Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Highly sensitive SERS platform for pathogen analysis by cyclic DNA nanostructure@AuNP tags and cascade primer exchange reaction.

The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One F508del Allele.

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one F508del-CFTR allele but has not been studied in younger children. Objectives: To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. Methods: In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.5 mg each evening; children weighing ⩾14 kg received ELX 100 mg qd, TEZ 50 mg qd, and IVA 75 mg every 12 hours. Measurements and Main Results: The primary endpoints for part A (15-d treatment period) were pharmacokinetics and safety and tolerability. For part B (24-wk treatment period), the primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics and absolute changes from baseline in sweat chloride concentration and lung clearance index2.5 (LCI2.5, defined as the number of lung turnovers required to reduce the end tidal N2 concentration to 2.5% of its starting value) through Week 24. Analysis of pharmacokinetic data from 18 children enrolled in part A confirmed the appropriateness of the part B dosing regimen. In part B, 75 children (F508del/minimal function genotypes, n = 52; F508del/F508del genotype, n = 23) were enrolled and dosed. Seventy-four children (98.7%) had adverse events, which were all mild (62.7%) or moderate (36.0%) in severity. The most common adverse events were cough, fever, and rhinorrhea. Decreases in sweat chloride concentration (-57.9 mmol/L; 95% confidence interval [CI], -61.3 to -54.6; n = 69) and LCI2.5 (-0.83 U; 95% CI, -1.01 to -0.66; n = 50) were observed from baseline through Week 24. Mean body mass index was within the normal range at baseline and remained stable at Week 24. Conclusions: In this open-label study in children 2-5 years of age, ELX/TEZ/IVA treatment was generally safe and well tolerated, with a safety profile consistent with that observed in older age groups, and led to clinically meaningful reductions in sweat chloride concentration and LCI2.5. Clinical trial registered with www.clinicaltrials.gov (NCT04537793).

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial.

Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ⩾30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children (F/MF genotypes, n = 36; F/F genotype, n = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride concentration decreased (-62.3 [95% CI, -65.9 to -58.8] mmol/L), Cystic Fibrosis Questionnaire-Revised respiratory domain score increased (13.3 [95% CI, 11.4 to 15.1] points), and lung clearance index 2.5 decreased (-2.00 [95% CI, -2.45 to -1.55] units). Increases in growth parameters were also observed. The estimated pulmonary exacerbation rate per 48 weeks was 0.04. The annualized rate of change in percent predicted FEV1 was 0.51 (95% CI, -0.73 to 1.75) percentage points per year. Conclusions: ELX/TEZ/IVA continued to be generally safe and well tolerated in children aged ⩾6 years through an additional 96 weeks of treatment. Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX/TEZ/IVA in this pediatric population. Clinical trial registered with www.clinicaltrials.gov (NCT04183790).

UDP-glycosyltransferase gene SlUGT73C1 from Solanum lycopersicum regulates salt and drought tolerance in Arabidopsis thaliana L.

Among abiotic stresses, plants are the most vulnerable to salt and drought stresses. These stresses affect plant growth and development. Glycosyltransferases are involved in the responses of plants to abiotic stresses. In this study, a UDP-glycosyltransferase gene (SlUGT73C1) from Solanum lycopersicum was isolated and identified, which exhibited induction under salt or drought stress. The full length of SlUGT73C1 was 1485 bp, encoding 494 amino acids. Stress-related cis-acting elements were present in the promoter sequence of SlUGT73C1, such as ARE, LTR, and GC motifs. Compared with the wild-type plants, Arabidopsis thaliana overexpressing SlUGT73C1 exhibited increased seed germination rate and SOD and POD activities, decreased MDA content, and increased expression levels of osmotic stress regulators genes, rate-limiting enzymes genes in the proline synthesis pathway, Na+/K+ reverse transporter genes, and rate-limiting genes in the ABA biosynthesis pathway under salt or drought stress. These results indicated that SlUGT73C1 plays an important role in regulating salt and drought tolerance in plants.

Frequently expressed glypican-3 as a promising novel therapeutic target for osteosarcomas.

