Biomedical Diagnostic Tools Research Articles

A novel self-assembled dual-emissive ratiometric fluorescent nanoprobe for alkaline phosphatase sensing

BackgroundAlkaline phosphatase (ALP) is widely found in various organs and tissues of the human body which could assist in the verification of the presence of various diseases through its content in the blood. In the past few years, many analytical methods for ALP activity assays have been explored. However, a simple and economical method with high sensitivity and specificity also remains great challenge. Therefore, the development of sensitive and efficient approach for ALP analysis is of great significance in biomedical studies. ResultsHerein, we constructed a highly sensitive and label-free ratiometric fluorometric biosensing platform for the determination of ALP activity, which utilizing lysozyme(Ly)-functionalized 5-methyl-2-thiouracil(MTU)-modified gold nanoclusters (MTU-Ly@Au NC) and poly-dopamine (PDA) as signal indicators. Dopamine (DA) can self-polymerizes to form PDA under alkaline conditions that can further quenched the fluorescence of MTU-Ly@Au NC at 525nm due to fluorescence resonance energy transfer (FRET) and absorption competition quenching (ACQ) effects. In this process, the PDA fluorescence intensity at 325nm was nearly unchanged. After the addition of ALP, ascorbic acid (AA) which can alleviate the self-polymerization process of DA was generated from the substrate ascorbic acid 2-phosphate (AAP), thus changing ratiometric fluorescence intensity of I525/I325. Hence, by monitoring the fluorescence ratio (I525/I325), a ratiometric fluorescence biosensing platform for ALP was established with the linear calibration in the range of 0.5–8 U L−1 and the limit of detection of 0.157 U L−1. SignificanceThis work not only synthesized a novel fluorescence probe with simple preparation and low cost for ALP which has excellent anti-interference properties and selectivity. Furthermore, this biosensing platform was successfully applied for the determination of ALP activity in human serum samples. This work provided a potential tool for biomedical diagnostics in the future.

Nanothermometer Based on Polychlorinated Trityl Radicals Showing Two-Photon Excitation and Emission in the Biological Transparency Window: Temperature Monitoring of Biological Tissues.

Nanothermometers are emerging probes as biomedical diagnostic tools. Especially appealing are nanoprobes using NIR light in the range of biological transparency window (BTW) since they have the advantages of a deeper penetration into biological tissues, better contrast, reduced phototoxicity and photobleaching. This article reports the preparation and characterization of organic nanoparticles (ONPs) doped with two polychlorinated trityl radicals (TTM and PTM), as well as studies of their electronic and optical properties. Such ONPs having inside isolated radical molecules and dimeric excimers, can be two-photon excited showing optimal properties for temperature sensing. Remarkably, in TTM-based ONPs the emission intensity of the isolated radical species is unaltered increasing temperature, while the excimer emission intensity decreases strongly being thereby able to monitor temperature changes with an excellent thermal absolute sensitivity of 0.6-3.7%K-1 in the temperature range of 278-328K. The temperature dependence of the excimeric bands of ONPs are theoretically simulated by using electronic structure calculations and a vibronic Hamiltonian model. Finally, TTM-doped ONPs as ratiometric NIR-nanothermometers are tested with two-photon excitationwith enucleated pig eye sclera, as a real tissue model, obtaining a similar temperature sensitivity as in aqueous suspensions, demonstrating their potential as NIR nanothermometers for bio applications.

Plasmonic Biosensors Based on Deformed Graphene

Rapid, accurate, and label-free detection of biomolecules and chemical substances remains a challenge in healthcare. Optical biosensors have been considered as biomedical diagnostic tools required in numerous areas including the detection of viruses, food monitoring, diagnosing pollutants in the environment, global personalized medicine, and molecular diagnostics. In particular, the broadly emerging and promising technique of surface plasmon resonance has established to provide real-time and label-free detection when used in biosensing applications in a highly sensitive, specific, and cost-effective manner with small footprint platform. In this study we propose a novel plasmonic biosensor based on biaxially crumpled graphene structures, wherein plasmon resonances in graphene are utilized to detect variations in the refractive index of the sample medium. Shifts in the resonance wavelength of the plasmon modes for a given change in the RI of the surrounding analyte are calculated by investigating the optical response of crumpled graphene structures on different substrates using theoretical computations based on the finite element method combined with the semiclassical Drude model. The results reveal a high sensitivity of 4990 nm/RIU, corresponding to a large figure-of-merit of 20 for biaxially crumpled graphene structures on polystyrene substrates. We demonstrate that biaxially crumpled graphene exhibits superior sensing performance compared with a uniaxial structure. According to the results, crumpled graphene structures on a titanium oxide substrate can improve the sensor sensitivity by avoiding the damping effects of polydimethylsiloxane substrates. The enhanced sensitivity and broadband mechanical tunability of the biaxially crumpled graphene render it a promising platform for biosensing applications.

