Artificial Intelligence-Controlled Microfluidic Device for Fluid Automation and Bubble Removal of Immunoassay Operated by a Smartphone.

There have been tremendous innovations in microfluidic clinical diagnostics to facilitate novel point-of-care testing (POCT) over the past decades. However, the automatic operation of microfluidic devices that minimize user intervention still lacks reliability and repeatability because microfluidic errors such as bubbles and incomplete filling pose a major bottleneck in commercializing the microfluidic devices for clinical testing. In this work, for the first time, various states of microfluid were recognized to control immunodiagnostics by artificial intelligence (AI) technology. The developed AI-controlled microfluidic platform was operated via an Android smartphone, along with a low-cost polymer device to effectuate enzyme-linked immunosorbent assay (ELISA). To overcome the limited machine-learning capability of smartphones, the region-of-interest (ROI) cascading and conditional activation algorithms were utilized herein. The developed microfluidic chip was incorporated with a bubble trap to remove any bubbles detected by AI, which helps in preventing false signals during immunoassay, as well as controlling the reagents' movement with an on-chip micropump and valve. Subsequently, the developed immunosensing platform was tested for conducting real ELISA using a single microplate from the 96-well to detect the Human Cardiac Troponin I (cTnI) biomarker, with a detection limit as low as 0.98 pg/mL. As a result, the developed platform can be envisaged as an AI-based revolution in microfluidics for point-of-care clinical diagnosis.

Smartphone-Based Fully Automated Optofluidic Device with Laser Irradiation-Induced Image Whitening.

Herein, we have developed a fully automated optofluidic device to execute enzyme-linked immunosorbent assay (ELISA) using an active 96-well hybrid lab-on-a-chip (LOC) device. To automate the solution loading into the reaction zone of the device and the post-assayed signal analysis, laser irradiation-induced image whitening was utilized with a smartphone-based optical platform. Two optical phenomena were utilized in our platform to detect the liquid in the reaction chamber using a smartphone. First, by Fresnel's equation, the refraction difference between air and water resulted in the intensity change of the reflected light from the reaction chamber. Therefore, when the liquid was entering into the reaction chamber, the intensity of the reflected light was changed. Second, when the light intensity increases, the smartphone-captured image whitens out due to saturation, even when the red color light was incident. Therefore, by measuring the RGB value of the smartphone image, the intensity changes by the liquid movement in the reaction chamber were successfully monitored. Our platform showed a low detection limit of 7.81 pg/mL for the detection of the NT-proBNP human cardiac biomarker with almost a half standard deviation, compared to the manually operated LOC-based ELISA. As a fully automated LOC adopting a conventional 96-well ELISA platform, we thus concluded that the developed platform can be widely applied for point-of-care clinical tests.

Gamma band activity associated with BCI performance: simultaneous MEG/EEG study.

While brain computer interface (BCI) can be employed with patients and healthy subjects, there are problems that must be resolved before BCI can be useful to the public. In the most popular motor imagery (MI) BCI system, a significant number of target users (called "BCI-Illiterates") cannot modulate their neuronal signals sufficiently to use the BCI system. This causes performance variability among subjects and even among sessions within a subject. The mechanism of such BCI-Illiteracy and possible solutions still remain to be determined. Gamma oscillation is known to be involved in various fundamental brain functions, and may play a role in MI. In this study, we investigated the association of gamma activity with MI performance among subjects. Ten simultaneous MEG/EEG experiments were conducted; MI performance for each was estimated by EEG data, and the gamma activity associated with BCI performance was investigated with MEG data. Our results showed that gamma activity had a high positive correlation with MI performance in the prefrontal area. This trend was also found across sessions within one subject. In conclusion, gamma rhythms generated in the prefrontal area appear to play a critical role in BCI performance.

Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial.

BACKGROUND: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 µmol/mol creatinine vs ≥60 µmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00744497. FINDINGS: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2-25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3-22·8) in the dasatinib group and 21·2 months (20·0-23·4) in the placebo group (stratified hazard ratio [HR] 0·99, 95·5% CI 0·87-1·13; p=0·90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). INTERPRETATION: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. FUNDING: Bristol-Myers Squibb.