Sensors create an interface between the environment and an electronic system by converting physical, chemical and biological parameters of the environment into electrical signals. Up until now, sensors have been usually developed as stand-alone devices with the notable exception of imaging devices (as seen in digital cameras and mobile phones) and in automotive applications. By far the most success has been made with mechanical sensors (starting with the commercial success of airbag sensors in automotive design), and image sensors. Others, such as chemical and biological sensors, have been mainly developed for large scale laboratory analytical instrumentation with very few integrated applications. These include chemical gas sensors, liquid sensors, glucose-level sensors and large-scale bio-assays used for DNA sequencing.
The More than Moore platform sums up the expectation from the next generation of integrated systems. Additional value and applications beyond the down-scaling of electronic devices must be achieved. The "key" element in the More than Moore platform will be integrating a series of novel sensors into electronic systems, thus enabling these new integrated systems to interact directly with the environment. The electronic revolution has brought the computation power that was only available to super-computer systems to the common household. The expectation from More than Moore is to bring the sensing and detection capability that is only available in specialized laboratories to the common household as well.
There are a number of challenges for sensing. First of all there is the problem of sample preparation. This involves obtaining, transporting and pre-processing of the sample. In the past, this has been the limiting factor for integration. Sensors that require little (image sensors that require focusing, filtering) or no preparation (mechanical motion sensors) were developed much faster than biological sensors that require extensive preparation. As part of the Nano-Tera.CH project, we aim to refine current methods and develop new solutions to come up with viable and affordable sample preparation methods that can be integrated into next generation devices.
The second challenge for the sensor applications is performance. Sensor performance can generally be categorized in three components: Sensitivity, Specificity and Repeatability. The most obvious parameter is sensitivity, which essentially defines the accuracy of the sensing system. Especially for bio-chemical sensors, where the sample contains multiple similar substances, specificity is a very important parameter that defines how selective the sensing system is to the target substance. The third parameter repeatability, measures how reliable the sensing result is. The goal of the sensors developed by Nano-Tera.CH is to find ways for designing reliable, accurate sensors and integrate them in electronic systems without sacrificing key parameters like sensitivity, specificity and repeatability.
And finally the third challenge is to integrate these new sensors into systems with practical applications. Key application fields targeted for Nano-Tera.CH include implantable sensors and bio-sensors for health applications, environmental sensing and stand-alone sensor nodes, and ambient intelligence. These projects require solutions in packaging, digital post-processing, communication and security.
New sensing elements: New developments in nanotechnology and in photonics offer great potential for the realization of novel sensor elements. Examples include sensors based on:
- Measuring deflection and oscillation of micro-fabricated and functionalized cantilevers
- Mechanical and (bio)chemical sensitivity of carbon nanotubes
- Electron transport properties of transistors containing conducting polymers, carbon allotropes or other novel nano-materials
- Optical absorption
Each of these methods has their own advantages and limitations. Sensors based on the modification of the electron transport or of the mechanical force have the great advantage of being small and can usually be easily fabricated in large quantities at a low cost. Disadvantages are often a poor selectivity, need for periodic comparisons with references if one need accurate measurements as well as lack of good absolute accuracy.
On the other hand, the greater availability of optical sources at competitive costs open the possibility of sensors based on optical absorption. Those are usually more bulky and complex but offer better selectivity and accuracy. In addition, the recent development of semiconductor sources in the mid-infrared and the terahertz region of the spectrum opens new avenues for sensing as these region highly sensitive and selective sensing of chemical and biological compounds.
Miniature atomic clocks and quantum coherent systems as sensors: Quantum metrology has pushed atomic clocks to accuracies of 10-15 in the lab, and 1 nanosecond/day instability in space. Performances such as these are required in telecommunications and satellite navigation systems. A host of related and new applications will become accessible provided that higher performance or much smaller size is obtained. Next generation atomic clocks - sensors - with the performance required for future systems of secure telecommunication and navigation/positioning, will be developed through three complementary approaches: Very high performance oscillators based on femto-second lasers and optical combs, compact space-clocks for space, in particular for the 2nd generation of GALILEO satellites, and ultra-miniature clocks and quantum sensors (magnetic field, rotation). These achievements rely on the synergy between several fields of micro-nano-technology as well as the mastery of tera- to peta-hertz frequency synthesis.
