Continuous Biopotential Monitoring via Carbon Nanotubes Paper Composites (CPC) for Sustainable Health Analysis.

Skin-based wearable devices have gained significant attention due to advancements in soft materials and thin-film technologies. Nevertheless, traditional wearable electronics often entail expensive and intricate manufacturing processes and rely on metal-based substrates that are susceptible to corrosion and lack flexibility. In response to these challenges, this paper has emerged with an alternative substrate for wearable electrodes due to its cost-effectiveness and scalability in manufacturing. Paper-based electrodes offer an attractive solution with their inherent properties of high breathability, flexibility, biocompatibility, and tunability. In this study, we introduce carbon nanotube-based paper composites (CPC) electrodes designed for the continuous detection of biopotential signals, such as electrooculography (EOG), electrocardiogram (ECG), and electroencephalogram (EEG). To prevent direct skin contact with carbon nanotubes, we apply various packaging materials, including polydimethylsiloxane (PDMS), Eco-flex, polyimide (PI), and polyurethane (PU). We conduct a comparative analysis of their signal-to-noise ratios in comparison to conventional gel electrodes. Our system demonstrates real-time biopotential monitoring for continuous health tracking, utilizing CPC in conjunction with a portable data acquisition system. The collected data are analyzed to provide accurate heart rates, respiratory rates, and heart rate variability metrics. Additionally, we explore the feasibility using CPC for sleep monitoring by collecting EEG signals.

Highly Sensitive Immunoresistive Sensor for Point-Of-Care Screening for COVID-19.

Current point-of-care (POC) screening of Coronavirus disease 2019 (COVID-19) requires further improvements to achieve highly sensitive, rapid, and inexpensive detection. Here we describe an immunoresistive sensor on a polyethylene terephthalate (PET) film for simple, inexpensive, and highly sensitive COVID-19 screening. The sensor is composed of single-walled carbon nanotubes (SWCNTs) functionalized with monoclonal antibodies that bind to the spike protein of SARS-CoV-2. Silver electrodes are silkscreen-printed on SWCNTs to reduce contact resistance. We determine the SARS-CoV-2 status via the resistance ratio of control- and SARS-CoV-2 sensor electrodes. A combined measurement of two adjacent sensors enhances the sensitivity and specificity of the detection protocol. The lower limit of detection (LLD) of the SWCNT assay is 350 genome equivalents/mL. The developed SWCNT sensor shows 100% sensitivity and 90% specificity in clinical sample testing. Further, our device adds benefits of a small form factor, simple operation, low power requirement, and low assay cost. This highly sensitive film sensor will facilitate rapid COVID-19 screening and expedite the development of POC screening platforms.

Simultaneous multiparameter whole blood hemostasis assessment using a carbon nanotube-paper composite capacitance sensor.

Rapid and accurate clinical assessment of hemostasis is essential for managing patients who undergo invasive procedures, experience hemorrhages, or receive antithrombotic therapies. Hemostasis encompasses an ensemble of interactions between the cellular and non-cellular blood components, but current devices assess only partial aspects of this complex process. In this work, we describe the development of a new approach to simultaneously evaluate coagulation function, platelet count or function, and hematocrit using a carbon nanotube-paper composite (CPC) capacitance sensor. CPC capacitance response to blood clotting at 1.3 MHz provided three sensing parameters with distinctive sensitivities towards multiple clotting elements. Whole blood-based hemostasis assessments were conducted to demonstrate the potential utility of the developed sensor for various hemostatic conditions, including pathological conditions, such as hemophilia and thrombocytopenia. Results showed good agreements when compared to a conventional thromboelastography. Overall, the presented CPC capacitance sensor is a promising new biomedical device for convenient non-contact whole-blood based comprehensive hemostasis evaluation.

Osteogenic Capacity of the Prefabricated Periosteofascial Flap using Vascular Induction with Skeletonized Pedicle Transfer in Rabbit Calvarium.

