Optogenetics is commonly used for precision modulation of the activity of specific neurons within neural circuits ^[1] , but assessing the impact of optogenetic neuromodulation on the neural activity of local and global circuits remains difficult. Our collaborative team recently initiated a project (Scholvin et al., SFN 2011) to design and implement 3-D silicon-micromachined electrode arrays with customizable electrode locations, targetable to defined neural substrates distributed in a 3-D pattern throughout a neural network in the mammalian brain and compatible with simultaneous use of a diversity of existing light-delivery devices.

We have developed a series of innovations aimed at facilitating the scalability aspect of these probes, i.e., aspects of probe design that should enable them to scale to 1000 channels of neural recording or more.  First, we have developed streamlined electrode fabrication methodologies that enable micromachined probes to be first fabricated using conventional silicon micromachining, then rapidly assembled into custom 3-D arrays, with semi-automated formation of the necessary electrical connections and mechanical constraints.  Second, we have developed a set of surgical and insertion technologies towards the goal of enabling the insertion of electrode arrays with a high number of electrode shanks into the brain, while minimizing probe insertion damage.  Finally, to facilitate scaling of the channel count beyond what is feasible with external amplifiers, we are exploring new approaches for integration of amplifier circuits directly on the probe arrays themselves, to remove bottlenecks associated with connecting of probes to the outside world.

1. X. Han and E. S. Boyden, “Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution,” PLoS ONE, vol. 2, no. 3, p. e299, Mar. 2007.

We have demonstrated for the first time in-plane InGaAs/InP laser diodes recess-integrated with SiON waveguides on silicon substrates using a modular heterogeneous integration technique ^[1] .  This technique allows pre-testing and selection of devices before integration, it is compatible with integration on full CMOS wafers after conventional back-end processing is completed, and it can be used to integrate multiple types of devices on a single wafer.  We feel it is superior to other optoelectronic integration techniques; more broadly, it is ideally suited to realizing robust, planar, monolithically integrated micro-systems incorporating a variety of materials and devices.

In this research, 1.55-µm InGaAs/InP ridge laser diodes were fabricated in the form of platelets 150 µm wide, 300 µm long, and 6 µm thick ^[2] .  With a micropipette vacuum pick-up tool, we placed pre-selected platelet lasers into similarly sized recesses etched in a thick SiO₂ layer on a silicon wafer substrate.  The recesses intersect SiON waveguides fabricated earlier within the SiO₂ layer ^[3] and the In/Al bonding layer thicknesses were chosen so that after assembly, the waveguides of the platelet lasers will be co-axial with the SiON waveguides.  Once all the lasers are in position, the substrate is placed on a heater strip and all lasers are simultaneously bonded in place using a pressurized thermoplastic membrane to apply a uniform vertical force (20 psi) to hold them against a contact pad on the bottom of the recess while a solder bond forms. We made contact to the upper p-contact of the integrated lasers by direct probing; thin-film metal contacts deposited and patterned on the top surface could also have been used ^[1] .

The integrated laser/waveguide units operate at room temperature with lasing thresholds of 17 mA pulsed and 19 mA CW, both of which are lower than the thresholds of comparable devices on InP substrates (consistent with the higher thermal conductivity of Si) ^[4] .  Single-mode CW output powers in excess of 1 mW are measured from 1-mm-long waveguides.  Side mode suppression ratios in excess of 20 dB have been observed, and laser-to-waveguide coupling losses less than 1 dB have been measured.

The integration of pre-selected laser diodes with waveguides on Si using a simple, flexible, modular, CMOS-compatible technique is itself a significant achievement in the field of optoelectronic integration.  More generally, this approach to heterogeneous integration can be used by anyone interested in the simultaneous integration of multiple types of compound semiconductor devices with Si integrated circuits, or on other substrates.

1. J. M. Perkins and C. G. Fonstad, “ Full recess integration of small diameter low threshold VCSELs within Si-CMOS ICs,” Optics Express, vol. 16, no. 18, pp. 13955-13960, 2008.
2. J. J. Rumpler and C. G. Fonstad, IEEE Photonics Technology Letters, vol.21, no. 13, pp. 827-829, July 2009.
3. E. Barkley, PhD Thesis, Massachusetts Institute of Technology, Cambridge, 2007.
4. S. Famenini and C. G. Fonstad, “Integration of edge emitting laser diodes with dielectric waveguides on silicon,” in review.

The use of magnetic forces to improve fluidic self-assembly of micro-components has been investigated using Maxwell 3D to model the forces between Ni thin films on semiconductor device micro-pills and Sm-Co thin films patterned on target substrates ^[1] .  Orienting and restraining forces on pills far in excess of gravity are predicted, and it is found that the fall-off of these forces with pill-to-substrate separation can be engineered through the proper design of the Sm-Co patterns to retain only properly oriented pills ^{[1] [2]} .

