Vikram (Vik) Bajaj GRAIL, Verily Life Sciences (Google/Alphabet), Stanford School of Medicine Sat, 01 Oct 2016 13:26:48 +0000 en-US hourly 1 40765664 Why I decided to join GRAIL’s quest to detect cancer early Sat, 01 Oct 2016 13:26:48 +0000 This month, I stepped down as Verily’s Chief Scientific Officer and joined GRAIL, a startup focused on the early detection of cancer, to guide its precision medicine and translational science efforts. I’ll still be affiliated with Verily through its Science Board, which I’ll chair. I write about the reasons for my decision here:

Parminder Bajaj

Seeing deeply into cancer: early disease interception for improved outcomes.
How can we detect cancer early so that we can treat it more effectively?

A note about why I’m stepping down as Verily’s CSO after four years to become Chair of its Science Board, and my exciting new role at GRAIL, a startup focused on early cancer detection.

My reasons for this move are partly personal. As some of you know, my father, Parminder Bajaj, died of cancer last year. We discovered his cancer far too late for effective treatment. GRAIL’s mission to “detect cancer early, while it can be cured” addresses this significant unmet medical need.

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Cover Article in JMR: Gradient-Free Microfluidic Flow Labeling Using Thin Magnetic Films and Remotely Detected MRI Sun, 23 Nov 2014 19:32:53 +0000

Gradient-free microfluidic flow labeling using thin magnetic films and remotely detected MRI

Nicholas W. Halpern-Manners, Daniel J. Kennedy, David R. Trease, Thomas Z. Teisseyre, Nicolas S. Malecek, Alexander Pines, Vikram S. Bajaj


Magnetic barcoding and remote detection of fluid flowing in a microfluidic device.


Microfluidic flow phantom used in this experiment.


Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) may be employed as noninvasive measurements yielding detailed information about the chemical and physical parameters that define microscale flows. Despite these advantages, magnetic resonance has been difficult to combine withmicrofluidics, largely due to its low sensitivity when detecting small sample volumes and the difficulty of efficiently addressing individual flow pathways for parallel measurements without utilizing large electric currents to create pulsed magnetic field gradients. Here, we demonstrate that remotely-detected MRI (RD-MRI) employing static magnetic field gradients produced by thin magnetic films can be used to encode flow and overcome some of these limitations. We show how flow path and history can be selected through the use of these thin film labels and through the application of synchronized, frequency-selective pulses. This obviates the need for large electric currents to produce pulsed magnetic field gradients and may allow for further application of NMR and MRI experiments on microscale devices.

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Cover Article, Angewandte Chemie: Ultra-Low-Field NMR Relaxation and Diffusion Measurements Using an Optical Magnetometer Sun, 03 Aug 2014 23:52:51 +0000

Angewandte Cover150300Ultra-Low-Field NMR Relaxation and Diffusion Measurements Using an Optical Magnetometer

Paul J. Ganssle, Hyun D. Shin, Scott J. Seltzer, Vikram S. Bajaj, Micah P. Ledbetter, Dmitry Budker, Svenja Knappe, John Kitching, and Alexander Pines

a) T1–T2 and b) T2-diffusion Laplace pseudospectra of decane and water. The extra peak in the T2-diffusion spectrum is an artifact of the inversion procedure used. The colors in the figure correspond to relative intensity, normalized to 100.

a) T1–T2 and b) T2-diffusion Laplace pseudospectra of decane and water. The extra peak in the T2-diffusion spectrum is an artifact of the inversion procedure used. The colors in the figure correspond to relative intensity, normalized to 100.


Nuclear magnetic resonance (NMR) relaxometry and diffusometry are important tools for the characterization of heterogeneous materials and porous media, with applications including medical imaging, food characterization and oil- well logging. These methods can be extremely effective in applications where high-resolution NMR is either unnecessary, impractical, or both, as is the case in the emerging field of portable chemical characterization. Here, we present a proof- of-concept experiment demonstrating the use of high-sensitivity optical magnetometers as detectors for ultra-low-field NMR relaxation and diffusion measurements.