The study investigated the osteogenic capacity of a prefabricated periosteal flap created using only skeletonized pedicle transfer without fascia or muscle for vascular induction in rabbit calvarium. A critical-sized bone defect was made in the parietal bone centered on the sagittal suture, and the demineralized bone matrix was implanted. The periosteofascia over the defect was used as a form of prefabricated periosteofascial flap (PPF group, N=10), conventional periosteofascial flap (CPF group, N=10), and nonvascularized free periosteofascial graft (FPG group, N=6). The prefabricated flap was designed via vascular induction by transferring the central artery and vein of the right auricle onto the periosteofascia for 4 weeks prior to flap elevation. A quantitative comparison of volume restoration and radiodensity in the bone defect and a histological study were performed after 6 weeks of covering the bone defect with periosteofascia. The volume restoration of the bone defect covered with the PPF (43.4%) was not different from that of the CPF (46.2%), but significantly increased compared with that of the FPG (24.6%). The radiodensity of the bone defect covered with the PPF (-186.3 HU) was not different from that of the CPF (-153.6 HU), but significantly increased compared with that of the FPG (-329.8 HU). The results were based on adequate vascular development of the periosteum and were closely related to the osteogenic changes in the implanted demineralized bone matrix (DBM). In conclusion, even in the PPF created by transferring only skeletonized vascular pedicles, the osteogenic capacity of the periosteofascial flap is well maintained.

Carbon nanotube-based thin-film resistive sensor for point-of-care screening of tuberculosis.

For point-of-care diagnosis of tuberculosis (TB), current TB diagnostic approaches need to be further improved for achieving an accurate diagnosis that is rapid and low-cost. This paper presents an immuno-resistive sensor on a plastic film for inexpensive, simple TB screening. The sensor is composed of single-walled carbon nanotubes (SWCNTs) functionalized with polyclonal antibodies raised against the MPT64 surface antigen from Mycobacterium tuberculosis (MTB). The target analyte of either MTB or MPT64 is spiked in tongue swab and sputum samples. Under optimized conditions, targets are directly detected from tongue swab samples by resistive measurement. Target analytes spiked into human sputa are enriched with a magnetic bead protocol followed by resistive detection. This highly sensitive film sensor will facilitate rapid TB screening with the added benefits of a small form factor, simple operation, low power requirement, and low cost.

Nanoink bridge-induced capillary pen printing for chemical sensors.

Single-walled carbon nanotubes (SWCNTs) are used as a key component for chemical sensors. For miniature scale design, a continuous printing method is preferred for electrical conductance without damaging the substrate. In this paper, a non-contact capillary pen printing method is presented by the formation of a nanoink bridge between the nib of a capillary pen and a polyethylene terephthalate film. A critical parameter for stable printing is the advancing contact angle at the bridge meniscus, which is a function of substrate temperature and printing speed. The printed pattern including dots, lines, and films of SWCNTs are characterized by morphology, optical transparency, and electrical properties. Gas and pH sensors fabricated using the non-contact printing method are demonstrated as applications.

Nanostructured Tip-Shaped Biosensors: Application of Six Sigma Approach for Enhanced Manufacturing.

Nanostructured tip-shaped biosensors have drawn attention for biomolecule detection as they are promising for highly sensitive and specific detection of a target analyte. Using a nanostructured tip, the sensitivity is increased to identify individual molecules because of the high aspect ratio structure. Various detection methods, such as electrochemistry, fluorescence microcopy, and Raman spectroscopy, have been attempted to enhance the sensitivity and the specificity. Due to the confined path of electrons, electrochemical measurement using a nanotip enables the detection of single molecules. When an electric field is combined with capillary action and fluid flow, target molecules can be effectively concentrated onto a nanotip surface for detection. To enhance the concentration efficacy, a dendritic nanotip rather than a single tip could be used to detect target analytes, such as nanoparticles, cells, and DNA. However, reproducible fabrication with relation to specific detection remains a challenge due to the instability of a manufacturing method, resulting in inconsistent shape. In this paper, nanostructured biosensors are reviewed with our experimental results using dendritic nanotips for sequence specific detection of DNA. By the aid of the Six Sigma approach, the fabrication yield of dendritic nanotips increases from 20.0% to 86.6%. Using the nanotips, DNA is concentrated and detected in a sequence specific way with the detection limit equivalent to 1000 CFU/mL. The pros and cons of a nanotip biosensor are evaluated in conjunction with future prospects.

Dielectrophoretic characterization of antibiotic-treated Mycobacterium tuberculosis complex cells.

