Summary description of project context and objectives

Existing therapeutic devices for diabetic patients suffer from bulky size, inaccurate measurements and difficult handling of two body interfaces. Suboptimal control of blood glucose levels in patients with type 1 or type 2 diabetes mellitus results in periods of hypo- and hyperglycemia leading to severe and life-threatening complications. Exploiting a novel glucose sensor technology, SPIDIMAN aims to improve glycemic management for better quality of life and healthier aging. The consortium will develop a new coating technology to apply a glucose sensitive fluorescent dye onto a standard insulin catheter and incorporate this integrated glucose sensor into a single-port artificial pancreas system. Advanced optical continuous glucose monitoring technology (smart tattoos) with improved sensor accuracy, faster response times, wider dynamic range and higher signal stability will advance diabetes management by reducing hypo- and hyperglycaemic episodes. Within SPIDIMAN, research-intensive European SMEs will test an innovative artificial pancreas approach, and experienced partners will perform clinical validation in a European network of specialised diabetes centres. SPIDIMAN will thus pave the way for a single-port device that integrates improved glucose measurement and more accurate insulin delivery to provide better glycemic management in patients with insulin-dependent diabetes. The new device is expected to be particularly suitable for patients in childhood and adolescence, who will form a specific focus of the project.


Description of work performed and main results

The second period of the SPIDIMAN project was dedicated to drive the single components of the SPIDIMAN single-port system to a level that allows system integration to an AP device and to perform clinical investigations of the system in patients with type 1 diabetes.


Despite the vast expertise in sensor chemistry design in the SPIDIMAN consortium it was exceptionally challenging to develop a biocompatible and adhesive sensor chemistry for steel needles. The developed chemistry is now suitable for a coating process onto steel needles with an outer diameter of 0.4mm and allows transcutaneous readout of fluorescence signals at a signal to noise ratio of at least 10.
However, the functional characteristics of the sensor chemistry were already well defined during the course of this period and were suitable, but the adhesion issue still remained unsolved for a long time. This circumstance forced the consortium to turn the focus on adhesion because it would have been unethical and a risk for the volunteering subjects to start clinical tests with this unsolved issue. Solving the adhesion issue consumed a lot more time and resources as foreseen in the project plan.
Another unforeseeable effect caused a further delay: to improve adhesion, special adhesion promoters were added into the sensor chemistry, leading to suitable adhesion of the sensors but a reduction in the dynamic range of the sensor. It also imposed a second biocompatibility testing to confirm biocompatibility of the changed sensor chemistry.

Optical reader:

The SPIDIMAN system requires an optical detector that reads out sensor signals transdermally. A second generation of the glucose readers was developed. It uses custom made optical filters for enhanced discrimination between glucose and oxygen channel, and it is strongly reduced in size and weight.

The optoelectronics of the glucose readers were divided in two parts to reduce the size of the device placed on the skin for patient convenience. The reader itself has a diameter of 25mm, a thickness of 8mm and a weight of 8g. The housing consists of black anodized aluminium. It includes LEDs, LED drivers, photodiodes, amplifiers and the optical filters. The interface electronics is connected with a thin cable. It includes A/D and D/A converters, microcontroller, and USB interface chips. The housing of this part is made of polyamide by selective laser sintering.

The readers will allow readout of sensors applied on cannulas inserted 90° as well as cannulas inserted slanted at an angle of about 15 – 30°. The second generation glucose readers constitute the final system that is used in the clinical studies (Deliverable 3.2).

Patent safety, regulatory issues and system integration:
The SPIDIMAN-System was classified as active invasive medical device for short term use, which is Class IIb. A major achievement was that the developed sensor chemistry passed the biocompatibility tests which allowed to move on to clinical performance tests of the sensor.

Clinical evaluation:

A first pediatric study was developed performed to assess glucose / insulin profiles in children in the age group between 6-12 years. It included two 17h afternoon-overnight profiles to get insights on the intra-patient variability in this patient group. This data is used to adapt the SPIDIMAN algorithm to this specific age group of patients with type 1 diabetes.

A first clinical sensor performance test was performed in 12 patients with type 1 diabetes. The results proved the potential of the SPIDIMAN sensor technology with retrospective sensor MARD values of 12-15%. However the sensor quality is varying due to the manual fabrication process, which led to a broad spectrum of sensor performance results.

Expected final results and potential impacts

The new SPIDIMAN device will integrate advanced glucose measurement and accurate insulin delivery in an artificial pancreas (AP) approach to improve diabetes management in adults and children suffering from insulin-dependent diabetes. To improve on continuous glucose monitoring, a standard insulin infusion cannula coated with a glucose sensor will be developed as a new single-port AP. The coated insulin catheter is inserted into the subcutaneous tissue and will simultaneously be used for both glucose concentration measurement and insulin delivery in an integrated therapeutic device that has great potential to improve diabetes management in adults and children.
To provide benefits to diabetes patients SPIDIMAN will meet the following objectives:
Develop a comprehensive coating technology.
The new coating technology will graft an optical glucose sensing layer ("smart tattoo") onto an off-the-shelf insulin infusion catheter.
Optimise the optical glucose measurement and control algorithms.
The optical reader will be optimised to increase the accuracy of glucose concentration measurements in tissue and, based on current approaches, appropriate control algorithms will be developed that incorporate the characteristics of the glycaemic management strategy for paediatric and adult type 1 diabetes patients.
Build a new single-port AP device.
All technical components and the optimised algorithm will be combined in a new single-port AP device with innovative optical glucose sensing technology.
Validate the new single-port AP in a preclinical setting.
The performance and applicability of the single-port AP device will be evaluated and optimised in a preclinical study and the control algorithm will be additionally evaluated using a novel in-silico approach.
Validate the new single-port AP in a clinical setting.
The performance and applicability of the single-port AP device and the complete single-port AP will be tested in clinical studies in adult and paediatric type 1 diabetes mellitus patients.
Due to the integration of a new sensor technology on existing cost- effective insulin infusion sets the expected costs for the new sensor-coated catheters will be low, thus helping to reduce the health care costs of diabetes management but also the cost stemming from inadequate glycaemic control. Inaccurate glycaemic management leads to hospitalisation cost for patients with both micro- and macrovascular complications that are 5.5 times higher than the costs for patients with no complications. In cooperation with the biomedical industry, SPIDIMAN prototypes can be used to improve glycaemic management, diabetes care, long-term prognosis, quality of life, life expectancy and general wellbeing for patients with diabetes through the availability of a highly acceptable, safe and effective AP device. This would have a significant impact on European healthcare expenditure by reducing costly long term complications associated with diabetes, making sustainable health care systems in Europe more sustainable.

Children with T1DM are particularly affected by insufficient diabetes management because of their highly variable lifestyles and their extreme insulin/glucose sensitivity, leading to hypo- and hyperglycaemic episodes. At a very young age many children are not able to communicate hypoglycaemic symptoms. The SPIDIMAN single-port AP system requires only one needle and provides a smaller monitoring device for better glycaemic management, increased quality of care and therefore quality of life and increased life expectancy. The use of a fully functional single-port AP will lead to tight glycaemic management particularly at night, and will provide a substantial improvement for paediatric T1DM patients and their families. It will offer an excellent treatment option for very young children due to the reduced number of insertion sites.