Smart innovations that can improve diabetes care are always welcome, and one of the endless pursuits of the past couple of decades seems to be that of a non-invasive means of monitoring glucose. If the number of adults and children who suffer from a needle phobia (estimates range from 3-10% of the population)1 can be assumed to be the same in the diabetes population, it makes sense that a non-invasive way to monitor glucose would be very welcome. Even the majority who don’t have a needle phobia would surely welcome the development of non-invasive glucose monitoring if it meant avoiding multiple daily needle pricks.
So researchers all over the world have dedicated decades of investigation into several different methods that could possibly deliver a non-invasive glucose monitoring system that works – efficiently and accurately. However, the results to date have been less than promising and we still await the holy grail of non-invasive testing.
Table 1. Innovative ways to measure glucose for diabetes management(click to enlarge)
Promising headlines
In this journal (under the previous name of Diabetes Professional) in Autumn 2012,2 a news headline read: ‘No more needle pricks for diabetes patients? Chip with built-in biosensor technology to transmit data’. This news reported on a German project at the Fraunhofer Institute for Microelectronic Circuits and Systems IMS. They had been working on a chip that could use sweat or tears to measure glucose in conjunction with Noviosense, a Dutch company. Noviosense had developed the glucose sensor for the chip that was going to revolutionise monitoring.
According to Noviosense’s website (www.noviosense.com) the company is expecting to begin market introduction in 2018, however, there is still scepticism about the viability of this technology.
Evaluation of innovations
John L Smith is an analytical chemist who has written an extensive evaluation of the above technology and many others in his online publication The Pursuit of Noninvasive Glucose: “Hunting the Deceitful Turkey”, the fourth edition of which was published as recently as in 2015.3
According to Smith, attempts at using tears for glucose readings were made as early as in the 1980s, however, there are concerns with this method, and Smith concludes that when it comes to eye, conjunctiva/tear solutions for glucose readings (whether through a chip or contact lens) “it is quite unlikely that any device or technique will produce clinically acceptable results for glucose based on measurements in tears, but it seems equally unlikely that people will stop trying to make this measurement.”3
The tear solution is only one of many innovations/attempts at finding a non-invasive solution. This article looks at some technologies that you may have heard of in the past couple of years.
Researchers will continue to look into the possibilities of non-invasive technologies as long as there is any tangible hope for success, because a success would not only be revolutionising for diabetes care, it would most likely also be very lucrative for the innovators.
Attempts at non-invasive innovations
There have been myriad attempts at finding a non-invasive method of monitoring or measuring glucose. A lot of products have made the headlines and you may recognise some of them. However, despite making the headlines, a lot of projects seem to have been abandoned.
There is of course also a more complex scenario, where innovations are bought up, sold on, change names, change indication, etc, and in these cases it becomes almost impossible to trace the original ‘ground-breaking’ innovation.
Onsens – a photonic glucose sensor
Onsens’ photonic glucose sensor (PGS) basically straps on to the wearer’s upper arm and transmits a near infrared light into the skin. Depending on the angle at which this light bounces back to the detectors on the sensor, it can apparently measure heightened or lowered levels of glucose, but not actual glucose levels.4
The Onsens PGS is a small, wearable device which also links data to an app on a smartphone for glucose trends. If the PGS senses a drop in blood glucose, it vibrates (or beeps) and can therefore be used for daytime and nighttime monitoring. However, while the product website (onsens.ca) is live, the product is not yet available on the market and an update query through their information contact details has had no response.
Mr Smith has dug deeper on this product and elicited that it was originally developed by a Canadian company called Cybiocare, whose website is now down. He also says that the principle behind the ‘science’ is not disclosed.3
HypoMon – physiological responses
HypoMon was developed by Australian AiMedics to measure physiological reactions to changes in blood glucose levels, particularly low levels. It was developed with type 1 children and adolescents in mind, to measure nighttime hypos.5
While not actually measuring accurate blood glucose levels, the physiological response would supposedly indicate changes in blood glucose levels. HypoMon was a wrap-around belt with a sensor and transmitter that measured electrical activity of the heart and movement information from the user. Data was then transferred wirelessly to a monitor, which would sound an alert if low blood glucose was detected.
