Suitability of Hood Geometry for Design of a PCM Neonate Incubator for Resource-Limited Clinical Applications.

To reduce dependence on electric-powered incubators, a number of alternate heat sources have been proposed. Phase change materials (PCM) are one of such because of their availability and cost effectiveness in rural areas. This study intends to explore the use of phase change material (PCM) such as paraffin wax as an alternative heat source over a variety of incubator hood geometries. This study presents three incubator hood geometries and their respective effects on maximum hood temperatures and time to reach these temperatures for a mainstream incubator. The three designs, cubic, pyramidal, and oval, were created using CAD software; mathematical computations for heat transfer analysis were undertaken using COMSOL Multiphysics software. Results show the maximum temperatures reached in the hoods were 308, 314.5, and 315 K for the cubic, pyramidal, and oval-shaped geometries respectively. This offers a promising application of PCM-based as a choice material for incubator design for rural applications.

Feasibility of Leveraging Consumer Wearable Devices with Data Platform Integration for Patient Vital Monitoring in Low-Resource Settings.

Manual monitoring of vital signs, which often fails to capture the onset of deterioration, is the main monitoring modality in most Ghanaian hospitals due to the high cost and inadequate supply of patient bedside monitors. Consumer wearable devices (CWDs) are emerging, relatively low-cost technologies for continuous monitoring of physiological status; however, their validity has not been established in low-resource clinical settings. We aimed to (1) investigate the validity of the heart rate (HR) and oxygen saturation (SpO2) data from two widely used CWDs, the Fitbit Versa 2 and Xiaomi Mi Smart Band 6, against gold standard bedside monitors in one Ghanaian hospital and (2) develop a web application to capture and display CWD data in a clinician-friendly way. A healthy volunteer simultaneously wore both CWDs and blood pressure cuffs to measure HR and SpO2. To test for concordance, we conducted the Bland-Altman and mean absolute percentage error analyses. We also developed a web application that retrieves and displays CWD data in near real time as text and graphical trends. Compared to gold standards (patient monitor and manual), the Fitbit Versa 2 had 96.87% and 96.67% measurement accuracies for HR, and the Xiaomi Mi Smart Band 6 had 94.24% and 93.21% measurement accuracies for HR. The Xiaomi Mi Smart Band 6 had 98.79% measurement accuracy for SpO2. The strong concordance between CWD and gold standards supports the potential implementation of these devices as a novel method of vital sign monitoring to replace manual monitoring, thus saving costs and improving patient outcomes. Further studies are needed for confirmation.

Seeing through bone with surface-enhanced spatially offset Raman spectroscopy.

Surface-enhanced spatially offset Raman spectroscopy (SESORS) is a label-free vibrational spectroscopy that has the potential for in vivo imaging. Previous SESORS experiments have been limited to acquiring spectra using SERS substrates implanted under the skin or from nanoparticles embedded in tissue. Here we present SESORS measurements of SERS active nanoparticles coated with a Raman reporter molecule (nanotags) acquired, for the first time, through bone. We demonstrate the ability of SESORS to measure spectra through various thicknesses (3-8 mm) of bone. We also show that diluted nanotag samples (~2 × 10(12) particles) can be detected through the bone. We apply a least-squares support vector machine analysis to demonstrate quantitative detection. It is anticipated that these through-bone SESORS measurements will enable real-time, non-invasive spectroscopic measurement of neurochemicals through the skull, as well as other biomedical applications.

An archetypal model of a breathable air-circuit in an electro-pneumatic ventilator device.