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Nature Communications: Optical Hyperpolarization and NMR Detection of 129Xe on a Microfluidic Chip Sun, 22 Jun 2014 15:11:15 +0000
Nature Communications: Optical Hyperpolarization and NMR Detection of 129Xe on a Microfluidic Chip

Optical hyperpolarization and detection chip

Optical hyperpolarization and NMR detection of 129Xe on a microfluidic chip

Ricardo Jiménez-Martínez, Daniel J Kennedy, Michael Rosenbluh, Elizabeth A Donley, Svenja Knappe, Scott J Seltzer, Hattie L Ring, Vikram S Bajaj, John Kitching




Optically hyperpolarized 129Xe gas has become a powerful contrast agent in nuclear magnetic resonance (NMR) spectroscopy and imaging, with applications ranging from studies of the human lung to the targeted detection of biomolecules. Equally attractive is its potential use to enhance the sensitivity of microfluidic NMR experiments, in which small sample volumes yield poor sensitivity. Unfortunately, most 129Xe polarization systems are large and non-portable. Here we present a microfabricated chip that optically polarizes 129Xe gas. We have achieved 129Xe polarizations 40.5% at flow rates of several microlitres per second, compatible with typical microfluidic applications. We employ in situ optical magnetometry to sensitively detect and characterize the 129Xe polarization at magnetic fields of 1mT. We construct the device using standard microfabrication techniques, which will facilitate its integration with existing microfluidic platforms. This device may enable the implementation of highly sensitive 129Xe NMR in compact, low-cost, portable devices.

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Some press reports:

  1. Producing Hyperpolarized Gas on a Microfluidic Chip
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Nature Communications: Optically Detected Cross-relaxation Spectroscopy of Electron Spins in Diamond Sun, 22 Jun 2014 15:05:45 +0000

NatureComms_CrossRelaxationOptically detected cross-relaxation spectroscopy of electron spins in diamond
Hai-Jing Wang, Chang S. Shin, Scott J. Seltzer, Claudia E. Avalos,  Alexander Pines, and Vikram S. Bajaj



The application of magnetic resonance spectroscopy at progressively smaller length scales may eventually permit ‘chemical imaging’ of spins at the surfaces of materials and biological complexes. In particular, the negatively charged nitrogen-vacancy (NV-) centre in diamond has been exploited as an optical transducer for nanoscale nuclear magnetic resonance. However, the spectra of detected spins are generally broadened by their interaction with proximate paramagnetic NV- centres through coherent and incoherent mechanisms. Here we demonstrate a detection technique that can resolve the spectra of electron spins coupled to NV- centres, in this case, substitutional nitrogen and neutral nitrogen-vacancy centres in diamond, through optically detected cross-relaxation. The hyperfine spectra of these spins are a unique chemical identifier, suggesting the possibility, in combination with recent results in diamonds harbouring shallow NV- implants, that the spectra of spins external to the diamond can be similarly detected.

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New Publication in Physical Review B: Optically Detected Nuclear Quadrupolar Interaction of 14N in Nitrogen-vacancy Centers in Diamond Sun, 22 Jun 2014 14:58:30 +0000 PRB_quadrupolarOptically Detected Nuclear Quadrupolar Interaction of 14N in Nitrogen-vacancy Centers in Diamond
Chang S. Shin, Mark C. Butler , Hai-Jing Wang , Claudia E. Avalos, Scott J. Seltzer, Ren-Bao Liu , Alexander Pines , and Vikram S. Bajaj



We report sensitive detection of the nuclear quadrupolar interaction of the 14N nuclear spin of the nitrogen-vacancy (NV) center using the electron spin echo envelope modulation technique. We applied a weak transverse magnetic field to the spin system so that certain forbidden transitions became weakly allowed due to second-order effects involving the nonsecular terms of the hyperfine interaction. The weak transitions cause modulation of the electron spin-echo signal, and a theoretical analysis suggests that the modulation frequency is primarily determined by the nuclear quadrupolar frequency; numerical simulations confirm the analytical results and show excellent quantitative agreement with experiments. This is an experimentally simple method of detecting quadrupolar interactions, and it can be used to study spin systems with an energy structure similar to that of the NV center.


