Nanophotonic Sensing of Light – The Art of Melding Science, Engineering and Medicine for Revolutionary Personalized Healthcare

Our image of the world around us is governed by what we perceive and light has fundamentally been the central and most vital constituent shaping our perceptions. Interestingly, light is often associated with the visible wavelengths. However, photons, the little packets of energy that make up light, travel at wavelengths far below and above the visible wavelengths even extending into the highly energetic regime classified as gamma-rays. A single gamma ray photon, for example, may carry energy anywhere between 105 to 107 times the energy of a single photon of visible light. Advances in instrumentation, science and technology over the past few centuries have opened the door to perceiving light and other phenomenon beyond that which we are directly capable of perceiving. The ever-increasing glimpses into how nature works and surprising possibilities that await us in a world at the confluence of macro forces and quantum uncertainties are truly exciting.

It is fairly recently now in human history that we are beginning to record detailed observations of the human body through optical technologies such as MRI, CT and PET scanners, fiber guided minimally invasive surgeries, and the latest infrared based heart rate monitor on the Apple iWatch. Optical technology continues to be highly preferred for diagnostics since light provides manipulation-free, non-destructive analysis and remote sensing capabilities. Most technology giants have made strategic plans for moving into the healthcare segment. The in-vitro diagnostics market alone was worth more than $50 billion in 2012 and is still rapidly growing. While we can easily monitor heart rate, count our footsteps, and even monitor our blood pressure using miniaturized personal electronic devices, this is just the beginning of personalized healthcare through point-of-care (POC) diagnostics. Nanophotonic technology, the technology that studies the interactions between light and matter at the nanoscale, is spearheading an unprecedented revolution in the medical diagnostics field. Soon, it might very well be possible for everyone to own a personal device like the tricorder machine on Star Trek.

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Figure 1. A futuristic representation of an ideal POC diagnostic device. The ideal POC device quantitatively detects several analytes, within minutes, at femtomolar (10-15 Molar) sensitivities from 1 μL of bodily fluid and reports the encrypted results to an electronic health record. Credit: Reproduced with permission from IBM, copyright 2010 IBM Corporation. (1)

So far, the two well-established industry standards for laboratory optical diagnostics are enzyme linked immunosorbent assays (ELISA) and surface plasmon resonance (SPR) sensors. While ELISA uses a color change induced by target specific enzymes, SPR sensors use the change in laser coupled angles for the excitation of a charge density oscillation at the interface of two media one of which is a metal and the other a dielectric. Both these techniques offer good detection sensitivities but are largely confined to well-equipped laboratories staffed with trained personnel due to the complexity of assay steps, and size of equipment. This invariably introduces wait times anywhere between 24 hours to a couple of weeks which in the case of rarer strains of viruses might come too late. As Bill Gates announced in his most recent TED Talk titled “The next outbreak? We’re not ready“, I believe the ability to diagnose infectious diseases and viruses quickly and accurately is one of the most pressing needs of the coming years. With increased forms of global trade and travel, viruses could potentially spread across the globe within 24 hours. Additionally, preventative healthcare is an aspect often neglected primarily due to the absence of personalized POC diagnostics. However, with advances in science and technology, and the emergence of computationally powerful tools such as smartphones that are becoming increasingly widespread, it is now possible to envision people having the option of tracking their own personal health on a much more frequent basis in the privacy and comfort of their own homes.

If optical sensors could be packaged in a cost-effective manner, with multiplexed detection capabilities for several disease biomarkers or antigens, a simple at-home pin-prick of blood could potentially help save millions of lives through either diagnosing the early stage of a disease such as cancer, a positive read-out of an infectious disease such as HIV or liquid biopsies through the detection of circulating cancer DNA fragments in the blood that correlates with the organ specific cancer spread in the body. POC diagnostics could also help monitor routine blood work tests and hormone levels such as dehydroepiandrosterone that is drawing particular interest as an anti-aging hormone. By integrating personalized health metrics into everyday lives, POC diagnostics offer the revolutionary possibilities of preventative healthcare to improve overall health, quality of life and longevity. As an example, such systems could be envisioned as lab-on-chip systems (Figure 1) capable of using a pin prick of blood to rapidly test for a wide range of disease specific biomarkers, as well as monitoring vital health signs at a cost of only a couple of dollars.