Micro-scale hybrid assembly is a potentially important way of doing heterogeneous integration, i.e., of integrating new materials on silicon integrated circuits to obtain functionality not readily available from silicon device structures alone, and fluidic self-assembly is an attractive way to automate micro-scale assembly.  A serious limitation of fluidic self-assembly, however, is the lack of a good method for holding properly assembled components in place and accurately positioned until all of the components have been assembled and permanently bonded in place.  We have shown, based on our modeling, that suitably patterned magnetic films can be used to provide the forces necessary to retain, and to accurately orient and position, assembled micro-components.

Our motivation for pursuing micro-scale hybrid assembly is our general interest in doing optoelectronic integration, specifically of vertical cavity surface emitting lasers (VCSELS), edge-emitting lasers (EELs), and light emitting diodes (LEDs), with state-of-the-art, commercially processed Si-CMOS integrated circuits.  Our ongoing research integrating these devices on silicon provides the context for this work and illustrates the types of applications we envision for magnetically assisted self-assembly using the results of this study.

Assembly experiments to verify and demonstrate the theoretical predictions are currently in progress using two sizes of 6-µm-thick pills (50 µm by 50 µm and 50 µm by 100 µm) and a variety of magnetic thin film patterns.  Recesses with different dimensions are also being studied ^[3] .

1. D. Cheng, “Theoretical and Experimental Study of Magnetically Assisted Fluidic Self Assembly,” Master’s thesis, Massachusetts Institute of Technology, 2008.
2. D. Cheng, J. J. Rumpler, J. M. Perkins, M. Zahn, C. G. Fonstad, E. S. Cramer, R. W. Zuneska, and F. J. Cadieu, “Use of patterned magnetic films to retain and orient micro-components during fluidic assembly,” Journal of Applied Physics, vol. 105, p. 07C123, 2009.
3. ref:1

Optoelectronic devices intimately integrated on silicon integrated circuits have long been sought for optical intercon-nect applications, optical communications modules, and–more recently–neural stimulation and sensing.  Toward this end we have recently demonstrated a new heterogeneous integration technique for integrating vertical cavity surface emitting lasers (VCSELs) and edge-emitting laser diodes (EELs) on silicon CMOS integrated circuits ^{[1] [2]} .

Fully processed and tested oxide-aperture VCSELs emitting at 850 nm have been fabricated as individual “pills” 55 µm in diameter and 8 µm tall with a disk contact on the n-type backside and a ring contact on the p-type, emitting top-side.  Similarly, 1.55-µm emitting micro-cleaved cavity EEL platelets 5 µm thick, 150 µm wide, and 300 µm long have also been fabricated.  Using a custom micro-pipette vacuum pick-up tool, these micro-laser pills and platelets have been placed on contact pads at the bottom of recesses etched though the dielectric over coating on a Si chip, and batch solder-bonded in place using a custom pressurized-diaphragm bonding apparatus.  Back-end processing of the chip then continues with surface planarization, contact via formation, and interconnect metal deposition and patterning.  An example of a completely integrated VCSEL pill appears in Figure 1.

No adverse effects are seen from fabricating laser diodes as freestanding pills and platelets.  Devices integrated in this manner show the same high performance as devices left on their native substrates and in fact have superior thermal characteristics, largely due to the better thermal conductivity of Si over that of GaAs and InP.

The technique demonstrated in this work offers numerous other advantages over alternative heterogeneous integration techniques.  Both the devices to be integrated, and the target circuit wafers, are fabricated under optimal conditions and are pre-tested and screened prior to integration to insure high yield.   Significantly, many different types of devices can be integrated on the same IC wafer, a feature unique to this approach.  Furthermore, the integration process effectively avoids thermal expansion mismatch limitations and wafer diameter mismatch issues, and it is compatible with parallel assembly techniques, such as fluidic self-assembly.

1. J. M. Perkins, and C. G. Fonstad, “ Full recess integration of small diameter low threshold VCSELs within Si-CMOS ICs,” Optics Express, vol. 16, no. 18 pp. 13955-13960, 2008.
2. J. J. Rumpler and C. G. Fonstad, Jr., “Continuous-wave electrically pumped 1.55 µm edge-emitting platelet ridge laser diodes on silicon,” IEEE Photonics Technology Letters, vol. 21, pp. 827-829, 2009.

Professor Ed Boyden uses light to precisely control neural activity.  His lab has invented safe, effective ways to deliver light-gated membrane proteins to neurons and other excitable cells (e.g., muscle, immune cells, pancreatic cells, etc.) in an enduring fashion, thus making the cells permanently sensitive to being activated or silenced by millisecond-timescale pulses of blue and yellow light, respectively ^[1] .  This ability to modulate neural activity with a temporal precision that approaches that of the neural code itself holds great promise for human health, and his lab has developed animal models of epilepsy and Parkinson’s disease to explore the use of optical control to develop new therapies.

