Understanding activity and physiology at scale: The Apple Heart & Movement Study.

Physical activity or structured exercise is beneficial in a wide range of circumstances. Nevertheless, individual-level data on differential responses to various types of activity are not yet sufficient in scale, duration or level of annotation to understand the mechanisms of discrete outcomes nor to support personalized recommendations. The Apple Heart & Movement Study was designed to passively collect the dense physiologic data accessible on Apple Watch and iPhone from a large real-world cohort distributed across the US in order to address these knowledge gaps.

Estimating Respiratory Rate From Breath Audio Obtained Through Wearable Microphones.

Respiratory rate (RR) is a clinical metric used to assess overall health and physical fitness. An individual's RR can change from their baseline due to chronic illness symptoms (e.g.

Smartwatch inertial sensors continuously monitor real-world motor fluctuations in Parkinson's disease.

Longitudinal, remote monitoring of motor symptoms in Parkinson's disease (PD) could enable more precise treatment decisions. We developed the Motor fluctuations Monitor for Parkinson's Disease (MM4PD), an ambulatory monitoring system that used smartwatch inertial sensors to continuously track fluctuations in resting tremor and dyskinesia. We designed and validated MM4PD in 343 participants with PD, including a longitudinal study of up to 6 months in a 225-subject cohort.

Photocleavable DNA Barcoding Antibodies for Multiplexed Protein Analysis in Single Cells.

We describe a DNA-barcoded antibody sensing technique for single cell protein analysis in which the barcodes are photocleaved and digitally detected without amplification steps (Ullal et al., Sci Transl Med 6:219, 2014). After photocleaving the unique ~70 mer DNA barcodes we use a fluorescent hybridization technology for detection, similar to what is commonly done for nucleic acid readouts.

Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates.

Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. We introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine-needle aspirates (FNAs), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing, where barcodes can be photocleaved and digitally detected without any amplification steps.

Rare cell isolation and profiling on a hybrid magnetic/size-sorting chip.

We present a hybrid magnetic/size-sorting (HMSS) chip for isolation and molecular analyses of circulating tumor cells (CTCs). The chip employs both negative and positive cell selection in order to provide high throughput, unbiased CTC enrichment. Specifically, the system utilizes a self-assembled magnet to generate high magnetic forces and a weir-style structure for cell sorting.

Ascites analysis by a microfluidic chip allows tumor-cell profiling.

Ascites tumor cells (ATCs) represent a potentially valuable source of cells for monitoring treatment of ovarian cancer as it would obviate the need for more invasive surgical biopsies. The ability to perform longitudinal testing of ascites in a point-of-care setting could significantly impact clinical trials, drug development, and clinical care. Here, we developed a microfluidic chip platform to enrich ATCs from highly heterogeneous peritoneal fluid and then perform molecular analyses on these cells.

Imaging therapeutic PARP inhibition in vivo through bioorthogonally developed companion imaging agents.

A number of small-molecule poly (ADP-ribose) polymerase (PARP) inhibitors are currently undergoing advanced clinical trials. Determining the distribution and target inhibitory activity of these drugs in individual subjects, however, has proven problematic. Here, we used a PARP agent for positron emission tomography-computed tomography (PET-CT) imaging ((18)F-BO), which we developed based on the Olaparib scaffold using rapid bioorthogonal conjugation chemistries.

Nanoparticle-mediated measurement of target-drug binding in cancer cells.

Responses to molecularly targeted therapies can be highly variable and depend on mutations, fluctuations in target protein levels in individual cells, and drug delivery. The ability to rapidly quantitate drug response in cells harvested from patients in a point-of-care setting would have far reaching implications. Capitalizing on recent developments with miniaturized NMR technologies, we have developed a magnetic nanoparticle-based approach to directly measure both target expression and drug binding in scant human cells.

Synthetic protein scaffolds provide modular control over metabolic flux.

Engineered metabolic pathways constructed from enzymes heterologous to the production host often suffer from flux imbalances, as they typically lack the regulatory mechanisms characteristic of natural metabolism. In an attempt to increase the effective concentration of each component of a pathway of interest, we built synthetic protein scaffolds that spatially recruit metabolic enzymes in a designable manner. Scaffolds bearing interaction domains from metazoan signaling proteins specifically accrue pathway enzymes tagged with their cognate peptide ligands.