Integrating Biology, Big Data and Technology in a Crucible of Enabling Health Solutions

From presidential recognition of The Kidney Project to coding moving images into the DNA of bacteria, Engineers at UCSF are making big moves.

Not all of UCSF’s excellent health engineers graduated from engineering schools. But those who did were attracted by UCSF’s health focus, grasping the opportunity of its unique strengths. Both professionals are bound by the desire to create meaningful and applicable forms and technologies that address people’s health and a lofty vision of human well-being. 

We need new and bold ideas; we need unfettered minds...

Dr. David Woods

UCSF Professor, Nov. 4, 1956

As Dr. Sunita Ho, bioengineer and Professor in the Department of Urology, School of Medicine, and in the Department of Preventive and Restorative Dental Sciences (PRDS), School of Dentistry says, “This is the reason I came to UCSF—to help people.”

Following is a sampling of UCSF’s continuing legacy of engineering achievements geared toward people’s health and well-being.

Droplet-based Microfluidic Technologies

Researcher/Team: Adam Abate

Diagram of microfluidic droplet cell sorting channels.

Microfluidics technology is the use of microdroplets of water (less than 1/10 the diameter of a human hair) as test tubes, which flow by in channels of inert oil at rates of about 1,000 droplets per second. By chaining together different microdevice components, the droplets can be used as tiny “test tubes” for performing chemical and biological reactions. This allows multiple, independent reactions to take place at the rate of thousands per second, while using minuscule amounts of total reagent. High-throughput sequencing precisely and super-rapidly analyzes the biological contents of those microdroplets—such as the genetic blueprints (genomes) and activity of millions of individual cells.

Single-Cell Analysis

SiC-seq (Single-Cell sequencing) is a single-cell microfluidic platform for sequencing the genomes of tens of thousands of cells simultaneously at low coverage. In this workflow, cells from a metagenomic sample are encapsulated in micron-scale hydrogels and individually lysed, tagmented, and merged with a microdroplet containing a unique nucleic acid barcode, which is spliced onto the cell’s genomic DNA via single overlap extension PCR. This innovation in single-cell sequencing technology enables low-coverage genome sequencing of tens of thousands of bacterial cells in a single experiment.

Printed Droplet Microfluidics 

The Printed Droplet Microfluidics (PDM) technology dispenses picoliter droplets and cells with complete, deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay. PDM technology is currently applied in metabolite screening, sequencing sample prep, and cell-cell interaction studies.


Systems, Compositions, and Methods for Local Imaging and Treatment of Pain

Researcher/Team: Drs. David Bradford and Jeffrey C. Lotz

A 3-D printed spine created from a clinical CT scan of a patient with a spinal deformity.

This invention of local imaging and treatment of pain pertains generally to imaging of tissues associated with skeletal joints. More particularly, it relates to the identification and/or characterization of localized factors associated with musculoskeletal pain using labeled markers and related imaging tools. The application includes a method for conducting a medical procedure on intervertebral discs in the spine of a patient who experiences back pain that originates from a damaged vertebral disc, particularly due to degenerative disc disease. The application also includes the therapeutic procedure adapted to the source of pain. The technology uses X-ray, MRI and ultrasound imaging systems configured specifically to locate pain factors.


Polymer Thin-film Intraocular Device

Researcher/Team: Tejal Desai, Bob Bhisitkul, Michelle Bloomer

A thin-film intraocular device made from polycaproloactone (PCL), a biodegradable polymer, that allows for zero-order release of two ocular hypotensive agents, timolol maleate and brimonidine tartrate, with intraocular pressure (IOP)-lowering effects for 3 months in vivo.

Learn more at UCSF Ophthalmology


Smart Diaphragm

Researcher/Team: Mozzi Etemadi 

The Smart Diaphragm is a low-cost, intra-vaginal device designed to detect preterm birth so that medical professionals can intervene if needed to improve pregnancy outcomes, especially in resource-deficit areas. The device is composed of a silicone vaginal probe, a sensor and a transmitter to relay the microstructural cervix tissue changes that precede pre-term labor. Data will be relayed daily to a server via a mobile app. If preterm birth risk elevates, an alert will be sent to both patient and clinician.


