Legend can measure blood sugar Google contact lenses have yellow?!

As you all know, not long ago the tech giant Google officially changed its name to Alphabet. A few days later, we saw another piece of news: Alphabetqixia's Google Life Sciences division signed a cooperation plan with Dexcom, the world's leading manufacturer of blood glucose meters, to jointly build a "coin-sized" blood glucose meter. Among them, Dexcom is responsible for the research and development of sensors, and Google Life Sciences is responsible for miniaturization and data processing.

Wait, did we really hear it wrong? To develop a blood glucose meter jointly with Dexcom? So where is the legendary Google contact lens that can measure blood sugar?! You know, at the beginning of last year, Google's contact lenses made enough eyeballs. Why after a year and a half, Google life sciences department has opened a new blood glucose meter research and development project?

Further research, we found that as early as 2011, Microsoft had already started a contact lens project to detect blood sugar, and Babak Parviz, co-founder of Google's contact lens project, was a member of Microsoft's contact lens research and development team that year. Now when searching for "Microsoft contact lenses", most of them are reports such as "Google smart contact lenses are not fresh and Microsoft has already started", and no special reports on Microsoft contact lenses can be found. So whether this technology is a "star of tomorrow" or a "king of cheating", let's look down.

Is there glucose in tears? Really!

The basic principle of measuring blood glucose with contact lenses is to determine that there is a definite correlation between the glucose content in tears and the glucose content in human blood, and then indirectly calculate the blood glucose value by measuring the glucose content in tears. So let's see, where does the glucose in the tears come from?

As shown in the figure below, tears are mainly secreted by the lacrimal gland (lacrimal gland) located in the upper part of the eye (cornea and conjunctiva also have a small amount of secretion). Under normal circumstances, tears are discharged at a constant speed through the lacrimal duct, through the whole eyeball, converge at the canthus near the bridge of the nose, then through the upper and lower lacrimal duct, enter the lacrimal sac, and finally into the nasal cavity [1]. Now think about "a snot and a tear", will it make sense.

However, where exactly the glucose in tears comes from is not yet conclusive [2]. There is little evidence that glucose in tears may come from the cornea and conjunctiva. For example, there is GLUT-1 glucose transporter in cornea [3], but not in lacrimal gland and conjunctiva [4]; However, there is sodium/glucose cotransporter SGLT-1 in conjunctiva [5], which can determine the transfer and transfer of glucose according to the concentration of sodium and glucose, so as to maintain the stability of glucose concentration in tears.

Although the source of glucose in tears is not clear, this does not affect the enthusiasm of scientists to study the relationship between tear glucose and blood glucose. The reason is also very simple: even if I don't know how tear glucose comes from, as long as it is related to blood glucose, we can use it. This seems to be the truth. Next, let's see if this is the case.

Why is this really a bad technology?

Since there is glucose in tears, and some researchers have assumed that it is related to glucose in the blood, let's first look at whether the glucose content in tears is well measured.

First, the amount of basal tear secretion is very small. Mishima et al. found as early as 1966 that under normal circumstances, the basic secretion of tears (normal secretion without stimulation) is between 0.5-2.2 μL/min, the average secretion is 1.2 μL/min[6], and the daily secretion is between 0.72-3.2mL. Generally, to complete a tear glucose measurement, at least 10 μL of tear fluid is required to fill the measurement chamber in the contact lens. It takes at least 5-20 minutes for the lacrimal gland to secrete 10 μL of tear fluid [7]. There is a serious lag in time.

Second, different test methods, sampling methods have an effect on the concentration of glucose in tears. The graph below shows tear glucose concentrations in healthy adults measured by different research teams since 1937 [2].

Some of the measurement methods in the above figure are the same and some are different. However, no matter using different methods or using the same method, a similar concentration range can hardly be obtained. In other words, when you use different measurement methods, sampling methods, and even select different experimental populations, you will find that the concentration of glucose in tears falls into completely different intervals. So which measurement should we believe?

Third, because the glucose concentration in tears is very low, the accuracy of the micro sensor is extremely high. Mass spectrometry (ESI-MS, the mass spectrometer is mostly a giant of several hundred kilograms or more) is considered to be a detection method with high specificity and high sensitivity at the same time. Therefore, the tear sugar concentration measured by the ESI-MS method in the above figure is the most recent The real tear sugar concentration. Judging from the measured concentration in the above figure, the tear sugar concentration should be only a few tenths or even a few 1‰ of the blood sugar concentration.

In the last article on blood glucose meters (click to view), we have summarized that the effective measurement range of the FDA-approved minimally invasive blood glucose meter Dexcom G4 is 2.22-22.2mmol/L. Therefore, miniature sensors still have a long way to go to measure such low glucose concentrations in tears. Although a large number of studies have shown that the tear sugar concentration of diabetic patients is higher than that of healthy people [9], this difference is completely negligible compared with the difference between them and blood glucose concentration.