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New publication in Nature Chemistry: Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging Mon, 12 May 2014 07:04:25 +0000  

2014_Nature_Gas_VesiclesGenetically encoded reporters for hyperpolarized xenon magnetic resonance imaging
Mikhail G. Shapiro, R. Matthew Ramirez, Lindsay J. Sperling, George Sun, Jinny Sun, Alexander Pines, David V. Schaffer and Vikram S. Bajaj



ABSTRACT Magnetic resonance imaging (MRI) enables high-resolution non-invasive observation of the anatomy and function of intact organisms. However, previous MRI reporters of key biological processes tied to gene expression have been limited by the inherently low molecular sensitivity of conventional 1H MRI. This limitation could be overcome through the use of hyperpolarized nuclei, such as in the noble gas xenon, but previous reporters acting on such nuclei have been synthetic. Here, we introduce the first genetically encoded reporters for hyperpolarized 129Xe MRI. These expressible reporters are based on gas vesicles (GVs), gas-binding protein nanostructures expressed by certain buoyant microorganisms. We show that GVs are capable of chemical exchange saturation transfer interactions with xenon, which enables chemically amplified GV detection at picomolar concentrations (a 100- to 10,000-fold improvement over comparable constructs for 1H MRI). We demonstrate the use of GVs as heterologously expressed indicators of gene expression and chemically targeted exogenous labels in MRI experiments performed on living cells.

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JACS Article: Hyperpolarized xenon-based molecular sensors for label-free detection of analytes Tue, 10 Dec 2013 12:45:00 +0000

Hyperpolarized xenon-based molecular sensors for label-free detection of analytes

Praveena D. Garimella, Tyler Meldrum, Leah Suzanne Witus, Monica Smith, Vikram Singh Bajaj, David E Wemmer, Matthew B Francis, and Alexander Pines

ABSTRACT: Nuclear magnetic resonance (NMR) can reveal the chemical constituents of a complex mixture without re- sorting to chemical modification, separation, or other perturbation. Recently, we and others have developed magnetic resonance agents that report on the presence of dilute analytes by proportionately altering the response of a more abun- dant or easily detected species, a form of amplification. One example of such a sensing medium is xenon gas, which is chemically inert and can be optically hyperpolarized, a process that enhances its NMR signal by up to five orders of mag- nitude. Here, we use a combinatorial synthetic approach to produce xenon magnetic resonance sensors that respond to small molecule analytes. The sensor responds to the ligand by producing a small chemical shift change in the Xe NMR spectrum. We demonstrate this technique for the dye, Rhodamine 6G, for which we have an independent optical assay to verify binding. We thus demonstrate that specific binding of a small molecule can produce a xenon chemical shift change, suggesting a general approach to the production of xenon sensors targeted to small molecule analytes for in vitro assays or molecular imaging in vivo.

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JACS Publication: Higher Order Amyloid Fibril Structure by MAS NMR and DNP Spectroscopy Tue, 10 Dec 2013 12:38:50 +0000

Higher Order Amyloid Fibril Structure by MAS NMR and DNP Spectroscopy

Galia T. Debelouchina, Marvin J. Bayro, Anthony W. Fitzpatrick, Vladimir Ladizhansky,  Michael T. Colvin, Marc A. Caporini, Christopher P. Jaroniec, Vikram S. Bajaj, Melanie Rosay, Cait E. MacPhee, Michele Vendruscolo, Werner E. Maas, Christopher M. Dobson, Robert G. Griffin*


