Affiliated Faculty: Burdick, Fraser, Gharib, Guo, Lester, Pine, Roukes, Tai, Yang

The BDBI group in Bioengineering at Caltech develops technologies for manipulating and probing biological systems.  Research areas include BioMEMS (micro-electro-mechanical systems), laboratories-on-a-chip, microfluidic devices, molecular devices, medical devices (e.g. neural interfaces and micropumps), non-invasive biological and biomedical imaging, optical trapping and manipulation of molecules, and novel instrumentation and measurement principles.

The following research projects illustrate current research activities:

Imaging Whole Embryos Via Surface Microscopy

An early frog embryo, imaged at high-resolution using surface imaging microscopy, a novel technique first applied to developmental biology in the Biological Imaging Center at Caltech. In this neurula stage embryo the archenteron (large cavity) has formed and the blastopore has closed, thus completing the major goals of gastrulation.  Subsequent work studied the molecular control of archenteron formation and blastopore closure and demonstrated that both processes require non-canonical Wnt signaling, acting through Dishevelled.  Quantitative analytical techniques demonstrate that the cellular events of gastrulation are dissociable, providing a possible explanation for the observed diversity of gastrulation mechanisms among amphibians.

The Optofluidic Microscope – Changing the Way We Use Microscopy

Linear array sensor

Microscope-on-a-chip

Image of C. elegans taken with microscope-on-a-chip

Do you have floaters in your eyes? Ever wondered why you see them? Our work on the Optofluidic Microscope (OFM) is inspired by the floater phenomenon. The OFM is a lensless, compact, high-resolution microscope that is no larger than Washington’s nose on a quarter and yet is able to deliver resolution that is comparable to a conventional microscope. This on-chip microscope system enables large scale massively parallel and automated bioscience imaging of cells and microorganisms. In the clinical setting, the OFM can form the heart of a blood analysis unit that a clinician can employ at a patient’s bedside. Finally, this technology can be a boon for third world healthcare by providing low cost and rugged malaria diagnosis devices that can fit in a doctor’s back pocket.

Neurochips For the Growth, Activation and Measurement of Synthetic Neural Networks

A parylene neuron cage, one of an array for holding individual neurons that can extend axons and dendrites out of the tunnels to form a living network. An electrode at the bottom of each cage provides an ability to stimulate or record from each neuron, individually or simultaneously. This extracellular connection is non-destructive, providing an opportunity to study the behavior of the network over a period of weeks and to modify its connections with external stimulation.

These cages were designed and constructed in collaboration with the Tai lab, using sacrificial layer technology to form the central cavity and the tunnels from vacuum- deposited parylene dimer. A trial "neurochip" with 16 cages in a 4 x 4 array is now being studied, with an 8 x 8 array planned for the final studies.

Imaging Collective Cytoskeletal Dynamics

Microfluidic device to manipulate cell-cell & cell-matrix interaction

Images of actin cable movement in the mating of budding yeast

Images of actin and keratin in a wounded human cornea epithelium cell

Single-molecule TIRF, multi-photon methods, and microfluidic devices are used to study the interplay between cytoskeleton biomechanics and small GTPase activity. In particular, we are interested in the collective dynamics of the cytoskeleton in cell migration (as in embryogenesis and wound healing), and cell-cell interactions in senescence and tumorigenesis.

Curriculum

Students in the BDBI program must demonstrate proficiency in imaging, microfabrication techniques, mathematics, and the application of these tools to biology. First- and second-year coursework in the program is intended to build upon undergraduate training and to complement concurrent research activities. The following table lists the coursework requirements of the BDBI academic program.

BDBI Requirements (Year 1)

BOOT CAMP:
Prior to first term

Math Track (3 terms):
ACM 95/100 abc, ACM 101 abc, AM 125 abc

Biology Track (2 terms):
BE 201 ab

BDBI core track (2 terms):
APh 109, Bi 227, EE/BE 166, EE 185

BDBI elective track (3 terms Selected from the following):

Research track:
Optional research rotations BE250

Research rotations
One-term research rotations allow first-year Bioengineering graduate students to sample relevant research activities in several labs before selecting a PhD advisor. Research rotations are required in the SSB sub-option and highly recommended in the BMBID and BDBI sub-options. Rotations should be organized by each student in collaboration with individual faculty.

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