The processes that keep a cell alive are constantly challenged by unpredictable changes in its environment. Cells manage to counteract these changes by employing sophisticated regulatory strategies that maintain a steady internal milieu. Recently, the antithetic integral feedback motif has been demonstrated to be a minimal and universal biological regulatory strategy that can guarantee robust perfect adaptation for noisy gene regulatory networks in Escherichia coli . Here, we present a realization of the antithetic integral feedback motif in a synthetic gene circuit in mammalian cells. We show that the motif robustly maintains the expression of a synthetic transcription factor at tunable levels even when it is perturbed by increased degradation or its interaction network structure is perturbed by a negative feedback loop with an RNA-binding protein. We further demonstrate an improved regulatory strategy by augmenting the antithetic integral motif with additional negative feedback to realize antithetic proportional–integral control. We show that this motif produces robust perfect adaptation while also reducing the variance of the regulated synthetic transcription factor. We demonstrate that the integral and proportional–integral feedback motifs can mitigate the impact of gene expression burden, and we computationally explore their use in cell therapy. We believe that the engineering of precise and robust perfect adaptation will enable substantial advances in industrial biotechnology and cell-based therapeutics.

In this work, we had investigated sputtering deposition of p-type SnO using the widely used and robust SnO2 target in a hydrogen-containing reducing atmosphere. The effects of the hydrogen-containing sputtering gas on structures, compositions, optical, and electrical properties of deposited SnOx films were studied. Results show that polycrystalline and SnO-dominant films could be readily obtained by carefully controlling the hydrogen gas ratio in the sputtering gas and the extent of reduction reaction. P-type conductivity was unambiguously observed for SnO-dominant films with traceable Sn components, exhibiting a p-type Hall mobility of up to ∼3 cm(2) V(-1) s(-1). P-type SnO thin-film transistors using such SnO-dominant films were also demonstrated.

P-type thin-film transistors using polycrystalline tin monoxide (SnO) active layers were achieved by an industry-compatible sputtering technique with a SnO ceramic target. The SnO films clearly exhibited p-type conduction with the p-type Hall mobilities of 1–4 cm2 V-1 s-1 and hole concentrations of 1017–1018 cm-3. The physical and chemical structures of SnO films were characterized by X-ray diffraction analysis and X-ray photoemission spectroscopy. It is concluded that amorphous and SnO-dominant films were obtained as deposited. Further annealing at ≤300 °C induces crystallization but no major chemical reaction. The transmission line method was adopted to characterize the contact resistance between SnO layers and various metal electrodes. Results show that Mo and Ni could be used as effective electrodes for p-type SnO, avoiding the use of noble metals. Finally, p-type SnO TFTs using practical metal electrodes were fabricated, where a field-effect mobility of up to 1.8 cm2 V-1 s-1 and an on/off current ratio of >103 were achieved.

No abstract