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Response to your editorial on PCCA glucose sensors
Response to comments on the Photonic Crystal Glucose-sensor Editorial
Re: Response to your editorial on PCCA glucose sensors
Re: Re: Response to your editorial on PCCA glucose sensors
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Anjal C Sharma, Research Scientist Lynntech, Inc., College Station, TX
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anjal.sharma{at}lynntech.com Anjal C Sharma
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Dear Dr. Khalil, Your recent editorial on the Asher group's novel photonic crystal sensors for glucose monitoring in tear fluids was extremely well written. The editorial brought the most important points about these new materials to the forefront in such a way that those not in the field would immediately be able to grasp the potential implications of this technologyand the impact that contact lens which utilize this technology would have on the diabetes monitoring market. However, there was a point which I felt was not emphasized enough. From the classical Bragg Diffraction equation, it stands to reason that the color of light which would be diffracted would depend dramatically on the incident (glancing) angle of light. Therefore, if a diabetic person were to utilize these envisioned contact lenses, and a compact mirror with a color chart to "read out" the glucose range in the tear fluid, there would be a large degree of error associated with the positioning of the compact and the viewing angle. Therefore this technique of read-out would not be the ideal choice for use by the patients, because the error may be severe enough that a large percent of the data points obtained would lie in the clinically unacceptable regions of the Clarke error grid. An instrumental read-out device is therefore a must. Another point which will significantly impact the functionality of this material for the envisioned use will be the response time of these materials. To be defined as truly continuous monitoring, the response time must be independent of the glucose concentrations within the tear fluid. In point of fact, the kinetics of response of these materials are heavily dependent on the glucose concentration within the tear fluid, where the response time is unacceptably high for lower concentrations, and may be adequate only at much higher levels of glucose. Your concerns for calibration of these materials and any associated instrumental read-out devices are extremely valid and have not been addressed adequately in my opinion. In addition, the group has not adequately addressed bio-compatibility issues, as well as issues related to degradation of the materials or the functional groups with continual exposure to tear fluid. It appears to me that these PCCAs have significant potential, but before animal or human testing is planned, all these issues must be addressed and ironed out. Sincerely, Dr. Anjal C. Sharma. |
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Omar S Khalil, Senior research Fellow Abbott Laboratories
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Omar.khalil{at}abbott.com Omar S Khalil
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Dear Dr. Sharma, Your points regarding my editorial that discussed the photonic crystals approach by Sanford Asher’s group are well taken. I agree with all your reservations. The Bragg shifts have to be measured at the same angle to get the dependence of the spectral shift on glucose concentration. That is a difficult feat. Alternatively the PCCA have to be designed for the color to be independent on the observation angle. During the Diabetes Technology and Therapeutics meeting last October in Philadelphia, Dr. Asher, in response to the same exact question, demonstrated to me that the color of a PCCA immersed in a glucose solution was insensitive to changing the angle of incidence of a light beam from a laser pointer. It was a qualitative demonstration, but they must address the effect of the angle of incidence and the angle of observation on the error in the measured spectral shift. The lag time between tear glucose and blood glucose is a controversial issue as I shown in the editorial. Asher’s group must address it, especially at low glucose concentrations. There is a lot of work to be done on this technology, but for some one who has seen so many chemometric approaches to NI glucose determinations and so many over-fitted models, I must admit that I may be biased towards simpler calculation methods. A simple relationship between a spectral shift, if it can be accurately measured, and a tear glucose concentration, if it does quantitatively relate to blood glucose concentration over the relevant clinical range, is a step in the right direction. This has not been conclusively proven yet. I still believe that an animal or human experiment will be very useful. It may reveal one or more major obstacles for the technology that we have not thought about yet. It may also dispel some of the reservations we have. Sincerely, Omar S. Khalil, Ph.D. |
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sanford a. asher, professor university of pittsburgh
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asher{at}pitt.edu sanford a. asher
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I appreciate your very nice article that highlighted our tear fluid glucose sensors, as well as Dr. Sharma's recent comments. I would, however, like to correct points made about two important issues raised by Sharma. Although Sharma is correct that there is an angular dependence of Bragg diffraction, use of our sensors with light close to normal incidence results in very small errors; sin a ~ 1 for angles close to 90 degrees. We estimate that use of a mirror to monitor the diffraction color of a contact lens would not result in errors of more than 10%. Dr. Sharma used to be correct that that our sensors showed a slow response to low concentration of glucose and that this would interfere with the possibility of continuous monitoring. We have now found methods to speed up the response such that at present it is faster than 5 min for ~2 mg/dL concentrations. We are continuing our development of faster sensors. Thus, we fully expect our sensors to be able to continuously monitor tear glucose. We are now writing up these results for publication. |
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Anjal C. Sharma, Research Scientist Lynntech, Inc., College Station, TX
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anjal.sharma{at}lynntech.com Anjal C. Sharma
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Dear Prof. Asher, I would like to thank you for pointing out the errors in my original comments. I have carefully re-examined the angular dependence relationship and have performed some calculations using Snell's law and Bragg's equation on the effect that a deviation from normal incidence even as large as 10 degrees would have on the diffracted wavelength. I am now convinced that the shift would be negligible and would have no impact on the visually percieved color of the sensor. Therefore, my worries about the angular dependence have been laid fully to rest and I completely agree with you in your response to my comments. Also, I want to thank you for bringing to my attention your latest results about the improved response time of the PCCA glucose sensors. Now this is a very important result and a response time of less than 5 minutes for glucose concentrations as low as 2mg/dL would indeed allow continuous glucose monitoring over the entire glycemic range expected in Diabetic patients. Clearly, after reading your response I am convinced that the PCCA materials are the ideal technology platform to perform non-invasive glucose monitoring. Please accept my apologies for any inconvenience my original erroneous post may have caused you. Sincerely, Dr. Anjal C. Sharma. |
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