Luminescence bioimaging is widely used for noninvasive monitoring of biological targets in real-time with high temporal and spatial resolution. For efficient bioimaging in vivo, it is essential to develop smart organic dye platforms. Fluorescein (FL), a traditional dye, has been widely used in the biological and clinical studies. However, visible excitation and emission limited their further application for in vivo bioimaging. Nearinfrared (NIR) dyes display advantages of bioimaging because of their minimum absorption and photo-damage to biological samples, as well as deep tissue penetration and low auto-luminescence from background in the living system. Thus, some great developments of near-infrared fluorescein-inspired dyes have emerged for bioapplication in vitro and in vivo. In this review, we highlight the advances in the development of the near-infrared chemodosimeters for detection and bioimaging based on the modification of fluoresceininspired dyes naphtho-fluorescein (NPF) and cyanine-fluorescein (Cy-FL).

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel inflammatory biomarker, which is useful as an adjunct identification tool for cardiovascular disease. However, the important limitation of the conventional enzyme-linked immunosorbent assay (PLAC ELISA) for Lp-PLA2 assay is its relatively low sensitivity and time consuming. A method to measure the Lp-PLA2 simply, rapidly and sensitively is essential for predicting cardiovascular events in clinic. Methods: We took advantage of magnetic separation integrated with chemiluminescence to detect Lp-PLA2. The concentration of Lp-PLA2 was measured through a one-step process by mixing antibody labelled magnetic beads, antigen and antibody at one time. Results: Our method realized the sample to answer within 17 min. The detection limit and measurement range were 0.18 ng/ml and 0.18-1350 ng/ml, respectively. The specificity assay showed that no appreciable interference was observed for the substances of bilirubin, triglyceride, hemoglobin, rheumatoid factor and human anti-mouse antibody up to the concentrations of 40 mg/dl, 1000 mg/dl, 2000 mg/dl, 1500 IU/ml and 30 ng/ml, separately. We also tested 122 clinical samples using our method, presenting good overall correlations (R2 = 0.979) to the PLAC ELISA. It is worth mentioning that, our method was faster, had a wider range of measurement and higher sensitivity compared with the PLAC ELISA. Conclusions: The Lp-PLA2 assay is straightforward, sensitive and precise, which is highly suitable to further explore the clinical performance of Lp-PLA2 in studies of cardiovascular risk management.

Creating complex three-dimensional structures from soft yet durable materials enables advances in fields such as flexible electronics, regenerating tissue engineering, and soft robotics. Tough hydrogels that mimic the human skin can bear enormous mechanical loads. By employing a spider-inspired biomimetic microfluidic nozzle, we successfully achieve continuous printing of tough hydrogels into fibers, two-dimensional networks, and even three-dimensional structures without compromising their extreme mechanical properties. The resultant thin fibers demonstrate a stretch up to 21 times of their original length at a water content of 52%, and are intrinsically transparent, biocompatible, and conductive at high stretches. Moreover, the printed robust tough-hydrogel networks can sense strain that are orders of magnitude lower than stretchable conductors by percolations of conductive particles. To demonstrate their potential application, we use printed tough-hydrogel fiber networks as wearable sensors for detecting human motions. The capability to shape tough hydrogels into complex structures by scalable continuous printing opens opportunities for new areas of applications such as tissue scaffolds, large-area soft electronics, and smart textiles.

Nanometer-scale pores have been developed for the detection, characterization, and quantification of a wide range of analytes (e.g., ions, polymers, proteins, anthrax toxins, neurotransmitters, and synthetic nanoparticles) and for DNA sequencing. We describe the key requirements that made this method possible and how the technique evolved. Finally, we show that, despite sound theoretical work, which advanced both the conceptual framework and quantitative capability of the method, there are still unresolved questions that need to be addressed to further improve the technique.

Flexible and low-voltage photosensors with high near-infrared (NIR) sensitivity are critical for realization of interacting humans with robots and environments by thermal imaging or night vision techniques. In this work, we for the first time develop an easy and cost-effective process to fabricate flexible and ultrathin electrolyte-gated organic phototransistors (EGOPTs) with high transparent nanocomposite membranes of high-conductivity silver nanowire (AgNW) networks and large-capacitance iontronic films. A high responsivity of 1.5 × 103 A·W1-, high sensitivity of 7.5 × 105, and 3 dB bandwidth of ∼100 Hz can be achieved at very low operational voltages. Experimental studies in temporal photoresponse characteristics reveal the device has a shorter photoresponse time at lower light intensity since strong interactions between photoexcited hole carriers and anions induce extra long-lived trap states. The devices, benefiting from fast and air-stable operations, provide the possibility of the organic photosensors for constructing cost-effective and smart optoelectronic systems in the future.

Leukocyte is an important indicator of a variety of blood-related diseases. In order to improve the efficiency of the manual diagnosis of abnormal white blood cells, this paper presents a self-focusing imaging method for automated white blood cell recognition. The method divides the process into two stages: coarse and fine focusing, and the PID algorithm is introduced to drive the samples for automatically imaging. The method proposed in this paper is superior to the traditional focusing algorithm in terms of accuracy and efficiency. On our hardware platform, it only takes 1.4 s for self-focusing with high accuracy at a resolution of 4070*3072.