Again, at the forefront of making all of these dreams realizable, is optical technology and our ability to manipulate and sense the flow of light. With greater advances in our capabilities of fabricating devices at ever-decreasing length scales, it is now routinely possible to engineer devices with features on par or smaller than the wavelengths of light they sense. This has afforded us with unprecedented control over the flow of light in ways that would have been impossible otherwise. Some of the most promising nanophotonic emerging sensors comprise ring resonators, 1D and 2D photonic crystals. Ring resonators as their name suggests, are micron-scale optical sensors that trap light from in-coupled waveguides, and cause it circulate around a circular geometry multiple times. Only those wavelengths of light that form integer multiples around the ring circumference, build up over time due to constructive interference and are referred to as resonance wavelengths. Immunoassays rely on the build-up of a series of linker molecules and antibodies to capture and detect disease specific biomarkers and target analytes. When these molecules covalently bind to the ring surface, circulating light sees this as an addition to the sensor surface, increasing the effective circumference of the ring and causing a corresponding shift in the trapped wavelengths of light. The shift in the circulating wavelengths of light or resonance wavelengths is then translated to the number of bound molecules. Currently, the detection limits for ring resonator sensors are on the order of approximately 1 ng/ml of biomarkers in blood samples. (2)

Figure 2. a) A computer-simulated ring resonator depicting continuous wave input at resonance. Credit: Wikipedia b) Microfluidic integration of a slotted ring resonator sensor with the insets showing capture of target biomolecules and circulating light path. (3)

Figure 2. a) A computer-simulated ring resonator depicting continuous wave input at resonance. Credit: Wikipedia b) Microfluidic integration of a slotted ring resonator sensor with the insets showing capture of target biomolecules and circulating light path. (3)

Moving to even smaller, subwavelength device features, 1D and 2D photonic crystal cavities (Figure 3) currently demonstrate unprecedentedly high sensitivities with capabilities of detecting single molecules at sub-fg levels. A photonic crystal is a periodic arrangement of low-loss dielectric media that prevent the propagation of a certain range of frequencies resulting in a so-called photonic bandgap. Some of the naturally occurring photonic crystals in nature are shown in Figure 4. From a fabrication perspective, the easiest method of introducing periodicity in a dielectric material, is to periodically etch holes into it.

Figure 3. a) 1D photonic crystal b) 2D photonic crystal with cavity. Credit: Shuren Hu

Figure 3. a) 1D photonic crystal b) 2D photonic crystal with cavity. Credit: Shuren Hu

As shown in Figure 3, the two geometries consist of either square or circular air holes. The deliberate introduction of defects within this periodic arrangement of dielectrics, results in certain allowed frequencies that may be trapped within the engineered cavities for surprisingly long durations (upto 1 ns) for a photon (5). The high photon confinement achieved by these structures translates to greater overlap between regions of intense light-matter interactions and active sensing regions where target analytes may be captured. For the case of optical sensors, this is an important advantage since even a small amount of captured target analyte will perturb the cavity wavelength significantly. As a result, photonic crystal cavities demonstrate some of the most sensitive signal transduction out of all the optical sensor technologies. For example, recent research demonstrates the detection of cancer-associated proteins in lung cancer cell lysates at concentrations as low as two cells per μL using 2D photonic crystal cavities. (6)

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Figure 4. Naturally occurring photonic crystals. (4)

The integration of science, engineering and medicine in the field of optical diagnostics, holds promise for rapid detection of rare or emerging virus strains, early stage detection of several diseases such as cancer, Alzheimer’s and Parkinson’s, providing round-the-clock monitoring of personal health through wearable or smartphone compatible technology and even facial analysis to ascertain health metrics such as obesity, and signs of premature aging! Once a realm of science fiction, researching the causes of aging and slowing it down is now a major focus area as well. With all these possibilities, and the fact that light is so vital for the continuation of life on our planet, it continues to become a more integral part of our lives.

Notes

1 – L. Gervais, N. de Rooij, and E. Delamarche,  Advanced Materials 23 (24), H151 (2011).

2 – Y. Z. Sun and X. D. Fan,  Analytical and Bioanalytical Chemistry 399 (1), 205 (2011).

3 – C. F. Carlborg, K. B. Gylfason, A. Kazmierczak, F. Dortu, M. J. Banuls Polo, A. Maquieira Catala, G. M. Kresbach, H. Sohlstrom, T. Moh, L. Vivien, J. Popplewell, G. Ronan, C. A. Barrios, G. Stemme, and W. van der Wijngaart,  Lab on a Chip 10 (3), 281 (2010).

4 – http://www.viewsfromscience.com/documents/webpages/natural_photonics_p1.html

5 – T. Tanabe, M. Notomi, E. Kuramochi, A. Shinya, and H. Taniyama,  Nature Photonics 1 (1), 49 (2007).

6 – S. Chakravarty, W. C. Lai, Y. Zou, H. A. Drabkin, R. M. Gemmill, G. R. Simon, S. H. Chin, and R. T. Chen,  Biosens Bioelectron 43, 50 (2013).


gaurGirija Gaur is a Ph.D. candidate and Provost’s Graduate Fellow in the department of electrical engineering and computer science at Vanderbilt University. Her research explores light-matter interactions at sub-wavelength scales and in nanometer sized quantum dots. She is an active member of the Society of Women Engineers and enjoys attending research presentations at conferences such as SPIE, CLEO and MRS. She grew up in Pune, India and a fascination for exploring science at the nanoscale brought her to graduate school in the United States.

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