Introduction to BioMEMS & Medical Microdevices, BMEn 5151
Course Introduction
Prof. Steven S. Saliterman, http://saliterman.umn.edu/
Topics
1) Nano- and Microfabrication of Silicon & Polymers.
2) Microfluidics - Design, Transport, and Electrokinetics.
3) Biosensors, Microsensors and Nanotechnology.
4) Lab, Organ and Body-on-a-Chip Systems.
5) Microactuators & Drug Delivery.
6) Clinical Laboratory Medicine & Micro Total Analysis Systems.
7) Genomics and Proteomics - Gene and Protein Chips.
8) Clinical Applications & Point-of-Service Devices.
9) Biocompatibility, FDA & ISO 10993.
10) Packaging, Power, Data & RF Safety.
Steven S. Saliterman
BioMEMS…
Biomedical Micro Electro-Mechanical Systems.
Devices or systems, constructed from nano or
microfabrication, that are used for processing, delivery,
manipulation, analysis or construction of biological and
chemical materials.
At least one dimension is from ~100 nm to 200 µm.
Incorporating new materials and an understanding of the
nano- microenvironment, and biocompatibility.
Harnessing any phenomenon that accomplish work at the
microscale.
Includes research and laboratory tools, and point-of-
service, therapeutic and implantable devices.
Steven S. Saliterman
Nano- and Micro Realm
Steven S. Saliterman US Department of Energy, Office of Science 2019
Silicon Nano- and Microfabrication
Steven S. Saliterman
Nano-Bio Lab Facility…
Steven S. Saliterman
Polymer Microfabrication
Image courtesy of Marco, CD Image courtesy of Bertsch A.
Image courtesy of Jaehoon Chung & Euisik Yoon
Steven S. Saliterman
Microfluidics
Science of fluid behavior in microchannels.
In lab-on-a-chip and µTAS devices, the following
features are often seen:
Microchannels,
Microfilters,
Microvalves,
Micropumps,
Microneedles,
Microreserviors,
Micro-reaction chambers.
Image courtesy of Micronit
Steven S. Saliterman
Rapid Prototyping Systems in PDMS…
Image courtesy of Sylgard
Duffy DC, McDonald JC, Schueller OJA, Whitesides GM. Rapid prototyping of microfluidic
Steven S. Saliterman systems in poly(dimethylsiloxane). Analytical Chemistry. 1998;70(23):4974-4984.
Large-Scale Integration…
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Left) Melin J, Quake SR. Microfluidic large-scale integration: The evolution of design rules for biological
automation. In: Annual Review of Biophysics and Biomolecular Structure. Vol 36.2007:213-231.
Right) Liu J, Hansen C, Quake SR. 2003. Solving the “world-to-chip” interface problem with a microfluidic matrix.
Steven S. Saliterman Anal. Chem. 75(18):4718–23
Electrokinetics…
Electrokinetic phenomenon:
Electroosmosis
Electrophoresis
Dielectrophoresis
An important tool for moving, separating and
concentrating fluid and suspended particles.
Hossan MR, Dutta D, Islam N, Dutta P. Review: Electric field driven
Steven S. Saliterman pumping in microfluidic device. Electrophoresis. 2018;39(5-6):702-731.
Transport Processes…
Fluid Mechanics:
Laminar flow,
Fluid kinematics.
Mixing by diffusion, special geometries and mechanical
means.
Effects of increased surface area-to- volume as
dimensions are reduced in microfluidic channels.
Steven S. Saliterman
Biosensors & Nanotechnology
Luka G, Ahmadi A, Najjaran H, et al. Microfluidics Integrated Biosensors: A Leading Technology
Steven S. Saliterman towards Lab-on-a-Chip and Sensing Applications. Sensors. 2015;15(12):30011-30031.
Microsensors…
Kottapalli AGP, Shen Z, Asadnia M, et al. Polymer MEMS sensor for flow monitoring Dinh T, Phan H, Qamar A, et al. Environment-friendly wearable
in biomedical device applications. 2017 IEEE 30th International Conference on thermal flow sensors for noninvasive respiratory monitoring. 2017
Micro Electro Mechanical Systems (MEMS); 22-26 Jan. 2017, 2017. IEEE 30th International Conference on Micro Electro Mechanical
Systems (MEMS); 22-26 Jan. 2017, 2017.
Steven S. Saliterman
Nanotransducers…
Nanoparticle transducers:
Quantum dots.
Carbon dots.
Nobel metal nanoparticles.
Lanthanide nanoparticles.
Label free transducers - rather than
relying on attachment to reporter
labels for signal transduction:
Nanowires
Nanotubes
Nanocantilevers
Mesoporous membranes.
Hildebrandt N, Spillmann CM, Algar WR, et al. Energy Transfer with Semiconductor Quantum Dot Bioconjugates: A Versatile
Steven S. Saliterman Platform for Biosensing, Energy Harvesting, and Other Developing Applications. Chemical Reviews. 2017;117(2):536-711.
Lab-on-a-Chip
Tran, S.B.Q., Marmottant, P., Thibault, P., 2012. Appl. Jubery, TZ and P. Dutta. A new design for efficient
Phys. Lett., 101. dielectrophoretic separation of cells in a microdevice .
