High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines—Fadu and Cal27—cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.

Suspension array platform based on aptamer for high-throughput detection of five environmental hormones

Background As a common small molecule substance, environmental hormones widely exist in nature, especially water sources, which have a profound effects in humans. Highly efficient and sensitive method for estrogens in the environment are essential. Results In this paper, a novel high-throughput platform was established based on five small hormones molecules specificity aptamer and magnetic beads (MBs). The results showed that the sensitivity of the proposed method are greatly improved. The limit of detection(LOD) of this method for atrazine(Atz), profenofos, bisphenolA(BPA), estradiol(E2), and polychlorinated biphenyls(PCBs) were 9.46, 20.75, 23.81, 8.97, 6.27 pg/mL, respectively. The Recovery rate of the diluted environmental hormones spiked in the samples of Haihe river were in the range of 87.5-111.02% with relative standard deviations (RSDs) lower than 28.44%. Conclusion This platform based on new complementary strand fragments can simultaneously rapid detection five environmental hormones. The whole procedure completed within 1.5h including sample treatment, incubation and detection, greatly improving the detection efficiency.