New and emerging non-invasive glucose monitoring technologies

Transcription

Horizon Scanning Research
& Intelligence Centre
New and emerging non-invasive
glucose monitoring technologies
May 2016
1
The National Institute for Health Research Horizon Scanning Research & Intelligence
Centre (NIHR HSRIC) is based at the University of Birmingham in the UK. The NIHR
HSRIC aims to supply timely information to key health policy and decision-makers and
research funders within the NHS about emerging health technologies that may have a
significant impact on patients or the provision of health services in the near future. The
scope of our activity includes pharmaceuticals, medical devices and equipment,
diagnostic tests and procedures, therapeutic interventions, rehabilitation and therapy,
and public health activities.
HSRIC reports can be accessed via our website at: www.hsric.nihr.ac.uk, and the
centre can be followed on Twitter at: @OfficialNHSC.
This report presents independent research funded by the National Institute for Health
Research (NIHR). The views expressed in this publication are those of the author(s)
and not necessarily those of the NHS, the NIHR or the Department of Health.
The NIHR Horizon Scanning Research & Intelligence Centre,
University of Birmingham, United Kingdom
[email protected]
www.hsric.nihr.ac.uk
Copyright © University of Birmingham 2016
2
CONTENTS
EXECUTIVE SUMMARY................................................................................................................................. 4
ACKNOWLEDGEMENTS ............................................................................................................................... 5
1 INTRODUCTION ………………………………………………………………………………………………………………………………… 6
1.1 DIABETES ........................................................................................................................................... 6
1.2 MANAGEMENT OF DIABETES ............................................................................................................ 7
1.3 BLOOD GLUCOSE MONITORING ........................................................................................................ 8
1.4 ALTERNATIVE GLUCOSE MONITORING TECHNOLOGIES ................................................................... 8
2 AIMS …………………………………………………………………………………………………………………………………………………..9
3 METHODS ............................................................................................................................................... 10
3.1 TECHNOLOGY IDENTIFICATION ....................................................................................................... 10
3.2 FILTRATION ...................................................................................................................................... 10
3.3 HEALTHCARE PROFESSIONALS’ PERSPECTIVE ................................................................................. 10
3.4 PATIENT AND CARER PERSPECTIVE ................................................................................................. 11
4 RESULTS .................................................................................................................................................. 12
4.1 IDENTIFICATION AND FILTRATION OF RESULTS .............................................................................. 12
4.2 TYPES OF NIGM TECHNOLOGIES ..................................................................................................... 14
4.3 NIGM TECHNIQUES ......................................................................................................................... 14
4.4 DEVELOPMENT STATUS ................................................................................................................... 17
4.5 HEALTHCARE PROFESSIONALS’ PERSPECTIVE ................................................................................. 18
4.6 PEOPLE WITH DIABETES AND CARERS PERSPECTIVE ...................................................................... 19
5 DISCUSSION ............................................................................................................................................ 21
APPENDICES............................................................................................................................................... 23
Appendix 1. Identification sources and search terms ....................................................................... 23
Appendix 2. List of developers identified .......................................................................................... 25
Appendix 3. Technical questionnaire sent to developers ................................................................. 26
Appendix 4: New and emerging NIGM technologies identified ........................................................ 27
Appendix 5: Pictures of NIGM technologies...................................................................................... 54
REFERENCES .............................................................................................................................................. 56
3
EXECUTIVE SUMMARY
Diabetes is a common life-long condition where the levels of glucose in the body are too high
because the body is unable to convert it to energy due to insufficient insulin or the insulin not
working properly. There are two main types of diabetes, type 1 and type 2. These are managed
on a daily basis by regular self-testing and depending on the type, insulin therapy, medication
and lifestyle changes to maintain appropriate blood glucose levels. Currently people with
diabetes monitor their blood glucose by drawing blood via a finger prick then using a hand-held
glucose meter. However, this method is generally disliked due to the pain and inconvenience
associated with finger pricking. The development of a safe and reliable non-invasive glucose
monitor may provide patients with an alternative, painless method.
This horizon scanning review aimed to identify new and emerging non-invasive glucose
monitoring (NIGM) technologies for people with type 1 and 2 diabetes. We identified relevant
technologies by searching online sources of information (such as clinical trials and bibliographic
databases, and the medical media) and the NIHR Horizon Scanning Research & Intelligence
Centre database of emerging technologies. We then approached developers to obtain further
information about the NIGM technologies identified. We also involved healthcare professionals
and people with type 1 diabetes and their carers to find out their perspectives on these
emerging technologies.
A total of 40 NIGM technologies were identified and are presented in this report. Thirty-nine
were being tested in clinical research studies and one is available through the developer’s
website. Of the 40 NIGM technologies identified, 24 were intermittent NIGMs and 16 were
continuous NIGMs. Three general glucose monitoring technique categories were identified:
optical, transdermal and electrochemical techniques. Potential sites of testing included skin,
tear fluid, saliva and breath.
The report also summarises the views expressed by healthcare professionals and people with
diabetes and their carers on the technologies identified. These include comments on the
benefits they think NIGM technologies might bring, the important features that they would like to
see in future commercial technologies, and what the key issues will be concerning their use
and adoption into the healthcare system. For many technologies development is still in the
early stages so there was limited information regarding safety and effectiveness. People with
diabetes and their carers were very interested in the development of NIGM technologies and
thought their use could potentially improve their quality of life but had reservations about
reliability, safety, appearance and usability.
We would welcome your views on this report.
Please take our brief online survey at this link:
https://www.surveymonkey.com/s/X7WW6QX
4
ACKNOWLEDGEMENTS
NIHR Horizon Scanning Research & Intelligence Centre review team
Angharad Slade
Dr Sue Simpson
Dr Annette Wood
Senior Analyst
Reviews team lead
Medical Advisor
Healthcare professionals
The following clinical experts gave us their advice and views on the new and emerging
non-invasive glucose monitoring technologies we identified:

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
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Dr Muhammad Ali Karamat, Consultant Physician, Heart of England Foundation
Trust, Birmingham and Honorary Senior Lecturer in Diabetes and Endocrinology,
University of Birmingham.
Dr Chris Walton, Consultant in Diabetes, Hull and East Yorkshire NHS Hospitals
Trust, Hull.
Dr Jackie Elliott, Senior Clinical Lecturer in Diabetes, University of Sheffield, and
Honorary Consultant, Sheffield Teaching Hospitals.
Henrietta Mulnier, Lecturer in Diabetes Nursing, King’s College London.
The following expert provided technical advice on the non-invasive glucose monitoring
techniques identified within the report:

Dr Sandeep Kumar Vashist, Senior Scientist in Point of Care diagnostics, Royal
Melbourne Institute of Technology, Australia.
Members of the public with type 1 and 2 diabetes
Lesley Jordan, Chief Executive, and Melissa Holloway, Chief Adviser, INPUT Patient
Advocacy (www.inputdiabetes.org.uk) facilitated the involvement of four members of
the public (two people with diabetes and two carers of young people with diabetes) who
gave their views on the identified new and emerging non-invasive glucose monitoring
technologies.
The NIHR Horizon Scanning Research & Intelligence Centre is grateful to all
those who helped us to include both a healthcare professionals’ and potential
users’ perspective in this report. We thank them for their time and valuable
contributions.
5
1. INTRODUCTION
Non-invasive glucose monitoring
Currently the self-monitoring of blood
glucose requires people with diabetes to
draw blood via a finger prick, then use
tests strips and a hand-held blood
glucose meter to measure their glucose
levels1. However, this invasive method
is generally disliked due to the pain and
inconvenience associated with finger
pricking2. The development of a noninvasive glucose monitoring (NIGM) technology may provide people with diabetes with
an alternative method.
This horizon scanning review provides:
a) An overview of new and emerging NIGM technologies and the potential benefits
of these to people with diabetes who monitor their glucose levels.
b) Information about the individual new and emerging technologies identified by
researchers at the NIHR Horizon Scanning Research and Intelligence Centre
(NIHR HSRIC).
c) Views of healthcare professionals and potential users on the identified NIGM
technologies.
1.1 DIABETES
1.1.1 OVERVIEW
Insulin is a hormone produced by the pancreas that allows glucose to enter the body’s
cells. Glucose serves as the primary energy source for most cells in the body and plays
an important role in processes such as digestion and cellular respiration3,4. People with
diabetes either do not produce enough insulin or the insulin produced does not work
properly and as a result, glucose remains in the bloodstream instead of entering the
cells3.
There are two main types of diabetes, type 1 and type 2. Type 1 diabetes (also known
as type 1 diabetes mellitus, insulin dependent diabetes, T1DM and T1D) occurs as a
result of the immune system attacking and destroying beta cells in the pancreas that
are responsible for producing insulin5. Type 2 diabetes (also known as type 2 diabetes
mellitus, insulin resistant diabetes, T2DM and T2D) develops when the beta cells are
unable to produce enough insulin or when the insulin produced does not work
properly6.
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1.1.2 PREVALENCE
In 2015, the estimated prevalence of diabetes (both type 1 and 2) in adults between the
ages of 20-70 years worldwide was 415 million7. This is expected to increase to 642
million adults by 2040 (one person in 10)7. In the UK, it is estimated that one in 16
people (adults and children) have diabetes (diagnosed or undiagnosed), with
approximately four million people living with the condition7. This is estimated to
increase to five million by 20257. For all adults and children with diabetes in the UK, it is
estimated that 10% have type 1 diabetes and 90% have type 2 7, which equates to
approximately 400,000 and 3.6 million people respectively8.
There are around 31,500 children and young people under the age of 19 with diabetes
in the UK7. This may be an underestimate as not all children over the age of 15 are
managed in paediatric care. Around 95% have type 1 diabetes, 2% have type 2
diabetes and 3% have either maturity onset diabetes of the young (MODY), cystic
fibrosis related diabetes or their diagnosis has not been defined7.
1.2 MANAGEMENT OF DIABETES
Effective diabetes management reduces the risk of long-term complications associated
with the disease, which include heart disease, blindness, stroke, kidney disease and
amputations leading to disability and premature mortality5. The risk of complications is
greatly reduced with treatment that maintains the circulating glucose levels to as near
as normal as possible, thus reducing tissue damage9.
Short term complications can occur if blood glucose levels go too high
(hyperglycaemia) or too low (hypoglycaemia). In the latter, blood glucose levels fall to a
level that can potentially cause harm and causes symptoms such as sweating, feeling
shaky, hunger, tiredness, blurred vision, lack of concentration and headaches10. Severe
hypoglycaemia is more serious and requires urgent assistance. It can cause fits, loss of
consciousness, coma and even death. In contrast, hyperglycaemia symptoms include
an increase in urination (especially at night), headaches, tiredness, lethargy and an
increased thirst10. Consistently high blood glucose levels can lead to diabetic
ketoacidosis (DKA) where the body uses an alternative energy source to glucose such
as fat. This causes a build-up of a potentially harmful by-product called ketones and if
left untreated, can lead to diabetic coma or death10,11.
