Category: Student Spotlight

Background

After obtaining my Bachelor of Science degree in Mechanical Engineering at National Chung Hsing University (NCHU) in Taiwan, I joined Dr. Gale’s lab in 2009 to develop refilling tools in accordance with an intraocular capsule drug ring (CDR) for age-related macular degeneration (AMD) treatment.  I received my Master of Science degree in Mechanical Engineering at the University of Utah in May 2011 and continued to work on various kinds of medical devices and analyzed their efficacy.  I plan to obtain my PhD degree in Mechanical Engineering in 2013.

In addition to research, I like to hit the slope and get on road trips.

Contact: farmer.lin@utah.edu

Research

My research interest is to define and solve clinical problems using engineering approaches, especially BioMEMS and MEMS.  I work closely with Medical Doctors in both Ophthalmology and Reconstructive Surgery.

<PhD’s research>

PLGA drug-delivery nerve conduits for nerve regeneration

Peripheral nerve injuries affect about 3% of trauma patients and require special bridging techniques if the gap is greater than 1-2 cm.  In this work, an approach for repairing peripheral nerve gaps using a poly(lactic-co-glycolic acid) (PLGA) drug-delivery nerve conduit filled with either bovine serum albumin (BSA) or nerve growth factor (NGF) is described.  Since these two diffusion experiments share the same design, this paper only reports the design, fabrication, testing and discussion of several PLGA nerve conduits filled with four different dosages of NGF (n=3/group) for a 20 day in vitro drug release study.  NGF is stored in the space between two concentric PLGA tubes and is released through a polyethersulfone filter attached to a 0.8mm by 0.2mm window on the inner PLGA tube.  The conduits were filled with one of four different combinations (n=3/group): 1) 0.1mg/mL NGF with 25mg/mL polyvinyl alcohol (PVA), 2) 0.1mg/mL NGF with 12.5mg/mL PVA, 3) 0.05mg/mL NGF with 25mg/mL PVA, and 4) 0.05mg/mL NGF with 12.5mg/mL PVA.  A sealing test (with 0.1mg/mL NGF and 25mg/mL PVA) was added to verify the sealing of the device, and a release test with no PVA was used to compare the NGF release rate in the absence of PVA.  In the BSA diffusion experiment, these PLGA nerve conduits could deliver 8.8 or 4.3mg BSA (~98% and 48%, respectively, of the total loaded dose) in a 171 hour period.  A later study showed that these PLGA nerve conduits could also deliver NGF, which can promote axon growth, at an average rate of 32ng/day over a 20 day period.  It shows that the sample without PVA has the highest release rate of 5.69%/day, and the sample has higher NGF concentration and lower PVA concentration has the optimal release rate of 2.38%/day over a 20 day period.  Bioactivity tests using chick dorsal root ganglion also confirm the sample collected after 20 days can still promote axon growth.

 

New approaches to bridge nerve gaps: Development of a novel drug-delivering nerve conduit

Contemporary bridging techniques for repairing nerve gaps caused by trauma require autologous nerve grafts, which are difficult to harvest and handle and result in significant donor site deficit. Several nerve conduits with axon growth-enhancing potential have been proposed, developed and tested over the past fifteen years. In this work, prototypes of a nerve conduit designed to bridge large nerve gaps (≥10mm) end-to-end were incorporated with concentric drug reservoirs for constant and controlled drug delivery to enhance axon growth. These devices were designed, fabricated and tested in vitro in amber glass vials with bovine serum albumin in order to determine the drug release kinetics for future application. Our devices have shown the capability to deliver the drug of interest over a 6-day period.

 

Intraocular pressure sensors: New approaches for real-time intraocular pressure measurement using a purely microfluidic chip

Periodic monitoring of intraocular pressure (IOP) values is crucial in glaucoma treatment. Since current measuring techniques lack accuracy, a microfluidic device is designed, tested and discussed in this work to explore unpowered IOP sensing capability. This device achieves a 0.061mm/mmHg sensitivity for lower pressures and a 0.667mm/mmHg for higher pressures.

