1. Design of Health Technologies lecture 12 John Canny 10/17/05

2. Advanced Sensing Systems Biosensors: Glucose monitoring Other systems

3. Magneto-elastic sensors (Grimes) The magneto-elastic material resonates at a characteristic frequency when excited by a magnetic field.

4. Magneto-elastic sensors The magneto-elastic ribbon is made of a commercial sheet called Metglas. The polymer is a custom co-polymer made by the Grimes group. It is believed to work because glucose bonds to sites on polymer chains that separate them from other chains. This allows the polymer to absorb water.

5. Magneto-elastic sensors Its frequency response (in air) shows a sharp peak which is determined by the density of the polymer layer

6. Magneto-elastic sensors Resonant frequency in a liquid is lower, and the peak is not as sharp.

7. Magneto-elastic sensors Frequency response in water varies with the glucose concentration, in an almost perfectly linear curve.

8. Sensor measurement The electronics are simple. A sharp spike is applied to a driving coil, and a response is measured in a sense coil.

9. Sensor measurement The magnetic spike is short, about 3 gauss for 16 micro- seconds (earth’s magnetic field is about 0.5 gauss, and a refrigerator magnet about 10 gauss). The pickup coil measures sensor activity for a further 8 milli-seconds. The response is transformed with an FFT to determine the frequency peak. This should be easy to do with a small, battery-powered device. Because the sensor’s response is quite slow (tens of minutes to respond), it is enough to take readings every few minutes.

10. Biosensor status There are many promising systems on the horizon, but the only commercially-deployed biosensors are glucose monitors (~$4B). 3 main types: Single Use: Disposable sensing material, often “static” measurement. Cheap and portable, but low sensitivity and accuracy. Intermittent Use: Often use hydrodynamics – generally much better performance from sensing a moving fluid. Its still a challenge to move these out of the lab and onto a chip.

11. Biosensor status Continuous (In Vivo) Sensors: Very economical, but very hard to calibrate and may suffer from unknown amount of drift.

12. Biosensor design We give a brief introduction to micro-fluidic sensor design. While these were originally fabricated in silicon using MEMS techniques, the trend is toward glass and plastic as the substrate. Both glass and many plastics allow optical measurements, but silicon is opaque to visible light. Glass and plastic are also more resistant to contamination from the chemicals used in the measurement.

13. Biosensor design Surface immobilization: The first step is sensing is creating a selective surface to react to the sensed agent

14. Biosensor design Bead immobilization: A variation that uses beads to increase relative surface area.

15. Biosensor design Detection: Several methods, including resonant frequency of MEMS cantilevers. But amperometry (current measurement) is the most widely used approach. Typical mechanisms for current flow include redox cycles between the target group and variants.

16. Biosensor design Optical Detection: A 2D array of agent/antigen reactions produces fluorescent traces:

17. Biosensor design Magnetic Detection: The antibodies are immobilized on a surface and magnetic beads bind to sites where the analyte is attached.

18. Enzyme-Linked Immunosorbent Assay

19. Reuse Most immunosensors use bound antibodies and immobilization. Removing the bound species can be difficult without destroying the sensors. Methods and results vary, but a recent detector for Chagas disease used glycine-HCl to wash the sensor, and reported efficacy for more than 30 cycles.

20. Biosensor design Systems-on-a-chip: are promising but coming slowly. Biosensing still seems a long way from commercial viability. But there are some promising prototypes:

21. Discussion Questions 1. It may be a while before we have highly integrated sensors for many pathogens (and economics dictates that they will come for first-world diseases first). Can you think of telemedicine/information tools to help facilitate traditional (but simple) lab methods? 2. Sensors for medical diagnosis may always be a difficult economic proposition. Can you think of other models that might work? E.g. home testing?