Fast Fluorescence Imaging using Radiofrequency-tagged Emission (FIRE)

New development in microscopy inspired by wireless technology eliminates the speed limitation in biological imaging for blood diagnostics and brain mapping 

Fluorescence imaging is the most widely used method to analyze the molecular composition of biological specimens. Target molecules, when they are present, can be "tagged" with a fluorescence label and made visible. For example, the technique is used in screening blood for cancer cells, or to study biochemical reactions. In particular, the highly sensitive imaging technique is very good at detecting molecules present at extremely low concentrations.

However, because of the very small amount of light produced by fluorescent molecules, current state-of-the-art camera technologies must image samples slowly, in order to collect enough photons to generate an image. Further, these cameras typically read out individual pixels one at a time to create an image. These two factors limit the speed at which fluorescence imaging can be performed. 

Inspired by how wireless communication networks uses multiple radio frequencies to communicate with multiple users, and our own past work on radio frequency photonics, the Jalali-Lab has developed a new high-speed microscopy technique that is an order of magnitude faster than current fluorescence imaging technologies. 

Our camera encodes fluorescence emission from each pixel on a different radio frequency (RF). Each pixel on the image functions as a different RF channel. The light from all pixels is collected using a single pixel photodetector. The RF spectrum obtained via digital Fourier transform reveals the fluorescent image. The "fluorescence imaging using radiofrequency-tagged emission", or FIRE, is about 10 times faster than other techniques. 


Due to the high imaging speed, the technique can be applied in flow cytometry – which analyzes cells one-by-one in a flowing fluid. Unlike current imaging flow cytometers, the FIRE technique can keep up with conventional flow cytometry speeds, and image 50,000 cells per second. While most flow cytometers take only a single-point estimate of a cell’s fluorescence, FIRE can create an entire high-resolution, multi-color image of each cell, which can provide significantly more information to a biologist or clinician. This allows us to both detect and differentiate rare cells at high throughputs. The new technique can also be applied in vivo, for example, in neuroscience research to view neuron activity in the brain. Here the sub-millisecond response of the camera will image the action potential activity of neurons. 

We have extended radio frequency tagging idea to create a new instrument for dynamic light scattering (Mie scattering) for characterization of particles such as biological cells or pollutants in air and water. Ratio frequency encoded angular light scattering (REALS) measures the angular spread of scattered light in single shot with a single photodetector and without the need for mechanical scanning. It does so by encoding the optical excitation angle to radio frequency and obtains the angular spectrum of scattered light by simply examining the RF spectrum of scattered light measured at a single angle. Furthermore, the radio frequency encoding has led to a new method for precision measurement the fluorescent lifetime.

  1. Brandon W. Buckley, Najva Akbari, Eric D. Diebold, Jost Adam, and Bahram Jalali, "Radiofrequency encoded angular light spectroscopy", Applied Physics Letters, (2015). link pdf

  2. J. C.K. Chan et al., "Digitally synthesized beat frequency multiplexed fluorescence lifetime spectroscopy", Biomedical Optics Letters, (2014). link pdf

  3. Eric D. Diebold, BrandonW. Buckley, Daniel R. Gossett and Bahram Jalali, "Digitally synthesized beat frequency multiplexing for sub-millisecond fluorescence microscopy," Nature Photonics, (2013).link pdf"

  4. Researchers develop new type of fluorescent camera for blood diagnostics, brain mapping", Phys.Org. link


Serial Time-Encoded Amplified Microscopy (STEAM)

STEAM is a new type of imaging modality for continuous real-time observation of fast dynamical phenomena such as shockwaves, chemical dynamics in living cells, neural activity, laser surgery, and microfluidics. STEAM maps the spatial information (image) of an object into a serial time-domain data stream and simultaneously amplifies the image in the optical domain. It captures the entire image with a single-pixel photodetector, not 

by a CCD or CMOS camera. With the optical image amplification, STEAM overcomes the fundamental trade-off between sensitivity and frame rate - a predicament that affects virtually all optical imaging systems. As a result, STEAM can achieve ~10 MHz frame rate and ~100 ps shutter speed, enabling real-time observation of rapid transient processes in physics, chemistry, and biology.

1D STEAM - Principle of Operation:

2D STEAM - Principle of Operation:

High-Throughput Optical Microscopy for Cancer Detection

While useful for detailed examination of a small number of microscopic entities, conventional optical microscopy is incapable of statically relevant screening of large populations (> 1 billion) with high precision due to its low throughput and limited digital memory size. We are currently developing a new type of automated flow-through single-cell optical microscope that overcomes this

limitation by performing sensitive blur-free image acquisition and non-stop real-time image-recording and classification of a large number of cells during high-speed flow. The technology is expected to hold great promise for early, non-invasive, low-cost detection of cancer.

Interactive Steam Calculator link

Serial time-encoded amplified imaging/microscopy (STEAM) is a fast real-time optical 

imaging method that provides ~10 MHz frame rate, ~100 ps shutter speed, and ~30 dB ( 1000) optical image gain. As of today, STEAM holds world records for shutter speed and frame rate in continuous real-time imaging. STEAM employs the photonic time stretch along with optical image amplification to circumvent the fundamental trade-off between sensitivity and speed that affects virtually all optical imaging and sensing systems. With this calculator, you will be able to determine spatial and temporal resolution of 1D STEAM System. Please click the schematic or link to explore further.

[1] "Serial time-encoded amplified microscopy (STEAM)," Wikipedia

[2] K. Goda, K. K. Tsia, and B. Jalali, "Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena," Nature 458, 1145 (2009)
[3] K. Goda, K. K. Tsia, and B. Jalali, "Amplified dispersive Fourier-transform imaging for ultrafast displacement sensing and barcode reading," Applied Physics Letters 93, 131109 (2008)
[4] K. Goda, A. Ayazi, D. R. Gossett, J. Sadasivam, C. K. Lonappan, E. Sollier, A. M. Fard, S. C. Hur, J. Adam, C. Murray, C. Wang, N. Brackbill, D. Di Carlo, and B. Jalali, "High-throughput single-microparticle imaging flow analyzer," Proceedings of the National Academy of Sciences 10.1073/pnas.1204718109 (2012)
[5] B. Jalali, P. Soon-Shiong, and K. Goda, "Breaking speed and sensitivity limits," Optik & Photonik 2, 32 (2010)
[6] B. Jalali, K. Goda, P. Soon-Shiong, and K. K. Tsia, "Time-stretch imaging and its applications to high-throughput microscopy and microsurgery," IEEE Photonics Society Newsletter 24, 11 (2010)



Silicon Photonics

Empowering silicon with optical functions such as the ability to emit, guide, and modulate light could be the key to creating short-distance ultrafast optical interconnects that overcome one of the most formidable hurdles in scaling the speed of computing. An ultimate aim is the realization of silicon chips that communicate internally or with other chips using photons and optical waveguides and thus overcome the bandwidth limitations imposed by metallic interconnects. Yet 

another opportunity lies in optical sensors with on-chip communication circuitry that can form nodes of intelligent sensor networks used for environmental and health monitoring. Guided by such visions and propelled by pioneering research conducted in the 1980s and 1990s, silicon photonics has enjoyed spectacular progress in the past several years. In 2004, we demonstrated lasing in silicon for the first time. For 

past several years, we have developed various types of silicon-based photonic devices for next-generation optical communication and computing.

[1] P. T. S. DeVore, D. R. Sollli, C. Ropers, P. Koonath, and B. Jalali,

"Stimulated supercontinuum generation extends broadening limits in silicon," Applied Physics Letters 100, 101111 (2012)
[2] B. Jalali, "Nonlinear optics in the mid-infrared," Nature Photonics 4, 506 (2010)
[3] N. K. Hon, K. K. Tsia, D. R. Solli, and B. Jalali, "Periodically poled silicon," Applied Physics Letters 94, 091116 (2009)
[4] K. K. Tsia, S. Fathpour, and B. Jalali, "Electrical tuning of silicon's dispersion," Applied Physics Letters 92, 061109 (2008)
[5] B. Jalali, "Laser design: a cooler Raman laser," Nature Photonics 1, 691 (2007)
[6] B. Jalali, "Teaching silicon new tricks," Nature Photonics 1, 193 (2007)
[7] O. Boyraz and B. Jalali, "Demonstration of a silicon Raman laser," Optics Express 12, 5269 (2004)



Optical Logarithm

Optical computing accelerators help alleviate bandwidth and power consumption bottlenecks in electronics. We show an approach to implementing logarithmic-type analog co-processors in silicon photonics and use it to perform the exponentiation operation and the recovery of a signal in the presence of multiplicative distortion. The function is realized by exploiting nonlinear-absorption-enhanced Raman amplification saturation in a silicon waveguide.