For most people with diabetes, managing the condition has an impact on their lifestyle
and quality of life. Diabetes is managed on a daily basis by the person with the
condition or with the help of a carer. For type 1 diabetes it involves regularly testing
blood glucose levels and injecting insulin as and when needed to achieve an
appropriate level of glycaemic control and to identify low blood glucose levels before
the development of hypoglycaemia12,13.
NICE guidelines recommend that adults with type 1 diabetes test their blood glucose
levels at least four times a day, including before each meal and before going to bed9. It
is recommended that children with type 1 diabetes test their blood at least five times
per day14. People with type 2 diabetes do not routinely self-monitor blood glucose
levels unless they have insulin dependent type 2 diabetes; evidence of hypoglycaemic
episodes; or are on oral medication that may increase their risk of hypoglycaemia while
driving or operating machinery15.
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1.3 BLOOD GLUCOSE MONITORING
Monitoring blood glucose levels helps people with diabetes and their carers make
informed decisions about their diet, activity and medication requirements, such as
insulin dose. It can also help patients, carers and their healthcare team alter treatments
to help prevent long-term complications16.
The conventional way for people with diabetes to test their blood glucose levels is
through a portable device known as a blood glucose meter. First, the side of a finger is
pricked using a lancet to draw a small drop of blood. The blood is then transferred to a
test strip which is inserted into the blood glucose meter, which then provides a result.
There are currently over 65 blood glucose meters available in the UK varying in size,
weight, test time (time to results between 3 and 10 second), memory capabilities and
special features17.
1.4 ALTERNATIVE GLUCOSE MONITORING TECHNOLOGIES
1.4.1 CONTINUOUS GLUCOSE MONITORS
Devices that can monitor glucose continuously and automatically are also available,
and are known as ‘continuous glucose monitors’ (CGM) or real-time CGM. A typical
system includes:
1. a disposable glucose sensor placed just under the skin and worn for a few days
until replacement;
2. a link from the sensor to a non-implanted transmitter which communicates to a
radio receiver; and
3. an electronic reader/receiver worn like a pager that records and displays
glucose levels.
These devices measure the glucose levels in the interstitial fluid (ISF) in and around
cells18.
1.4.2 MINIMALLY INVASIVE GLUCOSE MONITORS
Minimally invasive glucose monitoring technologies are so-called because they
compromise the skin barrier but don’t puncture any blood vessels19. There has been
much research into their development through either decreasing the blood sample
volume collected, and/or measuring areas of the body less sensitive than fingertips,
such as the forearm, upper arm, or thigh20. However, such systems lack the accuracy
and control of currently available systems, especially during the night 20. Minimally
invasive systems have been developed that sample the ISF, such as the CGMs
described earlier. Nonetheless, they suffer from limitations, as the patient still
experiences discomfort and most require continuous calibration21.
8
1.4.3 NON-INVASIVE GLUCOSE MONITORS
NIGM technologies monitor glucose levels without compromising the skin barrier.
These technologies aim to provide continuous readings similar to the currently used
CGMs, or intermittent readings where patient activity is necessary to perform the test.
2 AIMS
The aims of this horizon scanning review were:
1. To identify new and emerging NIGM technologies for people with type 1 and
type 2 diabetes.
2. To determine the stage of development of the identified technologies and where
possible when they might become available for clinical use in the UK (private or
NHS).
3. To collect the opinions of experts and people with diabetes and their carers on
the potential impact of emerging NIGM technologies.
Inclusion criteria
The review sought to identify technologies that were:





New: a technology that is CE marked, has only been available for clinical use for
≤12 months and is generally in the launch or early post-marketing stages.
Emerging: a technology that is expected to be CE marked or launched within the
UK in the next five years.
Non-invasive: technologies that monitor glucose levels without compromising the
skin barrier or involving the introduction of instruments such as needles into the
body.
Used for both intermittent and continuous monitoring of glucose
Indication: Type 1 and 2 diabetes; adults and children.
Exclusion criteria
We excluded:
 Glucose sensing bio-implants
 Technologies in very early stage of development (pre-clinical) and technologies
that are already widely available in the NHS.
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3 METHODS
3.1 TECHNOLOGY IDENTIFICATION
We developed a search strategy to identify new and emerging NIGM technologies
using the following sources:






Technology databases, including the in-house NIHR HSRIC database,
international horizon scanning databases and commercial databases.
Clinical trial registries.
Bibliographic databases.
Relevant conferences reports and abstracts.
Review articles and commentaries in relevant specialist journals.
Websites and publications of relevant organisations and developers.
These searches were supplemented by searching more general sources of information,
such as Google, health media reports and industry news. The search process took
place between June and July 2015. A full list of identification sources and search terms
used is provided (Appendix 1).
3.2 FILTRATION
A first filtration of identified potential NIGM technologies was carried out by checking
the initially available information against our inclusion and exclusion criteria and also
removing any obvious duplicates. Next the developers of the remaining technologies
identified (Appendix 2) were contacted. A technical questionnaire (Appendix 3) was
sent to each developer to request further information to allow a second filtration against
the review’s inclusion and exclusion criteria and to enable us to present current and
accurate information on each technology.
3.3 HEALTHCARE PROFESSIONALS’ PERSPECTIVE
Seven healthcare professionals who specialise in type 1 and/or type 2 diabetes were
invited to comment on the identified technologies. Four agreed and these were:
 A consultant Physician and Honorary Senior Lecturer in Diabetes and
Endocrinology.
 A consultant Physician and Chair of the Association of British Clinical
Diabetologists (ABCD).
 A Senior Clinical Lecturer in Diabetes and Honorary Consultant.
 A lecturer in Diabetes Nursing.
The healthcare professionals were sent tables summarising the identified and filtered
technologies and a description of the techniques used and were asked to provide
comments on specific aspects of each NIGM technology:
1. Do you believe this technology and the technique used has potential to monitor
glucose levels accurately?
2. What features of the technology, if any, do you believe to be innovative? Are
these innovations significant?
10
3. What is the potential impact of the technology in terms of: patient outcomes
(including quality of life); NHS systems and resources; any other potential
impacts e.g. societal.
4. What potential barriers might there be to this technology coming into routine
NHS use? (e.g. cost, training, service reorganisation)
5. Do you know of any new or emerging non-invasive glucose monitoring
technologies that we have not identified? If so, please let us know about them.
Participants were given three weeks to return their comments.
3.4 PATIENT AND CARER PERSPECTIVE
We collaborated with INPUT Diabetes (http://www.inputdiabetes.org.uk/) to access and
enable us to involve people with type 1 and/or 2 diabetes who regularly monitor their
blood glucose levels at home. INPUT Diabetes is an organisation that aims to help
people access diabetes technology and support from the NHS, including insulin pumps,
smart glucose meters and continuous glucose monitoring. A list of technologies
identified was sent to the Chief Executive and Chief Adviser of INPUT diabetes and
these were circulated via email to two people with diabetes and two carers of children
with diabetes. These were:
 Female with type 1 diabetes who currently uses finger pricks and a CGM. Also
uses an insulin pump.
 Female with type 1 diabetes who currently uses interstitial and finger prick
glucose monitoring
 Carer of a young boy who currently uses a CGM.
 Carer of a teenage girl who currently uses a CGM.
The people with diabetes and carers were sent tables summarising the identified and
filtered technologies and a description of the techniques used and asked to provide
comments on specific aspects of each NIGM technology:
1. Do you think the technology would improve your quality of life? And if so, what
issues might it help with?
2. Would you be willing to use this technology? If not, why not?
3. Have you had any personal experience of using this type of technology? If so,
please tell us about your experience.
4. Are you aware of any other non-invasive glucose monitoring technologies that
we have not identified? If so please let us know about them.
Participants were given three weeks to return their comments.
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4 RESULTS
4.1 IDENTIFICATION AND FILTRATION OF RESULTS
A total of 1,971 technologies were found at the initial identification stage. Searches
produced a varying number of relevant technologies depending on the source (Table
1). After the initial filtration, 1,629 were found not to meet the review’s inclusion criteria.
Of the remaining 342 technologies, 254 were duplicates and 38 were further excluded
as publically available information indicated they were invasive, already available for
use or in pre-clinical stages of development (Figure 1).
Table 1: Search results by source
Source
General
Published medical literature
Clinical trial registry & research funding
databases
Horizon Scanning Health technology
assessment and research funding databases
Med-tech specific sources
Regulatory authorities
Professional and patient groups
Specialist journals and conferences
Developers – diabetes leaders (glucose
monitoring)
Total
Number of
results
100
113
113
Number of potentially
relevant technologies
33
55
14
237
66
296
65
269
774
4
97
0
26
50
1
1,971
342
Developers were contacted for information on the remaining 50 technologies – 15
responded. Using the information recieved and other publically available information, a
further six technologies were excluded due to the technologies no longer being in
development.
Information on the 44 remaining technologies was sent to the health care professionals
and the people with diabetes/carers. The technologies were grouped initially by
technology type (continuous NIGM or intermittent NIGM) and further sub grouped by
target site, resulting in five tables of technologies. Grouping the technologies allowed
comparison between similar technologies within each section.
No further technologies were identified by the health professional and people with
diabetes. However a further four technologies were excluded based on information that
they provided. Thus a total of 40 NIGM technologies met the inclusion criteria and are
presented in this review (Appendix 4 and 5). These technologies are referred to by the
corresponding number throughout the text.
12
Figure 1: Identification and filtration results.
Search hits
(n = 1,971)
Non-relevant hits
(n =1,629)
Technologies identified
(n =342)
Duplicates removed
(n = 254)
Technologies further excluded
(n = 38)
Technologies filtered
(n = 50)
Technologies excluded
(n = 6)
Technologies included in
tables for consideration by
clinical experts & people with
diabetes
(n = 44)
Technologies excluded by
clinical experts and people
with diabetes
(n = 4)
Additional technologies
identified
(n = 0)
Technologies included in the
final report
(n = 40)
13
4.2 TYPES OF NIGM TECHNOLOGIES
4.2.1 INTERMITTENT NIGM
There were 24 intermittent NIGM technologies identified. Of these, 12 used the skin as
a target site (finger, arm, hand and ear lobe), seven used breath or saliva and five used
tear fluid.
4.2.2 CONTINUOUS NIGM
There were 16 continuous NIGM technologies identified. Of these, 13 used the skin as
a target site (finger, arm, hand and ear lobe), and three used tear fluid.
