Defect height estimation via model-less TSOM under optical resolution.

We propose a new method of through-focus scanning optical microscopy (TSOM) without a reference database, i.e., a model-less TSOM method. Building a TSOM reference database is time-consuming or even impractical in some TSOM applications that involve complex structures, such as 3D NAND, or irregular shapes such as defects. The proposed model-less TSOM method was used to determine just the height of defect particles, for the first time as far as we are aware. Defect height is the only relevant dimension for the display panel application. Specifically, we analyzed 40 organic light-emitting diode (OLED) surface defects using a lab-developed motion-free TSOM tool consisting of a 50× objective lens (numerical aperture (NA) 0.55), a 532-nm light source, an imaging detector with a 7.5-µm pitch, and a deformable mirror. The tool is in-line and capable of achieving high throughput non-destructively, both relevant features for industrial applications. We investigated linear regression relations between newly defined TSOM parameters (TSOM height, TSOM area and TSOM volume) and the defect heights, which were first measured by atomic force microscopy (AFM). Following defect classification based on in-focus images, we successfully found that the AFM height has a linear correlation with 50% TSOM height (H50%) within ± 20.3 nm (1σ) error over the range of 140 to 950 nm. The one-sigma error, i.e., 20.3 nm, was approximately λ/26 or 1/43 of the depth of focus (DOF) of the applied microscope.

Prediction of occult central lymph node metastasis in papillary thyroid carcinoma by preoperative BRAF analysis using fine-needle aspiration biopsy: a prospective study.

CONTEXT: Few reports have determined whether preoperative detection of the BRAF V600E mutation in fine-needle aspiration biopsy (FNAB) may influence determination of surgical extent such as prophylactic central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). OBJECTIVES: Our objectives were to investigate whether preoperative BRAF analysis may assist determination of surgical extent, including prophylactic CLND with variable clinicopathological risk factors for central lymph node metastasis, in patients with PTC and clinically node-negative neck. PATIENTS AND METHODS: From July 2009 to May 2011, we prospectively enrolled 148 PTC patients with clinically node-negative neck who received a total thyroidectomy and prophylactic CLND. BRAF mutation by pyrosequencing was tested on preoperative FNAB specimens. The relationships between occult central lymph node metastasis and preoperative BRAF mutation or clinicopathological factors were analyzed. Additionally, we assessed the associations between preoperative BRAF mutation status and various clinicopathological characteristics of PTC revealed postoperatively. RESULTS: The prevalence of the BRAF V600E mutation was 53.4%, and the rate of occult central lymph node metastasis was 25.7%. Multivariate analysis showed that tumor size over 1 cm [P = 0.006; odds ratio (OR) = 3.559], perithyroidal invasion (P = 0.023; OR = 2.893), and preoperative positive BRAF mutation (P = 0.029; OR = 2.727) were independent risk factors for the presence of occult central lymph node metastasis. BRAF mutation examined in FNAB specimens, compared with the wild-type allele, strongly predicted perithyroidal invasion (48 vs. 29%; P = 0.017), extracapsular spread (65 vs. 45%; P = 0.017), occult central lymph node metastasis (35 vs. 15%; P = 0.004), and advanced TNM stage (44 vs. 28%; P = 0.035). In the multivariate analysis, patients with preoperative positive BRAF mutation were significantly more likely (P = 0.023; OR = 2.848) to have occult central lymph node metastasis. CONCLUSION: Preoperative BRAF analysis by FNAB and primary tumor size based on ultrasonography may assist in predicting occult central lymph node metastasis in patients with PTC and clinically node-negative neck.