Protein magic angle spinning (MAS) NMR spectroscopy has generated structural models of several amyloid fibril systems, thus providing valuable information regarding the forces and interactions that confer the extraordinary stability of the amyloid architecture. Despite these advances, however, obtaining atomic resolution information describing the higher levels of structural organization within the fibrils remains a significant challenge. Here, we detail MAS NMR experiments and sample labeling schemes designed specifically to probe such higher order amyloid structure and we have applied them to the fibrils formed by an eleven-residue segment of the amyloidogenic protein transthyretin (TTR(105-115)). These experiments have allowed us to define unambiguously not only the arrangement of the peptide β-strands into β- sheets but also the β-sheet interfaces within each protofilament, and in addition to identify the nature of the protofilament-to-protofilament contacts that lead to the formation of the complete fibril. Our efforts have resulted in 111 quantitative distance and torsion angle restraints (10 per residue) that describe the various levels of structure organization. The experiments benefited extensively from the use of dynamic nuclear polarization (DNP), which in some cases allowed us to shorten the data acquisition time from days to hours and to improve significantly the signal-to-noise ratios of the spectra. The β-sheet interface and protofilament interactions identified here revealed local variations in the structure that result in multiple peaks for the exposed N- and C-termini of the peptide and in inhomogeneous line- broadening for the side-chains buried within the interior of the fibrils.

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Little evidence for health effects of contaminated fish following Fukushima accident Sat, 09 Nov 2013 23:56:37 +0000 Recent reports in the popular press cite evidence for contamination of tuna and other fish by unnatural radionuclides released after the Fukushima nuclear disaster.  These reports occasionally assert possible consequences to human health, usually without context or reference to rigorous, evidence-backed models. Some reports state that the mere presence of these elements is dangerous without explaining that many of the methods employed (e.g. ICP-MS) are capable of detecting them in processed samples in trace or even parts per trillion quantities, below the levels of at which any effects to human health should be reasonably predicted, and far below the levels of naturally occurring radioactive elements such as polonium 210.

[See image gallery at]

Ken Buesseler of the Wood Hole Oceanographic Institution has compiled an authoritative FAQ explaining the nature of the measurements, worthy of study by legislators and consumers alike. Below are some links to the primary literature, including a 2013 PNAS paper by Fisher et al., “Evaluation of radiation doses and associated risk from the Fukushima nuclear accident to marine biota and human consumers of seafood,” stating

Radioactive isotopes originating from the damaged Fukushima nuclear reactor in Japan following the earthquake and tsunami in March 2011 were found in resident marine animals and in migratory Pacific bluefin tuna (PBFT). Publication of this information resulted in a worldwide response that caused public anxiety and concern, although PBFT captured off California in August 2011 contained activity concentrations below those from naturally occurring radio- nuclides. To link the radioactivity to possible health impairments, we calculated doses, attributable to the Fukushima-derived and the naturally occurring radionuclides, to both the marine biota and human fish consumers. We showed that doses in all cases were dominated by the naturally occurring alpha-emitter 210Po and that Fukushima-derived doses were three to four orders of magnitude below 210Po-derived doses. Doses to marine biota were about two orders of magnitude below the lowest benchmark protection level proposed for ecosystems (10 μGy·h−1). The additional dose from Fukushima radionuclides to humans consuming tainted PBFT in the United States was calculated to be 0.9 and 4.7 μSv for average consumers and subsistence fishermen, respectively. Such doses are comparable to, or less than, the dose all humans routinely obtain from naturally occurring radionuclides in many food items, medical treatments, air travel, or other background sources. Although uncertainties remain regarding the assessment of cancer risk at low doses of ionizing radiation to humans, the dose received from PBFT consumption by subsistence fishermen can be estimated to result in two additional fatal cancer cases per 10,000,000 similarly exposed people.


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