4.3 NIGM TECHNIQUES
From the 40 new and emerging NIGM technologies identified (Table 2), three general
categories of techniques for measuring glucose levels were identified:
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Optical techniques
Transdermal techniques
Electrochemical techniques
Table 2: Non-invasive glucose monitoring technique and number of technologies
General Technique
Specific techniques
Optical techniques
Absorption spectroscopy
Raman spectroscopy
Fluorescence
Surface plasmon resonance interferometry
Optical coherence tomography
Photoacoustic spectroscopy
Impedance spectroscopy
Reverse iontophoresis
Enzymatic detection of glucose
Amperometry
Refractive changes in the eye
Ultrasonic, electromagnetic and heat
capacity
Micro sensor and computer technology
Unknown
Transdermal techniques
Electrochemical
techniques
Other
Number
5
4
4
2
1
1
5
5
7
1
2
1
1
1
40
4.3.1 OPTICAL TECHNIQUES
Optical techniques utilise the different properties of light to interact with glucose in a
concentration-dependent manner22. Within this category there were a number of
techniques identified that were apparent in the emerging NIGM technologies:
14
Absorption spectroscopy is employed as an analytical chemistry tool to determine
the presence of a particular substance in a sample, and, in many cases, to quantify the
amount of the substance present21,22.

Technology 13 (breath, intermittent monitor).
Relevant types of absorption spectroscopy include:
1. Near-infrared absorption spectroscopy (NIR) which uses a beam of light with
a wavelength in the range of 600-2,500nm, which is focused on the body to
determine the concentration of glucose within the tissues21,22.
 Technology 2 (finger, intermittent).
2. Mid-infrared absorption spectroscopy (MIR) which uses a beam of light with
wavelength in the range of 2,500-10,000nm. It is based on the same principles
as NIR but has reduced scattering and increased absorption (high
wavelengths)21,22.
 Technology 1 (Ball of thumb, index finger, palm below the little finger,
ear lobe, intermittent)
 Technology 5 (palm, intermittent).
Raman spectroscopy assesses the scattering of single wavelength light. This is
dependent on rotational or vibrational energy states within a molecule 22.
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Technology 6 (finger, intermittent).
Technology 7 (arm or finger, intermittent).
Technology 29 (wrist, continuous).
Technology 36 (finger, continuous).
Photoacoustic spectroscopy uses the principle that absorption of light causes
ultrasonic waves22. The tissue is illuminated by a light source at a specific wavelength
and the absorbed energy results in localised heating22. The small temperature increase
results in volumetric expansion which causes an ultrasound pulse to be generated and
this can be detected. It is suggested that high tissue glucose concentrations reduce the
heat capacity of a tissue and as a result increases the velocity of the generated pulse22.
 Technology 10 (ear, intermittent).
Optical coherence tomography (OCT) systems use a low-power laser source, an indepth scanning system, a sampling device and a light detector 22. OCT determines the
amount of glucose present by assessing the intensity of the reflected/scattered and
transmitted light upon interaction with the subcutaneous tissue glucose concentration1.
 Technology 24 (eye, intermittent).
Fluorescence involves the absorption of light at a high wavelength and the emission of
light at a second, less energetic wavelength23.
 Technology 31 (abdomen or upper arm, continuous).
 Technology 32 (finger, continuous).
 Technology 39 (eye, continuous).
15
Surface plasmon resonance interferometry
When particles of light hit a metal surface they cause the electrons within the metal to
vibrate. This results in the generation of waves of electrons known as surface
plasmons24. The thin metal surface is usually coated with a glucose sensitive ligand
and this will bind to glucose molecules detected in the sample of interest. This reaction
produces a change in the reflected light which can be measured.
 Technology 19 (saliva, intermittent).
 Technology 21 (eye, intermittent).
4.3.2 TRANSDERMAL TECHNIQUES
Transdermal techniques involve the measurement of glucose through the skin using
either chemicals, electricity or ultrasound. A number of emerging NIGM technologies
were found that use a transdermal technique. These can be subdivided into:
Reverse iontophoresis
This is a transdermal technique that uses the application of physical energy to access
the interstitial fluid20,22. A low energy electrical current is applied across the skin by two
electrodes that are located next to one another22. The current causes glucose
molecules to move across the skin and collect at one of the electrodes20.
 Technology 25 (skin, continuous).
 Technology 27 (wrist/arm/leg, continuous).
 Technology 28 (arm, continuous).
 Technology 34 (arm, continuous).
Impedance spectroscopy
This is also known as dielectric or electrochemical impedance spectroscopy. It
measures the dielectric properties of a tissue. A small alternating current is passed
across a tissue and the impedance is recorded as a function of frequency. Glucose is
indirectly measured by its concentration-dependent interaction with red blood cells22.
 Technology 9 (skin between the thumb and forefinger or earlobe, intermittent).
 Technology 11 (thumb, intermittent).
 Technology 26 (hand, continuous).
 Technology 35 (upper arm, continuous).
 Technology 37 (wrist, continuous)
4.3.3 ELECTROCHEMICAL TECHNIQUES
This can be subdivided into:
Amperometry
This is the detection of ions in a solution based on electric current or changes in electric
current25.
 Technology 38 (eye, continuous).
16
Enzymatic
Glucose may be sensed using enzymatic electrodes which catalyse reduction-oxidation
reactions. Glucose oxidase (GOx) produces hydrogen peroxide which is directly
proportional to the concentration of glucose22.
 Technology 18 (breath, intermittent).
 Technology 22 (tears, intermittent).
4.3.4 OTHER
Other techniques were also identified that didn’t fit into the above three general
categories:
Micro sensor and computer technology
Involves the use of small sensors that are sensitive to glucose26. Readings can be
transmitted to a smartphone device.
 Technology 40 (tears, continuous).
Refractive changes in the eye
This measurement is based on polarised light entering the eye and detecting optically
active solutes such as glucose which cause the light entering to rotate. The amount the
light is rotated by the glucose molecules present can be measured 21,23.


Technology 20 (tears, intermittent).
Technology 23 (tears, intermittent)
Ultrasonic, electromagnetic and heat capacity
Involves the combination of three non-invasive methods (ultrasonic, electromagnetic
and thermal).
 Technology 12 (ear, intermittent).
4.4 DEVELOPMENT STATUS
Seventeen of the NIGM technologies identified are at the early development stage
which ranges from prototype testing to looking for a commercial partner. Twenty-six of
the NIGM technologies are currently being developed by commercial companies and
14 by non-commercial developers (research centres and collaborations).
Information on timeframe to product launch is limited and only eight of the 40
developers provided details of provisional commercialisation plans. Information on
product launch was available in the public domain for two of the technologies. One
technology is currently available through the developers’ website (technology 3), two
may become commercially available during 2016 (technology 27 & 31), two during
2017 (technologies 1 & 14), three by the beginning of 2018 (technology 35, 36 & 38),
one by the beginning of 2019 (technology 20) and one by 2020 (technology 13). One of
the technologies received a CE mark approval in April 2014 and is currently being
17
distributed in Europe and Asia but no information on UK launch plans was available
(technology 12).
No information about timeframe to product launch was available in the public domain
for twelve of the technologies identified (technologies 6, 7, 8, 11, 15, 19, 24, 25, 29, 32,
37, 39).
4.5 HEALTHCARE PROFESSIONALS’ PERSPECTIVE
In this section we present a summary of comments made by the healthcare
professionals on the NIGM technologies identified. Further comments on the individual
technologies can be found in Appendix 4 & Appendix 5
4.5.1 ACCURACY OF THE TECHNOLOGY AND THE TECHNIQUE USED
Most of the healthcare professionals felt unable to comment on the accuracy of the
technology and the technique used for measuring glucose levels. This was due to there
being “little evidence available” as well as the development stages of most technologies
being “too early” to accurately comment. Specific concerns were that the techniques
used seemed “too indirect to satisfy the demanding standards which would be required,
for instance, by driving regulatory authorities” and that some of the methods used
“would be affected by how quickly the glucose changes compared to the capillary”.
A general consensus indicated that fluorescence and spectroscopic techniques may
provide the most accurate glucose readings: “I doubt if it will be as robust as or
compete with the best of spectroscopic and fluorescent technologies”; “I’m not
convinced this technique will survive to completion compared to fluorescence and
spectroscopic methodologies”.
4.5.2 TECHNOLOGY INNOVATION
All the healthcare professionals agreed that all of the technologies identified were
innovative. Comments included “Not many non-invasive devices currently in
development use radiowave spectroscopy” and “It’s innovative because it lasts for so
long and is accurate”
The ability of a technology to “test for other parameters” or “factor for exercise, diet and
BMI” was thought “very exciting”. The specificity of a test was also considered an
innovative feature: “This is interesting in that they can use it for lower blood sugar
concentrations – I’d want people to be putting dextrose in their mouth at that stage”.
Positive comments were also made around the connectivity of the technologies, which
included “The ability to transfer wireless data to a smart phone and the cloud and to
record other data increases its attractiveness”
4.5.3 TECHNOLOGY IMPACT
Comments around the impact the technology may have on people with diabetes
included:
18
“The features of the technology may have a big quality of life impact on patients. It may
reduce complications and ambulance call outs”
“The reduced financial burden on the NHS in the future could be big if these types of
technologies (NIGMs) work”
“This is well liked because it’s quick, displays arrows, displays line graph, simple to
learn (for patient and healthcare), simple to insert, handset has a long battery life,
typically does not need re-charging for 2 weeks, and also has a built in blood glucose
meter – so any reading that seems wrong can quickly be checked”
4.5.4 POTENTIAL BARRIERS
Multiple barriers were identified for NIGM technologies coming into routine NHS use.
These included “The cost and clumsy kit”, “the size described…make it difficult for day
to day use”, “risks of infection”, “reluctance….due to the eyes being involved” and “not
prescribed so cannot be used to replace blood glucose monitoring strips for meters”.
A comment was made that “trust is a very important issue. If a patient doesn't believe
the result in front of them they will quickly discard the whole technology, they generally
do not like allowing for lag times, so something that samples slowly, or inaccurately will
not be widely accepted”. Similarly it was thought “this methodology seems far too
indirect to satisfy the demanding standards which would be required for instance by
driving regulatory authorities”.
4.6 PEOPLE WITH DIABETES AND CARERS PERSPECTIVE
In this section we present a summary of comments made by the people with diabetes
and their carers on the NIGM technologies identified. Further comments on the
individual technologies can be found in Appendix 4 & Appendix 5
4.6.1 TECHNOLOGY INNOVATION AND IMPACT
Most of the comments received indicated that a device to replace fingerprick testing
would be welcomed.