Mechanical ventilator is a machine that is mechanically designed to deliver breathable air in and out of the lungs to provide a breathing mechanism for a patient who is physically unable to breathe, it is an indispensable life-support device in critical care medicine and medical emergencies such as scenarios during the COVID-19 pandemic. This research presents a model design of the pneumatic circuit that is electronically controlled, by using computer-aided pneumatic rig over selected 5/3, 5/2, 3/2 solenoid gating valves, the performance of these valves must be investigated to ascertain the most appropriate valve to be used for the electro-pneumatic mechanical ventilator. An elaborate parametric investigation reported for volume-controlled ventilators illustrate the influences of key parameters on the dynamics of the ventilated respiratory system. This study presents the linearity of tidal volume, peak pressure and lung compliance for the parameters considered. However, the maximum pressure of the ventilation device increases slowly when the tidal volumes exceed 600 ml. In addition, influence of evacuation time of the ventilator predicted over high throughput in time regimes of 1 s; 1.2 s; 1.4 s; 1.6 s, and 1.8 s showed that the pressure platform in the pipe might not appear if the exhaust time of the ventilator is less than 1.6 s. The 5/2 solenoid valve was considered the best with consistent flowrate. The archetypal model of the pneumatic circuit developed in this research could find vital application in the design of patient-interfacing devices particularly in ventilators and neonatal incubator.

In vivo, transcutaneous glucose sensing using surface-enhanced spatially offset Raman spectroscopy: multiple rats, improved hypoglycemic accuracy, low incident power, and continuous monitoring for greater than 17 days.

This paper presents the latest progress on quantitative, in vivo, transcutaneous glucose sensing using surface enhanced spatially offset Raman spectroscopy (SESORS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in Sprague-Dawley rats. The glucose concentration was monitored in the interstitial fluid of six separate rats. The results demonstrated excellent accuracy and consistency. Remarkably, the root-mean-square error of calibration (RMSEC) (3.6 mg/dL) and the root-mean-square error of prediction (RMSEP) (13.7 mg/dL) for low glucose concentration (<80 mg/dL) is lower than the current International Organization Standard (ISO/DIS 15197) requirements. Additionally, our sensor demonstrated functionality up 17 days after implantation, including 12 days under the laser safety level for human skin exposure with only one time calibration. Therefore, our SERS based sensor shows promise for the challenge of reliable continuous glucose sensing systems for optimal glycemic control.

Transcutaneous glucose sensing by surface-enhanced spatially offset Raman spectroscopy in a rat model.

This letter presents the first quantitative, in vivo, transcutaneous glucose measurements using surface enhanced Raman spectroscopy (SERS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in a Sprague-Dawley rat. The glucose concentration was monitored in the interstitial fluid. SER spectra were collected from the sensor chip through the skin using spatially offset Raman spectroscopy (SORS). The combination of SERS and SORS is a powerful new approach to the challenging problem of in vivo metabolite and drug sensing.

Prediction range estimation from noisy Raman spectra with robust optimization.

Inferences need to be drawn in biological systems using experimental multivariate data. The number of samples collected in many such experiments is small, and the data are noisy. We present and study the performance of a robust optimization (RO) model for such situations. We adapt this model to generate a minimum and a maximum estimation of analyte concentration for a given sample, producing a prediction range. The calibration model was applied to sets of Raman spectra. In particular we used normal Raman measurements of pyridine/deuterated pyridine mixtures and spectra from a more complex glucose detection system based on surface-enhanced Raman spectroscopy. The results from the RO model were compared with prediction intervals estimated from partial least squares (PLS) method. We find that the RO prediction ranges included the actual concentration value of the sample more consistently than the 99% prediction intervals built with PLS methods.

C-THAN: A new research center for the development of point-of-care technology for HIV/AIDS.

The Center for Innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern University (C-THAN) is a partner in the Point-of-Care Technologies Research Network (POCTRN) of the National Institutes of Biomedical Imaging and Bioengineering. POCTRN's mission is to drive the development of appropriate point-of-care (POC) diagnostic technologies through collaboration that merges scientific and technological capabilities with clinical need. C-THAN develops POC technologies for improved management of HIV/AIDS in low- and middle-income countries with a focus on sub-Saharan Africa. C-THAN incorporates clinical and user needs with technology expertise and resources to address commercialization and implementation barriers through: 1) assessment of unmet clinical needs in POC testing for HIV/AIDS and its comorbidities; 2) collaborations with physicians, researchers and engineers; 3) development of technical, clinical, industrial and regulatory partnerships; 4) clinical testing of prototype devices; and 5) creation of training opportunities for technology developers, evaluators, and other stakeholders. Technologies supported include tests for detection and monitoring of HIV/AIDS and its common comorbidities including tuberculosis, non-tuberculous mycobacteria, viral hepatitis and HIV-related malignancies. CTHAN relies on collaborations established by Northwestern University in Nigeria, South Africa, Mali and Tanzania, to have impact on the prevention and clinical management of HIV/AIDS.

