In biology, fluorescent dyes are routinely used for biochemical measurements such as pH and ion concentrations. They, especially when used for detecting a low concentration of ions, suffer from low signal-to-noise ratios (SNR); and increasing the concentration of fluorescent dyes causes more sever cytotoxicity. We invented a new approach that uses a low amount of fluorescent dye-coated magnetic nanoparticles for on-demand, accurately aggregating the nanoparticles and thus fluorescent dyes in a local region inside a cell for intracellular measurement. Experiments proved this approach is capable of achieving a significantly higher SNR and lower cytotoxicity. Different from existing magnetic micromanipulation systems that generate large swarms (several microns and above) or cannot move the generated swarm to an arbitrary position, we developed a five-pole magnetic micromanipulation system and technique for generating a small swarm (e.g., 1 μm; capable of generating a magnetic swarm from 0.52 μm to 52.7 μm with an error <; 7.5 %) and accurately positioning the small swarm (position control accuracy: 0.76 μm). As an example, the system performed intracellular pH mapping using a 1 μm swarm of pH sensitive fluorescent dye-coated magnetic nanoparticles. The swarm had an SNR inside a cell 10 times that by the traditional method, i.e., global dye treatment, with both cases using the same fluorescent dye concentration. Our intracellular measurement results, for the first time, quantitatively revealed the existence of pH gradient and polarized pH distribution in live migrating cells.

Existing approaches for robotic control of magnetic swarms are not capable of generating magnetic aggregates precisely in an arbitrarily specified target region in a fluidic flow environment. Such a swarm control capability is demanded by medical applications such as clinical embolization (i.e., localized clogging of blood vessels). This paper presents a new magnetic swarm control strategy to generate aggregates only in a specified target region under fluidic flow. Within the target region, the magnetic field generates sufficiently large magnetic forces among magnetic particles to maintain the aggregates' integrity at the junctions of blood vessels. In contrast, unintended aggregates outside the target region are disassembled by fluidic shear. The aggregation control approach achieved a mean absolute error of 0.15 mm in positioning a target region and a mean absolute error of 0.30 mm in controlling the target region's radius. With thrombin coating, 1 μm magnetic particles were controlled to perform embolization both in vitro (using microfluidic channel networks) and ex vivo (using porcine tissue). Experiments proved the effectiveness of the swarm control technique for on-demand, targeted embolization.