Hyperpolarized Molecular Probes and NMR-compatible Cell & Tissue Culture Bioreactors

Researcher/Team: John Kurhanewicz, Sarah Nelson, Dan Vigneron

The thorny issue of accurate characterization of prostate cancer in individual patients led Dr. Kurhanewicz and his collaborators to an extraordinary new molecular imaging technique utilizing hyperpolarized 13C labeled metabolic substrates that has the potential to revolutionize the way MR imaging is used in the risk assessment of prostate cancer patients. He led the first clinical trial of this technology at UCSF and is involved in three ongoing clinical trials investigating its clinical utility. In order to develop new hyperpolarized 13C labeled metabolic probes for cancer and other diseases, Dr. Kurhanewicz developed a device for direct Magnetic Resonance Imaging (MRI) of living patient derived tissues. 


Vesicoamniotic Shunt

Researcher/Team: Dr. Michael Harrison

The vesicoamniotic shunt is a pioneering double pig-tailed catheter to relieve urinary tract obstruction in utero for fetuses 18-32 weeks of gestational age to allow drainage of fetal urine. If the condition is left untreated, the obstruction can lead to kidney abnormalities and can be fatal for the fetus. The placement of the Harrison vesicoamniotic shunt in utero in 1981 became the first fetal surgery performed at UCSF.


Magnet-based Pediatric Technologies

Researcher/Team: Dr. Michael Harrison

Magnetic Mini Mover

The Magnetic Mini Mover is a device that treats sunken chest disorder. The device places a small magnet internally in the sternum while wearing an orthotic device with a magnet to gradually pull the chest to a normal position via the magnetic inside-outside connection.
 

Magnap Procedure

 
The Magnap procedure addresses obstructive sleep apnea by implanting a small magnet encased in titanium on a patient’s hyoid bone, which is attached to soft tissue in the neck that blocks the airway in obstructive sleep apnea. Just before bedtime, patients place a plate with a second magnet above the throat area, which opens up the airway by using the pull of the external magnet.
 

Magnamosis

 
Magnamosis is a novel form of anastomosis, or the stitching together of two previously unconnected tubes—for example, sewing together two pieces of the large intestine to create a detour around a bowel obstruction. The standard procedure is a surgical cut. Using magnamosis, a minimally invasive procedure, the surgeon places magnets on the inside of each of the intestine’s “loose ends” the surgeon wants to connect. The magnets snap together and cut off blood supply to the compressed tissue. This tissue, deprived of blood, dies. After five days, the dead tissue and the magnets fall inside the bowel and are excreted. Meanwhile, the connected tubes heal and form a healthy connection.
 

Magnetic Grow Rod

 
The Magnetic Grow Rod addresses scoliosis by using the magnetic-coupling technology to activate and lengthen and shorten an internal growing rod for treatment of scoliosis and for limb lengthening. 
 

Precise Patient Monitoring Solutions—Super Alarm

Researcher/Team: Dr. Xiao Hu

A dashboard view of SuperAlarm score and trend for patients and a drill-down view of alarms, vitals, and physiological waveforms.

To combat hospital staff alarm fatigue, Dr. Xiao Hu and his team are developing more precise algorithms that analyze streaming data from patient monitors and data from the electronic health record system. The Super Alarm integrates information across different data modalities and adds the temporal dimension to quantify a monitored patient’s risk of acute deterioration toward catastrophic events, such as cardiopulmonary arrest. This solution has been programmed into an easy-to-use, web-based platform that is at the final stage of tuning with real-time patient data before launching a prospective validation study and, eventually, clinical trials.


Smart Derm

Researcher/Team: Hanmin Lee

Earlier prototype of SmartDerm device with a tablet displaying the pressure readings at each end point, which update in real time. 

