ESCHILO

Early Stage Cancer diagnosis via HIghly sensitive Lab-On-chip multitarget systems

Funding Institution: Regione Lombardia and Fondazione Cariplo, grant 2013
People: Prof. Marco Sampietro (Project leader), Prof. Riccardo Bertacco (Unit leader)
Partners: IFOM-Fondazione Istituto FIRC di oncologia Molecolare; Euroclone S.p.A.; ST Microelectronics S.r.l.
Duration: 2 years (2013-2015)

The project aims to provide an innovative, low-cost and sensitive technological platform for the early diagnosis of tumors. Starting from a small drop of blood or urine and applying proprietary techniques developed by partners in the fields of spintronics, the project aims to realize a miniaturized lab-on-chip that can identify the genetic mutations, which give rise to cancerous tumors. In this context, the project is focused on the detection of the mutation of the KRAS gene, associated to the formation of the lung adenocarcinoma. The lab-on-chip platform developed here will contain all the functionalities traditionally present in a biomedical analysis laboratory, from the capture and extraction of DNA from the biological sample to the detection and classification of the significant genetic mutations. The project will exploit a proprietary technology of the NaBis group, called “domain wall tweezers” [1] in combination with properly functionalized magnetic particles, in order to extract the target DNA from the biological sample. This first platform will implement the “immunoaffinity capture” scheme. Then, the target DNA detection will be performed by means of a magnetic platform [2, 3] based on magnetic tunneling junctions and magnetic nanoparticles labelling the hybridization events.

(a) Integrated platform for the DNA detection; b) particular of the modulus with the chip holder, the contact tips, the microfluidic cell and electromagnet; c) optical image of the chip containing twelve magnetoresistive sensors; d) detection principle; e) SEM image of the chip after a DNA detection experiment; the sensor is covered by magnetic particles specifically attached after biomolecular recognition took place.

(a) Integrated platform for the DNA detection; b) particular of the modulus with the chip holder, the contact tips, the microfluidic cell and electromagnet; c) optical image of the chip containing twelve magnetoresistive sensors; d) detection principle; e) SEM image of the chip after a DNA detection experiment; the sensor is covered by magnetic particles specifically attached after biomolecular recognition took place.

Publications

[1] [doi] M. Donolato, P. Vavassori, M. Gobbi, M. Deryabina, M. F. Hansen, V. Metlushko, B. Ilic, M. Cantoni, D. Petti, S. Brivio, and R. Bertacco, “On-Chip Manipulation of Protein-Coated Magnetic Beads via Domain-Wall Conduits,” Advanced Materials, vol. 22, iss. 24, p. 2706–2710, 2010.
[Bibtex]
@Article{ADMA:ADMA201000146,
Title = {On-Chip Manipulation of Protein-Coated Magnetic Beads via Domain-Wall Conduits},
Author = {Donolato, Marco and Vavassori, Paolo and Gobbi, Marco and Deryabina, Maria and Hansen, Mikkel F. and Metlushko, Vitali and Ilic, Bojan and Cantoni, Matteo and Petti, Daniela and Brivio, Stefano and Bertacco, Riccardo},
Journal = {Advanced Materials},
Year = {2010},
Number = {24},
Pages = {2706--2710},
Volume = {22},
Doi = {10.1002/adma.201000146},
ISSN = {1521-4095},
Keywords = {magnetic nanoparticles, bio-nanotechnology, magnetic materials, microstructures, microfluidics},
Publisher = {WILEY-VCH Verlag},
Url = {http://dx.doi.org/10.1002/adma.201000146}
}
[2] [doi] E. Albisetti, D. Petti, M. Cantoni, F. Damin, A. Torti, M. Chiari, and R. Bertacco, “Conditions for efficient on-chip magnetic bead detection via magnetoresistive sensors,” Biosensors and Bioelectronics, vol. 47, pp. 213-217, 2013.
[Bibtex]
@Article{Albisetti2013,
Title = {Conditions for efficient on-chip magnetic bead detection via magnetoresistive sensors },
Author = {E. Albisetti and D. Petti and M. Cantoni and F. Damin and A. Torti and M. Chiari and R. Bertacco},
Journal = {Biosensors and Bioelectronics},
Year = {2013},
Number = {0},
Pages = {213 - 217},
Volume = {47},
__markedentry = {[User:6]},
Abstract = {Abstract A commonly used figure of merit of magnetoresistive sensors employed to detect magnetic beads labeling biomolecules in lab-on-chip applications is the sensor sensitivity (S0) to external magnetic fields in the linear region of the sensor. In this paper we show that, in case of lock-in detection and bead excitation by a small \{AC\} magnetic field, \{S0\} is not the good figure of merit to optimize. Indeed, the highest sensitivity to the magnetic beads is achieved biasing the sensor in the region of its characteristics where the product between the \{DC\} bias field and the second derivative of the resistance with respect to the magnetic field is maximum. The validity of this criterion, derived from a phenomenological model of bead detection, is proved in case of magnetic tunneling junction sensors detecting magnetic beads with 250 nm diameter. This work paves the way to the development of a new generation of sensors properly designed to maximize the bead sensitivity. },
Doi = {http://dx.doi.org/10.1016/j.bios.2013.03.016},
ISSN = {0956-5663},
Keywords = {Magnetic biosensor},
Owner = {User},
Timestamp = {2015.07.02},
Url = {http://www.sciencedirect.com/science/article/pii/S0956566313001759}
}
[3] [doi] E. Albisetti, D. Petti, F. Damin, M. Cretich, A. Torti, M. Chiari, and R. Bertacco, “Photolithographic bio-patterning of magnetic sensors for biomolecular recognition,” Sensors and Actuators B: Chemical, vol. 200, pp. 39-46, 2014.
[Bibtex]
@Article{Albisetti2014,
Title = {Photolithographic bio-patterning of magnetic sensors for biomolecular recognition},
Author = {E. Albisetti and D. Petti and F. Damin and M. Cretich and A. Torti and M. Chiari and R. Bertacco},
Journal = {Sensors and Actuators B: Chemical},
Year = {2014},
Number = {0},
Pages = {39 - 46},
Volume = {200},
__markedentry = {[User:]},
Abstract = {Abstract In the last years, magnetoresistive biosensors arrays have drawn a great interest due to their high sensitivity and integrability in lab-on-chip platforms. In such devices, the selective functionalization of the sensor active area is a major issue, in order to achieve high sensitivity and quantification capability. Here, we present a straightforward photolithographic procedure to create patterns of bio-reactive polymer regions on the sensor's surface, with micrometric resolution. The effectiveness of the procedure in providing high specificity and improved sensor performance is demonstrated in the case of magnetoresistive biosensors based on magnetic tunneling junctions (MTJs). On-chip biomolecular recognition assays demonstrate an enhanced sensitivity in selectively functionalized sensors with respect to non-patterned sensors, eventually leading to a limit of detection below the pM range, without target pre-concentration or chemical amplification. },
Doi = {http://dx.doi.org/10.1016/j.snb.2014.04.055},
ISSN = {0925-4005},
Keywords = {Magnetic biosensor},
Owner = {User},
Timestamp = {2015.07.02},
Url = {http://www.sciencedirect.com/science/article/pii/S0925400514004560}
}