Multi-drug resistant tuberculosis (MDR-TB) has become a serious concern for proper treatment of patients. As a phenotypic method, dielectrophoresis can be useful but is yet to be attempted to evaluate Mycobacterium tuberculosis complex cells. This paper investigates the dielectrophoretic behavior of Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) cells that are treated with heat or antibiotics rifampin (RIF) or isoniazid (INH). The experimental parameters are designed on the basis of our sensitivity analysis. The medium conductivity (σ(m)) and the frequency (f) for a crossover frequency (f(xo1)) test are decided to detect the change of σ(m)-f(xo1) in conjunction with the drug mechanism. Statistical modeling is conducted to estimate the distributions of viable and nonviable cells from the discrete measurement of f (xo1). Finally, the parameters of the electrophysiology of BCG cells, C(envelope) and σ(cyto), are extracted through a sampling algorithm. This is the first evaluation of the dielectrophoresis (DEP) approach as a means to assess the effects of antimicrobial drugs on M. tuberculosis complex cells.

Amperometric immunosensor for rapid detection of Mycobacterium tuberculosis.

Tuberculosis (TB) has been a major public health problem, which can be better controlled by using accurate and rapid diagnosis in low-resource settings. A simple, portable, and sensitive detection method is required for point-of-care (POC) settings. This paper studies an amperometric biosensor using a microtip immunoassay for a rapid and low cost detection of Mycobacterium Tuberculosis (MTB) in sputum. MTB in sputum is specifically captured on the functionalized microtip surface and detected by electric current. According to the numerical study, the current signal on microtip surface is linearly changed with increasing immersion depth. Using a reference microtip, the immersion depth is compensated for a sensing microtip. On the microtip surface, target bacteria are concentrated and organized by a coffee ring effect, which amplifies the electric current. To enhance the signal-to-noise ratio, both the sample processing- and rinsing steps are presented with use of deionized water as a medium for the amperometric measurement. When applied to cultured MTB cells spiked into human sputum, the detection limit was 100 CFU/mL, comparable to a more labor-intensive fluorescence detection method reported previously.

A novel technique for robot assisted latissimus dorsi flap harvest.

BACKGROUND: A robotic surgery technique of harvesting the latissimus dorsi muscle flap has technical advantages over endoscopic harvest and cosmetic advantages over the open technique. The authors introduce a new transaxillary gasless technique using an articulated long retractor for robot assisted latissimus dorsi flap harvest. METHODS: Twelve robot assisted latissimus dorsi muscle flaps were harvested: 3 cases of delayed reconstruction following tissue expander insertion or breast conserving surgery; 4 cases of immediate reconstruction following nipple-sparing mastectomy; and 5 cases of chest wall deformity correction in patients with Poland syndrome. A specially designed articulated long retractor was used to maintain adequate working space and enable latissimus dorsi muscle dissection without gas insufflation. RESULTS: Twelve muscle flaps were successfully harvested in 12 patients without converting to an open technique. The mean docking time was 54.6 min, and the mean operative time and robotic time were 400.4 min and 85.8 min, respectively. There were no donor site complications or flap problems. Average follow-up was 15.7 months. All patients were satisfied with their esthetic results, especially the absence of visible scars. CONCLUSION: The novel robot assisted latissimus dorsi harvest technique is a safe alternative to the conventional method.

Immunofluorescence microtip sensor for point-of-care tuberculosis (TB) diagnosis.

A immunofluorescence microtip sensor was developed for specific detection of Mycobacterium cells in sputum samples by the combination of electric field, streaming flow, and immuno-affinity binding. The detection limit was 200 CFU/mL in human sputum, which was comparable to PCR but without requiring bacteriological culture, centrifugation, or nucleic acid amplification. In spite of the complex nature of physical, chemical, and biological mechanisms, the simple operation of "dipping and withdrawal" of tips will allow for screening by minimally trained personnel within 30 min. In addition, the minimal power requirement (5 W) combined with low assay cost is ideal for point-of-care (POC) screening in resource-limited settings.

Single walled carbon nanotube-based junction biosensor for detection of Escherichia coli.

