Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

A pilot clinical validation study of a self-collected vaginal swab device for the detection of chlamydia trachomatis in women.

Chlamydia trachomatis (C. trachomatis) is one of the most prevalent preventable sexually transmitted diseases (STDs) in the world. In women, C. trachomatis infection can lead to long-term complications such as pelvic inflammatory disease (PID), and other related conditions such as ectopic pregnancies and even tubal factor infertility. These complications are preventable given early detection and clinical intervention, but these efforts are often hampered by asymptomatic silent infections, and non-compliance to screenings for STDs. Some women do not get tested out of concerns for violation of privacy, and fear of discomfort. Clinicians often use a multitude of tests to determine if a patient is infected by C. trachomatis, including a Polymerase Chain Reaction (PCR) test of First catch urine (FCU) samples. However, these tend to be inconvenient to store and transport, as they carry risk of spillage and have stringent refrigeration requirements. Moreover, given the gold-standard recommendations set forth by the Centres for Disease Control (CDC), the current technique can be inconvenient in remote areas where refrigeration and transport may not always be reliable. The current study therefore looks at the potential of a self-collected vaginal swab device that relies on Nucleic Acid Amplification Tests (NAATs), is dry-stored, and does not require refrigeration, to detect the presence of C. trachomatis in women. The study found evidence to suggest that the self-collection device has the potential to aid clinicians in the diagnosis of C. trachomatis in women when compared to doctor-collected vaginal discharge samples as the designated standard, FCU, and blood serology. Moreover, as a self-collection device it has the potential to break down some of the barriers to STD screening especially in young women, such as violation of privacy. The device therefore has a potential to encourage screening and therefore a potentially effective tool in the fight against the spread of preventable sexually transmitted diseases.

Interleukin-6 Test Strip Combined With a Spectrum-Based Optical Reader for Early Recognition of COVID-19 Patients With Risk of Respiratory Failure.

The COVID-19 pandemic has had a globally devastating impact. This highly contagious virus has significantly overburdened and undermined medical systems. While most infected patients experience only mild symptoms, those who are severely affect require urgent medical interventions and some develop acute respiratory failure and require mechanical ventilation. The broad and potentially deadly impact of infection underscores the critical need for early recognition, especially for those at risk for respiratory failure. Those who are severely impacted and at high risk for respiratory failure have been found to present high levels of serum cytokines, such as interleukin-6 (IL-6). Timely diagnosis and management of those at risk for respiratory failure is crucial. Measurement of IL-6 may provide a means for distinguishing such patients. Currently, most serum IL-6 detection relies on the use of laboratory-based conventional enzyme-linked immunosorbent assays. Although some rapid assays have been developed recently, they need to be conducted by specific technicians in central laboratory settings with advanced and expensive equipment. In this study, we propose an IL-6 test strip combined with a spectrum-based optical reader for early recognition of COVID-19-infected patients at imminent risk of acute respiratory failure requiring mechanical ventilator support. For our analyses, clinical demographic data and sera samples were obtained from three medical centers, and test strip specificity and detection performance were analyzed. This would help healthcare personnel stratify the risk of respiratory failure and provide prompt, and suitable management.

Clinical Evaluation of a Self-Testing Kit for Vaginal Infection Diagnosis.

Vaginitis is a common disorder among women of varying ages that arises from a change in the normal pH balance of vaginal bacteria or an infection. Characteristic symptoms of itching, irritation, and odor cause considerable discomfort and increase the risk of contracting other sexually transmitted infections. Because of the sensitive and personal nature of the condition, some women may be reluctant to seek treatment. This behavior not only fails to solve the problem but may also delay medical treatment and result in additional medical complications. The pH changes associated with vaginitis and vaginosis, which are characterized by the presence or absence of inflammation, respectively, are well known but can vary. For example, bacterial vaginosis and trichomoniasis infection will raise vaginal pH above 4.5, while vulvovaginal candidiasis does not result in any measurable change to pH. Nonetheless, diagnostic tools relying on pH measurement are a valuable approach from which additional testing and treatment may be launched. Here, we focused on the use of a vaginal self-test tool and tested 50 patients, including pregnant women. When used according to the instructions, the Hygeia Touch Self-Testing Kit for Vaginal Infection demonstrated over 88% accuracy compared to a clinical diagnostic workup, with a sensitivity of 87% and a specificity of 89% in the patients where the swab was correctly interpreted. This study demonstrated an effective self-test method with high acceptability among women that provided them with greater autonomy regarding health management.

Point-of-care semen analysis of patients with infertility via smartphone and colorimetric paper-based diagnostic device.

Male infertility affects millions of males worldwide and is rising in prevalence due to social and environmental conditions. However, men often feel too embarrassed to receive a semen analysis in the hospital due to social stigmas. To overcome this problem, we developed a 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test strip to distinguish semen samples with low total motile sperm concentration from those with normal motile sperm concentration. This is a point-of-care colorimetric semen analytical method with a one-step, inexpensive, equipment-free evaluation process, and adequate accuracy validated in a 42-sample clinical trial. In this study, results were evaluated visually and with a smartphone application. Using visual observation methods, the area under the curve (AUC) was 0.71 (95% of confidence interval = 0.55-0.86; p = 0.021), sensitivity was 41%, specificity was 95%, positive predictive value was 90%, negative predictive value (NPV) was 59.4%, and accuracy was 67%. Using a smartphone recording and analytical system, AUC was 0.766 (95% of confidence interval = 0.612-0.92; p = 0.003), sensitivity was 96%, specificity was 65%, PPV was 75%, NPV was 92.9%, and accuracy was 80.9%. This work demonstrated a screening tool that could elevate semen analysis to the level of routine healthcare and provide for private, in-home self-assessment.

Urinalysis Using a Diaper-Based Testing Device.

Urinary tract infections (UTI), one of the most common bacterial infections, annually affect 150 million people worldwide. Infants and the elderly are likely to have missed or delayed diagnosis of UTI due to difficulty clearly describing their symptoms. A rapid screening method for UTI is a critical and urgent need for these populations. The aim of our study is to develop a diaper-based testing device to assay urine biomarkers including pH, leukocyte, and nitrite level. This all-in-one device assists in urine collection and testing using a colorimetric approach to provide easily read visual results on the outside surface of a test strip-integrated diaper. In this study, we tested samples from 46 patients using testing strips and examined the results from 7 patients recruited to validate the strip-integrated diaper. In conclusion, this new diaper-based testing device is easy to use, rapid, and inexpensive, all of which imbue it with tremendous potential for development into a commercially viable UTI screening system.

Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed.

Probing neural cell behaviors through micro-/nano-patterned chitosan substrates.

In this study, we describe the development of surface-modified chitosan substrates to examine topographically related Neuro-2a cell behaviors. Different functional groups can be modified on chitosan surfaces to probe Neuro-2a cell morphology. To prepare chitosan substrates with micro/nano-scaled features, we demonstrated an easy-to-handle method that combined photolithography, inductively coupled plasma reactive ion etching, Ag nanoparticle-assisted etching, and solution casting. The results show that Neuro-2a cells preferred to adhere to a flat chitosan surface rather than a nanotextured chitosan surface as evidenced by greater immobilization and differentiation, suggesting that surface topography is crucial for neural patterning. In addition, we developed chitosan substrates with different geometric patterns and flat region depth; this allowed us to re-arrange or re-pattern Neuro-2a cell colonies at desired locations. We found that a polarity-induced micropattern provided the most suitable surface pattern for promoting neural network formation on a chitosan substrate. The cellular polarity of single Neuro-2a cell spreading correlated to a diamond-like geometry and neurite outgrowth was induced from the corners toward the grooves of the structures. This study provide greater insight into neurobiology, including neurotransmitter screening, electrophysiological stimulation platforms, and biomedical engineering.

Using cell structures to develop functional nanomaterials and nanostructures--case studies of actin filaments and microtubules.

This article is based on the continued development of biologically relevant elements (i.e., actin filaments and microtubules in living cells) as building blocks to create functional nanomaterials and nanostructures that can then be used to manufacture nature-inspired small-scale devices or systems. Here, we summarize current progress in the field and focus specifically on processes characterized by (1) robustness and ease of use, (2) inexpensiveness, and (3) potential expandability to mass production. This article, we believe, will provide scientists and engineers with a more comprehensive understanding of how to mine biological materials and natural design features to construct functional materials and devices.

Monitoring the VEGF level in aqueous humor of patients with ophthalmologically relevant diseases via ultrahigh sensitive paper-based ELISA.

The vascular endothelial growth factor (VEGF) level in aqueous humor has been used as an indicator to monitor specific diseases in the retinal ischemic condition. For clinical diagnosis, only about 200 µL of aqueous humor can be collected from the anterior chamber before the threat of anterior chamber collapse. It is necessary to develop an inexpensive diagnostic approach with the characteristics of highly sensitive, short operation duration, and requires small clinical sample quantities. To achieve the main objective of this study, we first prepared bevacizumab to be conjugated with HRP. We then deposited 2 µL aqueous humor from patients with different diseases onto each test zone of paper-based 96-well plates. After the colorimetric results were performed via ELISA protocol, the output signals were recorded using a commercial desktop scanner for analysis. In this study, only 2 µL from the aqueous humor of each patient was required for paper-based ELISA. The mean aqueous VEGF level was 14.4 pg/mL from thirteen patients (N = 13) with senile cataract as the control. However, the mean aqueous VEGF level from other patients with proliferative diabetic retinopathy (N = 14), age-related macular degeneration (N = 17), and retinal vein occlusion (N = 10) showed VEGF increases to 740.1 pg/mL, 383 pg/mL, and 219.4 pg/mL, respectively.

Probing cellular behaviors through nanopatterned chitosan membranes.