Finally, the composition of tears is more complex and is greatly influenced by the outside world. At present, some studies have shown that there is a correlation between tear glucose concentration and blood glucose concentration [10,11,12]. However, these studies were either animal experiments, in vitro experiments, or single-factor variable control experiments. It is difficult to simulate the real environment of the human eye.

Although the current understanding of the basic amount of tear secretion has not changed since the study of Mishima et al. in 1966. But the source of tears has been controversial. Traditional research has always believed that the basic tear is basically secreted by the lacrimal gland, and the secretion of other parts such as conjunctiva is less [13]. However, in recent years, studies have found that conjunctival secretion accounts for 25% of basal tears [14]. When exposed to external stimuli (emotions, foreign bodies, onions, yawning), then the mass of tears (secretion rate is about 100 times normal) is secreted by the lacrimal gland.

As mentioned earlier, the concentration of glucose in tears from different sources varies (determined by the glucose transporters on the secretory organs). Therefore, studies have shown that in order to accurately measure the concentration of tear glucose, it is necessary to avoid external stimuli (such as emotion, foreign body, onion, yawning). Of course, when doing research, we can control the sampling time to avoid the interference of external stimuli on tears. But under normal circumstances, emotions, foreign bodies, onions, yawning and other effects on the composition of tears, the basic is no way to control.

After reading the above four difficulties, we should have a basic understanding of reality. Although, some studies have established a relationship between tear sugar and blood sugar. However, these relationships are based on a series of constraints. These relationships are not tested in reality. Therefore, in the current field of research on the relationship between tear glucose and blood glucose, the mainstream view is that the correlation between tear glucose concentration and blood glucose concentration is uncertain [15,16]. This is not cheating! This one alone is enough for Microsoft and Google to drink a pot!

Another important difficulty I almost forgot to mention is that many people with diabetes suffer from dry eye [17]. The disease affects the amount of tear secretion and the composition of the tear. Of course, scientists do not choose such patients when doing research.

So, are Google contact lenses a joke?

Just when Google released the contact lens project for measuring blood sugar in 2014, Google claimed that "we have completed a number of clinical studies and the results are helping to improve our prototype" (we 've completed multiple clinical research studies which are helping to refine our prototype). However, Dr. Bill Quick, an American health expert, after checking ClinicalTrials.gov (almost every recent clinical study will be included), did not find Google's clinical research experiment on the hidden glasses project to measure blood sugar. Bill Quick later called the founder of Google's hidden glasses project and got the answer that "the data will be released at the appropriate time" [18].

No wonder a few days ago after Google and Dexcom cooperation, Dexcom executive vice president Steve Pacelli in an interview with MobiHealthNews, Google tacit glasses project a little disdain said "it's just a scientific project".

Of course, it's not that contact lenses can't measure blood sugar, it's just that it can't be done at the current level of research. I hope that after Google cooperates with Dexcom, Professor Babak Parviz's research and development team can send several good articles!

References

[1] http：//www.eyedrnyc.com/dry-eye-syndrome-and-symptoms/；

[2] Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. The Ocular Surface，2007；

[3] GLUT1 glucose transporter expression in the diabetic and nondiabetic human eye. Invest Ophthalmol Vis Sci 1994；

[4] Glucose transporters are abundant in cells with “occluding” junctions at the blood-eye barriers. Proc Natl Acad Sci USA 1990；

[5] Immunolocalization of Na-K-ATPase， Na-K-Cl and Na-glucose cotransporters in the conjunctival epithelium. Curr Eye Res 2000；

[6] Determination of tear volume and tear flow，Invest Ophthalmol 1966；

[7] Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose. Journal of Diabetes Science and Technology，January 2011；

[8] Implanted electrochemical glucose sensors for the management of diabetes. Annu. Rev. Biomed. Eng. 1999；

[9] Tear glucose levels in normal people and in diabetic patients. Br J Ophthalmol. Sep 1980；

[10] Measurement of Tear Glucose Levels with Amperometric Glucose Biosensor/Capillary Tube Configuration. Anal. Chem. 2011；

[11] Tear glucose detection of hyperglycemia. Am J Ophthalmol. 1968；

[12] The glucose content of the tear fluid in normal and diabetic subjects. Jpn J Clin Ophthalmol. 1971；

[13] Clinical biochemistry of tears. Surv Ophthalmol 1981；

[14] Tear dynamics model. Curr Eye Res 2007；

[15] Novartis signs up for Google smart lens，Nature Biotechnology，September 2014；

[16] Evaluation of Commercial Glucometer Test Strips for Potential Measurement of Glucose in Tears. Anal. Chem，January 15， 2014；

[17] Dry eye in diabetic patients. Am J Ophthalmol 2005；

[18]http：//www.healthcentral.com/diabetes/c/110/166605/measuring-tear-glucose-levels/

Source: Singularity Network