 

<Master’s research>

Refilling mechanism to stabilize a free-floating intraocular capsule drug ring (CDR)

In 2009, 15.1 million cataracts were extracted and replaced with intraocular lenses (IOL). Because IOLs are smaller in diameter than natural lenses, there is real estate in the periphery of the IOL unused. The Capsule Drug Ring (CDR) is an implantable device that stores and releases drug inside the capsular bag in this unused periphery. The objective of the refilling mechanism is to stabilize a free-floating body to allow penetration through the refilling ports. Two ports at each ends of the CDR allow the reservoir to be refilled with bevacizumab (Avastin) every six months to one year. Avastin is an antivascular endothelial growth factor which inhibits blood vessel proliferation. The maximum width of the refilling mechanism is about 23 gauge. The 23 gauge refilling device will constitute an inner 30 gauge needle which will penetrate the ports, injecting Avastin into the CDR reservoir. Lasso loop is applied to grab and fix CDR while refilling. There are several structures on the CDR such as lasso guiding loop and protection wall to allow lasso grabbing mechanism. We developed several shapes of loop to ease the refilling process since it will be operated by normal ophthalmologist.

 

Publications

1. Keng-Min Lin, Bruce Gale, Himanshu Sant, Jill Shea, William Sanders, Christi Terry and Jay Agarwal. BSA-Filled PLGA nerve conduits for potential applications in nerve regeneration. The BMES 2013 Annual Meeting. SEP 2013
2. Keng-Min Lin, Himanshu J. Sant, Balamurali K. Ambati and Bruce K. Gale. Intraocular pressure sensors: New approaches for real-time intraocular pressure measurement using a purely microfluidic chip. The 16^th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS). OCT 2012. Paper M.7.156
3. Keng-Min Lin, Himanshu J. Sant, Jayant Agarwal and Bruce K. Gale. New approaches to bridge nerve gaps: Development of a novel drug-delivering nerve conduit. 34^th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (IEEE EMBS). AUG 2012. Paper WeB 15.7
4. Keng-Min Lin, Corey J. Bishop, Himanshu J. Sant, Balamurali K. Ambati and Bruce K. Gale. Refilling mechanism to stabilize a free-floating intraocular capsule drug ring (CDR). 2010 AIChE Annual meeting poster section: Engineering Fundamentals in Life Science. NOV. 2010. Paper 568v.
5. Keng-Min Lin, Ian Harvey and Brian Baker. Design and actuation of SEM-energized MEMS levitation trains. 2010 Nano Utah Conference: Poster section. OCT. 2010.

Unpublished work

1. Keng-Min Lin, Himanshu Sant, Corey Bishop, Nathan Gooch, Balamurali Ambati and Bruce K. Gale. Design, manufacturing and testing of an intraocular refillable capsule drug ring and its refilling tools. Biomedical Microdevices (in preparation)
2. Keng-Min Lin, Himanshu Sant, Balamurali Ambati and Bruce Gale. An unpowered microfluidic intraocular pressure sensor. Lab on a Chip (in preparation)
3. Keng-Min Lin, Bruce Gale, Himanshu Sant, Srinivas Chennamaneni, Michael Burr, Balamurali Ambati and Jay Agarwal. PDMS drug delivery devices: potential application in nerve regeneration. Biomedical Microdevices (in preparation)
4. Keng-Min Lin, Bruce Gale, Himanshu Sant, Jill Shea and Jay Agarwal. Drug-delivery PLGA conduits for nerve regeneration. Proceedings of National Academy of Sciences in USA (PNAS) (in preparation)

Thesis

1. Keng-Min Lin, Refilling mechanism to stabilize a free-floating intraocular capsule drug ring. Master’s Thesis, University of Utah, May 2011.

Patent pending

1. Keng-Min Lin, Ian Harvey and Brian Baker. SEM actuated levitation devices. (US 20120091336A1)
2. Jay Agarwal, Bruce Gale, Himanshu Sant and Keng-Min Lin. Methods and devices for connecting nerves

Funded by the Department of Defense, my specific research aim is to develop an electrochemical method and assay for the detection of viruses in water and food samples. This research is part of a multi-pathogen detection platform directed by the talented Dr. Himanshu Sant. We are passionate about providing innovative solutions to this highly challenging and high impact worldwide issue.

I am invested in other research that includes a microfluidic system that enables high throughput, non-destructive genotyping of live zebrafish embryos. This technology led to the successful startup company wfluidx. Other research includes a minimally invasive glaucoma surgery implant device. This device, developed with renowned doctors Bala Ambati and Alan Crandall, has now been in licensed development with promising results.

Other notable research includes an interstitial fluid collection device for chronic pain management and experience in the design and fabrication of microfluidic chips and systems across a broad range of materials and applications. I’ve held key leadership roles in collaboration and consulting for microfluidic research by groups located at the University of Utah, MAYO Clinic, Becton Dickenson, Broad Institute, UC Berkley, Harvard, and Boston University among others.
It continues to be an absolute pleasure as well as an invaluable experience to work with and be mentored by Dr. Bruce Gale.

Linkedin: www.linkedin.com/in/christopher-j-lambert