New insight into the application of fluorescence platforms in tumor diagnosis: From chemical basis to clinical application.

Early and rapid diagnosis of tumors is essential for clinical treatment or management. In contrast to conventional means, bioimaging has the potential to accurately locate and diagnose tumors at an early stage. Fluorescent probe has been developed as an ideal tool to visualize tumor sites and to detect biological molecules which provides a requirement for noninvasive,real-time, precise, and specific visualization of structures and complex biochemical processes in vivo. Rencently, the development of synthetic organic chemistry and new materials have facilitated the development of near-infrared small molecular sensing platforms and nanoimaging platforms. This provides a competitive tool for various fields of bioimaging such as biological structure and function imaging, disease diagnosis, in situ at the in vivo level, and real-time dynamic imaging. This review systematically focused on the recent progress of small molecular near-infrared fluorescent probes and nano-fluorescent probes as new biomedical imaging tools in the past 3-5years, and it covers the application of tumor biomarker sensing, tumor microenvironment imaging, and tumor vascular imaging, intraoperative guidance and as an integrated platform for diagnosis, aiming to provide guidance for researchers to design and develop future biomedical diagnostic tools.

Plasmonic Biosensors: Review.

Simple SummaryPlasmonic biosensors have extremely unique properties due to their high specificity and sensitivity in the detection of pathogens, making them of great interest to be used in various areas such as viral detection, diagnosing pollutants in the environment, and monitoring biomolecules in food. Plasmonic biosensors work by functionalizing a surface with an antibody which upon binding to an antigen results in variation in the angle of reflection which represents changes in the resonance conditions observed. Plasmonic biosensors are therefore thoroughly designed, fabricated, and optimized using explicitly selected plasmonic substrates. Hence, choosing the appropriate materials, structures, and functionality is of great importance to develop plasmonic biosensors highly specific for their application in real-life situations. Sensors based on surface plasmon resonance (SPR), localized SPR (LSPR), and Surface-enhanced Raman scattering (SERS) have been used over the years to monitor environmental biological molecules, ensure food safety, and detect up-to-date pathogens and viruses. This review article will discuss the mechanism of plasmonic biosensors, methods of controlling the efficiency, and their different designs when used in various applications.Biosensors have globally been considered as biomedical diagnostic tools required in abundant areas including the development of diseases, detection of viruses, diagnosing ecological pollution, food monitoring, and a wide range of other diagnostic and therapeutic biomedical research. Recently, the broadly emerging and promising technique of plasmonic resonance has proven to provide label-free and highly sensitive real-time analysis when used in biosensing applications. In this review, a thorough discussion regarding the most recent techniques used in the design, fabrication, and characterization of plasmonic biosensors is conducted in addition to a comparison between those techniques with regard to their advantages and possible drawbacks when applied in different fields.

Invited Article: Comparison of hyperspectral coherent Raman scattering microscopies for biomedical applications

Raman scattering based imaging represents a very powerful optical tool for biomedical diagnostics. Different Raman signatures obtained by distinct tissue structures and disease induced changes provoke sophisticated analysis of the hyperspectral Raman datasets. While the analysis of linear Raman spectroscopic tissue data is quite established, the evaluation of hyperspectral nonlinear Raman data has not yet been evaluated in great detail. The two most common nonlinear Raman methods are CARS (coherent anti-Stokes Raman scattering) and SRS (stimulated Raman scattering) spectroscopy. Specifically the linear concentration dependence of SRS as compared to the quadratic dependence of CARS has fostered the application of SRS tissue imaging. Here, we applied spectral processing to hyperspectral SRS and CARS data for tissue characterization. We could demonstrate for the first time that similar cluster distributions can be obtained for multispectral CARS and SRS data but that clustering is based on different spectral features due to interference effects in CARS and the different concentration dependence of CARS and SRS. It is shown that a direct combination of CARS and SRS data does not improve the clustering results.