Supporting Diagnosis and Management of HIV/AIDS Patients Through Point-of-Care Technology Development.

The HIV pandemic disproportionately impacts sub-Saharan Africa where in 2017, 71% of people living with HIV resided, 65% of new infections and 75% of deaths were reported. Prevention, screening and treatment strategies have led to progress in addressing this disease. HIV diagnostics have been crucial for prevention and treatment but more progress is required to reduce HIV infection. The Center for Innovation in Point-of-Care Technologies for HIV/AIDS at Northwestern University (C-THAN) is a vital partner in the National Institute of Biomedical Imaging and Bioengineering Point-of-Care Technologies Research Network. C-THAN's mission is to develop and commercialize a pipeline of point-of-care technologies critical for improved prevention and management of HIV in low- and middle-income countries with specific emphasis on sub-Saharan Africa.

Progress toward an in vivo surface-enhanced Raman spectroscopy glucose sensor.

BACKGROUND: In this report, we detail our current work towards developing a surface-enhanced Raman spectroscopy (SERS) based sensor for in vivo glucose detection. Despite years of innovations in the development of blood glucose monitors, there remains a need for accurate continuous glucose sensors to provide care to rising numbers of diagnosed diabetes patients and mitigate secondary health complications associated with this metabolic disorder. METHODS: SERS is a highly specific and sensitive optical technique suitable for direct detection of glucose. The SERS effect is highly distance dependent, thus the glucose molecules need to be within a few nanometers or adsorbed to an SERS-active surface. In our sensor, this is achieved with a self-assembled monolayer (SAM) that facilitates reversible interactions between glucose molecules and the surface. The amount of glucose near the surface is proportional to its concentration in the surrounding environment. RESULTS: We determined that the SAM-functionalized surface is stable for at least 10 days and provides rapid, reversible partitioning. In vitro experiments in bovine plasma as well as in vivo experiments in rats demonstrated quantitative detection. CONCLUSIONS: We show successful use of the SERS glucose sensor in rats, making it the first in vivo SERS sensor. Furthermore, we demonstrate free space transdermal detection of a SERS signal through the rat's skin as an initial step toward developing a transcutaneous sensor.

The effect of the rate of hydrostatic pressure depressurization on cells in culture.

Changes in hydrostatic pressure, at levels as low as 10 mm Hg, have been reported in some studies to alter cell function in vitro; however, other studies have found no detectable changes using similar methodologies. We here investigate the hypothesis that the rate of depressurization, rather than elevated hydrostatic pressure itself, may be responsible for these reported changes. Hydrostatic pressure (100 mm Hg above atmospheric pressure) was applied to bovine aortic endothelial cells (BAECs) and PC12 neuronal cells using pressurized gas for periods ranging from 3 hours to 9 days, and then the system was either slowly (~30 minutes) or rapidly (~5 seconds) depressurized. Cell viability, apoptosis, proliferation, and F-actin distribution were then assayed. Our results did not show significant differences between rapidly and slowly depressurized cells that would explain differences previously reported in the literature. Moreover, we found no detectable effect of elevated hydrostatic pressure (with slow depressurization) on any measured variables. Our results do not confirm the findings of other groups that modest increases in hydrostatic pressure affect cell function, but we are not able to explain their findings.

Bond-detach lithography: a method for micro/nanolithography by precision PDMS patterning.

We have discovered a micro/nanopatterning technique based on the patterning of a PDMS membrane/film, which involves bonding a PDMS structure/stamp (that has the desired patterns) to a PDMS film. The technique, which we call "bond-detach lithography", was demonstrated (in conjunction with other microfabrication techniques) by transferring several micro- and nanoscale patterns onto a variety of substrates. Bond-detach lithography is a parallel process technique in which a master mold can be used many times, and is particularly simple and inexpensive.

KGF prevents oxygen-mediated damage in ARPE-19 cells.

