Frequency tuning allows flow direction control in microfluidic networks with passive features.

Frequency tuning has emerged as an attractive alternative to conventional pumping techniques in microfluidics. Oscillating (AC) flow driven through a passive valve can be rectified to create steady (DC) flow, and tuning the excitation frequency to the characteristic (resonance) frequency of the underlying microfluidic network allows control of flow magnitude using simple hardware, such as an on-chip piezo buzzer. In this paper, we report that frequency tuning can also be used to control the direction (forward or backward) of the rectified DC flow in a single device. Initially, we observed that certain devices provided DC flow in the "forward" direction expected from previous work with a similar valve geometry, and the maximum DC flow occurred at the same frequency as a prominent peak in the AC flow magnitude, as expected. However, devices of a slightly different geometry provided the DC flow in the opposite direction and at a frequency well below the peak AC flow. Using an equivalent electrical circuit model, we found that the "forward" DC flow occurred at the series resonance frequency (with large AC flow peak), while the "backward" DC flow occurred at a less obvious parallel resonance (a valley in AC flow magnitude). We also observed that the DC flow occurred only when there was a measurable differential in the AC flow magnitude across the valve, and the DC flow direction was from the channel with large AC flow magnitude to that with small AC flow magnitude. Using these observations and the AC flow predictions from the equivalent circuit model, we designed a device with an AC flowrate frequency profile that was expected to allow the DC flow in opposite directions at two distinct frequencies. The fabricated device showed the expected flow reversal at the expected frequencies. This approach expands the flow control toolkit to include both magnitude and direction control in frequency-tuned microfluidic pumps. The work also raises interesting questions about the origin of flow reversal behavior that may be addressed by the further study of the circuit model behavior or dynamic modeling of the fluid-solid mechanics of the valve under the AC flow.

Flow control using audio tones in resonant microfluidic networks: towards cell-phone controlled lab-on-a-chip devices.

Fluid control remains a challenge in development of portable lab-on-a-chip devices. Here, we show that microfluidic networks driven by single-frequency audio tones create resonant oscillating flow that is predicted by equivalent electrical circuit models. We fabricated microfluidic devices with fluidic resistors (R), inductors (L), and capacitors (C) to create RLC networks with band-pass resonance in the audible frequency range available on portable audio devices. Microfluidic devices were fabricated from laser-cut adhesive plastic, and a "buzzer" was glued to a diaphragm (capacitor) to integrate the actuator on the device. The AC flowrate magnitude was measured by imaging oscillation of bead tracers to allow direct comparison to the RLC circuit model across the frequency range. We present a systematic build-up from single-channel systems to multi-channel (3-channel) networks, and show that RLC circuit models predict complex frequency-dependent interactions within multi-channel networks. Finally, we show that adding flow rectifying valves to the network creates pumps that can be driven by amplified and non-amplified audio tones from common audio devices (iPod and iPhone). This work shows that RLC circuit models predict resonant flow responses in multi-channel fluidic networks as a step towards microfluidic devices controlled by audio tones.

Impact of forced vital capacity loss on survival after the onset of chronic lung allograft dysfunction.

RATIONALE: Emerging evidence suggests a restrictive phenotype of chronic lung allograft dysfunction (CLAD) exists; however, the optimal approach to its diagnosis and clinical significance is uncertain. OBJECTIVES: To evaluate the hypothesis that spirometric indices more suggestive of a restrictive ventilatory defect, such as loss of FVC, identify patients with distinct clinical, radiographic, and pathologic features, including worse survival. METHODS: Retrospective, single-center analysis of 566 consecutive first bilateral lung recipients transplanted over a 12-year period. A total of 216 patients developed CLAD during follow-up. CLAD was categorized at its onset into discrete physiologic groups based on spirometric criteria. Imaging and histologic studies were reviewed when available. Survival after CLAD diagnosis was assessed using Kaplan-Meier and Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS: Among patients with CLAD, 30% demonstrated an FVC decrement at its onset. These patients were more likely to be female, have radiographic alveolar or interstitial changes, and histologic findings of interstitial fibrosis. Patients with FVC decline at CLAD onset had significantly worse survival after CLAD when compared with those with preserved FVC (P < 0.0001; 3-yr survival estimates 9% vs. 48%, respectively). The deleterious impact of CLAD accompanied by FVC loss on post-CLAD survival persisted in a multivariable model including baseline demographic and clinical factors (P < 0.0001; adjusted hazard ratio, 2.73; 95% confidence interval, 1.86-4.04). CONCLUSIONS: At CLAD onset, a subset of patients demonstrating physiology more suggestive of restriction experience worse clinical outcomes. Further study of the biologic mechanisms underlying CLAD phenotypes is critical to improving long-term survival after lung transplantation.