Real‐time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical ...agents with high renal clearance and high signal‐to‐background ratio (SBR). Herein, a second near‐infrared (NIR‐II) fluorescent molecular semiconductor (CDIR2) is synthesized for real‐time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post‐injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real‐time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR‐II fluorescent agents.
A second near‐infrared (NIR‐II) fluorescent molecular semiconductor is synthesized. The fluorophore not only has a high renal clearance efficiency, but also undergoes unidirectional glomerular filtration into urine, enabling real‐time NIR‐II fluorescence imaging of kidney dysfunction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel ternary-emission fluorescence sensor was proposed by post-imprinting mixing blue-/green-/red-emission bovine hemoglobin (BHb) imprinted polymers (b-MIPs, g-MIPs, and r-MIPs) at a proper ratio ...and realized the multiplexed and visual detection of BHb. The three MIPs were individually embedded with blue-emission 7-hydroxycoumarin, green-emission CdTe quantum dots (QDs), and red-emission CdTe/ZnS QDs. Upon interaction with BHb within 8 min, the fluorescence of CdTe and CdTe/ZnS QDs were simultaneously turned off, whereas the 7-hydroxycoumarin turned on the fluorescence intensity. Thereupon, the ratiometric fluorescence intensity of the ternary emission linearly varied within 0.025–3 μM BHb, accompanying the profuse fluorescence color evolution from yellowish green to yellow to salmon to plum to purple to finally blue. In comparison with the dual- or single-emission sensor, the ternary-emission fluorescence MIPs sensor provided a wider color variation covering the green–red–blue window for accurate naked-eye determination of BHb, as well as a lower detection limit down to 7.8 nM and a higher imprinting factor of 15.2. Moreover, the satisfactory recoveries of 99.25–111.7% in determining the spiked BHb in bovine urine samples, as well as the optical stability and post-imprinting construction convenience, indicated that the developed tricolor-emission fluorescence MIPs sensor provided an ideal alternative for rapid, sensitive, and visual determination of proteins in complicated samples.
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IJS, KILJ, NUK, PNG, UL, UM
Smartphone-based point-of-care testing (POCT) is rapidly emerging as a potential alternative to the traditional laboratory-based diagnostic testing owing to economic considerations and availability ...of medical equipment especially in resource-limited areas. A smartphone, combined with a biosensor and other related accessories, can offer high accuracy and sensitivity for medical testing. Moreover, the ubiquity of smartphone has propelled the development considerably, and accordingly research in recent years has shown promising progress in POCT. Here, we used samples (blood, urine, sweat, saliva and tears) of liquid biopsy as the standard for classification of smartphone-based POCT devices, considering that these samples contain multiple biomarkers of serious diseases. The colorimetric, fluorescent, brightfield, and electrochemical methods were utilized to examine these samples. We performed a comprehensive review of the development of smartphone-based POCT devices over the past two years (2017–2018) and assessed their relative merits and drawbacks. Based on the progress of POCT development, it illustrates that the various technological and economical requirements are urgent and tremendous. The tendency of high-quality, low-cost smartphone-based POCT devices, feature of biosensors (paper-based sensor, flexible device, microfluidic chip, et al.) currently widely used in POCT and recommendations of future works were summarized.
•The samples of liquid biopsy as the standard for classification of point of care testing since those samples often contain multiple important biomarkers.•The development of smartphone-based POCT devices in last two years (2017–2018) was comprehensively reviewed.•Novel directions of POCT application and research were proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at ...recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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KISLJ, NUK, SBMB, UL, UM, UPUK
Despite the many ergonomic advantages of eccrine perspiration (sweat) compared to other possible biofluids (particularly in “wearable” devices), sweat remains an underrepresented source of biomarker ...analytes compared to the established biofluids blood, urine, and saliva. Upon closer comparison to other non‐invasive biofluids, the advantages may even extend beyond ergonomics: sweat might provide superior analyte information. A number of challenges, however, have historically kept sweat from its place in the pantheon of clinical samples. These challenges include very low sample volumes (nL to µL), unknown concentration due to evaporation, filtration and dilution of large analytes, mixing of old and new sweat, and the potential for contamination from the skin surface. More recently, rapid progress in “wearable” sweat sampling and sensing devices has resolved several of the historical challenges. However, this recent progress has also been limited to high concentration analytes (µM to mM) sampled at high sweat rates (>1 nL/min/gland, e.g. athletics). Progress will be much more challenging as sweat biosensing moves towards use with sedentary users (low sweat rates or not sweating at all) and/or towards low concentration analytes (pM to nM). Addressing these unresolved challenges will require significant advances in sweat stimulation, sample collection efficiency, compact sensors, and likely more. Fortunately, none of the remaining challenges appear to be fundamentally blocking, and scientific and engineering innovations have the opportunity to enable broader application of sweat biosensing technology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A negatively charged poly(para‐phenyleneethynylene) (PPE) forms electrostatic complexes with four positively charged antimicrobial peptides (AMP). The AMPs partially quench the fluorescence of the ...PPE and discriminate fourteen different bacteria in water and in human urine by pattern‐based fluorescence recognition; the AMP‐PPE complexes bind differentially to the components of bacterial surfaces. The bacterial species and strains form clusters according to staining properties (Gram‐positive and Gram‐negative) or genetic similarity (genus, species, and strain). The identification and data treatment is performed by pattern evaluation with linear discriminant analysis (LDA) of the collected fluorescence intensity data.