Foodborne pathogen detection using biomolecules and nanomaterials may lead to platforms for rapid and simple electronic biosensing. Integration of single walled carbon nanotubes (SWCNTs) and immobilized antibodies into a disposable bio-nano combinatorial junction sensor was fabricated for detection of Escherichia coli K-12. Gold tungsten wires (50 µm diameter) coated with polyethylenimine (PEI) and SWCNTs were aligned to form a crossbar junction, which was functionalized with streptavidin and biotinylated antibodies to allow for enhanced specificity towards targeted microbes. In this study, changes in electrical current (ΔI) after bioaffinity reactions between bacterial cells (E. coli K-12) and antibodies on the SWCNT surface were monitored to evaluate the sensor's performance. The averaged ΔI increased from 33.13 nA to 290.9 nA with the presence of SWCNTs in a 10(8) CFU/mL concentration of E. coli, thus showing an improvement in sensing magnitude. Electrical current measurements demonstrated a linear relationship (R2 = 0.973) between the changes in current and concentrations of bacterial suspension in range of 10(2)-10(5) CFU/mL. Current decreased as cell concentrations increased, due to increased bacterial resistance on the bio-nano modified surface. The detection limit of the developed sensor was 10(2) CFU/mL with a detection time of less than 5 min with nanotubes. Therefore, the fabricated disposable junction biosensor with a functionalized SWCNT platform shows potential for high-performance biosensing and application as a detection device for foodborne pathogens.

Flow-induced immobilization of glucose oxidase in nonionic micellar nanogels for glucose sensing.

A simple microfluidic platform was utilized to immobilize glucose oxidase (GOx) in a nonionic micellar scaffold. The immobilization of GOx was verified by using a combination of cryogenic electron microscopy (cryo-EM), scanning electron microscopy (SEM), and ultraviolet spectroscopy (UV) techniques. Chronoamperometric measurements were conducted on nanogel-GOx scaffolds under different glucose concentrations, exhibiting linear amperometric responses. Without impacting the lifetime and denaturation of GOx, the nonionic nanogel provides a favorable microenvironment for GOx in biological media. This flow-induced immobilization method in a nonionic nanogel host matrix opens up new pathways for designing a simple, fast, biocompatible, and cost-effective process to immobilize biomolecules that are averse to ionic environments.

USNCTAM perspectives on mechanics in medicine.

Over decades, the theoretical and applied mechanics community has developed sophisticated approaches for analysing the behaviour of complex engineering systems. Most of these approaches have targeted systems in the transportation, materials, defence and energy industries. Applying and further developing engineering approaches for understanding, predicting and modulating the response of complicated biomedical processes not only holds great promise in meeting societal needs, but also poses serious challenges. This report, prepared for the US National Committee on Theoretical and Applied Mechanics, aims to identify the most pressing challenges in biological sciences and medicine that can be tackled within the broad field of mechanics. This echoes and complements a number of national and international initiatives aiming at fostering interdisciplinary biomedical research. This report also comments on cultural/educational challenges. Specifically, this report focuses on three major thrusts in which we believe mechanics has and will continue to have a substantial impact. (i) Rationally engineering injectable nano/microdevices for imaging and therapy of disease. Within this context, we discuss nanoparticle carrier design, vascular transport and adhesion, endocytosis and tumour growth in response to therapy, as well as uncertainty quantification techniques to better connect models and experiments. (ii) Design of biomedical devices, including point-of-care diagnostic systems, model organ and multi-organ microdevices, and pulsatile ventricular assistant devices. (iii) Mechanics of cellular processes, including mechanosensing and mechanotransduction, improved characterization of cellular constitutive behaviour, and microfluidic systems for single-cell studies.

Contact angle changes induced by immunocomplex formation.

Immunoassays analyzing interactions between antigens and antibodies can be affected by capillary action together with binding affinity. This paper studies contact-angle changes of bacterial suspensions on antibody immobilized surfaces. The capillary action and the dried pattern of the bacterial suspensions are analyzed and correlated with specific- and nonspecific bindings between bacteria and antibodies.

Semi-automated, occupationally safe immunofluorescence microtip sensor for rapid detection of Mycobacterium cells in sputum.

An occupationally safe (biosafe) sputum liquefaction protocol was developed for use with a semi-automated antibody-based microtip immunofluorescence sensor. The protocol effectively liquefied sputum and inactivated microorganisms including Mycobacterium tuberculosis, while preserving the antibody-binding activity of Mycobacterium cell surface antigens. Sputum was treated with a synergistic chemical-thermal protocol that included moderate concentrations of NaOH and detergent at 60°C for 5 to 10 min. Samples spiked with M. tuberculosis complex cells showed approximately 10(6)-fold inactivation of the pathogen after treatment. Antibody binding was retained post-treatment, as determined by analysis with a microtip immunosensor. The sensor correctly distinguished between Mycobacterium species and other cell types naturally present in biosafe-treated sputum, with a detection limit of 100 CFU/mL for M. tuberculosis, in a 30-minute sample-to-result process. The microtip device was also semi-automated and shown to be compatible with low-cost, LED-powered fluorescence microscopy. The device and biosafe sputum liquefaction method opens the door to rapid detection of tuberculosis in settings with limited laboratory infrastructure.

