Spintronic Biosensors for Medicine

(SpinBioMed)

ABSTRACT

The ability to perform biological laboratory operations via biomolecular recognition in miniaturized

(lab-on-a-chip) devices has many technological, economic and social benefits: reduction of the time and cost of the analysis, highsensitivity and wide screening of patients in point of care applications.In this context,spintronics devicesoffer a unique combination of features, making them very promising for the implementation ofhighly sensitive biosensors: magnetoresistive transducers, like giant magnetoresistance (GMR)or tunnelling magnetoresistance (TMR) sensors, are employed for the detection of themagnetic beads, which are used as labels of target molecules. The sensor, or its active area, has tobe functionalized with the complementary molecular probe to immobilize the target moleculesbound to the beads at its surface, thus giving an electrical signal via the magnetoresistive behaviourof the spintronic transducer.

The goal of the present project is to advance in the design and realization of microarrays of biosensors based on spintronic transducers, pushing the limit of detection towards or beyond the

actual values of standard bulky techniques based on fluorescence.

The main advantages of this approach are:

i)magnetic beads are poorly affected by the environmental conditions, as organic materials (as the fluid in which the beads are suspended, e.g. serum or blood) do not perturb their magnetic properties;

ii)highsensitivities can be achieved (ideally down to the single molecule) by shrinking the devicedimensions to make them comparable to that of the bead and target molecule;

iii)thereading of the transducers is electric, allowing for a true miniaturization of the diagnostic tool.

The research consortium of the present project is made up of three Units:

I) LNESS - Politecnico diMilano

II)ICRM-CNR - Institute of Chemistry and Molecular Recognition

III)IFOM - Fondazione Istituto FIRC di Oncologia Molecolare

LNESS has a considerable experience inspintronics, from the growth of the epitaxial hetero-structures to the realization and test of thedevices. ICRM possess the know-how for the functionalization of surfaces, having alreadydeveloped and applied suitable protocols of immobilization of probes to other biosensors based onfluorescence. IFOM is active in the field of molecular oncology, where we are planning to validateour biosensors.

The final aim is developing a lab-on-chip system based on spintronic biosensors with biological sensitivity comparable or better thanthat of standard bulky systems like fluorescence.

The development of the lab-on-chip will be done with reference to a relevant clinicalapplication which will be used for the comparative validation of the lab-on-chip system, i.e. themeasurement of the level of mRNA prep1 in tumors for the identification of patients affected bylung cancer who do not need chemotherapy after a surgical removal.

OBJECTIVES

The proposed project aims to enhance understanding and advance in the design and construction of

a new type of compact diagnostic tool for the analysis of biomarkers in biological samples, oriented

to point of care medical applications and based on a lab on chip approach including microarrays of

spintronic biosensors. As specific application for validation we will consider the identification of

patients affected by lung cancer who do not need chemotherapy after a surgical removal of a tumor,

via measurements of the level of Prep1 mRNA in biological samples taken during the surgical

intervention.

Our design will consist in a chip with 24 sensor points functionalized with specific oligonucleotides

and coupled to a microfluidic apparatusfor the delivery and transport of the liquids onto the sensor surface.

The realization of spintronic transducers and coatings for probe immobilization is based on the development of innovative materials: complex epitaxial heterostructures are the basic ingredients for the subsequent realization ofspintronic devices, via micro and nanofabrication techniques for the lateral definition, andbufferpolymeric layers with high density of binding sites uniformly distributed on their surface arenecessary for the immobilization of biologic probes.

The following specific objectives will be pursued during the project:

Objective 1: Development and microfabrication of microarrays of spintronic transducers able

to detect magnetic beads used for labelling the target biomolecules, in a chip with typical dimensions of10x10mm2(LNESS)

Objective 2: Development of protocols for the functionalization of the sensor surface and

magnetic labelling, in order to ensure high sticking efficiencyand minimum perturbation of biochemical affinity (ICRM)

Objective 3: Coupling of the microfluidics to the spintronic chip and development of protocols

for the realization of biological assays (LNESS, ICRM)

Objective 4: Determination of the performances of spintronic biosensors in prototypical

biological assays of DNA recognition (LNESS, ICRM)

Objective 5: Validation of microarrays of spintronic biosensors with reference to a specific

application in molecular oncology (LNESS, ICRM, IFOM)

The relevant output of the project will be the evaluation of the viability of application of spintronic

biosensors to medical diagnosis. In fact the research on spintronic biosensors is really at the early

stage and comparative studies of their performances in connection with those of bulky standard

techniques are of major importance.

PERSONNEL:

LNESS - Politecnico di Milano:

Riccardo Bertacco – group leader

Matteo Cantoni – researcher

Marco Donolato – Ph.D. student

Andrea Torti - Ph.D. student (recruited for SPINBIOMED)

Daniela Petti – post doc (recruited for SPINBIOMED)

Marco Leone – technician

ICRM-CNR - Institute of Chemistry and Molecular Recognition

Marcella Chiari - group leader

Marina Cretich - researcher

IFOM - Fondazione Istituto FIRC di Oncologia Molecolare

Francesco Blasi – group leader

Livia Modica - researcher

STATE OF PROJECT

PUBLICATIONS