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Background: Quantifying the robustness of biochemical models is important both for determining the validity of a natural system model and for designing reliable and robust synthetic biochemical networks. Several tools have been proposed in the literature. Unfortunately, multiparameter robustness analysis suffers from computational limitations.

Abstract-The input/output dynamic behavior of a biomolecular system is affected by interconnection to other downstream systems through impedance-like effects called retroactivity. In this paper, we study the effects of retroactivity at the interconnection between two transcriptional modules, focusing on stochastic behavior. In particular, we describe the system through the Master equation and develop a singular perturbation theory to obtain a reduced Master equation. We prove that the solution of the original Master equation converges fast to an neighbor of the solution of the reduced Master equation, in which is the singular perturbation parameter. Our analysis shows that the upstream system and the downstream one are statistically independent at the steady state. However, the interconnection slows down the dynamics of both the expectation and the variance of the output of the upstream transcriptional module.

Two microfluidic devices (pneumatic chip and FlexiChip) have been developed for immobilization and live-intact fluorescence functional imaging of Drosophila larva's Central Nervous System (CNS) in response to controlled acoustic stimulation. The pneumatic chip is suited for automated loading/unloading and potentially allows high throughput operation for studies with a large number of larvae while the FlexiChip provides a simple and quick manual option for animal loading and is suited for smaller studies. Both chips were capable of significantly reducing the endogenous CNS movement while still allowing the study of sound-stimulated CNS activities of Drosophila 3rd instar larvae using genetically encoded calcium indicator GCaMP5. Temporal effects of sound frequency (50-5000 Hz) and intensity (95-115 dB) on CNS activities were investigated and a peak neuronal response of 200 Hz was identified. Our lab-on-chip devices can not only aid further studies of Drosophila larva's auditory responses but can be also adopted for functional imaging of CNS activities in response to other sensory cues. Auditory stimuli and the corresponding response of the CNS can potentially be used as a tool to study the effect of chemicals on the neurophysiology of this model organism.

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