Fabrication of Biomedical Components & Systems Using Ink Jet Microdispensing

Transcription

1 Fabrication of Biomedical Components & Systems Using Ink Jet Microdispensing IEEE Engineering in Medicine and Biology Dallas Chapter Seminar David Wallace Technologies, Inc. February 10, 2012

2 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

3 Continuous Mode Ink-Jet Jet of water breaking up into 120 m droplets at 20kHz 90 m droplets of 63/37 Sn/Pb solder being formed at 8kHz

4 Continuous Mode Ink-Jet µm droplets 10kHz - 1MHz Transducer Charge Electrode High Voltage Deflection Plates Substrate Motion out of Plane Orifice Pump Charge Driver Substrate Driver Fluid Supply Character Data Catcher

5 Continuous Mode Ink-Jet 70μm diameter breaking up into 140μm droplets at 40kHz

6 Demand Mode Ink-Jet µm droplets, 0-25kHz Transducer (piezo or heater) Orifice Substrate Substrate Motion Driver Character Data Fluid at Ambient Pressure Data Pulse Train

7 Demand Mode Ink-Jet 60µm droplets of alcohol, 4kHz

8 Why Ink-Jet? Additive Data-driven directwrite flexible, no tooling Non-contact No crosstalk between processes Wide range of materials biological, metals, polymers, fluxes wide operating temperature range -110ºC to 370ºC High resolution, high rate (throughput) 15µm - 120µm drops 1Hz-1MHz

9 Why Additive? Low cost for expensive materials Examples: biologicals, display materials, precious metals, etc. Environmentally friendly Less waste, no solvents* Thick films Range of materials Fewer process steps Low cost

10 Ink-Jet as a Tool for Not a new idea! Manufacturing Lewis for direct write of materials: 1967 Vest, et al. for hybrid microelectronics: 1983 Kimura, et al. for ISFET biosensors (glucose): 1988 Hayes, et al. for medical diagnostics: 1988 Southern for DNA synthesis: 1988 Wallace for electronics manufacturing: 1989

11 Ink-Jet as a Tool for Manufacturing Printed Electronics ( 1988) Resist Printing Cu circuit after etch Supported by NSF Grant # ISI um lines on 250 um centers

12 Ink-Jet as a Tool for Manufacturing Printed Medical Diagnostics ( 1985) Blood typing (four colors ) antibodies Siemens printhead

13 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

14 Printed Diagnostics Antibodies for Diagnostics Patterns and Gradients Four printed reagents, anti A, B, RH+ & control Two printed reagents, hcg & control

15 Printed Diagnostics Microspot Multi-reagent Assays Miscrospot Assays less reagen ($), more sensitivity, less waste DNA: 100µm spots in HIV immunoassay. (Boehringer Roche) Protiens: 100µm spots of biotin labeled cytochrome C printed at seven concentrations.

16 Sensors Indwelling Brain Probe Implantable (brain) microelectrode with four 20x60µm electrochemical measurement sites on a ceramic substrate, coated with a glutamate oxidase enzyme and overcoated with gluteraldyhyde, a fixative; two of the four electrodes have been coated with a fluorescent dye.

17 Sensors Chemo-Resistive 250µm diameter dual electrode spiral in a 350µm SU-8 well; sensor element printed with 225 nominally 30pl drops of solution containing gold-thiolate nanoparticles; multiple sensing and reference elements on a 2.65mm die; C, sensor device in a TO-5 package. Sensor printed in package. Carnegie-Mellon

18 Sensors Preconcentrator MEMS-based hotplate coated with a viscous chemoselective polymer, t=3µm. Left = uncoated, right = coated. NRL 400 m

19 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

20 Localized Drug Delivery Systemic drug delivery: Oral, intravenous Delivered to entire body, large potential for side effects Local drug delivery Larger range of drugs, dosages, delivery rate possible with fewer side effects

21 Drug Eluding Stents

22 Drug Eluding Stents Stents Implantable medical device to support artery after angioplasty (clearing of clogged coronary artery) Goal is to avoid open heart (bypass) surgery 30% of patients have artery close up again (restenosis) due to body s reaction to stent Drugs applied to stent to prevent restenosis

23 Drug Eluding Stents Typical stent: 1mm diameter, 15mm long, µm wide structural features Coating protocols Coat all features Coat outside only Fill local features (wells)

24 Drug Eluding Stents Vascular stent, 1.0mm diameter, 100µm struts coated with two fluorescent dyes; actual stents coated with antirestenotic drugs.

