Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip)

Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip–phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 μg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers

Optically-Gated Self-Calibrating Nanosensors: Monitoring pH and Metabolic Activity of Living Cells

Quantitative detection of biological and chemical species is critical to numerous areas of medical and life sciences. In this context, information regarding pH is of central importance in multiple areas, from chemical analysis, through biomedical basic studies and medicine, to industry. Therefore, a continuous interest exists in developing new, rapid, miniature, biocompatible and highly sensitive pH sensors for minute fluid volumes. Here, we present a new paradigm in the development of optoelectrical sensing nanodevices with built-in self-calibrating capabilities. The proposed electrical devices, modified with a photoactive switchable molecular recognition layer, can be optically switched between two chemically different states, each having different chemical binding constants and as a consequence affecting the device surface potential at different extents, thus allowing the ratiometric internal calibration of the sensing event. At each point in time, the ratio of the electrical signals measured in the ground and excited states, respectively, allows for the absolute concentration measurement of the molecular species under interest, without the need for electrical calibration of individual devices. Furthermore, we applied these devices for the real-time monitoring of cellular metabolic activity, extra- and intracellularly, as a potential future tool for the performance of basic cell biology studies and high-throughput personalized medicine-oriented research, involving single cells and tissues. This new concept can be readily expanded to the sensing of additional chemical and biological species by the use of additional photoactive switchable receptors. Moreover, this newly demonstrated coupling between surface-confined photoactive molecular species and nanosensing devices could be utilized in the near future in the development of devices of higher complexity for both the simultaneous control and monitoring of chemical and biological processes with nanoscale resolution control

Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations

Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the “monitoring” of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously “control” and “monitor” chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen–antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth

Excited-State Proton Transfer and Proton Diffusion near Hydrophilic Surfaces

Time-resolved emission techniques were employed to study the reversible proton photoprotolytic properties of surface-attached 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) molecules to hydrophilic alumina and silica surfaces. We found that the excited-state proton transfer rate of the surface-linked HPTS molecules, in H₂O and D₂O, is nearly the same as of HPTS in the bulk, while the corresponding recombination rate is significantly greater. Using the diffusion-assisted proton geminate-recombination model, we found that the best fit of the time-resolved fluorescence (TRF) signal is obtained by invoking a two-dimensional diffusion space for the proton to recombine with the conjugated basic form, RO^–*, of the surface-linked HPTS. However, we obtain an excellent fit by a three-dimensional diffusion space for diffusional HPTS in bulk water. These results indicate that the photoejected solvated protons are confined to the surface for long periods of time. We suggest two plausible mechanisms responsible for two-dimensional proton diffusion next to hydrophilic surfaces

Real‐world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study

Abstract Objectives We conducted a retrospective multi‐centre study to assess the real‐world outcome of regorafenib (REGO) and cabozantinib (CABO) in recurrent/refractory bone tumours (BTs) including osteosarcoma (OST), Ewing sarcoma (EWS) and chondrosarcoma (CS)/extra‐skeletal mesenchymal CS (ESMC). Methods After regulatory approval, data from patients with recurrent BT (11 institutions) were extracted from CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) database. Patient characteristics, treatment and outcomes were collected. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From July 2018 to May 2022, 66 patients received REGO or CABO; 39 OST, 18 EWS, 4 CS and 5 ESMC. Median age was 27.8 years (range 12–76); median starting dose was 60 mg for CABO (n = 37, range 40–60) and 120 mg for REGO (n = 29, range 40–160). Twenty‐eight (42.4%) patients required dose reduction: hand‐foot syndrome 7 (10.6%), nausea/vomiting 1 (1.5%), diarrhoea 1 (1.5%), 2 elevated LFTs (3%), elevated bilirubin 1 (1.5%) and mucositis 1 (1.5%). The median OS for patients with OST, EWS, CS and ESMC was 8.5 months (n = 39, 95% CI 7–13.1); 13.4 months (n = 18, 95% CI 3.4–27.2), 8.1 (n = 4, 95% CI 4.1–9.3) and 18.2 (n = 5, 95% CI (10.4–na), respectively. Median PFS for OST, EWS, CS and ECMS was 3.5 (n = 39, 95% CI 2.8–5), 3.9 (n = 18, 95% CI 2.1–5.9), 5.53 (n = 4. 95% CI 2.13–NA) and 11.4 (n = 5, 95% CI 1.83–14.7), respectively. Age, line of therapy, REGO versus CABO, or time from diagnosis to initiation of TKI were not associated with PFS on univariable analysis. Conclusion Our real‐world data show that TKIs have meaningful activity in recurrent BT with acceptable toxicities when started at modified dosing. Inclusion of TKIs in earlier lines of treatment and/or maintenance therapy could be questions for future research