We have recently developed mass-fabricatable multiple light guide microstructures produced using standard microfabrication techniques to deliver light to activate and silence neural target regions along their length as desired ^[2] .  Each probe is a 100- to 150-micron-wide insertable micro-structure with many miniature lightguides running in parallel and delivering light to many points along the axis of insertion.  Such a design maximizes the flexibility and power of optical neural control while minimizing tissue damage.  We are currently developing 2-D arrays of such probes so multiple colors of light can be delivered to 3-dimensional patterns in the brain, at the resolution of tens to hundreds of microns, thus furthering the causal analysis of complex neural circuits and dynamics.  Such devices will allow the substrates that causally contribute to neurological and psychiatric disorders to be systematically analyzed via causal neural control tools.  Given recent efforts to test such reagents in nonhuman primates, these devices may also enable a new generation of optical neural control prosthetics, contributing directly to the alleviation of intractable brain disorders.

The initial light-guide structures have been fabricated from silicon oxynitride clad with silicon dioxide, and tests show excellent transmission of light with no visible loss in the taper and bend regions of the patterns ^[2] .  Significantly, the novel 90˚ bend invented to direct light laterally out the side of the narrow probe functions as designed ^[2] .  The optical sources for initial tests with the probe are independent laser modules coupled to one end of a fiber-optic ribbon cable (see Figure 2).  The other end of the ribbon cable is butt-coupled to the inputs of the probe via a standard fiber-optic connector ferrule.  This allows for increased modularity and control in initial probe testing.

We are now utilizing transgenic mice, which express optogenetic activators and silencers in cortical pyramidal neurons, to demonstrate optogenetic control of neural circuits in a fashion appropriate for in vivo circuit mapping or brain machine interface prototyping.  Our goal is to explore the degree to which this technology can be used to functionally map neural network connectivity over large, multi-region circuits in the brain, and to subserve a new generation of neural control prosthetics.

1. X. Han and E. S. Boyden, “Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution,” PLoS ONE, vol. 2, no. 3, p. e299, Mar. 2007.
2. A. N. Zorzos, E. S. Boyden, and C. G. Fonstad, “A multi-waveguide Implantable probe for light delivery to distributed brain targets,” Applied Optics Letters vol. 35, no. 12, pp. 4133-4135, Dec. 2010.

Collaborators

• E. S. Boyden, MIT
• F. J Cadieu, Queens College of  CUNY
• A. Postigo, Instituto de Micro-electronica, Madrid, Spain
• M. Zahn, MIT

Postdoctoral Associate

• J. Scholvin, EECS

Graduate Students

• S. Famenini, Research Assistant, EECS
• A. Zorzos, Graduate Fellow, Media Lab

Support Staff

• J. Lee, Administrative Assistant

Publications

A. N. Zorzos, E. S. Boyden, and C. G. Fonstad, “A Multi-Waveguide Implantable Probe for Light Delivery to Distributed Brain Targets,” Applied Optics Letters Vol. 35, No. 12, pp. 4133-4135, December 15, 2010.

A. N. Zorzos, C. G. Fonstad, and E. S. Boyden, “Multi-waveguide Needle Arrays and Integrated Laser Diodes for Opto-genetic Neural Studies,” Technical Digest of the Workshop on Compound Semiconductor Devices and Integrated Circuits (WOCSDICE), Catania, Italy, May 29-June 1, 2011.

M. M. Doroudchi, K. P. Greenberg, A. N. Zorzos, W. W. Hauswirth, C. G. Fonstad, A. Horsager, and E. S. Boyden, “Towards Optogenetic Sensory Replacement,” 33rd Annual International IEEE Engineering in Medicine and Biology Conference, Boston, MA, Aug. 30-September 3, 2011; invited paper.

S. Famenini and C. G. Fonstad, “In-line Integration of Micro-Cleaved Edge-Emitting Platelet Laser  Diodes with SiON Wave-guides on Si,” Workshop on Compound Semiconductor Microwave Materials and Devices (WOCSEMMAD), Napa, CA, February 19-22, 2012; oral presentation.

C. G. Fonstad and S. Famenini, “Pre-screened CW RT  1.55 µm Laser Diodes Recess-Integrated with Waveguides on Silicon,” Proceedings of the 36th Workshop on Compound Semiconductor Devices and Integrated Circuits (WOCSDICE), Island of Porguerolles, France, May 28-30, 2012; invited oral presentation.

S. Famenini and C. G. Fonstad, “Recess Integration of Platelet Laser Diodes with Waveguides on Silicon,” 2012 Device Research Conference, University Park, PA, June 18-20, 2012; poster presentation.

S. Famenini and C. G. Fonstad, “CMOS Compatible Planar Integration of Compact Semiconductor Laser Diodes with Wave-guides on Silicon,” 2012 International Semiconductor Laser Conference, San Diego, CA, October 7-10, 2012; oral presentation.

S. Famenini and C. G. Fonstad, “Integration of Edge Emitting Laser Diodes with Dielectric Waveguides on Silicon,” IEEE Photonics Technology Letters, accepted for publication (in press).