Electrophoresis 2013, 34, 643–650
Schutte J, Freudigmann C, Benz K, Bottger J, Gebhardt R and Stelzle M 2010 A method for
Steven S. Saliterman patterned in situ biofunctionalization in injection-molded microfluidic devices Lab Chip 10 2551–8
Detection Strategies…
Image courtesy of Micronit
Image courtesy of Olympus
Gencoglu, A and Adrienne R. Minerick . Electrochemical detection techniques
in micro- and nanofluidic devices. Microfluid Nanofluid (2014) 17:781–807
Steven S. Saliterman
Organ-on-a-Chip…
Reproducing the Tissue Barrier Function
PDMS membranes. Perfusion bioreactor and synthetic microfabricated scaffold.
a) Huh, D. et al. Reconstituting organ- level lung functions n a chip. Science 328, 1662–1668 (2010).
b) Zhang, B. et al. Biodegradable scaffold with built- in vasculature for organ- on-a- chip engineering and direct surgical anastomosis. Nat.
Steven S. Saliterman Mater. 15, 669–678 (2016).
From Organ to Body-on-a-Chip…
Body-on-a-Chip
Lung-on-a-Chip
“Organ Coupling”
Zhang B, Korolj A, Lai BFL, Radisic M. Advances in organ-on-a-chip engineering.
Steven S. Saliterman Nature Reviews Materials. 2018;3(8):257-278.
Clinical Laboratory Medicine
http://www.umass.edu/microbio/rasmol/padlan.htm Laposata M, Laboratory Medicine, Clinical Pathology in
the Practice of Medicine, ASCP Press, Chicago (2002).
Steven S. Saliterman
Microactuators and Drug Delivery
Steven S. Saliterman Sutradhar KB, Sumi CD. Implantable microchip: the futuristic controlled drug delivery system. Drug Deliv. 2016;23(1):1-11.
Genomics, Proteomics and µTAS
Esfandyarpour R, Esfandyarpour H, Harris JS, Davis RW. Simulation and fabrication of a new novel 3D injectable biosensor for
Steven S. Saliterman high throughput genomics and proteomics in a lab-on-a-chip device. Nanotechnology. 2013;24(46):465301-465301.
Clinical Applications
Neurovent P-tel implantable piezoresistive ICP monitoring iSTAT cartridge and handheld system. Image
sensor. Telemetric reader is placed over intact skin and courtesy of Abbot Laboratories.
collects intracranial pressure readings. Image courtesy of
Raumedic, Inc.
Steven S. Saliterman
Biocompatibility, FDA & ISO 10993
Image courtesy of Voskerician, G. Image courtesy of NAMSA
Barkam, S, et al. Fabricated micro-nano devices for in vivo and in vitro
biomedical applications. WIREs Nanomed Nanobiotechnol 2013, 5:544–
568
Barkam, S, et al. Fabricated micro-nano devices for in vivo and in vitro biomedical
Steven S. Saliterman applications. WIREs Nanomed Nanobiotechnol 2013, 5:544–568
Packaging, Power, Data & RF Safety
Lab-on-a-chip / µTAS
Interconnections.
Biocompatibility with specimen.
Reagent addition and waste removal.
Date of expiration.
Other BioMEMS/MEMS devices
Sensors and actuators.
Point-of-care and human interface.
Implanted devices
A device that is either partly or totally
introduced, surgically or medically, into
the human body and is intended to
remain there after the procedure. Image courtesy of Valtronics
Biocompatibility with the body.
Power and wireless communication.
Microsurgical instruments.
Steven S. Saliterman
Energy Harvesting…
Lueke, J. and W.A. Moussa. MEMS based power generation techniques for implantable biosensing applications. Sensors 2011, 11, 1433-1460
Steven S. Saliterman Hannan, MA et al. Energy harvesting for implantable biomedical devices: issues and challenges. BioMedical Engineering OnLine 2014, 13:79
Team Projects
Purpose: To study further a particular bioMEMS concept or device
that you are interested in.
Format: Team presentation of 4 students as a 20 minute Power
Point® presentation at the end of the semester. Submitting a
paper is not required, although you may wish to distribute a
handout. A brief class discussion will follow each talk.
Description: Propose a new bioMEMS device, or expand upon a
previously published device or useful methodology. Discuss the
purpose of your concept, and if appropriate, the theory (what
principles are at work), fabrication (materials and techniques),
testing, limitations, and biocompatibility of your device.
Steven S. Saliterman
Projects 2020…
A BioMEMS Implant to Treat Spinal Cord Injuries
A Mobile Neurostimulation Electrode
Assay of Testicular Germ Cell Tumors
COVID-19 High Throughput Serology Chip
Detection of the SARS-COV-2 Using SPR
Heart-on-a-Chip
Microfluidic Device for Cancer Diagnosis & Monitoring of
Metastasis
Organ-on-a-Chip Model for COVID-19
Piezoelectric Patch & Pump for Drug Delivery in Tumors
Quantum Dots for Auditory Brainstem Prosthesis
Real Time Drug Monitoring Peritoneal Dialysis
Steven S. Saliterman
Summary
1) Nano- and Microfabrication of Silicon & Polymers.
2) Microfluidics - Design, Transport, and Electrokinetics.
3) Biosensors, Microsensors and Nanotechnology.
4) Lab, Organ and Body-on-a-Chip Systems.
5) Microactuators & Drug Delivery.
6) Clinical Laboratory Medicine & Micro Total Analysis Systems.
7) Genomics and Proteomics - Gene and Protein Chips.
8) Clinical Applications & Point-of-Service Devices.
9) Biocompatibility, FDA & ISO 10993.
10) Packaging, Power, Data & RF Safety.
Steven S. Saliterman
