Gilbert, Barry K.

ABSTRACT The Mayo Foundation Special Purpose Processor Development Group has been supporting a serial link development effort. In order to characterize serial link performance, two versions of a multi-chip module (MCM) test vehicle were assembled to study the effects of the substrate and the integrated circuit input/output buffer technologies on basic signal integrity performance parameters at data rates of 2.5 GHz. The difference between the test vehicles was the substrate technology used: ceramic and laminate. This paper describes the steps taken to develop an assembly process for the ceramic version of the test vehicle. The ceramic test vehicle consisted of a high thermal coefficient of expansion ceramic substrate, 2 CMOS chips with IBM high lead content (hereafter: “high lead”) bumps, 16 surface mount (SMT) capacitors, and an interposer. Assembly processes needed to be developed for SMT attach of the capacitors, flip-chip attach of the chips, and ball grid array (BGA) attach of the interposer. Based on Mayo's suite of assembly equipment, three process flows could have been used to attach the capacitors and the chips to the substrate: High lead attach of the capacitors and chips; Eutectic attach of capacitors, high lead attach of chips; Eutectic attach of the capacitors and chips. Assembly process flow 1 required the least number of steps. Therefore, it was initially selected as the process flow. However, this process flow was found to be unsatisfactory due to problems with flux charring around the capacitors and a high incidence of chip to substrate opens. Assembly process flow 2 was then evaluated. Assembly process flow 3 was considered the least desirable because eutectic solder paste had to be coated on the substrate die pads and Mayo did not have capability to do this. In order to develop the capacitor and die attach processes and to set up the interposer attach process, two assembly test vehicles were built on glass substrates. A capacitor attach process was devised that involved stenciling the eutectic solder paste, placing the capacitors, and then reflowing the assembly. The flip-chip attach process development required greater effort. Experimental matrices were run that allowed an assessment of bond strength as a function of flux quantity, bond force, and reflow temperature and time. Water-soluble flux was used for the chip attach process, so a de-fluxing process had to be developed. The chips then needed to be underfilled. The underfill dispense pattern and substrate heating were evaluated. The interposer was attached using eutectic solder paste stenciled on the back of the substrate. A BGA style attach process was set up to do this. The result of this process development activity was the successful assembly of 21 modules with no defects. Lessons were learned during the assembly process development regarding the difficulties associated with attaching components with high lead solder.

Abstract Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, in addition to interindividual heterogeneity, systemic immune signatures display longitudinal stability within individuals, and these signatures may reliably dictate how given individuals respond to immune perturbations. We hypothesize that analyzing relationships among these signatures at the population level may uncover baseline immune phenotypes that correspond with response outcomes to immune stimuli. To test this, we quantified global gene expression in peripheral blood CD4+ cells from healthy individuals at baseline and following CD3/CD28 stimulation at two time points 1 mo apart. Systemic CD4+ cell baseline and poststimulation molecular immune response signatures (MIRS) were defined by identifying genes expressed at levels that were stable between time points within individuals and differential among individuals in each state. Iterative differential gene expression analyses between all possible phenotypic groupings of at least three individuals using the baseline and stimulated MIRS gene sets revealed shared baseline and response phenotypic groupings, indicating the baseline MIRS contained determinants of immune responsiveness. Furthermore, significant numbers of shared phenotype-defining sets of determinants were identified in baseline data across independent healthy cohorts. Combining the cohorts and repeating the analyses resulted in identification of over 6000 baseline immune phenotypic groups, implying that the MIRS concept may be useful in many immune perturbation contexts. These findings demonstrate that patterns in complex gene expression variability can be used to define immune phenotypes and discover determinants of immune responsiveness.

Large changes in stroke volume and peripheral vascular resistance were induced by varying the heart rate and by intra-aortically infusing acetylcholine or angiotensin II in six dogs with heart block and electromagnetic flowmeters chronically implanted around their ascending aortas. Changes in stroke volume, aortic and atrial pressures, and systemic resistance were monitored continuously for 3-6 hours under morphine-pentobarbital anesthesia. The characteristics of diastolic pressure decay at heart rates ranging from 60 beats/min to 200 beats/min and during transient periods of asystole were studied, especially with reference to the distortions caused by reflected pressure waves. The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale. Under the conditions of these experiments, changes in the slope of that line and of its reciprocal, the time constant, correlated well with concomitant variations in peripheral vascular resistance. This relationship appears to be of practical value for continuous monitoring of systemic resistance directly from the diastolic segments of pressure pulses recorded from the lower thoracic aorta.

An ultraminiature micropressure sensor to accurately measure intramuscular pressure has been developed. The MEMS sensor is fabricated through surface micromachining and consists of a capacitive array of eight 150 μm diameter sensing membranes connected in parallel. The membranes have been vacuum-sealed via a subsequent deposition and patterning batch microfabrication step. A deep reactive ion etcher (DRIE) based postfabrication self-release has been utilized to fabricate individual devices. Each device has an outline that incorporates specially designed “anchor” structures that are utilized to attach on the muscle tissue during measurements to minimize the effect of muscle contractions on sensor readings. Electrical isolation of the wire bonds and bonding pads has been accomplished by utilizing glob-topping technique. The fabricated sensor performance has been experimentally validated inside a pressure chamber. The current sensors have 0.2 mm Hg pressure resolution in the ±19 mm Hg dynamic range with negligible hysteresis and show a flat frequency response in the 0–5.5 Hz experimental test range.