We modeled flexible microelectronic systems and analyzed the stress and strain distribution assuming an international standard bending test evaluating flexible electronics. The flexible microelectronic system consisted of a flexible substrate, a thin silicon die bonded to the substrate using bumps, and an underfill and molding layer. The highest stress values were found at the square silicon die corners under bending deformation. After rounding the die corners, the copper bumps were the weakest component in the system. When polymer bumps replaced copper bumps to improve mechanical stability, the critical bending radius reduced from 13.5 to 8.0 mm, and the silicon die was again the most vulnerable component. When the die thickness decreased from 50 to 30 μm, the critical bending radius of the flexible system even decreased to 6.9 mm. Therefore, it is advantageous for mechanically reliable flexible microelectronic systems to bond thin silicon dies with rounded corners to a flexible substrate using polymer bumps.

Although the reliability of flexible electronics during bending deformation is of great interest nowadays, the mechanical reliability that has mainly been investigated is of single electronic components or simple devices, such as metal interconnect, transparent conductive electrode, or thin-film devices, rather than that of the real package sample having complex structure and various materials. This study systematically investigated the mechanical reliability of flexible Si package sample consisting of Si die, polymer bump, and polymer substrate, by using individual resistance monitoring of the metal line, bump array, and total interconnect. For the bending test, the sample consisting of only Si die and polymer substrate shows abrupt electrical resistance increase below a bending radius of 3 mm, due to cracking of the Si die. For the bending fatigue test, the electrical resistance increases after 2,000 cycles in 5 mm bending radius, due to fatigue failure of the metal line and bump array. Both the maximum bendability and fatigue lifetime can be significantly improved by covering with the molding layer. Finite element method simulation is conducted to analyze the mechanical stress distribution of the flexible package with and without molding layer during bending deformation. This study based on experimental results and simulation analysis can provide helpful guidelines for the design of highly reliable flexible packages.

Tofacitinib is an oral disease-modifying anti-rheumatic drug to selectively inhibit Janus kinases. Tofacitinib is a representative small molecule inhibitor that is used to treat many diseases including rheumatoid arthritis and various autoimmune conditions. Unlike biological agents, tofacitinib has several advantages, including the ability to be administered orally and a short half-life. This study aimed to evaluate the bioequivalence of the pharmacokinetics (PK) between tofacitinib aspartate 7.13 mg (test formulation) and tofacitinib citrate 8.08 mg (reference formulation; Xeljanz ®) in healthy subjects. A randomized, open-label, single-dose, 2-sequence, 2-period, 2-treatment crossover trial was conducted in 41 healthy volunteers. A total of 5 mg of tofacitinib as the test or the reference formulation was administered, and serial blood samples were collected up to 14 hours after dosing for PK analyses. The plasma concentration of tofacitinib was determined by ultraperformance liquid chromatography-tandem mass spectrometry. A non-compartmental analysis was used to estimate the PK parameters. A total of 35 subjects completed the study and the study drug was well-tolerated. The mean maximum concentration (C max) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC last) for the test formulation were 52.67 ng/mL and 133.86 ng•h/mL, respectively, and 50.61 ng/mL and 133.49 h•ng/mL for the reference formulation, respectively. The geometric mean ratios (90% confidence intervals) of the C max and AUC last between the 2 formulations were 1.041 (0.944-1.148) and 1.003 (0.968-1.039), respectively. Tofacitinib aspartate exhibited bioequivalent PK profiles to those of the reference formulation.