Cyto-Mine: An Integrated, Picodroplet System for High-Throughput Single-Cell Analysis, Sorting, Dispensing, and Monoclonality Assurance.

The primary goal of bioprocess cell line development is to obtain high product yields from robustly growing and well-defined clonal cell lines in timelines measured in weeks rather than months. Likewise, high-throughput screening of B cells and hybridomas is required for most cell line engineering workflows. A substantial bottleneck in these processes is detecting and isolating rare clonal cells with the required characteristics. Traditionally, this was achieved by the resource-intensive method of limiting dilution cloning, and more recently aided by semiautomated technologies such as cell sorting (e.g., fluorescence-activated cell sorting) and colony picking. In this paper we report on our novel Cyto-Mine Single Cell Analysis and Monoclonality Assurance System, which overcomes the limitations of current technologies by screening hundreds of thousands of individual cells for secreted target proteins, and then isolating and dispensing the highest producers into microtiter plate wells (MTP). The Cyto-Mine system performs this workflow using a fully integrated, microfluidic Cyto-Cartridge. Critically, all reagents and Cyto-Cartridges used are animal component-free (ACF) and sterile, thus allowing fast, robust, and safe isolation of desired cells.

Quantitative comparison of PZT and CMUT probes for photoacoustic imaging: Experimental validation.

Photoacoustic (PA) signals are short ultrasound (US) pulses typically characterized by a single-cycle shape, often referred to as N-shape. The spectral content of such wideband signals ranges from a few hundred kilohertz to several tens of megahertz. Typical reception frequency responses of classical piezoelectric US imaging transducers, based on PZT technology, are not sufficiently broadband to fully preserve the entire information contained in PA signals, which are then filtered, thus limiting PA imaging performance. Capacitive micromachined ultrasonic transducers (CMUT) are rapidly emerging as a valid alternative to conventional PZT transducers in several medical ultrasound imaging applications. As compared to PZT transducers, CMUTs exhibit both higher sensitivity and significantly broader frequency response in reception, making their use attractive in PA imaging applications. This paper explores the advantages of the CMUT larger bandwidth in PA imaging by carrying out an experimental comparative study using various CMUT and PZT probes from different research laboratories and manufacturers. PA acquisitions are performed on a suture wire and on several home-made bimodal phantoms with both PZT and CMUT probes. Three criteria, based on the evaluation of pure receive impulse response, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) respectively, have been used for a quantitative comparison of imaging results. The measured fractional bandwidths of the CMUT arrays are larger compared to PZT probes. Moreover, both SNR and CNR are enhanced by at least 6 dB with CMUT technology. This work highlights the potential of CMUT technology for PA imaging through qualitative and quantitative parameters.