July v071114BIOSENTECH sa1 BIOSENTECH

July v071114BIOSENTECH sa2 BIOSENTECH  The business field and the market  The history of the company  The team  The BIA-ATR technology Description Description Benefits for the user Benefits for the user  Contacts

July v071114BIOSENTECH sa3 The business field State of the art BIOSENSORS for the detection of biomolecules in medical applications, for the pharmaceutical industry, the agribusiness, environmental and defence applications.

July v071114BIOSENTECH sa4 A high growth world market

July v071114BIOSENTECH sa5 BIOSENTECH BIOSENTECH  SPIN-OFF of three Belgian universities ( UCL, ULB, UMH)  Founded in 2003 by private and industrial investors and universities.  Exclusive owner of the license on the patented BIA-ATR technology (2007) The history

July v071114BIOSENTECH sa6 BIOSENTECH / BIA-ATR A project … A team … Ideas …

July v071114BIOSENTECH sa7 Multidisciplinary teamwork involving three universities UMH: Prof. J. De Coninck - M. Voué UCL : Prof. J. Marchand-Brynaert ULB : Prof. E. Goormaghtigh - F. Homblé

July v071114BIOSENTECH sa8 The academic partners  More than 60 scientists  More than 10 patents  Several hundred scientific publications  Numerous international partnerships on all continents

July v071114BIOSENTECH sa9 A multidisciplinary team … Modification of the aliphatic chain for the receptors anchorage (UCL ) Binding monofunctional molecule (UMH ) IR detection (ULB ) Coverage rate evaluation and quality optimization (UMH-ULB )

July v071114BIOSENTECH sa10 …With industrial partners  Joël Demarteau  Founder and CEO of a company specialized in electro- mechanical systems.  Inventor of the « waves ball ».  Co-founder of several spin-off  Marc Van Ossel  Former Senior VP of large industrial multinational companies  Business Angel  Consultant in industrial strategy

July v071114BIOSENTECH sa11 Objectives :  Developing a new technological platform of multipurpose, high performance biosensors for a broad range of applications.  Functionalizing the platform for specific, bespoke requests and needs.

July v071114BIOSENTECH sa12 Biosensors : detection principles Molecular recognition : Molecular recognition : enzymes, antibodies, microorganisms, cells Transduction : Transduction : electro active substance, pH modification, heat, light, mass modification Signal Transduction Detection Device Molecular Recognition User

July v071114BIOSENTECH sa13 IR Beam Ligands Receptors Binding molecules Principe of multipurpose biosensor Direct method Liquid mobile phase: Solvent + ligands in solution Optical element Ge Linked receptors to the biosensor substrate interacting with ligands Infrared detection Leading to quantive informations concerning: - the quantity of bound ligands - the nature of ligands - the conformational transitions

July v071114BIOSENTECH sa14 IR Beam Principe of multipurpose biosensor Indirect method Liquid mobile phase: Solvent + ligands in solution The secondary receptors which are linked to the primary receptors will interact with the ligands Ligands or Primary or Secondary Receptors Binding molecule Optical element Ge Infrared detection Leading to quantive informations concerning: - the quantity of bound ligands - the nature of ligands - the conformational transitions

July v071114BIOSENTECH sa Publication : 2007

July v071114BIOSENTECH sa Surface Chemical Modification of Optical element for Spectroscopic detection of molecules and organic components", –WO 02/ – CA US AU Devices for spectroscopically monitoring the conformation and the reactivity of ligand/receptors – EP World class patents

July v071114BIOSENTECH sa17 Benefits of the BIA-ATR technology  Offers detection possibilities in complex environments  Offers chemical signature of the molecule and/or of its anchoring  Offers high speed and high throughput for:  The manipulation of samples  For the functionalization of biodetection.

July v071114BIOSENTECH sa18 Other benefits of the BIA-ATR technology 1. A very high sensitivity 2. The possibility to detect small molecules 3. The possibility to identify the nature of ligands 4. The detection of chemical reactions 5. The identification of dynamic measures and the determination of binding constants 6. The possibility to identify the conformational response of the receptor

July v071114BIOSENTECH sa19 Other benefits of the BIA-ATR technology quality of FTIR spectrometers  significant absorbance ~10 -5, i.e. a fraction of a mono molecular layer Example: Example: mono molecular OTS layer 1.Very high sensitivity 1.Very high sensitivity We can see a well drawn spectrum for just a mono molecular layer

July v071114BIOSENTECH sa20 2. The possibility to detect small molecules 2. The possibility to detect small molecules the consequence of this high sensitivity is that this technology can detect the fixation of very small molecules on a receptor Example Example: fixation of biotin on avidine The biotine is already detected for concentrations as low as 10 M -12

July v071114BIOSENTECH sa21 3. The possibility to identify the nature of ligands 3. The possibility to identify the nature of ligands The infrared spectrum provides an ID of the chemical nature of the molecule  identification of the anchored molecule Example Example: we can see the difference between the proteins structure fixation of the factor VIII on PS fixation of streptavidine on PE-Biotin  -sheet And  -helix

July v071114BIOSENTECH sa22 4. Detection of chemical reactions 4. Detection of chemical reactions chemical reactions modify the spectrum and for that reason these one can be detected Example: Example: reaction of rabeprazole with gastric ATPase We can see that the spectrum before the reaction is different than the spectrum after this one

July v071114BIOSENTECH sa23 5. The identification of dynamic measures and the determination of binding constants 5. The identification of dynamic measures and the determination of binding constants Quick response of the detector  modulation of the flux composition Example: Example: fixation of ATP on gastric ATPase  Km It is possible to see when a small phosphate is anchored on the big protein and when it is taken down from the big molecule and we can know the binding constant Km min cm

July v071114BIOSENTECH sa24 6. The possibility to identify the conformational response of the receptor 6. The possibility to identify the conformational response of the receptor The infrared spectrum of the proteins is a signature of their structure. The conformational response of the receptor can be an important indicator of the ligand’s action on its receptor. Example: Example: gastric ATPase Change of the secondary structure Less β-sheet More random structure We can see that there is a spectrum difference when gastric ATPase is in contact with NaCl and with KCl

July v071114BIOSENTECH sa25 Contacts BIOSENTECH Address:Rue Pieds d'Alouette NANINNE (Belgium) Address:Rue Pieds d'Alouette NANINNE (Belgium) Tel: Tel: Fax: Fax: WEB: WEB: