Chromophoric cerium oxide nanoparticle-loaded sucking disk-type strip sensor for optical measurement of glucose in tear fluid.

BACKGROUND: Noninvasive monitoring of tear glucose levels can be convenient for patients to manage their diabetes mellitus. However, there are issues with monitoring tear glucose levels, such as the invasiveness of some methods, the miniaturization, inaccuracy, or the high cost of wearable devices. To overcome the issues, we newly designed a sucking disk-type (SD) strip biosensor that can quickly suck tear fluid and contains cerium oxide nanoparticle (CNP) that causes a unique color change according to the glucose level of the tear without complicated electronic components. METHODS: The SD strip biosensor composed of three distinct parts (tip, channel, and reaction chamber) was designed to contain the sensing paper, onto which tear fluid can be collected and delivered. The sensing paper treated with CNP/APTS (aminopropyltriethoxysilane) /GOx (glucose oxidase) was characterized. Then we carried out the reliability of the SD strip biosensor in the diabetic rabbit animals. We quantitatively analyzed the color values of the SD strip biosensor through the colorimetric analysis algorithm. RESULTS: We contacted the inferior palpebral conjunctiva (IPC) of a diabetic rabbit eye using an SD strip biosensor to collect tears without eye irritation and successfully verified the performance and quantitative efficacy of the sensor. An image processing algorithm that can optimize measurement accuracy is developed for accurate color change measurement of SD strip biosensors. The validation tests show a good correlation between glucose concentrations measured in the tear and blood. CONCLUSION: Our findings demonstrate that the CNP-embedded SD strip biosensor and the associated image processing can simply monitor tear glucose to manage diabetes mellitus.

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

BACKGROUND: CT-P16 is a candidate bevacizumab biosimilar. OBJECTIVE: This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC). PATIENTS AND METHODS: Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg every 3 weeks; ≤ 6 cycles) with paclitaxel (200 mg/m2) and carboplatin (area under the curve 6.0; both for 4-6 cycles), as induction therapy. Patients with controlled disease after induction therapy continued with CT-P16 or EU-bevacizumab maintenance therapy. The primary endpoint was objective response rate (ORR) during the induction period. Time-to-event analyses, pharmacokinetics, safety, and immunogenicity were also evaluated. Results obtained after 1 year of follow-up are presented. RESULTS: Overall, 689 patients were randomized (CT-P16, N = 342; EU-bevacizumab, N = 347). ORR was 42.40% (95% confidence interval [CI] 37.16-47.64) and 42.07% (95% CI 36.88-47.27) for CT-P16 and EU-bevacizumab, respectively. The risk difference (0.40 [95% CI - 7.02 to 7.83]) and risk ratio (1.0136 [90% CI 0.8767-1.1719]) for ORR fell within predefined equivalence margins (- 12.5 to + 12.5%, and 0.7368 to 1.3572, respectively), demonstrating equivalence between CT-P16 and EU-bevacizumab. Median response duration, time to progression, progression-free survival, and overall survival were comparable between treatment groups. Safety profiles were similar: 96.2% (CT-P16) and 93.0% (EU-bevacizumab) of patients experienced treatment-emergent adverse events. Pharmacokinetics and immunogenicity were comparable between groups. CONCLUSIONS: Equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity support bioequivalence of CT-P16 and EU-bevacizumab in patients with nsNSCLC. TRIAL REGISTRATION NUMBER: NCT03676192.

Optical Assessment of Tear Glucose by Smart Biosensor Based on Nanoparticle Embedded Contact Lens.

Diabetes is a disease condition characterized by a prolonged, high blood glucose level, which may lead to devastating outcomes unless properly managed. Here, we introduce a simple camera-based optical monitoring system (OMS) utilizing the nanoparticle embedded contact lens that produces color changes matching the tear glucose level without any complicated electronic components. Additionally, we propose an image processing algorithm that automatically optimizes the measurement accuracy even in the presence of image blurring, possibly caused by breathing, subtle movements, and eye blinking. As a result, using in vivo mouse models and human tear samples we successfully demonstrated robust correlations across the glucose concentrations measured by three different independent techniques, validating the quantitative efficacy of the proposed OMS. For its methodological simplicity and accessibility, our findings strongly support that the innovation offered by the OMS and processing algorithm would greatly facilitate the glucose monitoring procedure and improve the overall welfare of diabetes patients.

Tear Glucose Measurement by Reflectance Spectrum of a Nanoparticle Embedded Contact Lens.

Glucose level is a primary indicator in the diagnosis and treatment of diabetes mellitus. According to the correlation between glucose concentration in blood and tears, measuring tear glucose can be an alternative to traditional strips test for blood glucose. Thus, measuring tear glucose levels could provide noninvasive monitoring of blood glucose. As a biocompatible biosensor, a nanoparticle embedded contact lens (NECL) is developed which is composed of glucose oxidase and cerium oxide (III). Using spectroscopy, we found the detectable changes in reflection spectrum of contact lenses with respect to the glucose concentration, and developed correlation curve of the reflection spectrum with known glucose level. Furthermore, we assessed tear glucose level and compared blood glucose level with the diabetic mouse model to evaluate this approach. Our algorithm for regular monitoring of glucose using contact lens biosensor may lead to noninvasive monitoring of tear glucose level. NECL may provide simple and noninvasive glucose monitoring based on the spectral changes in contact lens biosensor.

Antiferromagnetic coupling of van der Waals ferromagnetic Fe3GeTe2.

Among two-dimensional (2D) layered van der Waals materials, ferromagnetic 2D materials can be useful for compact low-power spintronic applications. One promising candidate material is Fe3GeTe2 (FGT), which has a strong perpendicular magnetic anisotropy and relatively high Curie temperature. In this study, we confirmed that an oxide layer (O-FGT) naturally forms on top of exfoliated FGT and that an antiferromagnetic coupling (AFC) exists between FGT and O-FGT layers. From a first-principles calculation, oxide formation at the interface of each layer induces an AFC between the layers. An AFC causes a tailed hysteresis loop, where two-magnetization reversal curves are included, and a negative remanence magnetization at a certain temperature range.

Materials and Applications of Smart Diagnostic Contact Lens Systems.

Contact lenses were originally developed for the purpose of vision correction, but they have recently been used for various purposes. Because contact lenses are minimally invasive, they are used in diagnostic and drug delivery applications. In particular, interest in using contact lenses for the purpose of diagnosing diseases by fusing contact lenses with information technology (IT), nanotechnology (NT), and biotechnology (BT) is increasing. These contact lens-based platforms are getting more attention as Google and Novartis develop contact lenses for diabetes diagnosis. Therefore, this chapter introduces materials that can be used for contact lens materials and diagnostic contact lenses, and discusses future prospects.