HypoMon reached the market in Australia and the UK (in 2012), but was withdrawn in 2013. At the time, statements said that HypoMon had not been performing as well as anticipated and Aimedics were withdrawing the product with the aim of “improving HypoMon’s reliability”.6,7
Since the withdrawal in 2013, there has been no recent news on HypoMon.
Glucoview – crystalline colloidal array
Glucoview by Sentek Group used a crystalline colloidal array to measure blood glucose levels in tear fluid, which has apparently been found to correlate well with that of glucose levels in the blood.5 A trademark registration was filed for Glucoview in the US as early as 2000.8 However, since then there have been no updates on this product.
One can still read about crystalline colloidal arrays in a Pittsburgh University paper;9 however, what happened to the glucose sensor use of the technology is unclear.
While there is a more recent article on the array from 2009,10 that’s now six years ago, which would lead one to conclude that the product was most likely abandoned. However, the colloidal array technology may still pop up in the future!
Google ‘smart lens’
More recently, Google announced its smart contact lens project in January 2014.11 In this announcement, Google explained that the lens was “built to measure glucose levels in tears using a tiny wireless chip and miniaturised glucose sensor that are embedded between two layers of soft contact lens material”.
Google has since partnered with Alcon (July 2014), which is the eye care division of Novartis. Alcon responded to a query relating to this smart lens and its use for glucose monitoring: “The project continues to be active and we are very pleased to be working with Google Life Sciences. Alcon expects to begin human clinical trials in 2016 on the accommodating smart contact lens, designed for patients with presbyopia. Specific to the glucose-sensing lens, exploratory clinical trials were initially conducted by Google Life Sciences and Alcon is not ready to comment as to when human clinical trials for this lens will begin. We are currently in the very early stages of developing the ‘smart lens’ technology for the accommodating intraocular smart lens.”
So whether the initial optimistic headlines on Google’s smart lens will come true in relation to glucose monitoring remains to be seen.
GlucoScope monitor
Similar to the Google lens, GlucoScope by Visual Pathways Inc measures glucose levels in the eye. However, this technology measures glucose in the fluid of the anterior chamber of the eye using a handheld device which looks like a pair of binoculars and uses infrared light for quick measurements.5 Similar to the Glucoview above, application for registering the trademark was filed back in 2000,12 however, since then there is no news, and there are no active websites directly related to ‘GlucoScope’ or ‘Visual Pathways Inc’.
A news source says that a patent was awarded for the product in 2004, and that the product is still in the research and development stage.13 However, with the company now inactive more than 10 years later, the conclusion leans towards ‘abandoned project’. A query to the chief scientific officer of the now inactive Pathways Inc has had no response.
Biosensor patch
Symphony Diabetes Management has been developing a continuous blood glucose monitor through a partnership with Sontra and Bayer AG, as mentioned in an article in January 2015.5 However, any searches for either Symphony Diabetes Management or Sontra reveals that the websites are no longer working and the project took place over a decade ago.
A query to Bayer in relation to this project has not had a response. However, there is a biosensor patch developed and seemingly almost ready to go by another company, Echo Therapeutics. Their biosensor patch works with an exfoliator, a sensor and a display unit.14 Information on the company website echotx.com reveals a relationship with Sontra, so it could be that this is a typical case of a project having passed hands through various companies. A query with EchoTX for an update on the biosensor patch has not received a response.
Electromagnetic radiant ray
Another non-invasive glucose monitoring system was being developed by a German company called ArithMed in conjunction with Samsung Fine Chemicals Co in the early 2000s.5 The GluControl CG300 was to use electromagnetic radiant rays to determine glucose levels. However, the ArithMed website is no longer available and there seem to be no recent updates on the product.
Another product using the same technology called the TouchTrak HC 300 was then apparently being developed by Samsung (without any connection to ArithMed), also in the late 1990s and early 2000s, but there is no recent news on this product either.15
Spectroscopy
LighTouch Medical is a company set up around 16 years ago and according to its website, its non-invasive blood chemistry monitor (NBCM) would allow for measurement of glucose, total protein and other blood and interstitial fluid-borne analytes by utilising LighTouch’s “proprietary tissue-modulated Raman spectroscopic process”.16 The company website has information about the device, but a query for an update on the product status has had no response.