[1] Yunshan Jiang, Peter TS DeVore, and Bahram Jalali, "Analog optical computing primitives in silicon photonics." Optics letters (2016). link pdf

[2] Yunshan Jiang, Peter TS DeVore, and Bahram Jalali, "Signal De-convolution with analog logarithmic computing primitives in silicon photonics." Photonics Society Summer Topical Meeting Series (SUM), IEEE, pdf 

[3] Yunshan Jiang, Peter T. Devore, Ata Mahjoubfar, and Bahram Jalali, "Analog logarithmic computing primitives with silicon photonics." CLEO: Applications and Technology. Optical Society of America, 2016. link pdf 

Center for Integrated Access Networks (CIAN)

The Center for Integrated Access Networks (CIAN) is a multi-institutional research effort consisting of more than several universities including UCLA. The vision of CIAN is to create transformative technologies for optical access networks where virtually any application requiring any resource can be seamlessly and efficiently aggregated and interfaced with existing and future core networks in a cost-effective manner. Analogous to the evolution over decades of today's computer laptop using massive integration of discrete electronic components, the CIAN 

vision would lead to the creation of the PC equivalent of the optical access network by employing optoelectronic integration to enable affordable and flexible access to any type of service, including delivery of data rates approaching 10 Gbits/s to a broad population base anywhere and at any time. We are currently developing novel methods and instruments to achieve the CIAN goal.

[1] Center for Integrated Access Networks (CIAN)

[2] A. Fard, S. Gupta, B. Jalali, "Ultrahigh bandwidth sampling scope via an NI5154 and a photonic time stretch pre-processor," NIWeek Conference (2009)
[3] A. Fard, S. Gupta, and B. Jalali, "Digital equalization of ultrafast data using real-time burst sampling," Optical Fiber Communication Conference / National Fiber Optic Engineers Conference (2010)
[4] A. Fard, B. Buckley, and B. Jalali, "Doubling the spectral efficiency of photonic time-stretch analog-to-digital converter by polarization multiplexing," Frontiers in Optics (2010)



Ultra-Wideband Time-Stretched Digitizer

With increasing bandwidth demands from internet backbones, optical links with 100 Gb/s and higher data rates per wavelength channel are being targeted. To meet these demands, spectrally efficient modulation formats are being developed. The receivers in such links will require very high speed and resolution analog-to-digital converters (ADCs), which are currently beyond the capability of present day electronics. High-bandwidth digitizers are also needed for defense applications such as radars, and in detection of ultrafast electromagnetic pulses. In science, such digitizers are central tools in particle accelerators or X-ray free electron laser systems as well as in time-resolved 

fluorescence microscopy. The goal of this research is to use photonics to extend the capabilities of electronics to meet these demands. This is achieved by photonic time-stretch technology, which uses photonics to slow down electrical signals in time. Hence, an electronic digitizer that would have been too slow to capture the original electrical signal can now capture the stretched and slowed down signal. We have a world record for analog-to-digital conversion rate.

[1] S. Gupta and B. Jalali, "Time stretch enhanced recording oscilloscope," Applied Physics Letters 94, 041105 (2009)

[2] J. Chou, O. Boyraz, D. R. Solli, and B. Jalali, "Femtosecond real-time single-shot digitizer," Applied Physics Letters 91, 161105 (2007)
[3] Y. Han, O. Boyraz, and B. Jalali, "Tera-sample-per-second real-time waveform digitizer," Applied Physics Letters 87, 241116 (2005)
[4] F. Coppinger, A. S. Bhushan, and B. Jalali, "Photonic time stretch and its application to analog-to-digital conversion," IEEE Transactions on Microwave Theory and Techniques 47, 1309 (1999)



Generation and Control of Optical Rogue Waves

Using real-time measurements, we have discovered a new phenomenon known as optical rogue waves, counterparts of the freak ocean waves thought to be responsible for destruction of ships on the open sea. Optical rogue waves arise in supercontinuum generation, a nonlinear process in which broadband radiation is generated from a narrowband light. By actively controlling the process behind the generation of rogue waves, we have shown that it is possible to produce a more stable and coherent white light source, which has the potential to impact many applications.