Quantum coherent systems are, by construction, extremely sensitive to the environment. This is usually seen as a drawback, but can be turned into an advantage if such system is used as a sensor. Cold atoms, for example, are seen as the ultimate distance sensor. Their technology is still relatively complex but rapid progress with the development of atoms-on-a-chip technology could potentially open the possibility of the manufacture of compact, practical systems.
In a related note, single electron transistors can be used as the ultimate current sensors as they are many orders of magnitude more sensitive than conventional electrometers.
Integrated bio-sensing technology: State-of-the-art bio-sensing methods are either based on large-scale laboratory equipment or large bio-assays, both of which are not applicable for integration. Integrated bio-sensors will be required to detect a multitude of different organic materials (DNA, proteins) with stringent specificity requirements. Bio-sensors based on optical, electrical (capacitive) and mechanical sensing principles will be designed.
Devices and Circuits
Probe Array Technology: Probe Array Technology (PAT) is a sensor & actuator platform based on massively parallel micro/nano-mechanical devices, which enable signal transduction from the physical/chemical/biological domain via mechanics to the opto/electronic domain with extremely high sensitivity, high-throughput and high bandwidth. PAT is generic and applicable to at least three application domains: a) for monitoring the environment (sensing), b) for interacting with surfaces (imaging, adhesion sensing including for soft/bio-matter), and c) for creating and assembling systems at the nanometer scale. Several Swiss institutions have demonstrated the scientific proof-of-principle of PAT for use in air and liquid environment, and even in space. A concerted engineering effort would enable developing PAT systems and methodologies for applications relevant within Nano-Tera.CH. The underlying technologies are individually mature for further integration into systems. PAT can be envisioned in various implementations, e.g. high-end desktop version for lab-based investigations, or low-cost disposable and portable and even wearable versions for in-the-field use. Silicon micro/nanofabrication and plastic replication technologies are candidates for high-volume PAT manufacturing. Novel parallel detection schemes have recently been optimized for use in array probe systems. Dispensing techniques based on parallel spotter or inkjet technology can be envisioned to functionalize the sensing platforms in a combinatorial way for accessing the full spectrum of sensing signals and to engineer personalized systems. To be successful, PAT will need close synergies between MEMS/NEMS fabrication and sensing concepts, (bio-) chemistry and life-sciences, as well as signal processing. PAT will deliver new competences for future high precision engineering, micro/nanotechnology, and life sciences, all highly valuable for future high-quality Swiss products.
Sensors for health: Efficient medical monitoring and therapeutics will be achieved by novel implantable devices, which are capable of continuous bio-monitoring and drug delivery functions. In the future, these systems will incorporate much more control and sensing functions, including physical parameter e.g. pressure and forces inside the body, and therefore will be applicable for a new range of therapies which are not addressed today. Implantable devices require extensive research on the development of bio-compatible packaging, biodegradable drug coatings, integration of electronics, and combination with micro-fluidic systems. Research is thus needed to develop more reliable micro-pumps, new biochemical sensors and monitoring concepts. Another approach for continues drug delivery is to use an external device, which is connected to a planar array of micro-needles, which allows transdermal perfusion without pain and risk of infection.
As part of the Nano-Tera.CH project, we plan do study and develop integrated micro- and nanotechnology based biosensors using electrical impedance or optical sensors to detect specific protein binding in micro-fluidics channels. The sample preparation techniques (separation, purification, concentration) will be studied and the use of magnetic carriers and their manipulation into micro-channels will be investigated. The development of new integrated optical techniques (leaky waveguide technologies, porous silicon as band gap structure) is also anticipated.
As another example of micro-devices, we can mention the sensors that are developed for monitoring the eye pressure (important parameter in glaucoma prevention) for ophthalmology. Whereas most research was done on invasive pressure sensor implants, an alternative was recently developed by incorporating a stress sensor directly in a soft contact lens with telemetry reading. The future direction could be, for example, to have new measurement parameters such as chemical or biochemical sensing for health monitoring.
Sensors for the environment: Micro-analytical systems will become very important for the monitoring of human environment (pollution, safety, food processing, biohazard). Development of new lab-on-chip platforms will be a key complement to existing continuous monitoring by sensors and timed sampling for analytical laboratories.