25 Drug Eluding Stents Vascular stent, 100µm struts with drug delivery wells filled with antirestenotic drugs and polymer to control release.

26 Drug Loaded Microspheres Localized delivery at tumor site Less toxicity Better drug bioavailability

27 Drug Loaded Microspheres Monodispersed 100µm polymer spheres loaded with anti-cancer drug Cumulative drug amount [ g ] Day

28 Drug Loaded Microspheres Ink-jet method Conventional method

29 Transdermal Drug Delivery Advantages of Transdermal Drug Delivery Steady blood-level profile of the drug Reduced systemic side effects Improved patient compliance Improved efficacy User-friendly Convenient Painless

30 Transdermal Drug Delivery Current Methods Patchs Micro-needles

31 Transdermal Drug Delivery Ink-Jet printing (filling) of microneedles Multiple drugs, multiple materials per well, no waste or crosstalk Array of conical holes similar to an array of hollow microneedles. The holes are conical with a top diameter of 90µm and a bottom diameter of 30µm. Fluorescent dye solution was dispensed in the odd rows with 14 drops in the 1st row, 12 drops in the 3rd row and 8 drops in the 5th row.

32 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

33 Tissue Engineering Scaffolds, Biomolecules, Cells 3-D biosorbable polymer structures embedded with growth factors (proteins) & cells. 1mm diameter polymer nerve guidance conduits, biosorbable polymer; simulated gradient loading of bioactive molecule (right) Human liver cells; no decrease in viability after jetting

34 Tissue Engineering Skin Regeneration for Burn Wound Repair 4 year, $8M US Army project with Wake Forest IRG Year 1 Concept

35 Tissue Engineering Skin Regeneration for Burn Wound Repair 4 year, $8M US Army project with Wake Forest IRG Year 4 Concept

36 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

37 Ink-Jet in Instrumentation Vapor Phase Instruments Aroma generation, vapor calibrators, olfaction testing (medical diagnostics) Protein structure Protein crystalization, separation, and analysis Microchemistry DNA & protein synthesis,

38 Vapor Calibrator Ink-jet devices produces small, precise & variable fluid mass dispense onto heater. Fluid mass is vaporized in <1s Gas stream carries vapor to detector. Applications: calibration of detectors for explosives, drugs, chemical agents, biological agents

39 Vapor Calibrator Fluid Drops Heated Wall Jet Air Flow Sensor Under Test Vaporizer (Heater)

40 Vapor Calibrator Bench-top prototype (lab, QC) and handheld (field) concept

41 Vapor Calibrator Data from the US National Institute for Standards and Technology Detector response Number of drops Detector response Amount of TNT dispensed [femtograms] Number of drops

42 Olfaction Diagnostics Early onset detection of neurodegenerative diseases (e.g. Alzheimer's) 1000 # of Drops DEFICIENT THRESHOLD Detected Not Detected Detected Not Detected NORMAL THRESHOLD 1 Test #

43 Aroma Generation Personal aroma, game, marketing, and virtual reality applications. 8 channel personal aroma generator 16 channel aroma kiosk

44 Protein Crystalization Protein structure, and thus function, determined via XRD of protein crystals Ink-jet used to increase number of test conditions / decrease time, & minimize rare materials usage.

45 Proteomic Analysis Scanning of tissue for distribution of protiens (MALDI mass spec) To MALDI sinapinic acid ink-jet deposited onto a rat liver tissue section (120μm spots)

46 Microchemistry In situ DNA synthesis of microspot arrays, down to 30µm spot size. In situ digestion of proteins for PMF. matrix water trypsin, etc. To MALDI

47 Microchemistry In situ DNA synthesis of microspot arrays, down to 30µm spot size. In situ digestion of proteins for PMF.

48 µdrop Assisted Laser Surgery Painless skin poration Diagnostics on interstitial fluid (glucose) Ablation of hard tissue Dental and orthopedic applications (no anesthesia) 1mm

49 Agenda Background on Ink-Jet Technology Printed Diagnostics & Sensors Localized Drug Delivery Regenerative Medicine Ink-Jet Based Instruments Ink-Jet Based Fabrication Equipment

50 Jetlab Printing Platforms