In this work, we investigate the pulsation of an electrically charged jet surrounded by an immiscible dielectric liquid in flow-focusing capillary microfluidics. We have characterized a low-frequency large-amplitude pulsation and a high-frequency small-amplitude pulsation, respectively. The former, due to the unbalanced charge and fluid transportation is responsible for generating droplets with a broad size distribution. The latter is intrinsic and produces droplets with a relatively narrow size distribution. Moreover, the average size of the final droplets can be tuned via the intrinsic pulsating frequency through changing the diameter of the emitted liquid jet. Our results provide degree of control over the emulsion droplets with submicron sizes generated in microfluidic-electrospray platform.

Personalized theranostics of cancer is increasingly desired, and can be realized by virtue of multifunctional nanomaterials with possible high performances. Gold nanoparticles (GNPs) are a type of especially promising candidate for cancer theranostics, because their synthesis and modification are facile, their structures and physicochemical properties are flexibly controlled, and they are also biocompatible. Especially, the localized surface plasmon resonance and multivalent coordination effects on the surface endow them with NIR light-triggered photothermal imaging and therapy, controlled drug release, and targeted drug delivery. Although the structure, properties, and theranostic application of GNPs are considerably plentiful, no expert review systematically explains the relationships among their structure, property. and application and induces the engineering rationales of GNPs for cancer theranostics. Hence, there are no clear rules to guide the facile construction of optimal GNP structures aiming at a specific theranostic application. A series of structural-engineering rationales of GNPs for cancer theranostics is proposed through digging out the deep relationships between the structure and properties of GNPs. These rationales will be inspiring for guiding the engineering of specific and advanced GNPs for personalized cancer theranostics.

Proteinaceous nanometer-scale pores are ubiquitous in biology. The canonical ionic channels (e.g., those that transport Na(+), K(+), Ca(2+), and Cl(-) across cell membranes) play key roles in many cellular processes, including nerve and muscle activity. Another class of channels includes bacterial pore-forming toxins, which disrupt cell function, and can lead to cell death. We describe here the recent development of these toxins for a wide range of biological sensing applications. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

In this paper, an automatic calibration system for binocular stereo imaging based on Zhang's 2D flat calibration method is proposed. Firstly, the interface of system is designed. After images being collected, the result of Harris corners detection extracted from the 2D flat are displayed on the interface, meanwhile, the system begins to compute intrinsic and extrinsic parameters of the stereo camera and then optimizes them by maximum likelihood estimate. Finally, mean reprojection error and the visualization of camera intrinsic parameters shown on the interface is convenient for users to analyze factors of effecting stereo camera calibration. The results appear that the proposed system not only operates easily but also obtains high precision of calibration, which improves the traditional method of camera calibration.

Organic water-gated transistors (OWGTs) have emerged as promising sensing architectures for biomedical applications and environmental monitoring due to their ability of in-situ detection of biological substances with high sensitivity and low operation voltage, as well as compatibility with various read-out circuits. Tremendous progress has been made in the development of p-type OWGTs. However, achieving stable n-type operation in OWGTs due to the presence of solvated oxygen in water is still challenging. Here, we report an ambipolar OWGT based on a bulk heterojunction active layer, which exhibits a stable hole and electron transport when exposed to aqueous environment. The device can be used as a photodetector both in the hole and electron accumulation regions to yield a maximum responsivity of 0.87 A W−1. More importantly, the device exhibited stable static and dynamic photodetection even when operated in the n-type mode. These findings bring possibilities for the device to be adopted for future biosensing platforms, which are fully compatible with low-cost and low-power organic complementary circuits.

To establish a high chemiluminescence immune analysis method for the determination of C-reactive protein (CRP) in human serum.6-[N-(4-Aminobutyl)-N-ethylamino]-2,3-dihydro-1,4-phthalazinedione (ABEI) was used as luminous marker, magnetic beads was used as solid-phase reaction carrier. When AFP in serum combined with anti-CRP monoclonal antibody labeled with ABEI and another anti-CRP monoclonal antibody labeled with fluorescein isothiocyanate isomer I (FITC) to form the "sandwich" immune complex, then added magnetic beads coupled with anti-FITC monoclonal antibody. After washing procedure, adding the substrate, the chemiluminescence reaction of immune response was triggered, and the optical signal was generated. The relative intensity (RLU) of the reaction was measured by the instrument, and the concentration of the CRP in the sample was calculated. A complete test can be completed within 25 minutes, the average recovery rate was between 90% and 110%.A good linear relationship was detected in the concentration range of human serum CRP, the linear correlation coefficient of linear dilution effect is more than 0.9900. The method was accurate and reproducible, and the sensitivity of CRP was less than 0.13 ng/ml, and the detection limit was 0.13 ng/ml. The average recovery rate was 99%, the intra coefficient of variation (CV) was 3.24%~4.21%, and inter-assay coefficient of variation was 8.73%~9.35%. We established a chemiluminescence immunoassay to quantify the level of CRP in human serum. The results of performance evaluation showed it was an accurate, reliable and meet the needs of clinical testing.

