Rational:
LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from benign solitary pulmonary nodules, which calls for better non-invasive diagnostic tools.
Methods:
We performed DNA methylation profiling by high throughput DNA bisulfite sequencing in tissue samples (nodule size < 3 cm in diameter) to learn methylation patterns that differentiate cancerous tumors from benign lesions. Then we filtered out methylation patterns exhibiting high background in circulating tumor DNA (ctDNA) and built an assay for plasma sample classification.
Results:
We first performed methylation profiling of 230 tissue samples to learn cancer-specific methylation patterns which achieved a sensitivity of 92.7% (88.3% - 97.1%) and a specificity of 92.8% (89.3% - 96.3%). These tissue-derived DNA methylation markers were further filtered using a training set of 66 plasma samples and 9 markers were selected to build a diagnostic prediction model. From an independent validation set of additional 66 plasma samples, this model obtained a sensitivity of 79.5% (63.5% - 90.7%) and a specificity of 85.2% (66.3% - 95.8%) for differentiating patients with malignant tumor (n = 39) from patients with benign lesions (n = 27). Additionally, when tested on gender and age matched asymptomatic normal individuals (n = 118), our model achieved a specificity of 93.2% (89.0% - 98.3%). Specifically, our assay is highly sensitive towards early‐stage lung cancer, with a sensitivity of 75.0% (55.0%-90.0%) in 20 stage Ia lung cancer patients and 85.7% (57.1%-100.0%) in 7 stage Ib lung cancer patients.
Conclusions:
We have developed a novel sensitive blood based non‐invasive diagnostic assay for detecting early stage lung cancer as well as differentiating lung cancers from benign pulmonary nodules.
We have increased organic field-effect transistor (OFET) NH3 response using tris-(pentafluorophenyl)borane (TPFB) as receptor. OFETs with this additive detect concentrations of 450 ppb v/v, with a limit of detection of 350 ppb, the highest sensitivity yet from semiconductor films; in comparison, when triphenylmethane (TPM) and triphenylborane (TFB) were used as an additive, no obvious improvement of sensitivity was observed. These OFETs also show considerable selectivity with respect to common organic vapors, and stability to storage. Furthermore, excellent memory of exposure was achieved by keeping the exposed devices in a sealed container stored at −30°C, the first such capability demonstrated with OFETs.
Printable and flexible electronics attract sustained attention for their low cost, easy scale up, and potential application in wearable and implantable sensors. However, they are susceptible to scratching, rupture, or other damage from bending or stretching due to their “soft” nature compared to their rigid counterparts (Si-based electronics), leading to loss of functionality. Self-healing capability is highly desirable for these “soft” electronic devices. Here, a versatile self-healing polymer blend dielectric is developed with no added salts and it is integrated into organic field transistors (OFETs) as a gate insulator material. This polymer blend exhibits an unusually high thin film capacitance (1400 nF cm −2 at 120 nm thickness and 20–100 Hz). Furthermore, it shows pronounced electrical and mechanical self-healing behavior, can serve as the gate dielectric for organic semiconductors, and can even induce healing of the conductivity of a layer coated above it together with the process of healing itself. Based on these attractive properties, we developed a self-healable, low-voltage operable, printed, and flexible OFET for the first time, showing promise for vapor sensing as well as conventional OFET applications.
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