MIRROR: A Chip-Scale Mid-IR Ring Resonance System for On-the-fly Reporting of Analytes - Abstract
Biopharmaceuticals represent one of the fastest growing product segments in the pharmaceutical industry, with
more than $US 229B in global annual sales. Protein biologics, as well as subunit vaccines, are currently
produced by mammalian cells or microorganisms in bioreactors. Therefore, analytical systems that can be used
to optimize the production of target molecules and control the processes, including in-line label-free bioreactor
monitoring systems, can add enormous value to the biopharmaceutical industry by increasing target molecule
output and reducing process inefficiencies. Unfortunately, analytical systems that address this need are currently
unavailable. Current analytical techniques such as fluorescence detection, mass spectrometry, or vibrational
spectroscopies (e.g., Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy) either do not have
sufficient molecular specificity, or the capability for specific label-free analysis, or sufficiently low cost enough to
be deployed ubiquitously, to provide a compelling solution. Here, we propose to address this unmet need by
developing a Mid-Infrared Ring Resonance system for On-the-fly Reporting of analytes (MIRROR), a sensor
platform that integrates mid-infrared (mid-IR) microphotonic circuits with microfluidic flow cells or microfluidic
bioreactor arrays to enable label-free real-time analysis of cellular products and cell culture environments in any
bioreactor volume. Mid-IR overlaps with the characteristic and the fingerprint absorption regimes of various
biochemical functional groups, while mostly avoiding the water absorption peaks, and thus enables label-free
analysis of biomolecules in aqueous phase. Compared to other label-free sensing techniques, FTIR is
significantly simpler to use and also low cost. However, the size of present mid-IR spectrometers and lack of
integrated photonic circuit technologies in this wavelength regions have made it difficult to integrate them into in-
line process monitoring systems or high-throughput microfluidic screening systems. In addition, their cost
remains relatively high. The proposed integrated microphotonic circuits consist of arrays of micro-ring resonators,
where every resonator structure is tuned to a particular wavelength. Thus, an array of such micro-ring resonators,
which resides at the center of the MIRROR platform, is essentially equivalent to a highly sensitive and chemically
specific chip-scale mid-IR spectrometer. The mass-producible and low-cost chip-scale photonics circuit will be
integrated into two types of broadly utilizable microfluidic platforms: 1) a microfluidic flow cell that will allow real-
time in-line monitoring of bioreactors of any size, and 2) a microfluidic cell culture bioreactor array for high-
throughput screening applications. In summary, MIRROR will enable new ways of analyzing cellular products
and their culture environments in a label-free, real-time fashion that can be applied to any bioreactor size, at low
cost, thereby constituting a broadly applicable solution to an important medical biotechnology need. Finally, a
highly multidisciplinary team that leverages complementary expertise in microfluidics, integrated photonics, mid-
IR spectroscopy, microbiology, and medical biotechnology supports this application.
