Introduction to Nanobiotechnology : Concepts and Applications

1. Introduction to Nanobiotechnology: Concepts and Applications ENSC E-150 12. 02. 09 Wednesday 5:30 - 7:30 PM Dr. Anas Chalah Director of Instructional Laboratories at Harvard School of Engineering and Applied Sciences (SEAS)

2. Introduction to Nanobiotechnology: Concepts and Applications Office Hours By Appointment Only - Email to: achalah@seas.harvard.edu E-150 Class Teaching Assistant: Heather Bowerman bowerman@fas.harvard.edu

3. FINAL PROJECT Now that you have experienced how it feels to be the reviewer of a grant proposal, it is your time to be reviewed FINAL PROJECT WRITE A GRANT PROPOSAL

4. Final Projects Choose ONE project out of the following possible three projects: Project A: HYBRID H1N1 NanoBiosensor Project B: CNT-based Retinal Photosensor Project C: Cancer-magnate Nanoplatform

5. GOAL: Design of a Hybrid NanoBiosensor to detect H1N1 virus in a human blood sample The design should incorporate/immobilize biofragments on a nanostructure to create a nanobiosensor that captures the virus or any related bio substances This is an immobilization/surface functionalization exercise Project A: HYBRID H1N1 NanoBiosensor

6. Project A: HYBRID H1N1 NanoBiosensor Describe the chosen nanostructure (the platform) and the sensor component (the nose) – both chemical & biological properties should be covered Describe the specific interaction between the biological component of the Nanosensor and the H1N1 virus: How would you design the nanosensor to detect only H1N1 and not other viruses Simple outline of the fabrication method: linking both components (nanostructure with the biological detector) Describe the signal generation and readout: How does the binding occur What signal does it generate How would one read it Discuss possible issues of degradation and/or instability of the biological component as well as any nonspecific binding to the surface of the biosensor (Noise)

7. Project B: CNT-based RETINAL PHOTOSENSOR GOAL: Design carbon nanotube-based retinal nanostructure “Photosensor” The designed nanostructure should compensate for the loss of light detectors in the retina (one of many major causes of blindness) The design should allow the nanostructure to interact with light and generate a signal – Delivery of the signalto the optic nerve is optional but highly recommended Explain similarities and differences between the designed nano biosensor and the human photoreceptors (Rods and Cones)

8. Quick Background: How Do We See Objects Steps of correct human vision: (1) Scattered light from the viewed object enters through the cornea (2) The light is projected onto the retina at the back of the eye (3) The retina sends messages to the brain through the optic nerve (4) The brain interprets what the viewed object is - We see the object

9. Retinal Structure The retina, 5 cm2 area in the back of the eye, is where light detection occurs The retina consists of a network of nerves connected to over 100 million photo-sensitive receptors (rods and cones) Signals created by rods and cones are sent via the optic nerve to the brain The top layer of the retina (Plexiform) does not interpret the light that strikes it. This is a layer of optical nerves which carry the signals from rods and cones to the optic nerve

10. Rods and Cones There are two types of photoreceptor cells in the retina: rods and cones Retina rods have little sensitivity to different wavelengths therefore they do not supply any color information On the other hand, retina cones are responsible for color vision

11. The Chemistry of Vision The outer segments of the rods and cones has a region which contains proteins bound to a chemical molecule referred to as 11-cis-Retinal Retinal is a chromophore- a molecule that can absorb light at a specific wavelength and undergo a conformational change In rod and cone cells, the retinal is found “at rest” in the cis form When visible light (photon - hν) hits the chromophore, it undergoes an isomerization, or change in molecular arrangement, from the cis to a trans-retinal form One of the p-bonds in retinal molecule is broken, causing the molecule to rotate and lock into the trans form, which has a complete different shape

12. The Chemistry of Vision The trans isomer of retinal does not fit well into the host protein, and so a series of conformational changes in the protein begins As the protein changes its conformation, it initiates a cascade of biochemical reactions that result in the closing of Na+ channels in the cell membrane The closing of Na+ channels results in a large potential difference builds up across the plasma membrane (the photoreceptor cell becomes more negative inside) This potential difference is passed along to nerve cells as electrical impulses at the synaptic terminal The nerve cell carries this impulse to the brain, where the visual information is interpreted trans-retinal molecules are twisted back “reset” into the cis form by another enzyme

13. Project B:CNT-based RETINAL PHOTOSENSOR How would you use CNT structure to build an artificial photosensor – Identify the players SWCNT vs. MWCNT What kind of surface modification/functionalization would you employ to obtain photosensitivity on the CNT surface Any possible incorporation of other nanostructures What kind of signal would your structure generate and how would it be translated Discuss connectivity to optic nerve Discuss possibility of implanting nanoplatforms for in vivo pre-clinicaltesting

14. Project C:Cancer-magnate Nanoplatform Goal: Design a Cancer-magnate nanoplatform The nanostructure is designed to perform as a magnate for travelling cancer cells (the soil and seed theory) The structure has to be extremely attractive for cancer cells traveling in the blood or lymph stream

15. Project C:Cancer-magnate Nano platform What is the designed nanostructure – The platform What are the molecules chosen for surface functionalization What is the capturing mechanism What is the destruction mechanism What is the clearance mechanism What is the proposed implant method – issue of toxicity and regeneration

16. Project Format Your final assignment should not exceed 2 pages Excluding Figures and references Submit your proposal in a PDF format State your name and the project you selected (A,B, or C) at the top left corner of your hand out Adhere to the format described next for writing your proposal

17. Project Format Introduction: Introduce the subject/problem to be solved How is your proposal justified as a nanotech study/proposal What is the theory behind the proposed structure – why is your proposed structure the best for tackling the subject The design: Clear description (chemical structure, physical properties, shape & dimensions) Cartoon drawings of structure and any interactions (HIGHLY RECOMENDED) Detailed analysis of the structure functionality – How would the proposed structure address the test Possible pitfalls and limitations - how would you address them Clear plan for testing the structure (tissue culture – animals – clinical testing)

18. Final’s Submission Send your final by e-mail to both addresses: achalah@seas.harvard.edu bowerman@fas.harvard.edu You shall receive a confirmation e-mail no longer than 6 hours after you sent your final - If you do not, please inquire by e-mail

19. Final’s Deadline Final’s deadline is: Wednesday 12. 16. 2009 @ 5:30 PM There are NO exceptions to this deadline

20. FINAL CLASS GRADE Homework assignments are worth 60% of the final course grade Final Project is worth 40% of the final course grade

21. ENSC E-150 Roadmap • Chemical Structures and Physical Properties of Nano Particles • Application of Nanotechnology in Biological Systems • Nanotechnology in Drug Discovery & Delivery • Nanotechnology in Cancer Diagnostics & Treatment • Nanotechnology in Tissue Engineering

22. Class Roadmap