“If this works and is no bigger in size than current fingerprick meters then I can see this
being popular”
“This sounds a lot better than having to do fingerprick on my son”
“This sounds good if it’s non-invasive and continuous”
“Brilliant – I would love this and is much easier for children”
4.6.2 USABILITY AND BARRIERS TO ADOPTION
Overall the people with diabetes and carers liked technologies that were small,
discreet, easy to use and had good connectivity. Positive comments included “I like this
one - continuous, non-invasive and cloud based”, “…you can see the results in realtime on your phone/watch/tablet and it takes readings every 5-10minutes”, “The size of
the patch sounds pleasingly small”, “I like the idea of a watch. It looks neat and many
parents and teens are now wearing watches so would be interested in trying this” and
that it was “a handheld device”. The people with diabetes and carers also provided
comments around possible barriers that may prevent the adoption of a technology.
19
 Accuracy
There were doubts about “whether fluorescence will be reliable based on individual
skin/tissue characteristics”, “the lag between blood and ocular fluid so am not keen on
any tear-based technology” and also “a time lag with this fluid (interstitial) so not as
accurate a reading as capillary blood which is not great if hypo”.
 Safety
Issues raised included “the risk of using lasers on my skin over the long term”, “risks
with using infrared over a prolonged period of time”, “the idea of a portable laser
doesn’t sound very safe” and “the transdermal nature...makes me weary of skin injury”
and the lack of information on “alarms for hypos and hypers”.
 Ease of use
Concerns were raised about “whether you would have to put the gel on your skin every
time you need to get a reading. I can’t see my teenager doing that every time”,
“keeping a small child still for long enough to do this”, “the idea of having to recharge
the watch every 24 hours”, “a 10 minute application process sounding inconvenient”,
whether “one child/teen who would allow anyone to insert anything into their eyes” and
being “bothered to take it [contact lens] out very night and clean it and reinsert in the
morning”.
 Discreteness
Concerns about the visibility of the product were raised including “this sounds big – I
don’t want any more big equipment”, “an earlobe sensor would be continuously on
display”, “This doesn’t sound very discreet – I would feel uncomfortable doing this in
public [licking a plastic lollipop stick]” and “I wouldn’t wear something on my finger
continuously unless it was very discreet”.
 Time to results
Products that reported slower result times were not popular:
“If this was more than 5 seconds, I would say there is little value compared to finger
sticks” and “A minute seems a long time to wait for a result”.
20
5 DISCUSSION
In this horizon scanning review, we sought to present an overview of current
developments in NIGM technologies. In addition, we explored the perspectives of
healthcare professionals and people with diabetes and their carers on emerging
technologies identified. In total, we identified 40 NIGM technologies, 39 of which were
still being tested in clinical trials and not available for routine use. One technology, (the
FreeStyle Libre Flash Glucose Monitoring System, Abbott) can be bought from the
developer, the health professionals were aware of its existence and one of the people
with diabetes commenting on the technologies had used the device but it is not in
routine use in the NHS. From information available at the time of writing this report, it is
anticipated that from the remaining 39 technologies, the next NIGM technology
currently being tested in clinical trials will appear on the UK market during 2016.
Technologies identified fell into one of two groups, intermittent NIGM technologies or
continuous NIGM technologies. The intermittent NIGM technologies enabled users to
measure glucose levels as and when required and patient activity was needed to
perform the test. The continuous NIGM technologies were placed on the target site,
such as the arm or wrist, and remained there until further action was needed (such as
calibration or charging). These devices provided continuous glucose readings
throughout the day/night and some incorporated an alarm which alerted the user if
glucose levels became too low or too high. Within these categories the technique used
and the target site to measure glucose levels non-invasively differed. Comments on the
accuracy of these techniques were limited due to sparse information and many of the
technologies being at early stages of development.
Comments from people with diabetes and their carers provided a useful insight into the
impact NIGM technologies may have on the quality of life of diabetes patients. People
with diabetes welcomed the idea of a technology that could monitor glucose levels
accurately without the need for finger pricks, eliminating the pain and discomfort
associated with this method. It was apparent that for a technology to have the most
impact it would need to be continuous, discreet, portable, have the ability to transfer
data to a mobile phone and, if intermittent, the time to results would need to be quick.
Comments from carers of people with diabetes also reflected the above but the ability
for a device to alarm was of particular importance. They commented that when caring
for young children who are not hypo aware a device that could provide warning and
alarm when intervention was needed would provide benefit over one that didn’t. Carers
also state that an intermittent NIGM would need to be easy to use and the non-invasive
site accessible - for example technologies using breath and eyes were not considered
child and carer-friendly.
Healthcare professionals were very interested in a technology that could measure
glucose along with other parameters such as Body Mass Index (BMI), exercise and
diet. Measurement of other analytes, such as total protein was also considered
innovative. However, these were less important to people with diabetes and carers who
were mainly interested in glucose measurements only.
The accuracy of the technique was, as to be expected, an important aspect of the
acceptability of the technology to both the healthcare professionals and people with
21
diabetes and carers. Both expressed concern over the delay that may occur in glucose
readings with some of the techniques and the target sites used.
Details about the technology design were limited, as many of the technologies are at
early stages of development. However, for the technologies where information was
available the design and sizes differed. Designs included watches, handheld laser
devices and tattoo transfers. Sizes also varied from small patches to a laptop sized
device. A summary of desired features from the perspective of healthcare professionals
and people with diabetes and carers for future NIGM technologies is provided in Table
3):
Table 3: Summary of the desirable features for future NIGM technologies.
Physical properties
Small.
Discrete (i.e. minimally noticeable to others).
Handheld (if an intermittent monitor).
Lightweight.
Wireless.
Compatible with existing pumps and CGMs.
Comfortable to wear (if a continuous monitor).
Appealing to the eye.
Dependability
Safe (including giving warnings and alarms when user intervention is needed).
Reliable (including good battery life).
Accurate.
Functionality
Easy to use.
Usable during exercise, swimming and showering (waterproof).
Overnight use, plus capable of working 24/7 (if continuous).
Doesn’t require calibration.
Clear visual display that is easy to read and understand.
Transmits glucose data rapidly and frequently (to a smartphone).
Quality of life is important in any chronic disease such as diabetes, where the burden of
self-management is demanding. Any new development need to add to rather than
detract from this. Although, there has been much research into the development of a
non-invasive glucose monitoring device1,2,19-23,27 the complexity and accuracy of the
measurement process remains a barrier to the development of a truly successful NIGM
technology. However, this horizon scanning review indicates that considerable
progress has been made in recent years with many technologies in development and
some nearing the market. People with diabetes and healthcare professionals will
continue to await developments in NIGM technologies with interest.
22
APPENDICES
Appendix 1. Identification sources and search terms
Identification sources
Source type
General
Published
medical literature
Clinical trial
registries &
research funding
databases
Horizon
Scanning, health
technology
assessment
(HTA), and
research funding
databases
Specific sources
Google
PubMed, Medline & Medline in
Progress, & EMBASE
ZETOC – British Library
Database
The Cochrane Library
ClinicalTrials.gov
UKCRN portfolio database
WHO International clinical
trials registry platform (ICRTP)
NIHR Evaluation Trials and
Studies Project portfolio
NIHR BRCs, BRU, CRF, HTC
and DEC dataset (2015).
i4i portfolio of funded projects
dataset (Feb 2015)
NIHR HSRIC Database
EuroScan International
Network
ECRI Institute
Med-tech specific
sources
Regulatory
authorities
AHRQ (Agency for Healthcare
Research and Quality) Horizon
Scanning System
CADTH (Canadian Agency for
Drugs and Technologies in
Health)
Clinica
Global Data Medical
Medical News Today
MedGadget
Fierce Network
MHRA (Medicines and Health
products Regulatory Agency)
FDA Approvals
Professional and
patient groups
Diabetes UK
Diabetes Forecast
William Sansum Diabetes
Center
American Diabetes
Association
Website link
http://www.google.co.uk/
Accessed via
http://www.elibrary.bham.ac.uk/
http://www.zetoc.mimas.ac.uk/
http://www.cochranelibrary.com/
http://www.clinicaltrials.gov/
http://public.ukcrn.org.uk/search/
http://www.who.int/ictrp/en/
http://www.nets.nihr.ac.uk/projects?coll
ection=netscc&meta_P_sand=Project
N/A
http://www.nihr.ac.uk/documents/resea
rch/CCF%20funded%20research%20d
ata/i4i%20Funded%20Research%20F
ebruary%202015.xlsx
http://www.hsric.nihr.ac.uk/ (database
not publically available)
http://euroscan.org/ (limited access to
database)
http://www.ecri.org (subscription
required)
http://www.effectivehealthcare.ahrq.go
v/
http://www.cadth.ca/
http://www.clinica.co.uk/
http://www.globaldata.com/
http://www.medicalnewstoday.com/
http://www.medgadget.com/
http://www.fiercemedicaldevices.com/
http://www.fiercediagnostics.com/
https://www.gov.uk/government/organi
sations/medicines-and-healthcareproducts-regulatory-agency
http://www.fda.gov/newsevents/produc
tsapprovals/default.htm
http://www.diabetes.org.uk/
http://www.diabetesforecast.org/
http://sansum.org/
http://www.diabetes.org/
23
Specialist
journals and
conferences
Advanced Therapies and
Technologies in Diabetes
(ATTD)
JDRF – Juvenile Diabetes
Research Foundation
Diabetes Research in Children
(DirecNet) – Jaeb Center for
Health Research
European Association for the
Study of Diabetes (EASD)
InDependent Diabetes Trust
INPUT Diabetes
Diabetes
Diabetes Care
Clinical Diabetes
Diabetes Spectrum
Journal of Diabetes &
Metabolic Disorders
Journal of Diabetes Nursing
Nutrition and Diabetes
Journal of Diabetes Science
and Technology
Diabetes UK Professional
Conference 2015
International Diabetes
Federation
http://www2.kenes.com/
http://www.jdrf.org.uk/
http://www.direcnet.jaeb.org/
http://www.easd.org/
http://www.iddt.org/
http://www.inputdiabetes.org.uk/
http://diabetes.diabetesjournals.org/
http://care.diabetesjournals.org/
http://clinical.diabetesjournals.org/
http://spectrum.diabetesjournals.org/
http://www.jdmdonline.com/
http://www.thejournalofdiabetesnursing
.co.uk/
http://www.nature.com/nutd/journal/v5/
n5/index.html
http://dst.sagepub.com/
https://www.diabetes.org.uk/diabetesuk-professional-conference/
http://www.idf.org/calendar
Search terms
The technology





Non-invasive glucose monitor; noninvasive glucose monitor
Non-invasive continuous glucose monitor
Home blood glucose monitoring (MeSH term)
Monitoring, home blood glucose (MeSH term)
Blood glucose self-monitoring (MeSH term)
The medical condition


Diabetes Mellitus, Type 1 (MeSH term)
Diabetes Mellitus, Type 2 (MeSH term)
Current phase of research


Clinical, human
Phase I – III
24
Appendix 2. List of developers identified
Commercial developers
DiaMonTech GmbH, Germany
OrSense Ltd, Israel
GlucoSense Diagnostics Ltd, UK
Lightouch Medical, Inc., USA
LEMM Technologies, LCC., USA
MediWise, UK
Pop Test LLC, USA
Eternity Healthcare, USA
Quick LLLC, USA
Xhale Inc., USA
Lein Applied Diagnostics Ltd., UK
Opticology, Inc., USA
Freedom Meditech, Inc., USA
Abbott Diabetes Care, Inc., UK
Nemaura Medical Inc., UK
Integrity Applications Ltd., Israel
Guided Therapeutics, Inc., USA
Echo Therapeutics, Inc., USA
Biovotion AG, Switzerland
DIRAmed LLC, USA
Calisto Medical, Inc., USA
Noviosense, Netherlands
Eyesense GmbH, Germany
Novartis Alcon, Switzerland
Company website
http://www.diamontech.de/
http://www.orsense.com/
http://www.glucosense.net/
http://www.lightouchmedical.com/
www.lemmtechnologies.com
http://www.gluco-wise.com/
http://www.diabetespoptest.com/
http://eternityhealthcare.com/
http://iquickitsalivaanalyzer.com/
http://xhale.com/
http://www.lein-ad.com/
http://www.opticology.com/
http://www.freedom-meditech.com/
http://www.freestylelibre.co.uk/
www.nemauramedical.com
http://www.integrity-app.com/
http://www.guidedinc.com/
http://echotx.com/
http://www.biovotion.com/
http://www.diramed.com/
http://www.calistomedical.com/
www.noviosense.com
http://en.eyesense.com/
http://www.alcon.com/
Non-commercial developers (research centres and collaborations)
Baylor University, USA
Princeton University, USA
Massachusetts Institute of Technology, USA
Oregon Health & Science University, USA
Islamic Azad University, Iran
Western New England University, USA
University of Newcastle, Australia
Brown University, USA
Mayo Clinic, USA
University of Texas, USA
University of Strathclyde, UK
Bar-Ilan University, Israel.
