Fabrication and Electrical Characterization of High Aspect Ratio Through-Silicon Vias with Polyimide Liner for 3D Integration.

High aspect ratio (HAR) through-silicon vias (TSVs) are in urgent need to achieve smaller keep-out zones (KOZs) and higher integration density for the miniaturization of high-performance three-dimensional (3D) integration of integrated circuits (IC), micro-electro-mechanical systems (MEMS), and other devices. In this study, HAR TSVs with a diameter of 11 µm and an aspect ratio of 10:1 are successfully fabricated in a low-cost process flow. Conformal polyimide (PI) liners are deposited using a vacuum-assisted spin coating technique, and the effects of spin coating time and speed on the deposition results are discussed. Then, continuous Cu seed layers are fabricated by sequential sputtering and ultrasound-assisted electroless plating. Additionally, void-free and seamless Cu conductors are formed by electroplating. Moreover, a semi-additive method is used to fabricate the redistribution layers (RDLs) on the insulating layers of photosensitive PI (PSPI). Notably, a plasma bombardment process is introduced to remove residual PSPI in the contact windows between RDLs and central pillars. Results show that the resistance of a single TSV from a daisy chain of 144 TSVs with density of 2000/mm2 is about 28 mΩ. Additionally, the S-parameters of a single TSV are obtained using L-2L de-embedding technology, and the experimental and simulated results agree well. The proposed low-cost fabrication technologies and the related electrical characterization of PI-TSVs are significant for the application of HAR TSVs in modern heterogeneous integration systems.

Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway of Platinum(IV) Complexes.

Platinum(IV) complexes are prodrugs of cisplatin with multiple potential advantages over platinum(II) drugs. Mitochondria play pivotal roles in producing energy and inducing death of cancer cells. Two platinum(IV) complexes, namely, c,c,t-[Pt(NH3)2Cl2(OH)(OCOCH2CH2CH2CH2PPh3)]Br and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2CH2CH2PPh3)2]Br2, were designed to explore the effect of mitochondrion-targeting group(s) on the bioactivity and cytotoxicity of platinum(IV) complexes. The complexes were characterized by electrospray ionization mass spectrometry, reverse-phase high-performance liquid chromatography, and multinuclear (1H, 13C, 31P, and 195Pt) NMR spectroscopy. The introduction of triphenylphosphonium targeting group(s) markedly influences the reactivity and cytotoxicity of the Pt(IV) complexes. The targeted complex displays more potent disruptive effect on mitochondria but less inhibitory effect on cancer cells than cisplatin. The lipophilicity of the Pt(IV) complexes is enhanced by the targeting group(s), while their reactivity to DNA is decreased. As a result, the mitochondrial morphology and adenosine triphosphate producing ability are impaired, which constitutes an alternative pathway to inhibit cancer cells. This study shows that both the reactivity of platinum(IV) center and the property of axial targeting ligand exert influences on the cytotoxicity of targeted Pt(IV) complexes. For targeting groups with pharmacological activities, their intrinsic function could enrich the anticancer mechanism of Pt(IV) complexes.

Glutathione boosting the cytotoxicity of a magnetic platinum(iv) nano-prodrug in tumor cells.

Superparamagnetic iron oxide nanoparticles (SPIONs) are potential vehicles for targeted drug delivery and viable contrast agents for magnetic resonance imaging (MRI). A PtIV prodrug (HSPt) derived from functionalization of cisplatin with hydroxyl and succinate is conjugated with a poly(ethylene glycol) (PEG)-modified SPION for cancer therapy and monitoring of therapeutic responses. The relaxivity of HSPt-PEG-SPIONs is larger than that of commercial contrast agent Feridex, and a tumor-selective negative contrast is observed in MRI in a magnetic field. HSPt-PEG-SPIONs can be dissociated and reduced into PtII species by glutathione (GSH). Instead of forming DNA-Pt crosslinks, the reduced product induces direct DNA single- or double-strand breaks, which is uncommon for Pt drugs. The cytotoxicity of HSPt-PEG-SPIONs is positively correlated with the GSH level of tumor cells, which is opposite to the scenario of current Pt drugs. HSPt-PEG-SPIONs are as cytotoxic as cisplatin against cancer cells but are almost nontoxic towards normal cells. Since the mechanism of action of the nanocomposite is different from the established paradigm for Pt drugs, it may become a special theranostic agent for cancer treatment.