Application of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Imaging Mass Spectrometry (MALDI-TOF IMS) for Premalignant Gastrointestinal Lesions

Imaging mass spectrometry (IMS) is currently receiving large attention from the mass spectrometric community, although its use is not yet well known in the clinic. As matrix-assisted laser desorption/ionization time-of-flight (MALDI)-IMS can show the biomolecular changes in cells as well as tissues, it can be an ideal tool for biomedical diagnostics as well as the molecular diagnosis of clinical specimens, especially aimed at the prompt detection of premalignant lesions much earlier before overt mass formation, or for obtaining histologic clues from endoscopic biopsy. Besides its use for pathologic diagnosis, MALDI-IMS is also a powerful tool for the detection and localization of drugs, proteins, and lipids in tissue. Measurement of parameters that define and control the implications, challenges, and opportunities associated with the application of IMS to biomedical tissue studies might be feasible through a deep understanding of mass spectrometry. In this focused review series, new insights into the molecular processes relevant to IMS as well as other field applications are introduced.

The negotiation of the sick role: general practitioners’ classification of patients with medically unexplained symptoms

In encounters between general practitioners (GPs) and patients with medically unexplained symptoms (MUS), the negotiation of the sick role is a social process. In this process, GPs not only use traditional biomedical diagnostic tools but also rely on their own opinions and evaluations of a patient’s particular circumstances in deciding whether that patient is legitimately sick. The doctor is thus a gatekeeper of legitimacy. This article presents results from a qualitative interview study conducted in Denmark with GPs concerning their approach to patients with MUS. We employ a symbolic interaction approach that pays special attention to the external validation of the sick role, making GPs’ accounts of such patients particularly relevant. One of the article’s main findings is that GPs’ criteria for judging the legitimacy of claims by those patients that present with MUS are influenced by the extent to which GPs are able to constitute these patients as people with social problems and problematic personality traits.

Support vector machine ensembles for breast cancer type prediction from mid-FTIR micro-calcification spectra

Over the past years Fourier transform infrared (FTIR) spectroscopy has been demonstrated as a prospective tool for cancer diagnostics. In order to apply FTIR spectroscopy as a routine tool for biomedical diagnostics of tissue samples, strong and reliable classifiers are needed. Frequently, the number of available tissue samples is restricted and due to that data sets consist of a small number of samples, often less than 100. This can result in unstable classifiers, which perform poorly on unseen data. In this work we present a way to overcome this limitation by aggregating several support vector machines in to an ensemble. Different ensemble systems, including bagging, boosting and tree-based models, were investigated for a FTIR data set acquired from different types and stages of breast cancer. It was found that an ensemble system predicts 88.9% of the unseen multi-class test set correctly. In comparison a single classifier only achieved a predictive performance of 66.7%. As these results show, the application of SVM ensembles in biomedical diagnostics using FTIR spectroscopy can be highly beneficial.

Magnetoliposomes as Multimodal Contrast Agents for Molecular Imaging and Cancer Nanotheragnostics

In the emerging field of molecular and cellular imaging, flexible strategies to synthesize multimodal contrast agents with targeting ligands are required. Liposomes have the ability to combine with a large variety of nanomaterials, including superparamagnetic iron oxide nanoparticles, to form magnetoliposomes (MLs). MLs can be used as highly efficient MRI contrast agents. Owing to their high flexibility, MLs can be associated with other imaging modality probes to be used as multimodal contrast agents. By using a thermosensitive lipid bilayer in the ML structure, these biocompatible systems offer many possibilities for targeting and delivering therapeutic agents for 'theragnostics', a coincident therapy and diagnosis strategy. This article deals with the fast-growing field of MLs as biomedical diagnostic tools. Different kinds of MLs, their preparation methods, as well as their surface modification with different imaging probes, are discussed. ML applications as multimodal contrast agents and in theragnostics are reviewed. Some important issues for the biomedical uses of magnetic liposomes, such as toxicity, are summarized.

Imaging Mass Spectrometry: Hype or Hope?

Imaging mass spectrometry is currently receiving a significant amount of attention in the mass spectrometric community. It offers the potential of direct examination of biomolecular patterns from cells and tissue. This makes it a seemingly ideal tool for biomedical diagnostics and molecular histology. It is able to generate beautiful molecular images from a large variety of surfaces, ranging from cancer tissue sections to polished cross sections from old-master paintings. What are the parameters that define and control the implications, challenges, opportunities, and (im)possibilities associated with the application of imaging MS to biomedical tissue studies. Is this just another technological hype or does it really offer the hope to gain new insights in molecular processes in living tissue? In this critical insight this question is addressed through the discussion of a number of aspects of MS imaging technology and sample preparation that strongly determine the outcome of imaging MS experiments.