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Genetic mutations play an important role in the development of most cancers; thus, they have become key targets of investigation in the discovery of new biomarkers to help with cancer diagnostic and prognostic prediction, as well as monitor the development of drug resistance in cancer cells. We have now developed a technique by designing several probes that contain with different types of mutations, including substitution, insertion and deletion mutations for 6 or 12 bps (Table 1). Following this, we then mapped a colorectal cancer wild type KRAS cell line Caco2. To screen for different types of gene alterations,an electrolyte-insulator-semiconductor (EIS) device, incorporating a high-κ Yb2Ti2O7 sensing membrane deposited on Si substrates through co-sputtering to screen the genetic mutations, was made. X-ray diffraction and X-ray photoelectron spectroscopy were used to explore the structural features of these films annealed at various temperatures. The Yb2Ti2O7 EIS device, which annealed at 900 °C, exhibited a higher sensitivity of 59.4 mV/pH (in the solutions from pH = 2 to pH = 12), a lower hysteresis voltage of 1.6 mV (in the pH = 7→4→7→10→7), and a smaller drift rate of 0.16 mV/h (in the pH = 7 buffer solution) than those of the other annealing temperatures. We successfully demonstrated that high-κYb2Ti2O7 EIS devices with DNA-immobilized alginate films were able to screen all the designed mutation probes in Caco2 cells, and there was clear distinction from wild type based lines. In addition, even the substitution mutations were presented high resolution. Current measurement system provides a simple and inexpensive method for rapid and accurate detection of genetic changes in target genes; therefore it provided the high potential to serve as a diagnosis tool in clinical practice in the future. Table 1.Design oligonucleotide probes.Oligonucleotide probessequencesTest 1wild type 24 bp5′-taggcaagagtgccttgacgatac-3′deletion 12 bp5′-taggca…………cgatac-3′deletion 6 bp5′-taggcaaga……tgacgatac-3′Test 2wild type 24 bp5′-ataggtgattttggtctagctaca-3′substitution 1 bp5′-ataggtgatttAggtctagctaca-3′insertion 6 bp5′-ataggtgattttGGGAACggtctagctaca-3′ Citation Format: Jhou Cheng Han, Kao Shin Hsun, Pang Sow Neng, Pan Tung Ming, Weng Wen Hui. The Emerging technology of Yb2Ti2O7 electrolyte-insulator-semiconductor biosensors for rapid screening of targeted mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4907. doi:10.1158/1538-7445.AM2015-4907