Smart Derm is a wound dressing that embeds a paper-thin grid of sensors that detects pressure at 16 different points. The sensors connect with a postage stamp-sized Bluetooth device which wirelessly feeds continuous pressure readings into a computer. A tablet displays pressure readings at each of the 16 points, colored green, yellow and red for low, medium and high pressure levels. As a patient moves or is turned, these pressure readings update in real time.

 

 


Multi-channel Cochlear Implant

Researcher/Team: Michael Merzenich, Robin Michelson, Robert Schindler, Patricia Leake, Mark White, Christoph Schreiner, Robert Shannon, et al.

The multi-channel cochlear implant (CI) has been a godsend for hundreds of thousands of totally deaf individuals. Most patients have recovered (or in the case of a deaf child, developed) nearly normal aural speech understanding with their implants. This work was controversial when Drs. Michelson and Merzenich initiated their collaboration on multi-channel CIs in the early 1970s. It culminated in one of the most sophisticated and effective implanted devices now applied in human medicine, the Advanced Bionics CI. As the UCSF project team lead, Dr. Merzenich was recognized by the National Academy of Engineering for this work as a co-recipient of the Russ Prize—often described as the “Nobel Prize in Engineering.”

Resource: A seminar paper, "Early UCSF Contributions to the Development of Multiple‐Channel Cochlear Implant" by Dr. Merzenich can be viewed here.


Neuroscience-Based Brain Training Software Programs

Researcher/Team: Michael Merzenich, William Jenkins, Christoph Schreiner, Srikantan Nagarajan, et al.

In the mid-1990s, a UCSF team led by Dr. Merzenich created the first neuroplasticity-based software-implemented brain training programs ("Fast ForWord", from Scientific Learning) initially applied to help millions of children overcome their developmental impairments in language, reading, attention, and cognition. These software tools were later extended to successfully address psychiatric and neurological illnesses in adult populations, and to grow resilience against progressions to Alzheimer’s and other neurodegenerative diseases in aging populations. This work has been recognized by Dr. Merzenich’s receipt of the Kavli Prize, the “Nobel Prize of Neuroscience.”

An early paper by Dr. Merzenich, “Temporal Processing Deficits of Language-Learning Impaired Children Ameliorated by Training” is available via UCSF Library login.


Tabla

Researcher/Team: Adam Rao

Adam Rao using TABLA on a patient. 

 

In 2015, pneumonia was the leading cause of death in patients under the age of five, claiming almost one million children worldwide. UNICEF reports the need for access to a more affordable diagnostic method in lieu of the current gold standard of a chest X-ray. Tabla is a device that sends sound waves into the body using a surface exciter—it records acoustic backscatter with a digital stethoscope, and analyzes the received signal in order to assess the presence of pneumonia. Tabla provides an order of magnitude improvement on portability, accessibility and cost, targeting patients in areas with limited access to advanced medical care. The device has IRB approval at UCSF and is currently being tested with adult and pediatric patients. For more info, please visit Tabla Devices.


The Kidney Project

Researcher/Team: Shuvo Roy

The Kidney Project seeks to develop a bioartificial kidney as a compact, surgically implanted, free-standing device to treat end-stage renal disease (ESRD). The bioartificial kidney seeks to perform the vast majority of the biological functions of the natural kidney.

The bioartificial kidney is composed of two components: a hemofilter and a bioreactor. For the hemofilter, the lab is using MEMS technology in the production of silicon nanopore membranes (SNMs) which will perform filtration using the body’s blood pressure. (Microelectromechanical systems (MEMS) technology was originally applied to electronics and automotive industries to create smaller, faster, more cost-effective parts for improved overall function.) The bioreactor will reabsorb a high volume of salt and water while maintaining a barrier to the reabsorption of toxins. To do this, the lab is using tissue engineering techniques to grow and maintain renal tubules that will be seeded into this portion of the device.

Learn more at The Kidney Project