Discriminated! Electrostatic complexes formed from four cationic antimicrobial peptides (AMPs) and one anionic poly(para‐phenylene‐ethynylene) (PPE) were examined as a new type of an array‐based sensor. The array identifies and discriminates 14 different types of bacteria according to Gram status and their genetic relationship in human urine by subjecting the obtained fluorescence response patterns to linear discriminant analysis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a ...comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Circulating miRNAs are detected in extracellular space and body fluids such as urine. Circulating RNAs can be packaged in secreted urinary extracellular vesicles (uEVs) and thus protected from ...degradation. Urinary exosome preparations might contain specific miRNAs, relevant as biomarkers in renal and bladder diseases. Major difficulties in application of uEVs into the clinical environment are the high variability and low reproducibility of uEV isolation methods. Here we used five different methods to isolate uEVs and compared the size distribution, morphology, yield, presence of exosomal protein markers and RNA content of uEVs. We present an optimized ultracentrifugation and size exclusion chromatography approach for highly reproducible isolation for 50-150 nm uEVs, corresponding to the exosomes, from 50 ml urine. We profiled the miRNA content of uEVs and total urine from the same samples with the NanoString platform and validated the data using qPCR. Our results indicate that 18 miRNAs, robustly detected in uEVs were always present in the total urine. However, 15 miRNAs could be detected only in the total urine preparations and might represent naked circulating miRNA species. This is a novel unbiased and reproducible strategy for uEVs isolation, content normalization and miRNA cargo analysis, suitable for biomarker discovery studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Serotonin (5‐hydroxytryptamine, HT), a neurotransmitter, and its main metabolite 5‐hydroxyindole‐3‐acetic acid (HIAA) are biomarkers for carcinoid tumors. They can be quantitatively detected by a new ...luminescent sensor based on a water stable lanthanide metal–organic framework (Ln‐MOF). This Ln‐MOF features a (3,4)‐connected topology containing 1D channels occupied by lattice water molecules. Luminescent studies reveal that high luminescence quenching efficiency occurs upon the addition of HT and HIAA. The Ln‐MOF also displays excellent sensitivity with fast response within 1 min, good reusability, and detection limits as low as 0.66 and 0.54 × 10−6m for HT and HIAA, respectively. In addition, the sensing function exhibits excellent selectivity even in the presence of other neurotransmitters and the main coexisting species in blood plasma and urine.
Two novel water stable lanthanide‐functionalized metal–organic frameworks(Ln‐MOFs) with a 3D open framework are synthesized under hydrothermal conditions. Ln‐MOF 1 has the capability of sensing 5‐hydroxytryptamine (HT) and its major metabolite 5‐hydroxyindole‐3‐acetic acid (HIAA), which are effective discriminating biomarkers for carcinoid tumors. In addition, the sensing function can prevent from the interference of other coexisting species in blood plasma and urine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The reuse of waste polyethylene terephthalate for green and low-cost synthesis of fluorescent carbon dots for “on-off-on” sensing of ferric and pyrophosphate ions.
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The increasing ...production of waste polyethylene terephthalate (PET) is a growing problem worldwide. Environmentally benign conversion of waste PET to valuable materials remains a substantial challenge. In this paper, we developed a green route to reuse waste PET for low-cost synthesis of fluorescent carbon dots (CDs) via air oxidation followed by hydrothermal treatment in aqueous H2O2 solution. No expensive, corrosive, or toxic reagents, or severe conditions were required in the synthetic process. The resultant CDs possessed abundant oxygenous groups and unique photoluminescence (PL) properties, which showed a highly selective and sensitive detection of ferric ion (Fe3+) through a PL quenching effect (on-off). The fluorescence of CDs quenched by Fe3+ could be restored specifically with pyrophosphate anion (PPi), rendering the CDs/Fe3+ sensor promising for PPi detection (off-on). The linear ranges for Fe3+ and PPi detections were 0.5–400 and 2–600 μM, and the limit of detections (LODs) were 0.21 and 0.86 μM, respectively. The sensing system applied for Fe3+ and PPi assays in real water samples and human urine achieved good results. After detailed investigations, a possible electron transfer process was proposed for explaining the “on-off-on” sensing mechanism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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