Alpha fetoprotein (AFP) has been identified as a specific marker of hepatocellular carcinoma (HCC). Our perpose is to develop a new fluorescence immunoassay based on Alexa fluor-647 to determine the concentration of AFP in serum. Alexa fluor-647 and magnetic beads were applied in labeling two different anti-AFP monoclonal antibodies. Both labeled antibodies and AFP antigen formed a sandwiched immunocomplex. After washing in a magnetic field, the fluorescent intensity of Alexa fluor-647 in the immunocomplex was measured and the value was directly in proportion to the levels of AFP present in the samples. The influence of two physicochemical parameters involved in the assay signals were optimized and the parameters of the proposed method were assessed. The consequence showed the detection limit of the proposed method was 1.1 ng/mL. The coefficient of variation (CV) was less than 6% for intra-assay precision. An entire assay could be finished in 25 min. This assay provided a new way to quantitatively measure AFP in serum for the diagnosis of HCC.

The scale space-based method has been recently studied for multispectral alignment; however, due to the significant intensity difference between the image pairs, there are usually not enough keypoint correspondences found, and the robustness of the alignment tends to be compromised. In this letter, we attempt to improve the performance from the following two aspects: 1) to avoid the boundary blurring of Gaussian scale space, we adopt nonlinear scale space to explore more keypoints with potential of being correctly matched, and 2) a robust feature descriptor is proposed, and the resulting feature matrix is matched using the previously proposed rotation-invariant distance to obtain more correct keypoint correspondences. Experimental results for multispectral remote images indicate that the proposed method improves the matching performance compared to state-of-the-art methods in terms of correctly matched number of keypoints, aligning accuracy, and rate of correctly matched image pairs. It is also revealed in this letter that, if the descriptor is carefully designed, the local features are distinctive enough for produce good matching even when the main orientation is not present.

Protein S100B is a clinically useful non-invasive biomarker for brain cell damage. A rapid chemiluminescence immunoassay (CLIA) for S100B in human serum has been developed. Fluorescein isothiocyanate (FITC) and N-(aminobutyl)-N-(ethylisoluminol) (ABEI) are used to label two different monoclonal antibodies of anti-S100B. Protein S100B in serum combines with labeled antibodies and can form a sandwiched immunoreaction. A simplified separation procedure based on the use of magnetic particles (MPs) that were coated with anti-FITC antibody is performed to remove the unwanted materials. After adding the substrate solution, the relative light unit (RLU) of ABEI is measured and is found to be directly proportional to the concentration of S100B in serum. The relevant variables involved in the CLIA signals are optimized and the parameters of the proposed method are evaluated. The results demonstrate that the method is linear to 25 ng/mL S100B with a detection limit of 0.02 ng/mL. The coefficient of variation (CV) is < 5% and < 6% for intra- and interassay precision, respectively. The average recoveries are between 97 and 107%. The linearity-dilution effect produces a linear correlation coefficient of 0.9988. Compared with the commercial kit, the proposed method shows a correlation of 0.9897. The proposed method displays acceptable performance for quantification of S100B and is appropriate for use in clinical diagnosis.

To satisfy the need of electrolyte tests of Automatic Biochemical Analyzer, a flow injection dynamic ion analysis method was proposed based on method and experiments, this new method combined the advantages of Flow Injection Analysis (FIA) and Ion Selective Electrode (ISE). With embedded technology, we developed a new electrolyte module and the clinical trials show that the electrolyte module meets the requirements of clinical application with the Coefficient of Variability (CV) of K+, Na+ and Cl- are 1.02%, 0.89% and 0.75% is better than the pre-existing analyzers. Compared with Electrolyte Analyzers, its test speed reaches an advanced level (150Samples/h) and can be associated with Automatic Biochemical Analyzer flexibly. The module has certain application prospect in the field of high-speed electrolyte analysis.

Our objective is to develop an assay based on magnetic particles (MPs) to determine the concentration of procalcitonin (PCT) using a chemiluminescence immunoassay (CLIA). Fluorescein isothiocyanate (FITC) and N-(aminobutyl)-N-(ethylisoluminol) (ABEI) were used to label two different anti-procalcitonin (PCT) monoclonal antibodies. The labeled antibodies, the PCT antigen, and the anti-FITC antibody-coated MPs formed a double-sandwiched immunocomplex. The measured relative light units (RLUs) of ABEI in the substrate solution were directly proportional to the amount of PCT present in the samples. The proposed method was linear to 600 ng/mL with a detection limit of 0.03 ng/mL. The coefficient of variation (CV) was <5% and <6% for the intra- and inter-assay precision, respectively. The average recoveries were between 95 and 107%. The linearity-dilution effect gave a linear correlation coefficient of 0.9912. This proposed assay provided an alternative method to quantitatively measure PCT in serum for the diagnosis of sepsis.