Dynamic Light Scattering Measuring Platelet Quality and Bacterial Contamination Elisabeth Maurer, Ph.D. Canadian Blood Services, R&D Vancouver UBC, Department of Pathology and Laboratory Medicine UBC Centre for Blood Research

2 of 17 The Problem Platelet transfusions used to treat and/or prevent bleeding Number of platelet transfusions produced per year: Canada: 300,000 United States: 2,000,000 Europe: 2,500,000 Platelets are sensitive to stress (e.g., cold damage) Activated platelets do not help patients. Storage at 22ºC to prevent cold damage Increased risk for bacterial growth Shortages - addressed by increasing donor recruitment

3 of 17Outline The Problem Clinical Situation Solving the problem Novel Approach Data Acquisition DLS-PM score The Invention Technology Background The DLS-PM Accomplishments Clinical Results Summary Other Technology Accuracy, Sensitivity

4 of 17 No non-invasive in vitro test available  Tested inventory cannot be transfused  Platelet quality / bacterial testing cannot be mandated Good outcome  Assumption: good platelets Bad outcome  Assumption: bad platelets Transfusion outcome serves as retrospective platelet quality indicator. The Problem: Clinical Situation

5 of 17 The Problem: Summary at least 20% discard rate Additional 10% discarded after testing (invasive technology)  Unknown quality of transfused platelets $1,000 / transfusion  Worldwide loss of at least 1 billion dollars per year In summary:  Unknown platelet quality is a safety issue  Discarded platelet transfusions are a financial burden

6 of 17 Multi-dimensional quality measurement DLS-PM detects discoid platelets activated platelets microparticles bacteria at the same time Solving the Problem: Novel Approach

7 of 17 88% 88% Platelets /- 173 nm nm 1200 nm Solving the Problem: Data Acquisition BACTERIA (if present) 500 +/- 60 nm 500 nm 10% 10% Microparticles 54 +/- 7 nm Transfus Med Rev 2007; 21(4):295

8 of 17 Solving the Problem: DLS-PM Score High DLS-PM score Medium DLS-PM score Low DLS-PM score Most fresh platelet transfusions Most platelet transfusions until day of storage Temperature Response Microparticles Platelet Size  

9 of 17 The Invention: The Dynamic Light Scattering Platelet Monitor (DLS-PM) The Invention: The Dynamic Light Scattering Platelet Monitor (DLS-PM) Non-invasive Small sample volume Fast Inexpensive Phys Med Biol 2006; 51:3747

10 of 17 The Invention: Accomplishments May - Aug 2007 First clinical pilot study 2006 Validation Latex beads Platelets Bacteria Proteins Nanoparticles Sept 2005 First generation instrument April 2005 First prototype Nov 2003 Proof of principle

11 of 17 Correlation of DLS-PM results with in vivo transfusion outcome  49 patients enrolled, 160 transfusions  Location: Vancouver General Hospital  Data collected:  DLS-PM scores  1h and 24h patient platelet counts transfusion merit  transfusion merit The Invention: Clinical Results DLS-PM score vs. transfusion merit

12 of /160 transfusions 65 % Transfusion merit correlates with DLS-PM score The Invention: CoDIVO Results

13 of 17 INVASIVE No single instrument can determine platelet quality and function in multiple dimensions Impedance Optical Immunofluorescence Hematology analyzers cannot assess bacterial contamination  BacT/Alert required Sysmex XE-2100 Kobe Advia 120 Siemens FacsCanto II BD Other Technology: Platelet Counting BacT/Alert bioMérieux

14 of 17 Sysmex XE2100 Optical platelet count + 1-micron beads Other Technology: Accuracy Without beads With beads Beads

15 of 17 Optical methods - Low sensitivity Especially for platelet counts < 15,000 /  L Other Technology: Sensitivity Segal et al. BrJ Haematol 2005; 128:520.

16 of 17  Mandated technology for hospitals / blood banks  10,000 hospitals / blood banks in North America  Extended shelf life - reduced outdate-discard rate  Patient safety  Monitor manufacturing processes Summary DLS-PM: The only technology for noninvasive bacterial detection and platelet quality testing at the same time

Thank You! Keddie Brown, iCapture Audrey Labrie, CBS Dr. Mark Scott, CBS Dr. Kate Chipperfield, VGH Cheryl Pittendreigh, CBS Nobu Kitamura, CBS CBS Intellectual Property, Intramural and Bridge Funding Keddie Audrey Nobu Cheryl