Biology on a chip - the rise of the machines

01 October 2007

Silicon is fast becoming the basic building block within the latest technological revolution: micromachines

These millimetric systems can equip entire biological analysis laboratories built on a single chip. Silicon is used for most electronic circuits although its mechanical properties vie with those of steel, although it has only recently become available at moderately low manufacturing costs, thanks to economies of scale in the microelectronics industry.

Micromachines are microelectromechanical systems, a few millimeters in size, built of silicon and usually constructed with the same planar and photolithographic processes used in the semiconductor industry for ‘wafers’. Special chemical processes, such as ‘freeing’ the structures to make them mobile, have been specifically developed.

Measuring position and vibrations
The most widespread and best known micromechanical object is the accelerometer. It is a sensor that measures acceleration (one of the most important kinematic quantities), which reflects the movement and change of speed of a body. It consists of a mass suspended on a spring that moves if subjected to acceleration so, by measuring the movement of the mass, it is possible to calculate acceleration. Accelerometers were first used in car airbag systems. When a car crashes, its acceleration increases suddenly and if the acceleration exceeds a defined value, the system inflates the airbags. Accelerometers
are triaxial, or sensitive along all three orthogonal axes, so can measure the magnitude and direction of the acceleration vector.

Applications using such accelerometers can be divided into two main categories: those measuring position in space and those measuring vibrations. Gravity is a constant acceleration, which is uniform everywhere on the earth. Accelerometers measure the gravity vector and establish direction with
respect to a local reference system, thus establishing the sensor's spatial orientation. A static position or movement can be recorded and translated into electrical signals, which can be saved and encoded for further processing.

If an accelerometer is put inside a pen, an authorised specimen signature can be compared in real time with the one the user is signing when making a purchase, thus increasing security in the case of credit card transactions. It is also possible to measure the footsteps and walk of an individual in order to determine their physical activity and calories consumed. The activity of an individual can be monitored in order to avert skeletal or muscular system ‘breakdowns’ before they occur. The sensor can warn that a trauma is imminent so the training can be stopped.

Elderly people living alone can be helped when they have difficulty moving, for example when they are unable to get up from sitting or lying down. This can be detected by an accelerometer system worn around their neck or waist and sent automatically by SMS through the GSM network. Using an accelerometer in pacemakers allows the cardiac rhythm to be adapted to the patient's activity during a normal day, thus minimising the hypochronotropism and hyperchronotropism typical of standard pacemakers programmed for average physical activity.

Movements that are typically assessed using qualitative methods, can be measured quantitatively in terms of amplitude, rotational speed or compliance with a predetermined pattern. The final assessment of the exercise can then be made more objective. Another important application is measurement of the position and movement of prostheses. The electrical and electronic system that drives the electric motors that move the limb can be improved if the actual movement and position of the prosthesis is known. Corrections to the force, direction and quality of the movement applied to the prosthesis can be made by local electronic circuitry without the patient needing to consciously ‘feel’ the limb.

Internal monitoring
Blood circulation causes the skin at our extremities to vibrate, and these vibrations are unique to each individual, like fingerprints. Mobile phones can now recognise their owners from the vibrations of their hand when they simply hold it and turn it on. Again, in the biomedical field, another interesting use is detection of high quantities of a few hormones or consumption of certain drugs. The presence of hormones and drugs may be detected and distinguished by placing accelerometers on the patient's wrists. This type of analysis may be carried out both positively, for example to detect the amount of stimulants taken by the patient, and negatively by detecting the administration of relaxants. This application has already become reality in the veterinary field, where an accelerometer collar is used to detect when dairy cows are on heat in order to shorten their non-productive period.

The progressive evolvement of degenerative diseases can also be quantitatively measured using these sensors, and the physician may choose a more gradual or a better targeted treatment during periods of rapid worsening of clinical conditions.

Laboratory on a chip
Silicon is also used in biological analysis microlaboratories. Thanks to its biocompatibility, it can handle minute quantities of organic liquids, from which DNA chains can be extracted. Their fragments can then be multiplied to identify the presence of pre-determined gene sequences. These microlaboratories consist of channels buried in the silicon into which the organic material is pushed, heated and left to react in order to produce the required results. All the processes needed for complete diagnosis can be created inside the silicon chip: specimen preparation, multiplication of the DNA fragments and detection of gene chains.

This type of microlaboratory can be used when it is necessary to check the presence of a DNA chain in an organic liquid, such as a predisposition for genetic diseases, diagnosis of infectious diseases, evidence in criminal proceedings, food analysis and in zoology and animal husbandry to select the most productive species.

At the micro level
Micromechanical actuators are mobile silicon systems that receive a command and drive external loads. They are sometimes also called micromotors and are used to move small objects or to move and switch laser rays in communication systems. Silicon micropumps have been developed for transdermal injections for drugs, such as insulin, that require particularly careful dosage and administration depending on the transitory conditions of the patient. They are driven by a control box which either includes a timer or is able to measure blood glucose concentrations in real time and automatically administer the necessary dose at the right-time as programmed by the specialist.

Another application is the monitoring of certain physiological parameters. Blood pressure in veins or arteries is measured with sensors implanted in the walls of the blood vessels. They are fitted with minute radio transmitters and use energy-scavenging techniques to recharge their internal microbatteries using the movements of the human body or its temperature. They can be implanted into the body and left there for several years without needing a power supply. When measurements are needed, a mini control box worn by the patient calls each of the sensors. Since it knows their positions, it can map the pressures and calculate their distribution, gradient and changes over time. It is also possible to program alarm thresholds, so signals are generated to warn of an anomalous condition to be kept under observation. Similar applications are possible with chemical sensors detecting concentrations of substances either dissolved in the blood or present in other tissues.

BENEDETTO VIGNA is MEMS business unit manager and Luca Fontanella is MEMS business unit marketing manager, STMicroelectronics.

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