Imperial College of Science, Technology and Medicine, UK
University of California, San Diego Jacobs School of Engineering, USA
25
Appendix 3. Technical questionnaire sent to developers
About the technology
Confidential Y
Name of the technology
(+ any other name it is known by)
Commercial developer or funder
(if any)
Web link to product page (if any)
Patient group and/or Indication
Please include whether type 1 and/or type 2 diabetes and targeted
patient groups (including sex, age-range etc).
Brief description of the technology
Please include what it is and how it works.
What is the non-invasive technique used e.g. reverse iontophoresis,
absorbance spectroscopy, Raman spectroscopy etc?
Where is the target site for the technology e.g. ear lobe, wrist,
abdomen?
Sample used (if applicable) e.g. saliva, breath?
Intended use:
 Who?
E.g. Patient, carer, health professional
 Where?
E.g. Home use, primary care (GP office), secondary care –
hospital?
 Usability?
E.g. Single-use, disposable, reusable
What is the cost of the technology?
Please indicate if there are any other additional costs related to your
technology e.g. service and delivery.
Do you have a picture or diagram of the technology? If so, we would
be grateful if you could attach a copy and indicate if we have
permission to use it in our report. We would acknowledge source.
Confidential Y
Stage of development
What phase of clinical research is it at? (e.g. Pre-clinical, Phase 1,
Phase 2, Phase 2/3)
Estimated timeframe for CE marking (e.g. Q1/2 2017)
Estimated timeframe for UK/EU launch (e.g. Q1/2 2017)
Is it available in the USA, Canada or Australia?
Research evidence
Please attach papers or provide web links to
publications and/or clinical trial registry records
Confidential Y
Published clinical research
(including conference
abstracts)
Completed but not yet
published clinical research
Ongoing clinical trials
26
Appendix 4: New and emerging NIGM technologies identified
Intermittent Glucose Monitors
Table 1: Intermittent Glucose Monitors - Target Site: Skin - Finger, arm, hand, ear lobe.
Technology Name and developer
1.
Infrared Laser Glucometer.
DiaMonTech GmbH, Berlin,
Germany.
http://www.diamontech.de/
Description
Technique used
Uses mid-infrared pulses from an infrared laser to excite Mid-infrared absorption
glucose molecules in the interstitial layer of skin. Absorption of spectroscopy.
these pulses depends on the concentration of glucose and
results in a heat wave migrating to the skin surface, where it is
picked up by photo-thermal detection.
For use by patients at home with a wearable device planned.
Calibration for several users is possible.
Indication: Type 1 & 2 diabetes, all ages.
Target site: Ball of thumb, index finger, palm below the little
finger, ear lobe. The sensor is placed on the skin.
Development status
Early clinical
development.
Mobile prototype for
clinical testing – 2016,
Home use – 2018
Wearable 2019-2020.
Est. CE marking
Q2/2017.
Est. EU/UK launch Q3
2017.
Comments:
Healthcare Professionals
This is a novel concept but there is little data available. Spectrometry or ultrasound techniques are also likely to be associated with less potential
danger/risk than the use of lasers.
Potential Users
This sounds like it could be difficult to use and I’m concerned around the use of lasers on my skin long term. How discreet would this be? I wouldn’t
be interested if it wasn’t portable. How long would it take to return a result? If this was more than 5 seconds, I would say there is little value
compared to fingerpricks. I would use this on my son if it didn’t need calibrating.
27
2.
OrSense NBM-200G.
OrSense Ltd., Israel.
http://www.orsense.com/
Description
Technique used
Detects the near-infrared optical signal of blood that reacts to Near-infrared
changes in glucose concentration in blood. Device is portable absorption
and claims to be easy to use with results in less than a minute. spectroscopy.
Also measures haemoglobin and oxygen saturation.
Indication: Type 1 & 2 diabetes.
Target site: Finger.
Development status
CE marked but not
commercialised.
Currently being used for
investigation and
market awareness
purposes only.
http://www.diabetesnet.co
m/diabetestechnology/metersmonitors/future-metersmonitors/orsense
Comments:
Novel concept but too early to consider its application for use in a clinical setting. Sounds like it is based on infrared technology that we used to use
for capillary testing, so likely to be do-able, but may not be totally accurate – I’ve read that this technique was affected by the patient’s hydration.
Potential Users
If this works and is no bigger than current fingerstick meters, then I can see this being popular. However, a minute seems a long time to wait for a
result, most meters now count down from 5 so much quicker.
3.
FreeStyle Libre Flash
glucose monitoring system
Abbott Diabetes Care, Inc.,
Berkshire, UK.
Tiny glucose sensor (0.5cm long, about the thickness of a hair) Unknown.
under the skin connected to a water resistant on-body patch
(1.5cm diameter), with a wireless touch screen reader device.
Sensor remains inserted for 14 days. When the touch screen
reader is placed over the sensor patch, it reads the glucose
http://www.freestylelibre.co value, shows a glucose trend arrow, and a trend graph for the
.uk/
last eight hours. Provides an Ambulatory Glucose Profile (AGP)
by utilizing hypoglycemic and hyperglycemic trends.
Target site: Arm.
Can be bought through
Abbott Diabetes Care.
Current use (if any) in
the NHS unknown.
28
Description
Technique used
Development status
Comments:
Excellent system currently being used by a number of patients on a self-funding basis within the NHS. However there is no uptake on funding via the
NHS. The results appear good and overall feedback from users has been excellent. Has good connectivity and usability of readouts such as line graphs
and arrows. It is quick, simple to learn (for patients and healthcare professionals), simple to insert, handset has a long battery life and does not need
re-charging for two weeks, and has a built in blood glucose meter so any reading that seems wrong can quickly be checked. Main disadvantage is
that it cannot be prescribed so cannot be used to replace blood glucose monitoring strips for meters and also not yet accepted as replacement for
blood glucose reading by DVLA in view of the lag between blood and interstitial glucose measurements. It also needs calibrating.
Potential Users
I have used it and it’s OK. Doesn’t have an automatic alarm and wouldn’t be suitable for people who are hypoglycaemia unaware. I find it accurate,
comfortable and user-friendly. It has improved my quality of life. It is useful for measuring glucose levels without having to prick my finger. Trend
arrows and graphs provide relevant and useful information. I am very happy with this product. It could be improved by making my pump
communicate one-way with the handset, so that a real-time bolus calculator could be created without having to input all my dosage times and
amounts manually. This would be a more appealing than making it continuously transmitting.
4.
Glucosense.
GlucoSense Diagnostics Ltd,
London, UK.
Based on photonics technology. A small portable laser. When Fluorescence.
the glass is in contact with the skin, the reflected fluorescence
signal varies with the concentration of blood glucose. Will
measure, process and display and, in advanced versions,
wirelessly transfer data to smart phone or PC.
Ongoing clinical trials
and product
optimisation required
before regulatory
approvals and launch.
Comments:
An innovative concept. A plausable technology likely to be of interest at least in its continuous monitoring form with ability to connect wirelessly to a
smartphone or PC.
Potential Users
Could be very attractive to a lot of people if it’s small, quick and reliable. Have doubts about whether fluorescence will be reliable based on individual
skin/tissue characteristics. The idea of a portable laser doesn’t sound very safe.
29
5.
Non-invasive laser device
Princeton University, New
Jersey USA.
Description
Technique used
Laser directed target dermal interstitial fluid, which has a strong Mid-infrared absorption
correlation with blood sugar.
spectroscopy.
Target site: Palm.
Development status
In process of
implementing field
trials. Next stages would
involve both hardware
and software
developments.
Comments:
Novel idea but not sure about its use in day to day care as it appears to be in very early stages of development.
Potential Users
Sounds potentially interesting but not sure if frequent exposure to laser would be safe. An interstitial fluid device and there is a time lag associated
with this fluid so not as accurate as capillary blood which is not great if hypo.
6.
Non-invasive blood
chemistry monitor
Lightouch Medical Inc.,
Pennsylvania, USA.
A three minute measurement to obtain both the current blood Raman spectroscopy.
glucose level and assess whether the blood glucose is rising or
falling. Will measure glucose, total protein and other blood and
interstitial fluid borne analytes.
http://www.lightouchmedica Target site: Finger.
l.com/services.html
No information
available.
Comments:
Sounds like a novel idea and it is also useful as testing for other parameters. However I’d need to know more about stage of development to
comment further. Also have concerns around accuracy of technique as there is a delay in glucose measured in forearm compared to finger.
Potential Users
Sounds like something that would be useful in a hospital environment rather than at home. Three minutes until a result seems a very long time and
I’m not interested in protein and other analyte measurements – just glucose!
30
7.
Non-invasive blood glucose
monitor.
Massachusetts Institute of
Technology, USA.