Comparison of Mechanical Stability between Fibular Free Flap Reconstruction versus Locking Mandibular Reconstruction Plate Fixation.

BACKGROUND: The fibular free flap has been used as the standard methods of segmental mandibular reconstruction. The objective of mandibular reconstruction not only includes restored continuity of the mandible but also the recovery of optimal function. This paper emphasizes the advantage of the fibular free flap reconstruction over that of locking mandibular reconstruction plate fixation. METHODS: The hospital charts of all patients (n=20) who had a mandibular reconstruction between 1994 and 2013 were retrospectively reviewed. Eight patients had plate-only fixation of the mandible, and the remaining 12 had vascularized fibular free flap reconstruction. Complications and outcomes were reviewed and compared between the 2 groups via statistical analysis. RESULTS: Overall complication rates were significantly lower in the fibular flap group (8.3%) than in the plate fixation group (87.5%; p =0.001). Most (7/8) patients in the plate fixation group had experienced plate-related late complications, including plate fracture or exposure. In the fibular flap group, no complications were observed, except for a single case of donor-site wound dehiscence (1/12). CONCLUSION: The fibular free flap provides a more stable support and additional soft tissue support for the plate, thereby minimizing the risk of plate-related complications. Fibular free flap is the most reliable option for mandibular reconstruction, and we believe that the flap should be performed primarily whenever possible.

Microfluidic one-step synthesis of alginate microspheres immobilized with antibodies.

Micrometre- and submicrometre-size functionalized beads are frequently used to capture targets of interest from a biological sample for biological characterizations and disease diagnosis. The main challenge of the microbead-based assay is in the immobilization of probe molecules onto the microbead surfaces. In this paper, we report a versatile droplet microfluidics method to fabricate alginate microspheres while simultaneously immobilizing anti-Mycobacterium tuberculosis complex IgY and anti-Escherichia coli IgG antibodies primarily on the porous alginate carriers for specific binding and binding affinity tests. The binding affinity of antibodies is directly measured by fluorescence intensity of stained target bacteria on the microspheres. We demonstrate that the functionalized alginate microspheres yield specificity comparable with an enzyme-linked immunosorbent assay. The high surface area-to-volume ratio of the functionalized porous alginate microspheres improves the detection limit. By using the droplet microfluidics, we can easily modify the size and shape of alginate microspheres, and increase the concentration of functionalized alginate microspheres to further enhance binding kinetics and enable multiplexing.

Electrolyte-free Amperometric Immunosensor using a Dendritic Nanotip.

Electric detection using a nanocomponent may lead to platforms for rapid and simple biosensing. Sensors composed of nanotips or nanodots have been described for highly sensitive amperometry enabled by confined geometry. However, both fabrication and use of nanostructured sensors remain challenging. This paper describes a dendritic nanotip used as an amperometric biosensor for highly sensitive detection of target bacteria. A dendritic nanotip is structured by Si nanowires coated with single-walled carbon nanotubes (SWCNTs) for generation of a high electric field. For reliable measurement using the dendritic structure, Si nanowires were uniformly fabricated by ultraviolet (UV) lithography and etching. The dendritic structure effectively increased the electric current density near the terminal end of the nanotip according to numerical computation. The electrical characteristics of a dendritic nanotip with additional protein layers was studied by cyclic voltammetry and I-V measurement in deionized (DI) water. When the target bacteria dielectrophoretically captured onto a nanotip were bound with fluorescence antibodies, the electric current through DI water decreased. Measurement results were consistent with fluorescence- and electron microscopy. The sensitivity of the amperometry was 10 cfu/sample volume (103 cfu/mL), which was equivalent to the more laborious fluorescence measurement method. The simple configuration of a dendritic nanotip can potentially offer an electrolyte-free detection platform for sensitive and rapid biosensors.