One application is developing sensor nodes for sampling of the food quality. The requirements of food are complex and require analysis ranging from genetics (in the case of detection of genetically modified organisms, or detection of bacterial infections), to chemistry and to mechanical properties.
Miniaturized gas sensors using IR optical spectrophotometric systems for pollution monitoring are one other example for environmental sensors. These sensors will also include sample handling and pre-concentration to reach selectivity and stability, which is required by the application. Chromatography based gas sensors in which a micro-fluidic column can be combined with new type of micro-sensors (micro-ionizer, carbon nanotubes) can be developed.
Another approach for environmental sensors is to construct whole cell biosensors using certain cells as recognition elements. The most common microorganisms are bacteria although cell types have been reported. The potential advantage of whole cell detectors is the biological relevance of sensing. There are already several types of bacteria, which have been specifically engineered for heavy metal detection. The main problem is to store the sensor and to maintain the cells in good physiological conditions during the measurement phase. Cell based environmental sensors requires research on genetic engineering of the cells, micro-fluidic chemostats for cell culture and the combination of optical micro-sensors for end-point detection.
Systems and Integration
Environmental sensing: Developments in recent years have increased the awareness of the environment in the public eye. There is an increased demand in monitoring climatic changes, global warming, and pollution levels. The Nano-Tera.CH project aims to provide solutions for environmental sensing and monitoring by developing sensor nodes based on new lab-on-chip platforms. For these lab-on-chip platforms we will need to develop new on-chip biochemical analysis methods and combine them with efficient signal analysis. These lab-on-chip systems will be integrated into autonomously communicating sensor nodes to enable wide-scale deployment of multiple modules in the environment.
New safety regulations and consumer demand will require more and more sampling of the food quality not only at the point of fabrication, but also at the store up to consumer home. To replace laboratory tests, new monitoring modules will have to be developed.
Biomedical monitoring: Diagnostics at hospitals is based either on large-scale automated equipment or ELISA techniques based on bioassays, which are not suitable for bedside and emergency medicine. The next-generation diagnostic systems based on biosensor technology should have new detection capabilities and integrated sample handling to address the most common diagnostic problems like cardiovascular disease, coagulation disorders, chronic/acute inflammation, cancer, thyroid disorders. New diagnostic micro-systems require research on robust and efficient biosensors, on micro-fluidics for sample collection and pretreatment and on transducers such as electrochemical sensor and integrated optical sensors. In new diagnostics, the cost limitations impose to find simple and reliable concepts with some disposable parts.
For example flow cytometry instruments will be miniaturized and brought to the doctors office or patients home. Lab-on-chip integration made it possible to run the optical analysis on a chip. In the future, more sensing and cell preparation functions will be added. For example, a cytometry analyzer based on micro-fluidics and dielectric spectroscopy will soon be on the market. Another activity will be directed to the combination of cell sorting with subsequent on-chip analysis and separation of cell constituents (proteins, RNA) in order to have information down to the gene expression level. We will push the limits of detection to single cell level, enabling minimal invasive human single cell therapy.
Micro-technology can have high impact in neuroprostetics. Deep brain and spinal chord electrical stimulation is available for Parkinson disease and for pain treatment. With the development of more sophisticated electrodes and electronics processing, new applications can be envisioned. Epilepsy, but also depression could potentially be controlled by neurostimualtion.
Ultimately, the best bio-monitoring system would be a system, which has a similar physiological behavior as the human body. The micro-fluidics allow in principle the realization of complex miniaturized culture chambers in which several cell types are co-cultured and where the system could maintain the transport of bio-fluids between the cells and thus keep as physiological as possible the cell-cell signaling path. This way, one can expect to build human organ models, which could be extremely efficient for toxicology screening and drug testing. Cell culture analogs require much more than micro-fluidics. Multi-parameters sensors, reagents supply and circulation, temperature control, encapsulation, biocompatibility, cell attachment are some of the scientific and technical challenges of the CGA. Examples of activities related to cell based sensor we will study (a) micro-bio-reactors to maintain the cells in a closed and controlled environments, (b) bacteria based sensors for monitoring of toxicants in water and (c) cell co-cultures. There are already some technological developments in this, but a lot remains to be done in term of reliability and monitoring of effective dose delivery.