Description
Technique used
Laptop-sized device using near-infrared light which measures Raman Spectroscopy.
blood glucose levels. Based on DCC (Dynamic Concentration
Correction)-Calibrated Raman Spectroscopy Technology.
Target site: Arm or finger.
Development status
No information
available.
Comments:
Concept is good however size described would make it difficult for day to day use, also appears in very early stages of development.
Potential Users
Sounds big – I don’t want any more big equipment. I want to use something that is portable and this doesn’t sound convenient to use several times
every day.
8.
Glycolaser® device
Pignolo SpA.
Handheld, mobile phone sized device. Patient rests finger in Near-infrared
front of a small window located on the front of the device, absorption
which uses a laser light to measure blood glucose. The value is spectroscopy.
then converted and appears on a small display screen.
No information
available.
Comments:
Sounds plausibly practical for one off glucose measurements but no indication whether it might be used for continuous monitoring or trend
determination
Potential Users
I like the sound of this as would give the finger a break from prick testing. I like that it’s a handheld device. This sounds like it would be much easier
for children, and would also be good for babies.
31
9.
Glucowise™
MediWise, London, UK.
http://www.gluco-wise.com/
Description
Technique used
Measures blood glucose in capillaries using high-frequency Radiowave
radio waves. Includes a wearable sensor and displays the data spectroscopy.
on smartphone. Integrates a range of measurements including
exercise, diet, body mass index, medication and illness and
includes cloud-based data management system to store
historical Glucowise data.
Target site: Skin between the thumb and forefinger or earlobe.
Development status
In development and will
be available once
clinical trials are
completed.
The company expect to
start taking pre-orders
in late 2016.
Comments:
Very exciting as it factors for exercise diet and BMI and the ability to transfer wireless data to a smart phone and the cloud and record other data
increases its attractiveness.
Potential Users
Claims to measure/track (exercise/diet/BMI/medication/illness) and would rely on the user entering the data, which is the biggest problem in trying
to bring data together.
I like the iphone, that it’s continuous and non-invasive. It would be good if it could also connect to an insulin pump. An earlobe sensor would be
continuously on display so not very discreet, unless it looked like an earring
10.
Analyte measuring device.
Oregon Health & Science
University, USA.
Handheld device to measure glucose in blood utilizing pressure Photoacoustic
signals related to otoacoustic emissions or middle ear muscle spectroscopy.
reflex.
Target site: Ear.
Looking for partners.
Comments:
Not convinced. We use the ear for temperature, but that is so easy in comparison to blood glucose measurements. Not sure how vascular the middle
ear is and think wax might cause problems with reliability especially in children.
Potential Users
I would not want to put something in my ear to read my glucose.
32
11.
Microwave sensor
Islamic Azad University
Description
Technique used
Microstrip that acts as a glucometer. Has a sensor that is a band Microwave
pass filter (passes frequencies within a certain range and rejects spectroscopy.
frequencies outside that range). The filter can detect changes in
blood glucose levels.
Target site: Thumb.
Development status
No information
available.
Comments:
Not sure about its use in day to day care and sounds very early.
Potential Users
What are the risks of using microwaves? It would give fingers a break and it does sound very useable.
12.
GlucoTrack™
Integrity Applications Ltd.,
Israel.
http://www.integrityapp.com/the-glucotrack/
Handheld device to measure blood glucose using an ear clip Ultrasonic,
equipped with sensors and calibration electronics. Uses three electromagnetic and
techniques - ultrasonic, electromagnetic and heat capacity.
heat capacity.
Target site: Ear.
CE mark approval in
April 2014.
Distributed in Estonia,
Turkey, Italy, Lithuania,
Latvia, Uruguay,
Thailand, Philippine,
Spain, Korea, Hong Kong
and China. No
information on UK
launch.
Comments:
Appears to be an interesting technology combining three different modalities of measuring glucose which is already operational in parts of Europe. It
doesn’t seem to have wireless transmission but appears relatively cheap compared with the one system operational in UK, although doesn’t appear
to have the sophistication of readout presentation and interconnectivity.
Potential Users
This is indiscreet and impractical and I would not want to put this on my ear!
33
Table 2: Intermittent Glucose Monitors - Target Site: Oral – breath and saliva
13.
Description
Technique used
Development Status
Diabetic breathalyzer,
Detects acetone in breath which correlates with blood glucose Absorption
No information
New England Breath
levels (picture in Appendix 5).
spectroscopy.
available.
Technology, Western New
Indication: Type 1 and 2 diabetes.
England University, USA.
Target sample: Breath.
Comments:
This is a very novel concept and could be used in hospitals. Acetone doesn’t always correlate with blood glucose and this methodology seems far too
indirect to satisfy demanding standards required for instance by driving regulatory authorities. This might be useful for measuring ketones, rather
than having to do a urine or blood test. Acetone can be high when glucose is high, but not sure how well it correlates with any level of glucose, but I
am no expert. Fantastic for ketones though. Diabetic ketoacidosis is life threatening and being able to measure ketones continuously would be so
useful and clinically in hospital (A&E and ITU) would be so helpful.
Potential Users
I think a breath test would be great for quick, non-invasive glucose measurements. I don’t think would be very suitable for a small child.
14.
Glucose Pop Test™.
Pop Test LLC, USA.
http://www.diabetespoptest
.com/
Credit card sized, colorimetric device. The patient applies saliva Enzymatic detection of
to a bend out lollipop which is bent back. The colour is glucose in saliva.
compared to a standardized colour chart. Single-use and
disposable. Point of care test to be used by patients, care giver
and/or health professional (picture in Appendix 5).
Target sample: Saliva.
CE mark and UK/EU
launch 2017.
Available in US 2016.
34
Description
Technique used
Development Status
Comments:
This is a very novel concept and I can see it being potentially exciting for use on near patient testing as long as accuracy is reasonable.
This methodology seems far too indirect to satisfy the demanding standards required for instance by driving regulatory authorities.
Potential Users
This doesn’t sound very discreet – I would feel uncomfortable doing this in public and it could be open to errors in comparing the colours on the stick
to the chart.
15.
Dual saliva-based sugar
monitor.
Eternity Healthcare.
Utilizes an ultrasensitive sugar monitor and a sensor for salivary Enzymatic detection of
amylase enzyme activity.
glucose in saliva.
No information
available.
http://eternityhealthcare.co
m/eternity-healthcare-todevelop-a-dual-sensornoninvasive-saliva-basedsugar-monitor-device-totest-for-diabetes
Comments:
This methodology seems far too indirect to satisfy the demanding standards required for instance by driving regulatory authorities.
Potential Users
I don’t think this would be very accurate and is unlikely to be close enough to real-time blood glucose levels to be a reliable method.
35
16.
iQuickIt saliva analyser
Quick LLC, Connecticut, USA.
http://iquickitsalivaanalyzer.
com/
Description
Technique used
Patients insert a stick-sized strip into mouth to collect saliva Enzymatic detection of
sample, which is inserted into a hand-held analyser that glucose in saliva.
produces a glucose reading within seconds. Results can be sent
to a smart device to be shared, monitored and stored by
parents, care-givers and medical professionals.
Development Status
Clinical studies
underway in America.
Comments:
I’m not convinced salivary glucose techniques will survive competition from fluorescence and spectroscopic methodologies.
Potential Users
I would not want to do this in public and doesn’t sound like it would be accurate. I really like this – if the accuracy is good and the reading appears on
the device then I would consider using it on my son.
17.
Glucose sensor
University of Newcastle,
Australia.
http://newcastleinnovation.c
om.au/partnershipopportunities/non-invasiveglucose-monitoring
Glucose sensors that integrate glucose oxidase enzyme into a Enzymatic detection of
film claimed to be capable of sensing blood sugar glucose in saliva.
concentrations 100 times lower than commercially available
glucose sensors.
Currently at proof-ofconcept stage.
36
Description
Technique used
Development Status
Comments:
I’m not convinced salivary glucose techniques will survive competition from fluorescence and spectroscopic methodologies. This is interesting in that
they can use it for lower blood sugar concentration.
Potential Users
I don’t like the idea of putting something in my mouth to find out what my glucose levels are, and it doesn’t sound like it would be accurate.
I really like this and would use it on my son if it is as accurate as they claim.
18.
Breath-based blood glucose
monitor
Xhale, Inc., Florida, USA.
Measures glucose in exhaled breath condensate. The user Enzymatic detection of
blows into the device, and obtains a read-out of blood glucose glucose in breath.
level.
Target site: Breath.
The company is looking
for partners to further
develop this technology.
http://xhale.com/
Comments:
This is a very novel concept but seems very early and as with the salivary technologies I doubt if it will be as robust or compete with the best of
spectroscopic and fluorescent technologies. This is interesting in that they can use it for lower blood sugar concentration.
Potential Users
I think a breath test would be great for quick, non-invasive glucose measurements but I foresee too many potential contaminants to have confidence
in this method.
19.
Saliva monitor
Brown University, Rhode
Island, USA.
Uses a sensor that relies on plasmonic interferometry, a light- Plasmonic
based way of detecting chemical compounds, and a dual- interferometry.
enzyme assay that works as a dye to mark glucose.
No information
available.
37
Description
Technique used
Development Status
Comments:
Very novel concept but seems very early and as with the salivary technologies I doubt if it will be as robust or compete with the best of spectroscopic
and fluorescent technologies. This is interesting in that they can use it for lower blood sugar concentration.
Potential Users
It’s hard to imagine how this device would look and feel from the information provided and I am very sceptical about this method of analysing
glucose. I foresee too many potential contaminants to have confidence in this method. Further, saliva-based measurement is unlikely to be close
enough to real-time blood glucose levels to be a reliable method.
Table 3: Intermittent Glucose Monitors - Target Site: Eye – tears
20.
One Look
Lein Applied Diagnostics Ltd.,
Reading, UK.
http://www.leinad.com/diabetes_care.html
Description
Mobile phone sized device that the user holds up to their eye and
looks into to obtain a reading. The meter measures refractive
changes in the anterior chamber of the eye that are related to
changes in glucose levels. Reusable meter (see picture in
Appendix 5).
Indication: Type 1 & 2 diabetes, gestational, both genders, all
ages.
Target site: Eye.
Technique used
Development Status
Refractive changes in CE mark Q4 2018.
anterior chamber of eye UK launch Q1 2019.
that are related to
changes in glucose
levels.
38
Comments:
An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I doubt if it will be as robust or compete
with the best of spectroscopic and fluorescence technologies.
This would be affected by how quickly the glucose changes in the tears compared to the capillary. We need to know the absolute value of the circulating
glucose is not what it was even 5 minutes ago. However, a guide is always useful just like the CGMs that we have now, so it’s not as much of a no as the
saliva – and could be used while people try to recover their lows.
