Over the past few decades, colorimetric paper-based lateral flow immunoassay (LFIA) has emerged as a versatile analytical tool for rapid point-of-care detection of infectious diseases with high simplicity and flexibility. The LFIA sensitivity is based on color visualization of the antibody-labeled nanoparticles bound with the target analytes at the test line. Therefore, the nanoparticle design is crucial for LFIA sensitivity. The traditional LFIA is based on spherical gold nanoparticles, which usually suffer from poor sensitivity because of very low optical contrast at the test line. To improve the LFIA sensitivity, we have developed an LFIA based on gold nanostars (GNSs) with different branch lengths and sharpness (GNS-1, GNS-2, and GNS-3), which possess higher optical contrast than conventional gold nanospheres (GNSPs). We have selected the bacterium Yersinia pestis as a model analyte system. The effective affinity of GNSPs and GNSs with the Y. pestis fraction 1 (F1) protein was quantitively investigated by colorimetric and optical density measurements of the test line. The results show that GNS-3, which has maximum spike length and branch sharpness, exhibits the highest analytical sensitivity based on the limit of detection of the LFIA readout compared to other GNSs and GNSPs. The detection limit of the Y. pestis F1 antigen was achieved up to 0.1 ng/mL for GNS-3, which is 100 times lower than that for the GNSP at a 1 pmol/L concentration and 10 times lower than that for the reported procedure based on traditional gold nanoparticles. Overall, our prototype LFIA platform based on a highly spiked GNS (GNS-3) exhibits high analytical sensitivity, indicating it to be a promising candidate for routine LFIA application to detect infectious diseases.

Depression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

Antibody microarrays have proven useful in immunoassay-based point-of-care diagnostics for infectious diseases. Noncontact piezoelectric inkjet printing has advantages to print antibody microarrays on nitrocellulose substrates for this application due to its compatibility with sensitive solutions and substrates, simple droplet control, and potential for high-capacity printing. However, there remain real-world challenges in printing such microarrays, which motivated this study. The effects of three concentrations of capture antibody (cAb) reagents and nozzle hydrostatic pressures were chosen to investigate three responses: the number of printed membrane disks, dispensing performance, and microarray quality. Printing conditions were found to be most ideal with 5 mg/mL cAb and a nozzle hydrostatic pressure near zero, which produced 130 membrane disks in a single print versus the 10 membrane disks per print before optimization. These results serve to inform efficient printing of antibody microarrays on nitrocellulose membranes for rapid immunoassay-based detection of infectious diseases and beyond.

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