[1] D. R. Solli, C. Ropers, and B. Jalali, "Rare frustration of optical supercontinuum generation," Physical Review Letters 96, 151108 (2010)

[2] B. Jalali, D. R. Solli, K. Goda, K. Tsia, and C. Ropers, "Real-time measurements, rare events, and photon economics," European Physical Journal Special Topics 185, 145 (2010)
[3] D. R. Solli, C. Ropers, and B. Jalali, "Active control of rogue waves for stimulated supercontinuum generation," Physical Review Letters 101, 233902 (2008)
[4] D. R. Solli, C. Ropers, P. Koonath, and B. Jalali, "Optical rogue waves," Nature 450, 1054 (2007)



Dispersive Fourier-Transform Spectroscopy

In contrast to traditional spectroscopy in which an optical spectrum is obtained by spatially dispersing light with a prism or diffraction grating onto a detector array, we employ a new type of spectroscopy method known as dispersive Fourier transformation - an optical process that maps the spectrum of an optical pulse into a time-domain waveform using group-velocity dispersion and simultaneously amplifies it in the optical domain. This technique removes spatial diffractive elements and a detector array in the conventional spectrometer and hence enables ultrafast real-time spectroscopic 

studies of various ultrafast phenomena for a better understanding of them as well as for developing a new class of applications.

[1] D. R. Solli, G. Herink, B. Jalali, and C. Ropers, "Fluctuations and correlations in modulation instability," Nature Photonics doi:10.1038/nphoton.2012.126 (2012)

[2] K. Goda, D. R. Solli, K. K. Tsia, and B. Jalali, "Theory of amplified dispersive Fourier transformation," Physical Review A 80, 043821 (2009)
[3] D. R. Solli, J. Chou, and B. Jalali, "Amplified wavelength-time transformation for real-time spectroscopy," Nature Photonics 2, 48 (2008)
[4] K. Goda, D. R. Solli, and B. Jalali, "Real-time optical reflectometry enabled by amplified dispersive Fourier transformation," Applied Physics Letters 93, 031106 (2008)
[5] J. Chou, D. R. Solli, and B. Jalali, "Real-time spectroscopy with subgigahertz resolution using amplified dispersive Fourier transformation," Applied Physics Letters 92, 111102 (2008)
[6] J. Chou, Y. Han, and B. Jalali, "Time-wavelength spectroscopy for chemical sensing," IEEE Photonics Technology Letters 16, 1140 (2004)
[7] P. V. Kelkar, F. Coppinger, A. S. Bhushan, and B. Jalali, "Time-domain optical sensing," Electronics Letters 35, 1661 (1999)



Hybrid Dispersion Laser Scanner

Laser scanning technology is one of the most integral parts of today's scientific research, manufacturing, defense, and biomedicine. In many applications, high-speed scanning capability is essential for scanning a large area in a short time and multi-dimensional sensing of moving objects and dynamical processes with fine temporal resolution. Unfortunately, conventional laser scanners are often too slow, resulting in limited precision and utility. We are currently developing a new type of laser scanner which we call the hybrid dispersion laser scanner that offers about 1,000 times higher scan rates than 

conventional state-of-the-art laser scanners. This technology is expected to be useful for a broad range of applications including imaging, surface vibrometry, and flow cytometry.

[1] K. Goda, A. Mahjoubfar, C. Wang, A. Fard, J. Adam, D. R. Gossett, A. Ayazi, E. Sollier, O. Malik, E. Chen, Y. Liu, R. Brown, N. Sarkhosh, D. Di Carlo, and B. Jalali, "Hybrid dispersion laser scanner," Scientific Reports 2, 445 (2012)


All-Dielectric Photonic-Assisted Radio Front-End Technology

The threats to civil society posed by high-power electromagnetic weapons are viewed as a grim but real possibility in the world after September 11, 2001. These weapons produce a power surge capable of destroying or damaging sensitive circuitry in electronic systems. Unfortunately, the trend towards circuits with smaller sizes and voltages renders modern electronics highly susceptible to such damage. RF communication systems are particularly vulnerable, because the antenna provides a direct port of entry for electromagnetic radiation. To address this problem, we have proposed and

demonstrated an all-dielectric photonic-assisted receiver. This RF receiver front-end features a complete absence of electronic circuitry and metal interconnects, the traditional 'soft spots' of a conventional RF receiver. The device exploits a dielectric resonator antenna to capture and deliver the RF signal onto an electro-optic field sensor. The dielectric approach has an added benefit in that it reduces the physical size of the front end, an important benefit in mobile applications.

[1] "Dielectric wireless receiver," Wikipedia

[2] R. C. J. Hsu, A. Ayazi, B. Houshmand, and B. Jalali, "All-dielectric photonic-assisted radio front-end technology," Nature Photonics 1, 535 (2007)
[3] A. Ayazi, R. C. J. Hsu, B. Houshmand, W. H. Steier, and B. Jalali, "All-dielectric photonic-assisted wireless receiver," Optics Express 16, 1742 (2007)


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