTCs) in blood were separated and detected through the decoration of anti-cancer drug on the target cells, along with chemical modification of the microfluidic channel walls using a lipid attached covalently to the conducting polymer. The working principle of the electrochemical microfluidic device was evaluated with experimental parameters affecting on the separation, in terms of mass and surface charge of target species, fluid flow rate, AC amplitude, and AC frequency. The separated CTCs were selectively detected via the oxidation of daunomycin adsorbed specifically at the cells using an electrochemical sensor installed at the channel end. The fluorescence microscopic examination also confirmed the separation of CTCs in the channel. To evaluate the reliability of the method, blood samples from 37 cancer patients were tested. The device was able to separate the CTCs with 92.0 ±â€¯0.5 % efficiency and 90.9% detection rate.

Development of a bifunctional nanobiosensor for screening and detection of chemokine ligand in colorectal cancer cell line.

Highly sensitive detection of chemokines in various biological matrices and its interaction with a natural receptor molecule has tremendous importance in cell signaling, medical diagnostics, and therapeutics. In this direction, we have designed the first bifunctional nanobiosensor for chemokine screening and detection in a single experimental setting. The sensor probe was fabricated by immobilizing CXCR2 on the gold nanoparticles (AuNPs) deposited 2,2':5',2''-terthiophene-3' (p-benzoic acid) (TBA) nanocomposite film. The interaction between CXCR2 and chemokines was studied using electrochemical impedance spectroscopy (EIS) and voltammetry. CXCL5 among three ligands showed the strongest affinity to CXCR2, which was further utilized to develop an amperometric CXCL5 biosensor. Analytical parameters, such as CXCR2 receptor concentration, temperature, pH, and incubation time were optimized to obtain the high sensitivity. A dynamic range for CXCL5 detection was obtained between 0.1 and 10ng/mL with the detection limit of 0.078 ± 0.004ng/mL (RSD < 4.7%). The proposed biosensor was successfully applied to detect CXCL5 in clinically relevant concentrations in human serum and colorectal cancer cells samples with high sensitivity and selectivity. Interference effect and the stability of the developed biosensor were also evaluated. Method verification was performed by comparing the results using commercially available ELISA kit for CXCL5 detection.

Magnetic force assisted electrochemical sensor for the detection of thrombin with aptamer-antibody sandwich formation.

A magnetic force assisted electrochemical aptamer-antibody sandwich assay (MESA) was developed for the detection of thrombin as a model protein in serum samples. The MESA using the formation of sandwich complexes on the electrochemical sensor probe for reaction and the removal of unbound bioconjugates from the sensor surface without washing are controlled by a magnetic field. Thrombin was determined by the cathodic currents of a toluidine blue O (TBO) attached with thrombin antibody modified magnetic nanoparticle (MNP) at the sensor surface. To detect thrombin in a serum sample, we applied a thrombin-specific aptamer as the capture molecule bound to the functionalized conducting polymer layer (poly-(2,2´:5´,5″-terthiophene-3´-p-benzoic acid) (pTBA)), and streptavidin and starch coated-MNP was conjugated with biotinylated thrombin antibodies (Ab) and TBO as the bioconjugate (MNP@Ab-TBO). The characterization of MNP@Ab-TBO and sensor probe was performed using voltammetry, impedance spectroscopy, XPS, and UV-VIS spectroscopy. The experimental conditions were optimized in terms of pH, binding time, removal time of unbound bioconjugates, and applied potential. The dynamic ranges of thrombin were from 1.0 to 500 nM with detection limit of 0.49 ( ±â€¯0.06) nM. The recovery test demonstrates the reliability of the proposed sensing system for a handheld device.

Sensitive NADH detection in a tumorigenic cell line using a nano-biosensor based on the organic complex formation.

A robust amperometric sensor for ß-nicotinamide adenine dinucleotide (NADH) detection was developed through the organic complex formation with ethylenediaminetetraacetic acid (EDTA) bonded on the polyethylenimine (PEI)/activated graphene oxide (AGO) layer. The EDTA immobilized sensor probe (GCE/AGO/PEI-EDTA) revealed a catalytic property towards NADH oxidation that allows for the highly sensitive electrochemical detection of NADH at a low oxidation potential. Surface characterization demonstrated that the negatively charged AGO acted as nanofillers in the positively charged PEI matrix through the charge interaction. The immobilization of EDTA on the polymer layer provided more surface area for NADH to interact with through the enhanced chemical interlocking between them. We observed the strong interaction between NADH and EDTA on the AGO/PEI layer using a quartz crystal microbalance (QCM), X-ray photoelectron spectroscopy (XPS), and the calculation of the minimized energy for complex formation. The dynamic range of NADH was determined to be between 0.05µM and 500µM with a detection limit (LD) of 20.0±1.1nM. The reliability of the developed sensor for biomedical applications was examined by detecting NADH in tumorigenic lung epithelial cells using the standard addition method.