Osteosarcoma (OS) is the most common bone malignancy without a reliable therapeutic target. Glypican-3 (GPC3) mutation and upregulation have been detected in multidrug resistant OS, and anti-GPC3 immunotherapy can effectively suppress the growth of organoids. Further profiling of GPC3 mutations and expression patterns in OS is of clinical significance. To address these issues, fresh OS specimens were collected from 24 patients for cancer-targeted next-generation sequencing (NGS) and three-dimensional patient-derived organoid (PDO) culture. A tumor microarray was prepared using 37 archived OS specimens. Immunohistochemical (IHC) staining was performed on OS specimens and microarrays to profile GPC3 and CD133 expression as well as intratumoral distribution patterns. RT-PCR was conducted to semiquantify GPC3 and CD133 expression levels in the OS tissues. Anti-GPC3 immunotherapy was performed on OS organoids with or without GPC3 expression and its efficacy was analyzed using multiple experimental approaches. No OS cases with GPC3 mutations were found, except for the positive control (OS-08). IHC staining revealed GPC3 expression in 73.77% (45/61) of OSs in weak (+; 29/45), moderate (++; 8/45), and strong (+++; 8/45) immunolabeling densities. The intratumoral distribution of GPC3-positive cells was variable in the focal (+; 10%-30%; 8/45), partial (++; 31%-70%; 22/45), and the most positive patterns (+++; >71%; 15/45), which coincided with CD133 immunolabeling (P = 9.89 × 10-10 ). The anti-GPC3 antibody efficiently inhibits Wnt/ß-catenin signaling and induces apoptosis in GPC3-positive PDOs and PDXs, as opposed to GPC3-negative PDOs and PDXs. The high frequency of GPC3 and CD133 co-expression and the effectiveness of anti-wild-type GPC3-Ab therapy in GPC3-positive OS models suggest that GPC3 is a novel prognostic parameter and a promising therapeutic target for osteosarcoma.

miR156 regulates somatic embryogenesis by modulating starch accumulation in citrus.

Somatic embryogenesis (SE) is a major regeneration approach for in vitro cultured tissues of plants, including citrus. However, SE capability is difficult to maintain, and recalcitrance to SE has become a major obstacle to plant biotechnology. We previously reported that miR156-SPL modules regulate SE in citrus callus. However, the downstream regulatory pathway of the miR156-SPL module in SE remains unclear. In this study, we found that transcription factors CsAGL15 and CsFUS3 bind to the CsMIR156A promoter and activate its expression. Suppression of csi-miR156a function leads to up-regulation of four target genes, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (CsSPL) genes, and reduction of SE efficiency. In the short tandem target mimic (STTM)-miR156a overexpression callus (MIM156), the number of amyloplasts and starch content were significantly reduced, and genes involved in starch synthesis and transport were down-regulated. csi-miR172d was down-regulated, whereas the target genes, CsTOE1.1 and CsTOE1.2, which inhibit the expression of starch biosynthesis genes, were up-regulated. In our working model, CsAGL15 and CsFUS3 activate csi-miR156a, which represses CsSPLs and further regulates csi-miR172d and CsTOEs, thus altering starch accumulation in callus cells and regulating SE in citrus. This study elucidates the pathway of miR156-SPLs and miR172-TOEs-mediated regulation of SE, and provides new insights into enhancing SE capability in citrus.

Higher efficacy of resveratrol against advanced breast cancer organoids: A comparison with that of clinically relevant drugs.

The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy against individual breast cancer cases remains unknown. This study aims to use ABC-derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res-treated, 28.6% (2/7) fulvestrant-treated, 66.7% (4/6) paclitaxel-treated, and 66.7% (6/9) gemcitabine-treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res-sensitive (17/19; 89.47%) than that (1/5; 20%) of Res-insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs.

Effect of early and late prenatal vitamin D and maternal asthma status on offspring asthma or recurrent wheeze.