PURPOSE: Oxidative stress has been implicated in a variety of diseases of the eye. In several other tissues, keratinocyte growth factor (KGF) has been shown to prevent negative cellular changes associated with oxidative insult, such as permeability increases and nuclear DNA damage. In this study, we looked at whether KGF provided these same protective effects to cultured human retinal pigmented epithelial (RPE) cells (ARPE-19). METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) using a published primer pair sequence followed by restriction endonuclease digestion with AvaI and HincII was used to look for the KGF receptor message in ARPE-19 cells. Cellular response to KGF was verified through proliferation assays and Western blot analysis for mitogen-activated protein kinase (MAPK). Single-cell gel electrophoresis was used to assess DNA damage, Western blot analysis was used to assay actin cytoskeletal changes, and electrical resistance and tracer experiments with Transwell tissue plates were used to assess permeability changes. Immunostaining was used to verify the existence of the tight junction protein occludin. RESULTS: It was verified through RT-PCR that the ARPE-19 cell line exhibited the message for FGFR2-IIIb, otherwise known as KGFR. KGF was also shown to increase cellular proliferation and activated the MAPK p44/p42 cascade. KGF ameliorated nuclear DNA damage and cytoskeletal rearrangement caused by oxidative stress through the addition of exogenous hydrogen peroxide but was unable to prevent permeability changes. CONCLUSIONS: KGF was shown to significantly reduce DNA damage and cytoskeletal rearrangement caused by oxidative stress in cultured ARPE-19 cells. This result may be useful in targeting future therapies to combat a multitude of diseases of the eye that result from increases in reactive oxygen species.

Optical monitoring of bubble size and shape in a pulsating bubble surfactometer.

The pulsating bubble surfactometer (PBS) is often used for in vitro characterization of exogenous lung surfactant replacements and lung surfactant components. However, the commercially available PBS is not able to dynamically track bubble size and shape. The PBS therefore does not account for bubble growth or elliptical bubble shape that frequently occur during device use. More importantly, the oscillatory volume changes of the pulsating bubble are different than those assumed by the software of the commercial unit. This leads to errors in both surface area and surface tension measurements. We have modified a commercial PBS through the addition of an image-acquisition system, allowing real-time determination of bubble size and shape and hence the accurate tracking of surface area and surface tension. Compression-expansion loops obtained with the commercially available PBS software were compared with those provided by the image-analysis system for dipalmitoylphosphatidylcholine, Infasurf, and Tanaka lipids (dipalmitoylphosphatidylcholine-palmitoyloleoylphosphatidyl-glycerol-palmitic acid, 68:22:9) at concentrations of 0.1 and 1.0 mg/ml and at frequencies of 1 and 20 cycles/min. Whereas minimum surface tension as determined by the image-analysis system is similar to that measured by the commercially available software, the maximum surface tension and the shapes of the interfacial area-surface tension loops are quite different. Differences are attributable to bubble drift, nonsinusoidal volume changes, and variable volume excursions seen with the modified system but neglected by the original system. Image analysis reveals that the extent of loop hysteresis is greatly overestimated by the commercial device and that an apparent, rapid increase in surface tension upon film expansion seen in PBS loops is not observed with the image-analysis system. The modified PBS system reveals new dynamic characteristics of lung surfactant preparations that have not previously been reported.

Design of Novel Mixer and Applicator for Two-Component Surgical Adhesives.

Current mixer and applicator devices on the market are not able to properly and efficiently mix two-component surgical adhesives in small volumes necessary to achieve economic viability. Furthermore, in these devices a significant amount of adhesive is wasted during the application process, as material within the dead space of the mixing chamber must be discarded. We have designed and demonstrated a new active mixer and applicator system capable of rapidly and efficiently mixing two components of an adhesive and applying it to the surgical site. Recently, Messersmith et al. have developed a tissue adhesive inspired by the mussel byssus and have shown that it is effective as a surgical sealant, and is especially suited for wet environments such as in fetal surgery. Like some other tissue sealants, this one requires that two components of differing viscosities be thoroughly mixed within a specified and short time period. Through a combination of compression and shear testing, we demonstrated that our device could effectively mix the adhesive developed by Messersmith et al. and improve its shear strength to significantly higher values than what has been reported for vortex mixing. Overall, our mixer and applicator system not only has potential applications in mixing and applying various adhesives in multiple surgical fields but also makes this particular adhesive viable for clinical use.

Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats.

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) mixed with radiopaque tracer was instilled as a plug into the trachea. The lungs were ventilated with a 4-ml tidal volume for 20 breaths at one of two respiratory rates: 20 or 60 breaths/min. The motion of radiodense surfactant was imaged at 30 frames/s with a microfocal X-ray source and an image intensifier. Dynamics of surfactant distribution were quantified for each image by use of distribution statistics and a homogeneity index. We found that the liquid distribution depended on the time to liquid plug rupture, which depends on ventilation rate. At 20 breaths/min, liquid was localized in the gravity-dependent region of the lung. At 60 breaths/min, the liquid coated the airways, providing a more vertically uniform liquid distribution.

Variation of corneal refractive index with hydration.

We report the effect of changes in the corneal hydration on the refractive index of the cornea. Using optical coherence tomography (OCT), the geometrical thickness and the group refractive index of the bovine cornea were derived simultaneously as the corneal hydration was varied. The corneal hydration was then calculated from the corneal thickness. The group refractive index of the cornea increased non-linearly as the cornea dehydrated. In addition, a simple mathematical model was developed, based on the assumption that changes in corneal hydration occur only in the interfibrilar space with constant water content within the collagen fibrils. Good agreement between the experimental results and the mathematical model supports the assumption. The results also demonstrate that the measurement of refractive index is a quantitative indicator of corneal hydration.

Force characterization of intracranial endovascular embolization: coil type, microcatheter placement, and insertion rate.

BACKGROUND: Intraoperative rupture (IOR) is a rare, but potentially morbid complication of endovascular aneurysm coil embolization. Yet, IOR predictors have remained relatively uninvestigated in relation to coil design. OBJECTIVE: To develop a novel in vitro aneurysm model to characterize forces exerted by coils of different design on the aneurysm during endovascular embolization that are hypothesized to contribute to IOR. METHODS: A 3-mm saccular aneurysm model was developed with flat latex membrane at the dome apex. Membrane deflection was observed throughout simulated embolization and converted to force measurement. Simultaneous coil insertion and force measurement were accomplished with a compression strength-testing machine. Membrane and insertion forces across coil type, microcatheter tip placement, and insertion rate were evaluated. RESULTS: Insertion force and force directly on the aneurysm wall exhibited a difference, with framing coils exerting greatest force, followed by filling and finishing coils. Regarding microcatheter placement, a similar graded response in membrane and insertion forces was observed with positioning in the top-third of the aneurysm generating the greatest force compared with central and bottom-third placement. Insertion rate was also a factor with the slowest rate (10 mm/min) exhibiting the greatest membrane force, followed by lower forces at 30 and 50 mm/min. A multiple linear regression model was created to assess the contributions of each factor toward aneurysm forces. CONCLUSION: Increased force on the aneurysm is associated with framing coil use, microcatheter placement proximal to aneurysm dome, and slow insertion rate. Further characterization remains necessary to reduce IOR risk, especially concerning the contributions of insertion rate.

Novel device to conduct flash-heat treatment in efforts to reduce mother-to-child HIV transmission in low-resource areas.

The objective of this design project was to create a device to prevent mother-to-child transmission (MTCT) of HIV through breast milk in preterm infants. Our team created a robust and intuitive device which utilizes Flash Heat Treatment (FHT), an established method to inactivate HIV. The FHT method heats jarred breast milk in boiling water for a short amount of time, enough to denature HIV reverse transcriptase while preserving the nutritional value of breast milk. Thorough observation of users and available resources in Cape Town, South Africa enabled establishment of a design that can be used in urban/peri-urban areas. User research conveyed that low cost and effortless household adaptability were the most important elements of the design. As a result, a modified electric kettle was designed to function as a breast milk pasteurization device. Published data illustrating temperature curves during FHT with corresponding virology tests on the pasteurized milk were used to verify whether the device is likely to function effectively. Experimental results indicate that the device matches the required temperature profile. After virology experimentation is complete, the new device may be incorporated into hospitals as well as households in the Cape Town area, and may be expanded to other low resource periurban/urban areas as well.