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Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I-III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

Epidermal growth factor receptor (EGFR) nuclear translocation correlates with the abnormal proliferation, migration, and anti-apoptosis of tumor cells. Monitoring EGFR nuclear translocation provides insights into the molecular mechanisms underlying cancers. EGFR nuclear translocation includes two processes, EGFR phosphorylation and phosphorylated EGFR translocation to the nucleus. With the help of aptamers, probes that can achieve the first step of anchoring phosphorylated EGFR have been developed. However, the EGFR nuclear translocation can last for hours, posing a challenge to monitor the entire nuclear translocation in living cells. Herein, we designed a circular bivalent aptamer-functionalized optical probe with greatly enhanced stability for long-term visualization of EGFR nuclear translocation in situ. The results of cell experiments show that the probe could monitor the entire nuclear translocation of EGFR. The findings of tissue and

Probe-modified nanopores/nanochannels are one of the most advanced sensors because the probes interact strongly with ions and targets in nanoconfinement and create a sensitive and selective ionic signal. Recently, ionic signals have been demonstrated to be sensitive to the probe-target interaction on the outer surface of nanopores/nanochannels, which can offer more open space for target recognition and signal conversion than nanoconfined cavities. To enhance the ionic signal, we investigated the effect of grafting density, a critical parameter of the sensing interface, of the probe on the outer surface of nanochannels on the change rate of the ionic signal before and after target recognition (β). Electroneutral peptide nucleic acids and negatively charged DNA are selected as probes and targets, respectively. The experimental results showed that when adding the same number of targets, the β value increased with the probe grafting density on the outer surface. A theoretical model with clearly defined physical properties of each probe and target has been established. Numerical simulations suggest that the decrease of the background current and the aggregation of targets at the mouth of nanochannels with increasing probe grafting density contribute to this enhancement. This work reveals the signal mechanism of probe-target recognition on the outer surface of nanochannels and suggests a general approach to the nanochannel/nanopore design leading to sensitivity improvement on the basis of relatively good selectivity.

Activity-based near-infrared (NIR) fluorescent probes provide powerful tools for diagnosis of diseases. However, most of these probes suffer from low specificity due to "off-target" reaction. The dual-locked strategy, which utilizes two biomarkers as triggers, can increase the specificity and precision of diagnosis. Here, we report a dual-locked NIR probe

Concurrent infection in cancer treatment is the leading cause of high cancer mortality that requires urgent action. Currently developed diagnostic methods are hindered by the difficulty of rapidly and reliably screening small amounts of pathogens in the blood and then release pathogens for downstream analysis, limiting the advance of cancer concurrent infection diseases diagnosis and targeted treatment. Herein, we present a near-infrared (NIR) light-responsive black phosphorus (BP)-based device that effectively captures and releases pathogen for downstream drug-resistance analysis. The aptamer-modified BP nanostructures exhibit enhanced topographical interactions and binding capabilities with pathogen, enabling highly efficient and selective capture of pathogen in serum. NIR light irradiation induces BP nanostructure to generate a local thermal effect, which regulates the three-dimensional structure of the aptamer and causes efficient release of pathogen from the substrate surface. The released pathogen is resistant to ampicillin as demonstrated by downstream genetic analysis. The design of the functionalized light-controlled device for monitoring pathogen behavior shows great potential for assisting in cancer therapy and promoting personalized healthcare.

Persistent nanophosphors can remain luminescent after excitation ceases; thus, they offer a promising way to avoid background fluorescence interference in bioimaging. In this work, Zn2GeO4:Ga,Mn (ZGO:Ga,Mn) persistent luminescence nanoparticles were developed and they were employed for time-gated imaging of latent fingerprints (LFP). The nanoparticles were functionalized with a carboxyl group and utilized to label LFP through reacting with the amino group in the LFP. Results proved the potent ability of ZGO:Ga,Mn in eliminating background fluorescence to afford highly sensitive LFP imaging. Moreover, LFP aged for 60 days were successfully detected due to the presence of highly stable amino acids. After being functionalized with concanavalin A, the nanoparticles achieved visualization of glycoproteins in LFP. This strategy provides great versatility in LFP imaging and good potential in uncovering the chemical information within LFP, making it valuable in forensic investigations and medical diagnostics.

