A novel implantable sensor for long-term continuous glucose - PowerPoint PPT Presentation

Sencell Development PRODUCT & TECHNOLOGY A novel implantable sensor for long-term continuous glucose measurement CORPORATE

THE READ-OUT OPTIONS TECHNOLOGY 2

The Challenge Miniaturization Project Lifecare AS is developing an implantable glucose sensor named SENCELL for positioning under the skin into the interstitial space. Starting from a laboratory working cell (5 x 3 x 3 cm), the company has achieved significant miniaturization and has performed preclinical proof-of-concept with a small working sensor model (2 x 1 x 0.5 cm) ? Laboratory Cell Preclinical I Preclinical II Clinical 3 TECHNOLOGY

TECHNOLOGICAL Osmotic pressure measurement offers several major advantages ADVANTAGES Detecting glucose by the principle of osmotic pressure holds promise of a glucose sensing technology that is suitable for both miniaturization and long term continuous monitoring in vivo without causing patient discomfort or reducing quality of life. Low cost operation No additional start-up time No reagent consumption Miniaturization No generation of poisonous by-products Unobtrusive High glucose specificity Implantation by injections/minimal surgery Long term stability Real time continuous operation Universal calibration Wireless communication No internal power supply TECHNOLOGY 4

MACROCELL IN-VITRO Factors influencing the performance time have been identified and characterized through a series of experiments with a novel The underlying principle test cell Sensing chamber height • Viscosity of sensing fluid • Temperature of sensor cell • Performance analysis is measured according to: Response time • Sensitivity • Reproducibility (stable response) • Precipitation • Interfering substances • Toxicology • TECHNOLOGY 5

SENCELL RESULTS IN- Key components selected and tested in macrocell (wired) in-vitro configuration VITRO • Very good active fluid composition with novel recipe • Stable measurements / signals → Measurements in -macro-cell with reproducible results for at least 3 months at RT → At least stable in -vitro at RT for over 3 months and at 37°C for 11 weeks → ConA stable for at least 3 months at 21°C → This new active fluid recipe stable responses can be obtained for 3 months at 21 °C → This is very promising for long -term implantation of ConA- based glucose sensors • Concentration measurements at 37°C show no loss of ConA over 3 months • Amplitudes acceptable. Similar at 37°C • Good understanding of kinetics, and response time → The use of fluidics inputs and outputs gives complex sensor responses on the order of 2 -3 minutes (in both directions) • The evaluation of six potentially interfering molecules revealed no problematic interferences at physiologically relevant concentrations. Potential Specificity of ConA/dextran chemistry sufficient for measurement of glucose in presence of physiologically relevant levels of α -D-mannose, maltose, xylose, transferrin, & fructose. For L-lactate interference detectable for levels reached by intense sportive activities (e.g. Marathon) TECHNOLOGY 6

Sensor Development Cambridge Consultants - A world leader in technology and product innovation KEY PARTNERS: IN-VIVO ▪ Each system consists of four similar hand made sensor implants wired to a break-out box that collected measurement data for the duration of the trial, and 1 x Dexcom 4 devices. Dexcom 4 TECHNOLOGY 7 Commercially Confidential 7

Pilot Animal Experiment Pig 3, Day 3, Sensor 1 (after mathematical correction for movement artefacts by using Sencell sensor pattern similarities) SENCELL 1 NORM. Dexcom 1,30 1,20 1,10 1,00 0,90 0,80 0,70 0,60 7:04 7:29 7:54 8:24 8:49 9:09 9:30 9:54 10:14 10:35 10:59 11:19 11:44 12:04 12:24 12:45 13:09 13:29 TECHNOLOGY 8

The mechanical design has been completely re-engineered to allow for 2. Pre -clinical the dual chamber (sensing and reference) Sencell Development ➢ Active Fluid was prepared using an established recipe except for clarification concerning the protocol for adding Dextran ➢ Reference Fluid was equivalent to the Buffer for the Active Fluid without ConA and Dextran ➢ Fluids were de-gassed and added to the Signal and Reference chambers before closing the device and monitoring pressures as the clamping screws were gradually tightened TECHNOLOGY 9

