We have developed an integrated array of microbioreactors, with 100 microL working volume, comprising a peristaltic oxygenating mixer and microfluidic injectors. These integrated devices were fabricated in a single chip and can provide a high oxygen transfer rate (k(L)a approximately 0.1 s(-1)) without introducing bubbles, and closed loop control over dissolved oxygen and pH (+/-0.1). The system was capable of supporting eight simultaneous Escherichia coli fermentations to cell densities greater than 13 g-dcw L(-1) (1 cm OD(650 nm) > 40). This cell density was comparable to that achieved in a 4 litre reference fermentation, conducted with the same strain, in a bench scale stirred tank bioreactor and is more than four times higher than cell densities previously achieved in microbioreactors. Bubble free oxygenation permitted near real time optical density measurements which could be used to observe subtle changes in the growth rate and infer changes in the state of microbial genetic networks. Our system provides a platform for the study of the interaction of microbial populations with different environmental conditions, which has applications in basic science and industrial bioprocess development. We leverage the advantages of microfluidic integration to deliver a disposable, parallel bioreactor in a single chip, rather than robotically multiplexing independent bioreactors, which opens a new avenue for scaling small scale bioreactor arrays with the capabilities of bench scale stirred tank reactors.
In a harmonically mode-locked laser multiple optical pulses propagate inside the laser cavity. The noise in different pulses inside the laser cavity is in general correlated. Information regarding the sign and magnitude of the noise correlations is contained in the distribution of the spectral weight among the supermode noise peaks that appear in the pulse energy and timing noise spectral densities. We show that the supermode noise spectrum obtained experimentally by measurement of the photodetector current noise spectral density can be used to determine the correlations in the energy and the timing noise of different pulses in the laser cavity. We also present simple models for the timing noise in harmonically mode-locked lasers that demonstrate the relationship between the noise correlations and the supermode noise peaks.
A polymer optical backplane capable of generic luminescence detection within microfluidic chips is demonstrated using large core polymer waveguides and vertical couplers. The waveguides are fabricated through a new process combining mechanical machining and vapor polishing with elastomer microtransfer molding. A backplane approach enables general optical integration with planar array microfluidics since optical backplanes can be independently designed but still integrated with planar fluidic circuits. Fabricated large core waveguides exhibit a loss of 0.1 dB cm(-1) at 626 nm, a measured numerical aperture of 0.50, and a collection efficiency of 2.86% in an n = 1.459 medium, comparable to a 0.50 NA microscope objective. In addition to vertical couplers for out-of-plane collection and excitation, polymer waveguides are doped with organic dyes to provide wavelength selective filtering within waveguides, further improving optical device integration. With large core low loss waveguides, luminescence collection is improved and measurements can be performed with simple LEDs and photodetectors. Fluorescein detection via fluorescence intensity with a limit of detection (3sigma) of 200 nM in a 1 microL volume is demonstrated. Phosphorescence lifetime based oxygen detection in water in an oxygen controllable microbial cell culture chip with a limit of detection (3sigma) of 0.08% or 35 ppb is also demonstrated utilizing the waveguide backplane. Single waveguide luminescence collection performance is equivalent to a back collection geometry fiber bundle consisting of nine 500 microm diameter collection fibers.
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