BACKGROUND: Childhood asthma developmental programming is complex. Maternal asthma is a strong risk factor for childhood asthma, whereas vitamin D (VD) has emerged as a modifiable prenatal exposure. OBJECTIVE: Our aim was to examine the combined effect of early and late prenatal VD status in during pregnancies in women with and without asthma on childhood asthma or recurrent wheeze development. METHODS: We conducted a cohort study using prospectively collected data from the Vitamin D Antenatal Asthma Reduction Trial, a randomized, double-blinded, placebo-controlled VD supplementation trial in pregnant women at high risk of offspring asthma (N = 806 mother-offspring pairs). 25-Hydroxyvitamin-D (25(OH)D) level was measured in early and late pregnancy. Our main exposure was an ordered variable representing early and late prenatal VD sufficiency (25(OH)D level ≥ 30 ng/mL) status during pregnancy in women with and without asthma. The primary outcome was offspring with asthma or recurrent wheeze by age 3 years. We also examined the effect of prenatal VD level on early life asthma or recurrent wheeze progression to active asthma at age 6 years. RESULTS: Among mothers with asthma versus among mothers with early and late prenatal VD insufficiency, those with early or late VD sufficiency (adjusted odds ratio = 0.56; 95% CI = 0.31-1.00) or early and late VD sufficiency (adjusted odds ratio = 0.36; 95% CI = 0.15-0.81) had a lower risk of offspring with asthma or recurrent wheeze by age 3 years (Pfor trend = .008). This protective trend was reiterated in asthma or recurrent wheeze progression to active asthma from age 3 to 6 years (Pfor trend = .04). CONCLUSION: This study implies a protective role for VD sufficiency throughout pregnancy, particularly in attenuating the risk conferred by maternal asthma on childhood asthma or recurrent wheeze development.

Dual Inhibition of BRAF-MAPK and STAT3 Signaling Pathways in Resveratrol-Suppressed Anaplastic Thyroid Cancer Cells with BRAF Mutations.

Anaplastic thyroid cancer is an extremely lethal malignancy without reliable treatment. BRAFV600E point mutation is common in ATCs, which leads to MAPK signaling activation and is regarded as a therapeutic target. Resveratrol inhibits ATC cell growth, while its impact on BRAF-MAPK signaling remains unknown. This study aims to address this issue by elucidating the statuses of BRAF-MAPK and STAT3 signaling activities in resveratrol-treated THJ-11T, THJ-16T, and THJ-21T ATC cells and Nthyori 3-1 thyroid epithelial cells. RT-PCR and Sanger sequencing revealed MKRN1-BRAF fusion mutation in THJ-16T, BRAF V600E point mutation in THJ-21T, and wild-type BRAF genes in THJ-11T and Nthyori 3-1 cells. Western blotting and immunocytochemical staining showed elevated pBRAF, pMEK, and pERK levels in THJ-16T and THJ-21T, but not in THJ-11T or Nthyori 3-1 cells. Calcein/PI, EdU, and TUNEL assays showed that compared with docetaxel and doxorubicin and MAPK-targeting dabrafenib and trametinib, resveratrol exerted more powerful inhibitory effects on mutant BRAF-harboring THJ-16T and THJ-21T cells, accompanied by reduced levels of MAPK pathway-associated proteins and pSTAT3. Trametinib- and dabrafenib-enhanced STAT3 activation was efficiently suppressed by resveratrol. In conclusion, resveratrol acts as dual BRAF-MAPK and STAT3 signaling inhibitor and a promising agent against ATCs with BRAF mutation.

Comparative study of serum sample preparation methods in aggregation-based plasmonic sensing.

The use of nanoparticle-based colorimetric methods has received considerable attention in a broad range of clinical and biomedical applications due to their high sensitivity, low cost, extreme simplicity and excellent analytical performance. However, the formation of a protein corona has severely limited the application of nanoparticles (NPs) in clinical samples, which can confer colloidal stability to serum-exposed nanoparticles compared to pristine particles. To address this challenge, dialysis, ultrafiltration and phenol : chloroform : isopentanol extraction methods were compared aiming at facile and routine protein separation methods to eliminate the formation of protein corona on NPs and the development of a sensitive and simple therapeutic drug monitoring (TDM) assay for the detection of aminoglycoside antibiotics in serum. Based on the comparison of the sensitivity of the localized surface plasmon resonance (LSPR) aggregation assay in pure water, untreated serum and serum after the different sample preparation methods, we revealed by Coomassie blue staining that proteins in the serum were the predominant interfering molecules to degrade the sensitivity of serum-based aggregation assays. Using dialysis, naked eye semi-quantification was achieved at the clinical level for amikacin, tobramycin and streptomycin. The dialysis efficiency and dialysis coefficient of amikacin were also measured to prove the efficacy of dialysis as a fast and efficient protein-removal method. This strategy is expected to be applicable universally as a pretreatment for the assay of small molecules with plasmonic assays in crude biological samples.

Linear-response and simple hot-wire fiber-optic anemometer using high-order cladding mode.

