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Sorting and recovering specific live cells from samples containing less than a few thousand cells have become major hurdles in rare cell exploration such as stem cell research, cell therapy and cell based diagnostics. We describe here a new technology based on a microelectronic chip integrating an array of over 100,000 independent electrodes and sensors which allow individual and parallel single cell manipulation of up to 10,000 cells while maintaining viability and proliferation capabilities. Manipulation is carried out using dynamic dielectrophoretic traps controlled by an electronic interface. We also demonstrate the capabilities of the chip by sorting and recovering individual live fluorescent cells from an unlabeled population.

The development of microfabricated devices manufactured in silicon, glass, or plastic materials is a well-known trend in the research of novel biological techniques and tools over the last two decades, resulting in a multitude of start-up companies serving the pharmaceutical, biotechnology, and diagnostics markets. However, the idea of implementing such devices on microelectronic substrates has been introduced only recently. This chapter aims to describe the state-of-the-art of microsystems for molecular and cell biology produced in general purpose CMOS (complementary metal oxide semiconductor) technology, emphasizing the advantages of this approach along with their challenges and limitations. This chapter discusses significant examples of fully tested devices in comparison with existing state-of-the-art techniques.

The recent development of advanced analytical and bioseparation methodologies based on microarrays and biosensors is one of the strategic objectives of the so-called post-genomic. In this field, the development of microfabricated devices could bring new opportunities in several application fields, such as predictive oncology, diagnostics and anti-tumor drug research. The so called “Laboratory-on-a-chip technology”, involving miniaturisation of analytical procedures, is expected to enable highly complex laboratory testing to move from the central laboratory into non-laboratory settings. The main advantages of Lab-on-a-chip devices are integration of multiple steps of different analytical procedures, large variety of applications, sub-microliter consumption of reagents and samples, and portability. One of the requirement for new generation Lab-on-a-chip devices is the possibility to be independent from additional preparative/analytical instruments. Ideally, Lab-on-a-chip devices should be able to perform with high efficiency and reproducibility both actuating and sensing procedures. In this review, we discuss applications of dielectrophoretic(DEP)-based Lab-on-a-chip devices to cancer research. The theory of dielectrophoresis as well as the description of several devices, based on spiral-shaped, parallel and arrayed electrodes are here presented. In addition, in this review we describe manipulation of cancer cells using advanced DEP-based Lab-on-a-chip devices in the absence of fluid flow and with the integration of both actuating and sensing procedures.

This contribution presents new algorithms for the automatic simplified computation of symbolic transfer functions of linear circuits. The problem of symbolic simplification of transfer functions is defined and a set of algorithms able to cope with this problem and the simplified computation of poles and zeroes is developed and discussed. Results are reported with examples of circuits analyzed by our algorithms, showing good accuracy in their approximation, when compared to the corresponding SPICE simulations. Our technique merges the simplification procedure and the evaluation of the transfer functions, thus achieving significant improvements in terms of CPU time, compared with direct evaluation of the functions themselves.

Bettelli: CellPly.S.r.l.: Employment. Ruggiano:Cellply S.r.l.: Employment. Bocchi:CellPly S.r.l.: Employment. Rocchi:CellPly.S.r.l.: Employment. Faenza:CellPly S.r.l.: Employment. Zamagni:Janssen: Honoraria, Other: Advisory board, Speakers Bureau; Amgen: Honoraria, Other: Advisory board, Speakers Bureau; BMS: Honoraria, Other: Advisory Board, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Sanofi: Honoraria, Other: Advisory Board, Speakers Bureau; Celgene Corporation: Honoraria, Other: Advisory board, Speakers Bureau. Bettelli:CellPly S.r.l.: Employment. Rambelli:CellPly S.r.l.: Employment. Guadagnuolo:CellPly S.r.l.: Employment. Pecorari:CellPly S.r.l.: Employment. Giulianelli:CellPly S.r.l.: Employment. Pisani:CellPly S.r.l.: Employment. Biscarini:CellPly S.r.l.: Employment. Cavo:amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Guerrieri:CellPly S.r.l.: Equity Ownership. Bocchi:CellPly S.r.l.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

There has been a fast progress in clinical use of antibody-based immunotherapy, given the superior efficacy commonly achieved in clinic and the limited toxicity. However, personalization of treatment remains of major importance, both to achieve better clinical performance for monotherapy and to identify the best combinations on a patient-by-patient basis. Predicting patient's response is complex due to the need to characterize both tumor response and immunologic mechanisms possibly activated by the therapy, including antibody dependent cellular cytotoxicity (ADCC).

Rocchi: CellPly S.r.l.: Employment. Faenza:CellPly S.r.l.: Employment. Rambelli:CellPly S.r.l.: Employment. Guadagnuolo:CellPly S.r.l.: Employment. Pecorari:CellPly S.r.l.: Employment. Giulianelli:CellPly S.r.l.: Employment. Biscarini:CellPly S.r.l.: Employment. Martinelli:Novartis: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy; Celgene: Consultancy, Speakers Bureau; Genentech: Consultancy. Guerrieri:CellPly S.r.l.: Equity Ownership. Bocchi:CellPly S.r.l.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Background:Patient stratification to match individual patients with the most effective drug treatment is still a major open challenge in cancer care. For instance, cytarabine is the main drug used for AML treatment but 30% of patients fail to respond to this agent. Laboratory developed tests determining ex-vivo cellular response to cytotoxic anticancer drugs have demonstrated good correlations with clinical response, sometimes surpassing the predictive power of molecular and genetic profiling. Standardizing sample processing to remove operator-dependent biases and maintaining live cells in a functional status that closely resembles in-vivo function are major challenges affecting these tests. Here we present the open microwell (OMW) platform, a microfluidic-based system that integrates the entire process of ex-vivo testing of anticancer drug efficacy and enables drug testing in the clinical setting prior to therapy administration. The concept was validated for the first time on 13 AML patients at Sant'Orsola hospital, Italy, showing the possibility to initiate the analysis readily after sample collection, thus minimizing drifts in cell function that typically start occurring within hours from sampling, and provide results in about 24 hours, with a fully-automated system.