Cite this: Lab Chip, 2013, 13, 3789 Cell chips as new tools for cell biology – results, perspectives and opportunities Received 2nd May 2013, Accepted 3rd July 2013 DOI: 10.1039/c3lc50550b www.rsc.org/loc Elisabetta Primiceri,* Maria Serena Chiriaco `, Ross Rinaldi and Giuseppe Maruccio Cell culture technologies were initially developed as research tools for studying cell functions, but nowadays they are essential for the biotechnology industry, with rapidly expanding applications requiring more and more advancements with respect to traditional tools. Miniaturization and integration of sensors and microfluidic components with cell culture techniques open the way to the development of cellomics as a new field of research targeting innovative analytic platforms for high-throughput studies. This approach enables advanced cell studies under controllable conditions by providing inexpensive, easy-to- operate devices. Thanks to their numerous advantages cell-chips have become a hotspot in biosensors and bioelectronics fields and have been applied to very different fields. In this review exemplary applications will be discussed, for cell counting and detection, cytotoxicity assays, migration assays and stem cell studies. Introduction Mechanisms at the basis of life and their malfunctions leading to diseases are key targets of biology research. However direct investigation on a whole organism is typically difficult or even not possible. Thus models are needed. In this respect, cell cultures provide a simple tool to investigate cellular mechan- isms and behavior both under physiological conditions or in response to chemical stimuli. As a consequence they are essential research tools. Nevertheless cell culture methodolo- gies remained basically unchanged for almost a century and thus have become increasingly limiting in modern studies when high-throughput is required, because of the difficulties for scaling up the number of assays. As a term of comparison, in the field of molecular biology microarray technologies led to a revolution in approaching biomedical studies. Several commercial systems are now considered as fundamental tools in many biology laboratories such as DNA and protein microarray technologies that strongly facilitate studies enabling rapid progress. For example Affymetrix microarrays offer multiple possibilities ranging from whole-transcriptome analysis of global changes in gene expression across the whole genome, to the identification of novel disease-relevant associations with more than 300 000 functional coding gene variants available (SNPs). Another example is offered by Invitrogen ProtoArray1, a Human Protein Microarray which enables rapid profiling of thousands of biochemical interactions in a single day for biomarker identification, drug target discovery, enzyme substrate identi- fication, antibody specificity profiling, and protein–protein interaction studies. In the field of cell biology such high- throughput approaches are still restricted to a few demon- strators without extensive diffusion in biomedical lab/practice. With respect to the previously mentioned platforms, progress in micromachining technology permitted miniatur- ization and integration of sensors and the development of inexpensive, easy-to-operate mobile devices for high through- put assays. These design routes towards a lab on chip format have a large potential to be applied also in cell culture applications allowing to overcome many of the present limitations. For example, most of the traditional methods lack the capability to monitor living cells in real-time and give only a snap-shot of a cellular process. Due to the dynamical nature of biological processes, this means a great loss of information, since real-time characterization is needed to investigate not only if a process happens but also which are the intermediate steps and the time scale. Moreover, the progress of cell culture technology enables the integration of living cells on solid-plates and three-dimensional cell cultures which better mimic the microstructure, mechanical properties and biochemical composition of the natural cell environment. In the past years, transfer of traditional methods to a microfabricated format 1 led to the birth of a new field known by the name cellomics, which provides an avenue to increase both the resolution of analysis and the sampling throughput by means of cell chips which are also able to reduce the cost per assay. 2 A cell chip can be defined as a miniaturized device where cells can be manipulated, treated and analyzed in a controlled and reproducible way. The combination of a culture chamber with suitable transducers able to translate a biological event in a measurable signal is thus crucial. 3 CNR Istituto Nanoscienze – NNL and Dipartimento di Matematica e Fisica ‘‘Ennio De Giorgi’’, Universita ` del Salento, Lecce, Italy. E-mail: elisabetta.primiceri@unisalento.it Lab on a Chip CRITICAL REVIEW This journal is ß The Royal Society of Chemistry 2013 Lab Chip, 2013, 13, 3789–3802 | 3789 Published on 03 July 2013. Downloaded by Universita del Salento on 28/02/2014 13:02:10. 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