ECE5320 Mechatronics Assignment#01: Literature Survey on Sensors and Actuators Topic: Biosensors

1. ECE5320 MechatronicsAssignment#01: Literature Survey on Sensors and Actuators Topic: Biosensors Prepared by: Shayok Mukhopadhyay Dept. of Electrical and Computer Engineering Utah State University E:shayok@gmail.com ; T: (435)754-5758 W: http://www.csois.usu.edu 3/10/2006

2. Outline • Reference list • To probe further • Major applications • Fiber optic based fluoroimmunosensors • Typical uses • Device configuration • Working principle • Sensing heads & their types. • A typical configuration in operation • Analysis of results & limitations • Major specifications • Cost, choice & manufacturers ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

3. Reference list • Fibre-Optic-Based Fluoroimmunosensors [and Discussion], M. J. Sepaniak; T. Vo-Dinh; G. S. Wilson; W. J. Albery; L. De Galan, Philosophical Transactions: Physical Sciences and Engineering, Vol. 333, No. 1628, Trace Analysis. (Oct. 15, 1990), pp. 85-92. • http://www.ornl.gov/sci/biosensors/ • http://www.chemicool.com/definition/fluorophor.html • en.wikipedia.org/wiki/Monochromator • www.areva.co.uk/Glossary/glossary_p.htm ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

4. To probe further (survival pointers of web references etc.) • http://www.jstor.org/view/09628428/ap000006/00a00150/0 • http://www.ornl.gov/info/ornlreview/rev29_3/text/biosens.htm • http://www.ornl.gov/sci/biosensors/ • http://www.sciencedirect.com/science/journal/0265928X • http://en.wikipedia.org/wiki/Biosensor ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

5. Major applications • Biosensors are used to selectively identify chemical compounds found at ultra trace levels in industrial plants, environment (i.e. air, water, soil) or in biological systems i.e. (bacteria, viruses, tissues etc.) • Antibody-based fluoroimmunosensors (FISs) : used to detect benzo[a]pyrene (BaP) which is a carcinogen. • Biochips :Biologically active DNA probes are immobilized on optical transducers which can be used to detect genetic diseases. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

6. Major applications continued • LIF (laser-induced fluorescence) : Cancer Diagnostics • Plasmonics : surface-enhanced Raman scattering (SERS) and surface-enhanced fluorescence (SEF), used for ultra sensitive detection of chemicals and biological substances. • Near-field scanning optical microscopy (NSOM) : Non-destructive imaging of biomolecules in nanoscale domains <=100 nanometers. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

7. Fiber-optic-based fluoroimmunosensors • These biosensors can be used for remote sensing of chemicals using fiber optic chemical sensors. • These instruments exploit the biological antibody-antigen reactions and also the sensitivity of laser excited flourimetry. • These devices are capable of highly selective measurements of ultra trace levels of chemicals. • Measurements can be done either remotely or in situ. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

8. Typical uses… • Measurement in hostile or not easily accessible locations. • “Continuous sensing of analytes*”. • These devices are useful in situations where conventional methods may alter the concentration of the analyte being measured. • *analyte is the chemical or biological substance being measured. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

9. Device configuration Phil.Trans. R.Soc.Lond. A(1990) ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

10. Configuration explained ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

11. Working principle • A suitable laser depending on the size and fluorescence emitting characteristics of the analyte is first selected. • The laser duty cycle is controlled by a shutter since excess power would result in photodegradation. The power at the incident end of the optical fiber is generally 1mW or less. • The laser beam then passes through a center hole in the mirror (25 mm diameter) into the optical fiber. • The beam passes through the fiber and is incident on the analyte at the sensing terminus. • The anayte being sensed exhibits fluorescence due to excitation. • This fluorescence emitted by the analyte passes through the fiber optic cable in a reverse fashion and reaches back to the incident end. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

12. Working principle contd… • The fluorescence received back at the incident end is at a fairly large angle and hence is collimated by a lense. • It is then reflected on the mirror and directed towards the monochromator. • An extra set of lenses may be required before the monochromator for achieving focus. • The monochromator is preset to select particular wavelengths of light which are expected to be emitted from the analyte. • The light is then passed through a photomultiplier which converts light to electric signals. • A picoammeter is then used to measure the signals since the signals may be very low.The output can be then analysed or recorded. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