We present a single walled carbon nanotubes (SWCNTs)-coated tilted fiber Bragg grating (TFBG) hot-wire anemometer (HWA) with simple configuration, linear response, and high sensitivity. TFBG is utilized to effectively couple a pumping laser at 1550 nm to the cladding mode that is absorbed by the SWCNTs film immobilized on the fiber surface with good light-heat conversion efficiency. As a result, the TFBG is converted to a "hot wire", and the wind speed can be deduced from the output power of the laser, which is a function of both the wind-induced temperature change and the spectral profile of the cladding mode. The most significant aspect of the HWA system is that we use the Gaussian shape of the high-order TFBG cladding mode to compensate for the inherent nonlinear relationship between the heat loss and the wind speed that is an undesirable characteristic of existing HWA systems. The validity of this novel operating principle was verified theoretically and experimentally. Via careful control of the parameters, a good linear response of the HWA system was achieved, especially for the low wind speed range where nonlinearity was more conspicuous. It was demonstrated that, with a low input power of only 29.3 mW of the pump laser, an R2 value of 0.9927 was obtained in this fiber-optic HWA system with high sensitivity 7.425 dBm / (m/s) and resolution 0.0027 m/s in a small wind speed range (0-2m/s) considering the intensity resolution of OSA and the noise of the pump laser. Furthermore, the system also exhibits a simple and low-cost design with only one laser source and one low-cost power measurement component.

Enhancement of Gold Nanoparticle Coupling with a 2D Plasmonic Crystal at High Incidence Angles.

2D nanoplasmonic substrates excited in transmission spectroscopy are ideal for several biosensing, metamaterial, and optical applications. We show that their excellent properties can be further improved with plasmonic coupling of Au nanoparticles (AuNPs) on gold-coated nanodisk arrays excited at large incidence angles of up to 50°. The Bragg modes (BM) thereby strongly couple to AuNP immobilized on the plasmonic substrate due to shorter decay length of the plasmon at higher incidence angles, leading to a further enhanced field between the AuNP and the plasmonic substrate. The field was highest and two hotspots were created at orthogonal positions for AuNP located close to the corner of the Au film and Au nanodisk, which was also observed for AuNP dimers. Hybridization between single-stranded DNA (ssDNA) immobilized on the surface of the AuNPs and the capture ssDNA on the gold-coated nanodisk arrays led to at least a 5-fold signal improvement and a 7-fold lower limit of detection at 7 pM for ssDNA-functionalized AuNPs at large incident angles. Thus, we demonstrate that higher field strength can be accessed and the significant advantages of working with high incidence angles with AuNP on a 2D plasmonic crystal in plasmonic sensing.

Dual channel multilayer-coated surface plasmon resonance sensor for dual refractive index range measurements.

We present a novel multilayer-coated surface plasmon resonance sensor for dual refractive index range measurements based on a capillary structure. The sensing elements include an internally coated Ag layer and an externally coated bilayer of Au with an overlayer of thin indium tin oxide (ITO). The internal Ag layer was sensitive to higher refractive index (RI) medium while the external Au/ITO layer was sensitive to lower refractive index medium. We evaluated the sensor performance by measuring RI changes in two channels, RI sensitivities were -1951 nm/RIU and 2496 nm/RIU, respectively. This compact, low-cost large RI detection range SPR sensor offers the possibility for wider RI detection range and highly sensitive SPR studies in industry and chemical sensing.

Liquid crystal filled surface plasmon resonance thermometer.

A novel surface plasmon resonance (SPR) thermometer based on liquid crystal (LC) filled hollow fiber is demonstrated in this paper. A hollow fiber was internally coated with silver and then filled with LC. The SPR response to temperature was studied using modeling and verified experimentally. The results demonstrated that the refractive index of LC decreases with the increasing temperature and the variation can be detected by the resonance wavelength shift of the plasmon resonance. The temperature sensitivities were 4.72 nm/°C in the temperature range of 20 to 34.5 °C and 0.55 nm/°C in the temperature range of 36 to 50 °C, At the phase transition temperature between nematic and isotropic phases of the LC, the temperature sensitivity increased by one order of magnitude and a shift of more than 46 nm was observed with only a 1.5 °C temperature change. This sensor can be used for temperature monitoring and alarming, and can be extended for other physical parameter measurement.

Narrow-band wavelength tunable filter based on asymmetric double layer metallic grating.