2. Pre -clinical ➢ The pre-clinical pilot study part II was performed from 22/08/-01/09/2016 at the Mfd Facility, Wendelsheim, ➢ Germany Three juvenile German landrace pigs were used for Sencell implantation (two males and one female ) Dexcom 4 Dexcom 6 TECHNOLOGY 10

KEY PARTNERS IN-VIVO 2. Pre -clinical Glucose signals after one-point calibrations VISION NOTIFIED BODY DISTRIBUTORS COMPETNT MANUFACTURERS & AUTHORITIES AUTHORIZED SUBCONTRACTORS REPRESENTATIVES TECHNOLOGY

Long term miniaturisation potential using 3D nano-printing technology Sencell Development Miniaturised pressure chamber using 3D nano-printing Nano-sensor 50 - 100 µm 3D-printed cantiMED nano-sensors A nano-sensor is an ultra-small device, measuring pressure, force or other quantities with highest resolution 100 - 500 µm Further potential in miniaturisation of Lifecare’s micro -sensor using cantiMED’s nano-sensors offer a significant reduction in production cantiMED’s 3D-printed nano-senors - target size 100 - 200 µm x 200 - cost 1000 µm Several standardised pressure sensors to be placed at the bottom of cantiMED technology has been ranked Technology Readiness Level (1) 7 the osmotic pressure chamber resulting in increased accuracy and (TRL) sensitivity in pressure measurements 3D nano-printing process employed by cantiMED has been Increased sensitivity allows for pressure measurements in increments implemented by Zeiss in mass production processes and is e.g. of less than 0.01 mbar considered to be the standard repair tool for high-end photomasks Source: Company information. Note: (1) Technology Readiness Levels (TRL) are a type of measurement system used by NASA to assess the maturity level of a particular technology. 12 TECHNOLOGY

Illustration of cantiMED 3D-printing technology Sencell Development Illustration of 3D-printed sensor Sense TM TM nano3DSe na Pressure Sensor 2 µm Membrane (Material free to choose) Tunneling-process («hopping») ∆R/R (%) Deflection (nm) Substantial change in resistance Miniaturisation through proven cantiMED nano-technology allows for increased sensor sensitivity and lower production costs 13 TECHNOLOGY

Precise nanoscale 3D-printing Sencell Development Resolution 10nm Print on any substrate material Rapid prototyping within minutes 14 TECHNOLOGY

Wafer-BatCH-Production KEY PARTNERS IN-VIVO Sencell Development VISION NOTIFIED BODY DISTRIBUTORS COMPETNT MANUFACTURERS & AUTHORITIES AUTHORIZED SUBCONTRACTORS REPRESENTATIVES TECHNOLOGY

KEY PARTNERS IN-VIVO Sencell Development Biocompatible Outer Membrane VISION Interstitial Fluid Sealed Fluidic Port NOTIFIED BODY Glucose Permeable Membrane Osmotic Pressure Chamber Fluidic Channel Pressure Membrane Circuitry Electronics Nanosensors TECHNOLOGY

KEY PARTNERS IN-VIVO Sencell Development Electrodes VISION Osmotic Pressure 1. Generation of Pressure Membrane NOTIFIED BODY DISTRIBUTORS Stable Frame Pressure COMPETNT MANUFACTURERS & AUTHORITIES Membrane AUTHORIZED SUBCONTRACTORS REPRESENTATIVES TECHNOLOGY

KEY PARTNERS IN-VIVO Sencell Development VISION NOTIFIED BODY Array of Membranes TECHNOLOGY

Batch fabrication of nanosensors incorporating 3D nanoprinting (Nano3DSense™) Sencell Developmentt Blow up image: Sensors with electrode structures Overview: Array of sensors, mass produced Electrode Electrode Electrode Nanosensors (3D-printed) Logo on very small scale Blow up image: A nanosensor 3D-printed electrodes Electrod 21 21 TECHNOLOGY e

KEY PARTNERS IN-VIVO GLUCOSE VISION NOTIFIED BODY DISTRIBUTORS COMPETNT MANUFACTURERS & AUTHORITIES AUTHORIZED SUBCONTRACTORS REPRESENTATIVES CORPORATE