13. The sensing head • The sensing head is the most critical component of the entire system. • The two types of heads are shown in the figure above, their operation is explained in the following slides. Phil.Trans. R.Soc.Lond. A(1990) ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

14. Passive diffusion sensor • This sensor has a 140nL chamber located at the end of the 600μm core diameter fiber (fiber optic cable). • The chamber is made of heat shrink tubing and is terminated with a thin cut of cellulose membrane. • The chamber is filled with an anti-BPT immunobead slurry* for every measurement. The chamber has to be filled before each measurement is done. • When the filled sensor head is placed in a BPT solution the analyte slowly diffuses into the chamber and becomes trapped due to reaction with the immunobead complex. It is trapped as a bead bound immune-complex. • Once trapped, the incident laser causes fluoroscence which can be detected and analysed. • *anti-BPT immunobead slurry contains 7μm diameter silica with covalently bound protein A-anti-BPT. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

15. Regenerable sensor • The regenerable sensor is a bit more complex, but it is able to operate in a pseudo continuous manner. • The core optic fiber passage has a diameter of 400μm. • The core column is surrounded by six columns of 200μm diameter. • The sensing chamber is a hollow stainless steel frit with diameter of 1.2mm and volume less than 1μL. • The system required to keep the regenerable sensor head in operation is shown in the next slide. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

16. Regenerable sensor, system of operation • The frit shown here is the sensing chamber of the regenerable sensor. • 50μL of immunobeads are delivered into the frit before the start of each measurement. Phil.Trans. R.Soc.Lond. A(1990) ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

17. Operation contd.. • First the sensor head is immersed in the analyte solution. • Approximately 10μL of the solution is taken into a 30cm length of capillary past the ‘T’ marked point as shown in the previous figure. • Immunobeads are then delivered to the frit through a HPLC (high performance liquid chromatography) valve. • Analyte is then admitted to the frit and about 100μL of analyte solution is used to rinse the immunobeads admitted in the frit. • The bead bound immune-complex is formed as in the case of a passive sensor and the fluorescent response to the incident laser can now be measured. • The chamber is the flushed. • The whole process takes around 20 minutes, but it can be setup in a loop so that continuous measurement is possible. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

18. Typical configuration in operation • The passive diffusion sensor was used to measure BPT concentration. • The BPT solution had concentration of 1.6x10-7mol/L • Selectivity, sensitivity obtained were good. • After 45 mins. Of accumulation of the immune-complex, the SNR achieved was 4 times that obtained when compared to the start, i.e. no presence of immune complex. Phil.Trans. R.Soc.Lond. A(1990) ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

19. Ananlysis of results and limitations • As seen from the figure in the previous slide, the sensor is able to selectively measure the BPT concentration. • Extremely low concentrations can also can be detected by the sensor. • The presence of a particular substance in the analyte can be done in 10 or 20 minutes. • But accurate measurement of the concentration takes a long time. • As seen from the previous figure, the reaction between BPT and the immunobeads reaches a saturation point beyond which the concentration measured is constant. Hence this is the true concentration of BPT in the analyte but it takes around 5 hours to arrive at the result. This time lag is a drawback. • Selectivity can be obtained but different chemicals need to be used each time the sensor is to be used for a different detection. • The passive sensor head although simple, cannot be run in a continuous fashion. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

20. Major specifications • Substance to be detected. • Type of sensor head. • Mode of operation (continuous/single use). • Time required to estimate concentration. • Threshold concentration for a particular substance to be detected. • Type of laser used (depends on substance) • Other specifications can be the various solutions used to rinse/flush the sensor head, the type of immunobeads used etc. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators

21. Cost, choice & manufacturers. • Axela biosensors : This site has many similar and often more complex devices or workbenches for such detection. http://www.axelabiosensors.com • Other places are, Innovative Biosensors Inc. or Biosensors International . All of them may have a similar configuration or more advanced devices. Many other manufacturers can also be found on the web. • Cost: Although just the basic operational parts may seem simple and may be moderately expensive or some may be inexpensive, yet the entire setup (in typical analysing workbenches) may be very costly, hence these are used only in extremely specialized and high accuracy requiring jobs. • How to choose: The foremost criteria is the substance to be detected. Also the size of the substance being measured, requirement of remote operation capabilities, operating time, detection threshold and accuracy should be important points to make a decision. ECE5320 Mechatronics. Assignment#1 Survey on sensors and actuators