Rare protein enrichment and sensitive detection hold great potential in biomedical studies and clinical practice. This work describes the use of aptamer-conjugated gold nanorods for the efficient enrichment of rare proteins from buffer solutions and human plasma. Gold nanorod (AuNR) surfaces were modified with a long PEG chain and a 15-mer thrombin aptamer for protein enrichment and detection. Studies of the effect of surface modification on enrichment efficiency of thrombin showed that a change of only one EG(6) linker unit, i.e, from 2EG(6) to 3EG(6), could increase thrombin protein capture efficiency by up to 47%. Furthermore, a 1 ppm sample of thrombin in buffer could be enriched with around 90% efficiency using a low concentration (0.19 nM) of gold nanorod probe modified with 3EG(6) spacer, and with the same probe, effective capture was achieved down to 10 ppb (1 ng) thrombin in plasma samples. In addition to alpha-thrombin enrichment, prothrombin was also efficiently captured from plasma samples via gold nanorods conjugated with 15-mer thrombin aptamer. Our work demonstrates efficient enrichment of rare proteins using aptamer-modified nanomaterials, which can be used in biomarker discovery studies.

We have developed DNA-functionalized silica nanoparticles for the rapid, sensitive, and selective detection of mercuric ion (Hg(2+)) in aqueous solution. Two DNA strands were designed to cap the pore of dye-trapped silica nanoparticles. In the presence of ppb level Hg(2+), the two DNA strands are dehybridized to uncap the pore, releasing the dye cargo with detectable enhancements of fluorescence signal. This method enables rapid (less than 20 min) and sensitive (limit of detection, LOD, 4 ppb) detection, and it was also able to discriminate Hg(2+) from twelve other environmentally relevant metal ions. The superior properties of the as-designed DNA-functionalized silica nanoparticles can be attributed to the large loading capacity and highly ordered pore structure of mesoporous silica nanoparticles, as well as the selective binding of thymine-rich DNA with Hg(2+) . Our design serves as a new prototype for metal-ion sensing systems, and it also has promising potential for detection of various targets in stimulus-release systems.

Hepatitis B virus (HBV) genotyping plays an important role in the clinical management of chronic hepatitis B (CHB) patients. However, the current nucleic acid based techniques are expensive, time-consuming, and inconvenient. Here, we developed a novel DNA-independent HBV genotyping tool based on a one-step fluorescent lateral flow immunoassay (LFIA). Epitope-targeting immunization and screening techniques were used to develop HBV genotype specific monoclonal antibodies (mAbs). These mAbs were used to develop a multitest LFIA with a matched scanning luminoscope for HBV genotyping (named the GT-LFIA). The performance of this novel assay was carefully evaluated in well-characterized clinical cohorts. The GT-LFIA, which can specifically differentiate HBV genotypes A, B, C, and D in a pretreatment-free single test, was successfully developed using four genotype specific mAbs. The detection limits of the GT-LFIA for HBV genotypes A, B, C, and D were 2.5-10.0 IU HBV surface antigen/mL, respectively. Among the sera from 456 CHB patients, 439 (96.3%; 95% confidence interval (CI), 94.1-97.8%) were genotype-differentiable by the GT-LFIA and 437 (99.5%; 95% CI, 98.4-99.9%) were consistent with viral genome sequencing. In the 21 patients receiving nucleos(t)ide analogue therapy, for end-of-treatment specimens that were HBV DNA undetectable and were not applicable for DNA-dependent genotyping, the GT-LFIA presented genotyping results that were consistent with those obtained in pretreatment specimens by viral genome sequencing and the GT-LFIA. In conclusion, the novel GT-LFIA is a convenient, fast, and reliable tool for differential HBV genotyping, especially in patients with low or undetectable HBV DNA levels.