Biological and biomedical platforms
Since the early 2000’s, INESC-MN is one of the leading R&D groups focusing on magnetoelectronics as a new technology applied to life sciences and biosensing applications. Main areas cover the biomedical, environmental, food and agriculture, biodefense and bioengineering fields. In this view, different spintronics-based devices and systems are under investigation and development including integrated biochip-platforms for diagnostics, cytometric applications, hybrid systems incorporating magnetoresistive (MR) sensors for neuroelectronic studies and biomedical imaging (e.g. magneto-encephalography, magneto-cardiography), and MR-based platforms to perform biological studies at the single molecule level.
Topical Reviews:
Lab on a Chip 12 (2012) 546
J Phys D: Appl Phys 50 (2017) 213001
Diagnostic platforms
In a standard MR biochip-based bioassay, a recognition probe immobilized over the sensor is used to interrogate an unknown sample potentially containing a target molecule of interest (e.g. nucleic acid sequence, protein, or cell antigens), labeled with a magnetic particle. Whenever there is a recognition event between the target and its probe, a detection event occurs. Applying an external magnetic field, the magnetic labels attached to the bound molecules will create a fringe field that is further detected by the MR sensor. The combination of MR biochips to electronic and microfluidic systems, enables the execution of complex analytical operations in one single integrated system. Our past research, within collaborative projects with INESC-ID, demonstrated the ability to scale-down the MR-based platforms into portable, lab-on-chip devices. A major impact was the creation of the spin-off company Magnomics S.A., targeting the development of a MR-biochip platform for the detection of bacterial infections.
ACS Nano 11 (2017) 10659
Analytical Methods 8 (1), 119-128 (2016)
Magnetoresistive cytometer platforms
MR platforms represent a new approach for cytometry analysis, where the integrated MR sensors are used to count magnetically labelled entities flowing inside microfluidic channels above the sensors. Compared to standard cytometer systems, this new approach allows to achieve smaller, simpler and less expensive instrumentation, with enhanced portability to on-site measurement. The first application of this technology was devoted to the counting of human cells from the cord blood, though detection of bacterial cells is also being explored. One important parameter when using this technique to count cells is the total magnetic moment of the labelled cells. Such value depends on the number of particles labelling the cells and their individual moment. This type of magnetization and detection strategy gives origin to bipolar pulses, with the amplitude being dependent on the number of labels and on the cell height.
Biomedical signal detection platforms
The two most studied biomagnetic signals sources are the heart and the brain. The magnetic field amplitude generated by these two systems is of the order of 1 pT and 50 fT, respectively for the signals from the heart at the skin level and from the electric currents flowing in active nerve cells in the brain. Fundamental studies related with neuron to neuron signal propagation have been conducted in an extracellular electrophysiology system using a microfabricated device comprising MR sensors (TMR and GMR) to measure the magnetic response from neurons in hypocampus brain slices. Alternatively, integrated MR sensors within Si needle probes can allow the direct detection of the magnetic field generated by the neurons while metallic microelectrodes included inside the needles may provide local electrical sensing ability.
From a medical diagnostic point of view, however there is an increasing interest in using non-invasive methods for the detection of biomagnetic signals. Therefore, our present main goal is to detect the magnetic field created by the activation of action/synaptic potential sources with MR sensors located several tens of micrometers above those sources. Since these signals are far below the magnetic field of the earth (~10-4 T), the development of these detection systems is challenging. We explore different strategies to reach such low detection levels (e.g. series of sensors, flux concentrators, MEMS).Standard commercial systems use SQUIDs (superconducting quantum interference devices). Although very sensitive when measuring magnetic flux, they require very low temperatures to operate which is a major drawback as it involves a large apparatus and may cause discomfort in patients. In a collaborative project with CEA we are exploring GMR sensors for the direct detection of magnetic fields. Major advantages include miniaturization and therefore increased spatial resolution with potential for signal mapping. Additionally, several attempts to integrate these sensors with flexible substrates, targeting wearable devices are being pursued.
Neuron 95 (2017) 1283
Micromachines 7 (2016) 88
IEEE Trans Instr Meas 63 (2014) 1171
IEEE Trans Mag 49 (2013) 3512
Single molecule actuation platforms
Cell dynamics including movement is powered by molecular motors resulting from the assembling of different molecular entities that can undergo geometrical changes and promote specific interactions or induce motion. Untapping such events is of great interest in many areas of biological research ranging from enzymatic activity to cell differentiation processes. Manipulation techniques at single molecule level with pN scale forces and measurement of displacements with 1 nm resolution are required for in vitro studies of such individual molecular motors. On-chip magnetic tweezers integrated with MR sensors produces forces up to 1.0 ± 0.3 pN capable of DNA stretching monitored in real time using MR sensors. A bead vertical displacement resolution of 60 nm is derived for DNA molecular motor activity in a tweezers steady current regime. The system can be used to characterize real-time DNA-enzyme interaction at the single molecule level.