Potential Users
I have concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology and I also wonder if dehydration would
affect the accuracy of the reading. It is interesting though. I’m not sure I could keep a small child still for long enough to do this.
21.
Ocular Tear Glucose Pen.
Glucopen, Ocular Glucose
Monitor.
Tear Glucose Research, LLC.
Opticology, Inc.
www.opticology.com
The small tip of a pen sized instrument touches the tear meniscus Surface plasmon
providing episodic measurements of ocular glucose. Laser light resonance.
interrogates a thin film of metal which has bound glucose
sensitive chemistry (ligand). This chemistry binds with glucose
(analyte) in the tears and produces a change in the reflected laser
light. The pen is single-use and comes with disposable sensor
tips. It is intended to be used by patients at home (see picture in
Appendix 5).
Indication: Type 2 diabetes.
Target site: Eye.
Early clinical
development.
Has been used in
informal studies for
measuring constituents
of the tear film. A study
on tear glucose should
be completed by
Q4/2015. No further
update available.
Comments:
An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I doubt if it will be as robust or compete
with the best of spectroscopic and fluorescence technologies.
Potential Users
I have serious concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology. I also wouldn’t want anything this
close to my eye and how would I perform a measurement on a moving bus or train? This does sound interesting but not great for contact lens wearers
and I can’t imagine this is child friendly.
39
22.
TOUCH tears glucose, tear
glucose biosensor.
Mayo Clinic, Arizona, USA.
This electrochemical based device uses GDH-FAD (glucose Enzymatic detection of
dehydrogenase-FAD dependent) enzyme. Captures basal tears glucose.
and measures the tear fluid glucose levels without stimulating a
glucose/stress response. It is intended to be used by patients,
http://labellelab.asu.edu/2011 carers and health professionals (see picture in Appendix 5).
/03/17/diabetes-selfIndication: Type 1 & 2 diabetes, all ages.
monitoring-shed-a-tear-toTarget site: Eye – tears.
test-blood-sugar-level/
Early clinical
development.
Clinical trials to be
conducted at Mayo
Clinic. The project team
will seek additional
support from the
National Institutes of
Health and industry to
fund the trials.
Comments:
An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I’m not convinced by this technology and it
misses out on the connectivity which comes with some of the fluoroscopic and spectroscopic devices.
Potential Users
23.
I-SugarX
Freedom Meditech, Inc.,
California, USA.
Takes direct measurement of glucose in aqueous humour of the Refractive changes in
eye.
the anterior chamber of
the eye.
Target site: Eye.
Human clinical trials
were planned to
commence in 2012 – no
further update
available.
40
Comments:
An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. It is also another indirect technique and I
have my reservations on its accuracy.
Potential Users
24.
Optical Coherence
Tomography
University of Texas, USA.
An optical tomography system which determines glucose levels Optical coherence
by assessing intensity of reflected/scattered and transmitted light tomography.
upon interaction with subcutaneous tissue glucose
concentration.
Target site: Eye.
No information
available.
Comments:
An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. It is also another indirect technique and I
have my reservations on its accuracy. Retinal tomography is already being used to understand more about diabetes eye disease, so this might be a
technology worth investigating and if it is looking at the subcutaneous tissue in the eye then that is through the arteries so would give a very precise
measurement.
Potential Users
I have serious concerns about the lag between blood and ocular fluid.
I like this if you only have to look into a machine rather than having something touch your eye.
41
Continuous Glucose Monitors
Table 4: Continuous Glucose Monitors - Target site: Skin – finger, arm, hand and ear.
25.
Non-invasive blood glucose
monitor
LEMM Technologies, LLC.
Description
Technique used
A portable, programmable, reverse iontophoresis (RI) based skin Reverse iontophoresis.
electrode/biosensor system which extracts glucose and lactate
using a gel electrode. It measures or/detects intermittently or
continuously glucose or lactate.
Target site: Skin (exact site unknown).
Development Status
No information
available.
Comments:
This is a novel idea and concept but there are no details of where the testing would be done and at what stage of development it is in.
A glucose monitoring watch type device was developed some years ago but fell by the wayside because of problems related to inaccuracy when a
patient sweated heavily. These devices can be affected by perspiration and climate – it makes them less reliable. They may have overcome that problem,
but people who are about to become hypoglycaemic sweat due to the effect of the low glucose on the autonomic nervous system.
Potential Users
I only want to know about my glucose and I would have concerns whether you would have to put the gel on your skin every time you need to get a
reading. I can’t see my teenager doing that every time. This sounds good if it’s non-invasive and continuous. The problem with a CGM and a small child is
continually finding sites to move the cannula around as there aren’t a lot of areas especially when dealing with a CGM cannula and a separate pump
cannula site.
26.
Ultra wide-band pulse
dispersion spectrometry.
Baylor University, Texas, USA.
Sends low level radiofrequency/microwave signals into patient’s Radiowave
tissue. Portable and reusable. For use by patients, initially as an spectroscopy.
alarm device; later as a glucometer for insulin dosing.
Target site: Hand; other application sites are being developed.
Early concept
demonstration.
42
Description
Technique used
Development Status
Comments:
Innovative technology, not many devices use radiowave spectroscopy. Could possibly monitor glucose levels accurately. The features of the technology
are significantly innovative and may have a big quality of life impact on patients. It may reduce complications and ambulance call outs. The reduced
financial burden on the NHS in the future could be big if these types of technologies (NIGMs) work. The potential barriers with this technology maybe
the cost and ‘clumsy’ kit. Using something that can test the trend that the blood glucose is going in would be useful, but in the long run it needs to give
absolute numbers.
Potential Users
This could be useful if it were indicated to replace fingersticks for insulin dosing but I have concerns about the risk of using microwave signals on my skin
over the long term.
27.
sugarBEAT™ system
Nemaura Medical Inc.,
Loughborough, UK.
www.nemauramedical.com
Disposable sensor-patch (1.5cm x 1.5cm) is applied to skin and Reverse iontophoresis.
connected to a laptop-like device. It painlessly extracts interstitial
fluid from beneath the skin into the sensor-patch. The patch
requires a two hour warm up period, during which it equilibrates
with the skin. After this it is designed to work continuously for at
least twelve hours. The device detects and records glucose
levels within the patch up to four times per hour. Glucose levels
can be seen on a display screen on the device, with additional
alarms to alert the user to very high or rapidly falling glucose
levels. Single use, disposable patches (see picture in Appendix 5).
Indication: Type 1 & 2 diabetes and pre-diabetic glucose
monitoring.
Target site: Wrist/arm, leg.
Estimated CE mark
2016. Estimated EU/UK
launch 2016.
The company
anticipates launching in
Europe and parts of the
Middle East and Hong
Kong in 2016.
43
Description
Technique used
Development Status
Comments:
It’s a novel concept however if the patients or carers have to change it every 12 hours I can see some reluctance in its uptake. If it is robust-they will
need to demonstrate that they have overcome the problems associated with excessive sweating.
Potential Users
I don’t like the idea of having to recharge the watch every 24 hours. Could this be worn underwater? Four readings per hour does not sound great – my
son’s levels can change dramatically in that time. I don’t like the sound of the 2-hour warm up period and it only lasting for 12 hours. It doesn’t sound
very practical.
28.
Transdermal continuous
glucose monitoring
technology
University of Strathclyde,
Glasgow, UK.
Extracts glucose using a sensor on the skin, connected to a hand- Reverse iontophoresis.
held analyser which continuously monitors glucose. Single use
and disposable.
Indication: Type 1 and type 2 diabetics who test blood glucose
daily.
Target site: Various sites but arm used most routinely to date.
CE marking and UK
launch, investor
dependent.
Initial funding from
EPSRC, subsequent
funding by Scottish
Enterprise’s Proof of
Concept Fund.
Subsequent
TSB/Innovate UK
funding with industry
partners
Healthy volunteer study
and small clinical study
in a diabetic population
has completed.
44
Description
Technique used
Development Status
Comments:
A good concept and I would be interested in seeing the data and its accuracy before considering its use. This has potential only if it can be demonstrated
that it has overcome the problems alluded to excessive sweating. I suspect the iontophoresis technologies might have a cost advantage over the
fluoroscopic and spectroscopic technologies but first it must be shown to be robust.
Potential Users
The transdermal nature of this device makes me weary of skin injury. I like the idea of this but would require alarms. How is the fluid ‘extracted’? Is this
information uploaded to the cloud for use on tablets and smart phones?
29.
Biometric glucose system
Bar-Ilan University, Israel.
A watch-like sensor with a laser that illuminates a patch of skin Raman spectroscopy.
on the wrist near an artery, and a camera that measures changes
over time in the light that is back scattered off the skin.
Target site: Wrist.
In 2014 the company
anticipated that a
commercial version of
the device would reach
the market within two
to three years. No
further update
available.
Comments:
More information is needed about the stage of development to comment its impact.
Potential Users
This sounds OK but not very practical and not so suitable for a child. What about exercise and swimming? I would need a device that can be used at all
times during all activities.
45
30.
Symphony®
Echo Therapeutics, Inc.
http://echotx.com/
Description
Technique used
A patch sensor is applied to an area of skin that is exfoliated using Glucose oxidase enzyme
a pen-like device. The glucose sensor continuously measures technology.
glucose utilises glucose oxidase enzyme technology. A
proprietary algorithm converts data to accurate glucose values
that are wirelessly transmitted. Results can be displayed on a
mobile platform or cloud service.
Target site: Skin.
Development Status
Developing commercial
partnerships for
marketing and
distribution in
discussion.
Comments:
This sounds an exciting concept but at very early stage of development. It potentially could be a very interesting technology because of the good
connectivity planned for device and possibly better affordability. This sounds like a possibility if it is not affected by heat, cold and sweat and abrasion is
not too severe, but probably relies on the right amount of exudates from the skin so may well be affected by heat cold and sweat.
Potential Users
The requirement to exfoliate the skin makes me nervous about the potential for irritation and how often would you need to change the sites?
I like this one – continuous, non-invasive, cloud based and you can see the results in real-time along with taking readings every 5-10 minutes. It would be
useful if it talked to the insulin pump.
31.
EyeSense fibre optic sensor
EyeSense GmbH, Germany.
http://en.eyesense.com/prod
uct/fibersense-technologycontinuous-glucosemonitoring/productinformation/
Continuous fibre optic sensor with built in alarms for hyper and Fluorescence.
hypoglycaemia.
Target site: Abdomen or upper arm.
The company
anticipates the market
launch of the fibre optic
sensor will likely be in
2016.
46
Description
Technique used
Development Status
Comments:
A Good concept especially with built in alarm systems as well. I can see it being useful in Type 1 DM. This sounds good. Eye’s need to be open for all of
the retinal ones, so perhaps worth a thought that they won’t be so practical for low glucose levels at night.