Meanwhile, Israel-based OrSense has developed the NBM 200, a non-invasive blood analytes monitor using occlusion spectroscopy. On the company website17 you can read the following about the technology: “OrSense’s patented SpectOLightTM technology, known as occlusion spectroscopy, uses a non-invasive optical measurement platform combined with a finger attached ring-shaped sensor probe. The pressure applied by the sensor temporarily occludes the blood flow in the finger, creating new blood dynamics which generate a unique, strong optical signal, yielding a high signal-to-noise ratio which is wholly blood specific.”
While this device has been mentioned as a potential future non-invasive monitor of blood glucose,5 a query response from OrSense clarifies that it is: “developing and marketing non-invasive, multi-parameter monitoring systems for measurements of haemoglobin.” They further add that: “most of our efforts are devoted to marketing of our haemoglobin product. The glucose product is still in research and development mode and is not expected to reach the market in the next three years.”
So while it is still possible that occlusion spectroscopy could be used for glucose monitoring in the future, it is not the immediate focus of the company.
GlucoWise – radio waves
GlucoWise by MediWise (Medical Wireless Sensing Ltd) uses two technologies to non-invasively measure blood glucose.18 It uses high-frequency radio waves to allow penetration through tissue, and sensors with integrated nano-composite films which temporarily make the skin transparent to the radio waves when a measurement is initiated. This measurement is taken eg. between the thumb and forefinger or the earlobe, as these areas have adequate blood supply and are thin enough for waves to pass through tissue.
According to MediWise, the product is ‘currently in development’ and will be available to purchase once clinical trials are completed.18 The company expects to start taking pre-orders by the end of 2016. A query regarding an update on the product has had no response.
Surgical and semi-invasive options
While this article has concentrated on presenting non-invasive ideas for glucose monitoring in order to avoid daily finger pricks, there are also semi-invasive and surgical innovations (or continuous monitoring). These innovations may not avoid ‘invasion’ of the skin, but what they do is eliminate the need for multiple daily needle pricks, which in itself may be an attractive goal for patients.
There has recently been some successful developments in the area of continuous blood glucose monitoring, and one product, Senseonics, is about to launch in Scandinavia. Senseonics glucose monitoring system will achieve readings for up to 90 days.19 Regular updates are available on the website senseonics.com
Another, GlySens ICGM is still in development, but regular updates on the current status can be found on the website glysens.com According to the developers, the main benefit of GlySens is that the implant is expected to last for one year or even longer.20
Microneedles seem to have been investigated for a very long time,3 and with some intermittent leaps of faith with eg. Kumetrix Inc, however, all projects related to microneedles now seem to have been abandoned.21
One already ‘on the market’ product is Abbott’s flash glucose monitor, the Freestyle Libre. It is so far only approved in Europe and available to be ordered on the UK website – www.freestylelibre.co.uk/ – which will also tell you [at time of going to press] that it’s not currently available in Ireland.
There was an update on ‘one year with flash glucose monitoring’ at the 2015 EASD held in Stockholm.22 The conclusion would seem to be that it has proven very reliable and could become an attractive product on a wider market if commercially viable.
Conclusion
There has been and still is an enormous amount of innovations and ingenuity in the search for a safe and reliable, and preferably long-term, non-invasive blood glucose monitor. For now, the semi-invasive or surgical options seem more realistic, and while ‘invasive’, if a surgical option can provide up to a year of accurate glucose monitoring, it would still help in avoiding the multiple daily needle pricks currently the norm.
However, while the results from most non-invasive projects haven’t been quite as promising for glucose monitoring, with the amount of ongoing projects, sooner or later one is bound to be successful and reach the market globally. The question is whether it will be within this decade; with some variation of the innovations mentioned above; or some completely new concept for glucose monitoring. Only time will tell.
References
Jenkins K. Needle phobia. A psychological persepctive. Br J Anaesth. 2014;113(1):4-6. as asccessed on http://www.medscape.com/viewarticle/830414
Diabetes Professional, 2012; 8(4):5. No more needle pricks for diabetes patietns? Chip with built-in biosensor technology to transmit data
Smith PL. The pursuit of non-invasive glucose – Hunting the deceitful Turkey. 4th edition 2015, as accessed on: http://www.mendosa.com/The%20Pursuit%20of%20Noninvsive%20Glucose,%20Fourth%20Edition.pdf
http://onsens.ca/pgs.htm
Messer C. Novel approaches to blood glucose monitoring as accessed on http://onsens.ca/pgs.htm
Table 1. Innovative ways to measure glucose for diabetes management(click to enlarge)