10 research outputs found
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 H<sub>2</sub>O and D<sub>2</sub>O, 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<sup>–</sup>*, 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