Potential Users
I like the sound of this one as it has alarms and it’s continuous. I’m not too sure about this one, it appears to be the same as Dexcom and it looks rather
large and sounds invasive.
32.
Glucosense CGM
GlucoSense Diagnostics Ltd,
London, UK.
Low-powered laser sensor head collects and measures data, and Fluorescence.
may be connected to a smart phone or PC to send alerts to the
user when needed.
No information
available (see
Technology 4 for
intermittent monitor).
Comments:
An interesting concept but no information about stage of development. A plausible technology likely to be of interest at least in its continuous
monitoring form with the ability to connect wirelessly to a smartphone or PC.
Potential Users
I wouldn’t wear something on my finger continuously unless it was very discreet, and the use of lasers in concerning. Talking to the phone is good.
33.
Microprobe Array Continuous
glucose monitor
Imperial College of Science,
Technology and Medicine.
London, UK.
A wearable patch (~1 cm2), containing microscopic projections Reverse iontophoresis.
(microprobes) that penetrate the outermost skin layer. It
accesses interstitial fluid to sense its glucose content without
stimulating skin nerve fibres or reaching blood vessels within skin
layers. The microprobe surface has the consistency of sandpaper.
It is pushed into the skin with an applicator to penetrate through
the skin layers and access the interstitial fluid. The device is
disposable.
Target site: Skin (exact site unknown).
The company aim to
further develop the
device through clinical
studies in non-diabetic
subjects and subjects
with T1DM. NIHR i4i
funded project.
47
Description
Technique used
Development Status
Comments:
A really interesting concept and I note the liaison with NIHR which should lead to good quality data on accuracy. Being a patch hopefully it won’t be
affected by heat cold and sweat.
Potential Users
This sounds interesting, especially if it is sturdy enough to withstand routine bathing, skin bending/stretching and contact with clothing (rubbing).
Would this hurt? I like the sound of it if not. I would be interesting I knowing how often would you have to change it and whether or not it would talk to
a smart phone. What about alarms? This sounds quite painful! The size of the patch sounds pleasingly small and I would be willing to try this.
34.
Temporary tattoo
UCSan Diego Jacobs School of
Engineering, California, USA.
http://www.jacobsschool.ucsd
.edu/news/news_releases/rel
ease.sfe?id=1691
Carefully patterned electrodes printed on temporary tattoo Reverse iontophoresis.
paper. A mild electrical current applied to the skin for 10 minutes
forces sodium ions in the fluid between skin cells to migrate
toward the tattoo’s electrodes. These ions carry glucose
molecules that are also found in the fluid. A sensor built into the
tattoo then measures the strength of the electrical charge
produced by the glucose to determine glucose levels.
Target site: Arm.
Very early – at the
moment the tattoo
doesn’t provide the
numerical readout that
a patient would need to
monitor his or her own
glucose.
Comments:
I’m not sure about this being able to apply to common use. A Tattoo insinuates puncturing the skin, so maybe it might be OK, but admits to needing
calibration, so the patient will still need to use a lancet.
Potential Users
This sounds interesting, especially if it is sturdy enough to withstand routine bathing, skin bending/stretching and contact with clothing (rubbing).
However, a 10 minute application process sounds inconvenient. My son would love a tattoo – this would not be a hard sell to get him to wear it! This
would also appeal to the majority of teens and young people.
48
35.
Vital Sign Monitor 3
Biovotion AG, Zurich,
Switzerland.
Description
Technique used
Designed to continuously monitor blood glucose levels using a A combination between
multi-sensor technology approach (see picture in Appendix 5).
dielectric, impedance
and optical
Target site: Upper arm.
spectroscopy
http://www.biovotion.com/
Comments:
A novel concept but at a very early stage of development.
Development Status
Phase 2/3 clinical trials.
Estimated CE mark Q2
2017. Estimated EU/UK
Q1 2018.
Potential Users
This sounds good and I like the idea of a watch. It looks neat and many parents and teens are now wearing watches so would be interested in trying this.
It looks too big to be worn discreetly and conveniently.
36.
Critical care glucose monitor
DIRAmed, LLC., Ohio, USA.
Transmits infrared light into skin. It is based on Raman Raman spectrometry.
spectroscopy. Sensors detect changes in properties of the light as
a result of interactions with analytes in the body. The company
http://www.diramed.com/dira intend on developing it for home and hospital use.
med_technology.html
Comments:
Potentially a reliable technology but insufficient detail available to comment.
The company intend on
developing their glucose
meters by 2018.
Potential Users
This sounds better than constantly finger pricking. A similar device that was in development found that raman spectroscopy suffered from light
scattering, meaning a large dark patch of fabric would be needed to shield the test area from scattered light. I doubt this will be any different.
49
37.
Glucoband®
Calisto Medical, Inc.,
Description
Technique used
A wrist-watch like device with fully integrated LCD screen, Impendence
electronic circuits, integrated electrodes, battery and adjustable spectroscopy.
wrist-band which utilizes impedance spectroscopy. The initial
measurement process takes only a few minutes, however, in the
monitoring mode, measurements can be continuous and only the
frequency of measurements must be determined. Glucoband®
targets diabetics, who are measuring their own blood glucose,
and medical personnel who are using blood glucose measuring
and monitoring devices in clinics, hospitals and other point-ofcare facilities.
Target site: Wrist.
Development Status
No information
available.
Comments:
A good idea however no information about stage of development and this could be affected by sweat when a patient is hypoglycaemic.
Potential Users
I don’t think my son would wear this – it sounds more suitable for adults. I like the idea of a watch and great if the measurements are continuous and I
would also want it to alarm.
50
Table 5: Continuous Glucose Monitors - Target site: Eyes – tears.
38.
Noviosense glucose sensor
Noviosense, Netherlands.
www.noviosense.com
Description
Technique used
The device consists of a 15mm-long, metal coil that is coated in a Amperometry.
hydrophilic gel, which the patient places into the lower eyelid.
The coil moves to the correct place in the eye and the gel coating
hydrates and swells creating a contact between the metal coil
and the fluid in the eye. A smart phone app measures the glucose
levels. The device is disposable (see picture in Appendix 5).
Target site: Eye.
Development Status
NovioSense is currently
actively seeking both
strategic partners and
risk capital to accelerate
the development of the
technology to clinical
validation and market
entry. They expect to
begin market
introduction Q1 2018.
Comments:
I can’t see it being commonly used due to the use of the eyes and risks of infection. I think this sound like a bad idea. In a similar way to inhaled insulin –
I wouldn’t want to put something in my lungs?? this is eyes!! that may cause harm when a needle works very well for 99.9% of people. Finger lancing
would be preferable to anything being invasive into the eye.
Potential Users
I would not put this in my eye – sounds scary! My son would not allow me to put this in his eye. I cannot think of one child/teen who would allow
anyone to insert anything into their eyes. I looked at the photos and absolutely could not have that anywhere near my eyes let alone inserted into the
lower lid. An awful idea! I would not consider using this. I can't imagine wearing a 15mm coil and it being comfortable.
51
39.
Description
Technique used
EyeSense eye sensor
EyeSense GmbH, Germany.
Inserted under the conjunctiva and continuously measures blood Fluorescence.
glucose levels. It reacts reversibly to the glucose concentration
and correspondingly emits fluorescence intensity, correlated to
http://en.eyesense.com/prod the glucose concentration. The implantation is painless and takes
uct/eyesense-technologyonly three minutes. The sensor is not visible and can be worn for
precise-glucose-monitoring-at- up to one year before being replaced. In this time, a small
the-eye/product-information/ monitoring hand device is used for monitoring. Its emitted light
falls on the eye sensor and reads out the returned optical signal
sent from the sensor. Once the device is calibrated the results are
expressed in the usual blood glucose measuring units.
Target site: Eye.
Comments:
I can’t see it being commonly used due to the use of the eyes and risks of infection.
Development Status
The eye sensor will be
launched after the fibre
optic sensor
(technology number
35).
Potential Users
I wouldn’t put this in my eye; what happens if it malfunctions? I’m not sure about this one. A 3 minute insertion that needs to be performed by a
healthcare professional makes this an expensive and inconvenient option, but if the sensor lasts for a year, that might make up for it. I don't like the idea
of a sensor inserted under the conjunctiva, though, and would be concerned about infection risk and irritation. It sounds like the handheld device needs
to emit light which is picked up by the sensor, so I can't imagine how this could be a continuous glucose monitor.
40.
Smart lens
Novartis Alcon, Surrey, UK and
Google[x] – team within
Google Ltd., London, UK.
Non-invasive sensors, microchips and other miniaturised Micro sensor and
electronics are embedded within contact lenses. Designed to computer technology.
measure tear fluid in the eye and connects wirelessly with a
mobile device (see picture in Appendix 5).
Target site: Eye.
Early stage
development.
52
Description
Technique used
Development Status
Comments:
I can’t see it being commonly used due to the use of the eyes and risks of infection. This sounds better as it states non-invasive and is working on tear
fluid. However, if it stays in the eye it is a risk of irritation and infection.
Potential Users
The potential cost/benefit ratio of this proposal is not positive. We’d also face the issues around people with diabetes who want to wear regular contact
lenses not being able to take up this technology, unless there is some magic way of doing 2 lenses or making the glucose sensing lens also corrective. As
an adult that wears contact lenses, if this was prescription strength too and the thickness of a daily disposable contact lens not an uncomfortable
monthly lens I would be interested. However, I’m not sure I could be bothered to take it out very night and clean it and reinsert in the morning, would
prefer continuous device 24 hours without the daily maintenance.
This is different! Many millions wear contact lenses, does it alarm for hypers and hypos? I have tried contact lenses and couldn't get on with them as my
eyes are too dry. This may be a problem for many people with long standing diabetes. This option would preclude anyone who wore corrective contact
lenses.
53
Appendix 5: Pictures of NIGM technologies
All pictures are presented with the permission of the named developer
Technology
number
Technology name
and developer
13
Diabetic breathalyzer,
New England Breath
Technology.
14
Glucose Pop Test™.
Pop Test LLC, USA.
20
One Look
Lein Applied
Diagnostics Ltd
21
Ocular Tear Glucose
Pen. Glucopen,
Ocular Glucose
Monitor.
Tear Glucose
Research, LLC.
Opticology, Inc.
Picture
54
22
TOUCH tears
glucose, tear glucose
biosensor.
Mayo Clinic, Arizona,
USA.
27
sugarBEAT™ system
Nemaura Medical
Inc., Loughborough,
UK.
35
Vital Sign Monitor 3
Biovotion AG, Zurich,
Switzerland.
38
Noviosense glucose
sensor
Noviosense,
Netherlands.
40
Smart lens
Novartis Alcon,
Surrey, UK and
Google[x] – team
within Google Ltd.,
London, UK.
55
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26
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56

New and emerging non-invasive glucose monitoring technologies

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