This paper describes a high-throughput method for developing physically modified chitosan membranes to probe the cellular behavior of MDCK epithelial cells and HIG-82 fibroblasts adhered onto these modified membranes. To prepare chitosan membranes with micro/nanoscaled features, we have demonstrated an easy-to-handle, facile approach that could be easily integrated with IC-based manufacturing processes with mass production potential. These physically modified chitosan membranes were observed by scanning electron microscopy to gain a better understanding of chitosan membrane surface morphology. After MDCK cells and HIG-82 fibroblasts were cultured on these modified chitosan membranes for various culture durations (i.e. 1, 2, 4, 12 and 24 h), they were investigated to decipher cellular behavior. We found that both cells preferred to adhere onto a flat surface rather than on a nanopatterned surface. However, most (> 80%) of the MDCK cells showed rounded morphology and would suspend in the cultured medium instead of adhering onto the planar surface of negatively nanopatterned chitosan membranes. This means different cell types (e.g. fibroblasts versus epithelia) showed distinct capabilities/preferences of adherence for materials of varying surface roughness. We also showed that chitosan membranes could be re-used at least nine times without significant contamination and would provide us consistency for probing cell-material interactions by permitting reuse of the same substrate. We believe these results would provide us better insight into cellular behavior, specifically, microscopic properties and characteristics of cells grown under unique, nanopatterned cell-interface conditions.

Functionalization, re-functionalization and rejuvenation of ssDNA nanotemplates.

Single-stranded DNA (ssDNA) with repetitive sequence was demonstrated to be a versatile nanotemplate for introducing biological activity in a self-assembled manner. Re-functionalization and rejuvenation of the ssDNA nanotemplate were achieved under mild biological conditions without using high temperature and strong alkaline treatment to denature DNA.

Micropatterning of mammalian cells on inorganic-based nanosponges.

Developing artificial scaffolding structures in vitro in order to mimic physiological-relevant situations in vivo is critical in many biological and medical arenas including bone and cartilage generation, biomaterials, small-scale biomedical devices, tissue engineering, as well as the development of nanofabrication methods. We focus on using simple physical principles (photolithography) and chemical techniques (liquid vapor deposition) to build non-cytotoxic scaffolds with a nanometer resolution through using silicon substrates as the backbone. This method merges an optics-based approach with chemical restructuring to modify the surface properties of an IC-compatible material, switching from hydrophilicity to hydrophobicity. Through this nanofabrication-based approach that we developed, hydrophobic oxidized silicon nanosponges were obtained. We then probed cellular responses-examining cytoskeletal and morphological changes in living cells through a combination of fluorescence microscopy and scanning electron microscopy-via culturing Chinese hamster ovary cells, HIG-82 fibroblasts and Madin-Darby canine kidney cells on these silicon nanosponges. This study has demonstrated the potential applications of using these silicon-based nanopatterns such as influencing cellular behaviors at desired locations with a micro-/nanometer level.

Cell adhesion, morphology and biochemistry on nano-topographic oxidized silicon surfaces.

Manipulating an incorporated scaffold to direct cell behaviors play a key role in tissue engineering. In this study, we developed novel nano-topographic oxidized silicon nanosponges capable of being modified with various chemicals of a few nm in thickness to gain further insight into the fundamental biology of cell-environment interactions in vitro. A wet etching technique was applied to fabricate the silicon nanosponges in a high-throughput manner and was followed by vapor deposition of various organo-silane chemicals to enable self-assembly on the surfaces of the silicon nanosponges. When Chinese hamster ovary cells were cultured on these chemically modified nano-topographic structures, they displayed distinct morphogenesis, adherent responses, and biochemical properties in comparison with those of their planar oxidized silicon counterparts. There were predominant nano-actin punches and slender protrusions formed while cells were cultured on the nano-topographic structures, indicating that cell behaviors can be influenced by the physical characteristic derived from nano-topography, in addition to the hydrophobicity of contact surfaces. This study demonstrates potential applications of these nano-topographic biomaterials for controlling cell development in tissue engineering as well as in basic cell biology research.

Investigation of multiphase liquid roughness using an atomic force microscope.

The roughness of a multiphase interface and the associated topography between silicone oil and an alcohol-based fluid were measured with an atomic force microscope (AFM) and compared with the results of calculations based upon a capillary-wave model. According to this theory, the interfacial roughness of a liquid-liquid interface depends on the density, interfacial tension, and temperature of the liquids. Test samples prepared with both silicone oil and an alcohol-based fluid at various volumetric ratios and controlled temperatures were carefully measured. The experimental results indicate that the interfacial roughness measured with an AFM was consistent with the capillary-wave model. The measured interfacial roughness is influenced mainly by the interfacial tension between the liquids and the temperature-driven Brownian motion of the molecules. Three-dimensional topographical pictures of the interfaces were constructed and archived digitally for subsequent investigation. By employing the outlined method, we examined the microscopic details of interfacial properties, with prospective applications in biochemical and biophysical research.