Biomedical Contrast Agents Research Articles

Enhanced Photoacoustic Detection of Heparin in Whole Blood via Melanin Nanocapsules Carrying Molecular Agents.

Photoacoustic (PA) imaging has proved versatile for many biomedical applications from drug delivery tracking to disease diagnostics and postoperative surveillance. It recently emerged as a tool for accurate and real-time heparin monitoring to avoid bleeding complications associated with anticoagulant therapy. However, molecular-dye-based application is limited by high concentration requirements, photostability, and a strong background hemoglobin signal. We developed polydopamine nanocapsules (PNCs) via supramolecular templates and loaded them with molecular dyes for enhanced PA-mediated heparin detection. Depending on surface charge, the dye-loaded PNCs undergo disassembly or aggregation upon heparin recognition: both experiments and simulation have revealed that the increased PA signal mainly results from dye-loaded PNC-heparin aggregation. Importantly, Nile blue (NB)-loaded PNCs generated a 10-fold higher PA signal than free NB dye, and such PNC enabled the direct detection of heparin in a clinically relevant therapeutic window (0-4 U/mL) in whole human blood (R2 = 0.91). Furthermore, the PA signal of PNC@NB obtained from 17 patients linearly correlated with ACT values (R2 = 0.73) and cumulative heparin (R2 = 0.83). This PNC-based strategy for functional nanocapsules offers a versatile engineering platform for robust biomedical contrast agents and nanocarriers.

Bright Silicon Nanocrystals from a Liquid Precursor: Quasi-Direct Recombination with High Quantum Yield.

Silicon nanocrystals (SiNCs) with bright bandgap photoluminescence (PL) are of current interest for a range of potential applications, from solar windows to biomedical contrast agents. Here, we use the liquid precursor cyclohexasilane (Si6H12) for the plasma synthesis of colloidal SiNCs with exemplary core emission. Through size separation executed in an oxygen-shielded environment, we achieve PL quantum yields (QYs) approaching 70% while exposing intrinsic constraints on efficient core emission from smaller SiNCs. Time-resolved PL spectra of these fractions in response to femtosecond pulsed excitation reveal a zero-phonon radiative channel that anticorrelates with QY, which we model using advanced computational methods applied to a 2 nm SiNC. Our results offer additional insight into the photophysical interplay of the nanocrystal surface, quasi-direct recombination, and efficient SiNC core PL.

Multiscale optical imaging of rare-earth-doped nanocomposites in a small animal model.

Rare-earth-doped nanocomposites have appealing optical properties for use as biomedical contrast agents, but few systems exist for imaging these materials. We describe the design and characterization of (i) a preclinical system for whole animal in vivo imaging and (ii) an integrated optical coherence tomography/confocal microscopy system for high-resolution imaging of ex vivo tissues. We demonstrate these systems by administering erbium-doped nanocomposites to a murine model of metastatic breast cancer. Short-wave infrared emissions were detected in vivo and in whole organ imaging ex vivo. Visible upconversion emissions and tissue autofluorescence were imaged in biopsy specimens, alongside optical coherence tomography imaging of tissue microstructure. We anticipate that this work will provide guidance for researchers seeking to image these nanomaterials across a wide range of biological models.

Emission enhancement through Nd3+-Yb3+ energy transfer in multifunctional NaGdF4 nanocrystals.

The growing need for biomedical contrast agents has led to the current development of multi-functional materials such as lanthanide-based nanoparticles (NPs). The optical and magnetic properties these nanoparticles (NPs) possess are important to enhance current biomedical imaging techniques. To increase the optical emissions of the nanoparticles, neodymium (Nd3+) and ytterbium (Yb3+) were introduced into a magnetic host of NaGdF4. The energy transfer between Nd3+ and the Yb3+ was then investigated at multiple concentrations to determine the optimal dopant levels. The NaGdF4:Nd3+,Yb3+ nanoparticles were synthesized through a modified solvothermal method, resulting in rectangular structures, with an average side length of 17.87 ± 4.38 nm. A double dopant concentration of 10% Nd3+ and 4% Yb3+ was found to be optimal, increasing the emission intensity by 71.5% when compared to the widely used Nd3+ single dopant. Decay measurements confirm energy transfer from Nd3+ to Yb3+, with a lifetime shortening from Nd3+ 1064 nm emission and a calculated lifetime of 12.72 ms with 98% efficiency. Despite NaGdF4:Nd3+,Yb3+ NPs showing a slight decrease in their magnetic response at the expense of optimizing optical emission, as it is directly dependent on the Gd3+ concentration, a strong paramagnetic behavior was still observed. These results corroborate that NaGdF4:Nd3+,Yb3+ NPs are viable candidates for multimodal imaging.

Propagation through nonlinear time-dependent bubble clouds and the estimation of bubble populations from measured acoustic characteristics

For several decades the propagation characteristics of acoustic pulses (attenuation and sound speed) have been inverted in attempts to measure the size distributions of gas bubbles in liquids. While this has biomedical and industrial applications, most notably it has been attempted in the ocean for defence and environmental purposes, where the bubbles are predominantly generated by breaking waves. Such inversions have required assumptions, and the state–of–the–art technique still assumes that the bubbles undergo linear, steady–state monochromatic pulsations in the free field, without interacting. The measurements always violate, to a greater or lesser extent, these assumptions. The errors incurred by the use of such assumptions have been difficult to quantify, but are expected to be most severe underneath breakers in the surf zone, where the void fraction is greatest. Very few measurements have been made in this important region of the ocean. This paper provides a method by which attenuation can be predicted through clouds of bubbles which need not be homogeneous, nor restricted to linear steady–state monochromatic pulsations. To allow inversion of measured surf zone attenuations to estimate bubble populations with current computational facilities, this model is simplified such that the bubble cloud is assumed to be homogeneous and the bubbles oscillating in steady state (although still nonlinearly). The uses of the new methods for assessing the errors introduced in using state–of–the–art inversions are discussed, as are their implications for oceanographic and industrial nonlinear bubble counters, for biomedical contrast agents, and for sonar target detection in the surf zone.