In this paper, the optical properties of asymmetric double layer metallic gratings are presented theoretically. The asymmetric structure is achieved by two main factors: one corresponding to moving alternatively metal nanowires of the top layer metallic grating, the other corresponding to possessing different thickness of the top and down layer metallic gratings. Our proposed structure shows one remarkable narrow-band transmission dip at normal incidence, which is distinct different from that of symmetric structure. The results are further confirmed by using different numerical computation methods, and explained by the analytical model of Fano-like resonance. We find that, only when the thickness of the down layer metallic grating has certain fixed value, transmission dip can be transformed from two to only one dip even if the existence of symmetry breaking. However, the wavelength position of the dip can be easily controlled by adjusting the thickness of the top layer metallic grating without the need to modify the structure period, and the width of metal nanowire. Moreover, the influence of other structure parameters on the dip is also investigated. Surprisingly, in order to keep the appearance of one dip in the transmission spectrum of designed structure, there is a good linear approximation between the refractive index of waveguide layer and the thickness of down layer metallic grating, and the relation of waveguide layer thickness and the thickness of down layer metallic grating satisfy secondary polynomial fitting. This work can be used to develop subwavelength metallic-grating-based and narrow-band tunable wavelength filters.

Symmetry-reduced double layer metallic grating structure for dual-wavelength spectral filtering.

In this paper, we propose a metal-dielectric dual-wavelength spectral filtering structure based on symmetry-reduced double layer metallic gratings (SRDMG) coupled to a guided-mode dielectric resonator. The grating symmetry is reduced by alternatively shifting metal nanowires of the top layer metallic grating. Compared to a symmetric double layer metallic grating that usually provides one resonance dip, this SRDMG structure generates two remarkable narrow band transmission dips with a transmission peak in-between at normal incidence. The appearance of the two narrowband resonance dips is attributed to the excitation of different current modes in the metallic grating, leading to different guided mode resonances in the dielectric layer, which is induced by the structural symmetry breaking. Moreover, these two guided modes do not split under oblique incidence and a flat dispersion band over a small angular range can be obtained. The positions of two dips and the frequency gap between them can be controlled by adjusting the thickness of metallic grating without the need to modify the structure period and width, which is an easy method to tune resonance position and bandwidth, and make the fabrication of some filters more convenient. This work can be used to develop subwavelength metallic-grating-based multi-wavelength and narrow-band spectral filters.

Customizable miniaturized SPR instrument.

Prism-based surface Plasmon resonance (SPR) system, as one of the leading candidate concepts for scale application and commercial solution, has good stability, high-sensitivity and greater theoretical/technical maturity. Therefore, to take advantage of prism-based SPR system fully, and break up limitations of complicated and bulky traditional prism-based SPR system, optimal and compact design of optical system is an effective solution. Herein, a customizable miniaturized prism-based SPR system is developed by optical system optimization and integrated design, combining portable data acquisition and processing technology (FPGA-based multifunctional data processing). This proposed prism-based SPR system can achieve a miniaturized SPR system, thus, it also can meet the requirements of flexibility configuration and customizable performance to accommodate the various needs of different users and application scenes. Additionally, the customizable features can make it to achieve the best performance optimization and differentiation.

Multi-channel prismatic localized surface plasmon resonance biosensor for real-time competitive assay multiple COVID-19 characteristic miRNAs.

A multi-channel prismatic localized surface plasmon resonance (LSPR) biosensor was developed for quantitative and real-time detection of multiple COVID-19 characteristic miRNAs. The well-dispersed and dense gold nanoparticles (AuNPs) arrays for LSPR biosensing were fabricated through a nano-thickness diblock copolymer template (BCPT). Both theoretical and experimental analyses were conducted to investigate the effects of particle size, interparticle spacing, and surface coverage on LSPR sensing spectrum and intensity sensitivity of varied AuNPs sizes. A competitive assay strategy was proposed and used for non-amplification miRNA detection with a low limit detection of 3.41 nM, while a four-channel prismatic LSPR system enables parallel detection of multiple miRNAs. Furthermore, this sensing strategy can effectively and specifically identify target miRNA, distinguish mismatched miRNA and interfering miRNA, and exhibit low non-specific adsorption. This BCPT-based LSPR biosensor demonstrates the practicality and potential of a multi-channel, adaptable, and integrated prismatic sensor in medical testing and diagnostic applications.