Yoko Yamanishi

On-chip magnetically actuated robot with ultrasonic vibration for single cell manipulations

This paper presents an innovative driving method for an on-chip robot actuated by permanent magnets in a microfluidic chip. A piezoelectric ceramic is applied to induce ultrasonic vibration to the microfluidic chip and the high-frequency vibration reduces the effective friction on the MMT significantly. As a result, we achieved 1.1 micrometre positioning accuracy of the microrobot, which is 100 times higher accuracy than without vibration. The response speed is also improved and the microrobot can be actuated with a speed of 5.5 mm s(-1) in 3 degrees of freedom. The novelty of the ultrasonic vibration appears in the output force as well. Contrary to the reduction of friction on the microrobot, the output force increased twice as much by the ultrasonic vibration. Using this high accuracy, high speed, and high power microrobot, swine oocyte manipulations are presented in a microfluidic chip.

Driving method of microtool by horizontally arranged permanent magnets for single cell manipulation

This paper presents an innovative driving method for a magnetically driven microtool to achieve precise positioning control while maintaining a high power output derived from commercialized permanent magnets. An effective driving methodology using permanent magnets, whose axes are parallel to driving direction, is applied to reduce friction force on the microtool. The positioning accuracy improves by five times and the response speed becomes ten times faster against the driving stage than in the conventional method. Furthermore, this method has been extended to two-degree-of-freedom movements, and the performance of the magnetically driven microtools is experimentally validated by oocyte manipulation.

Precise Control of Magnetically Driven Microtools for Enucleation of Oocytes in a Microfluidic Chip

This paper presents two innovative driving methodologies using a magnetically driven microtool (MMT) for precise cell manipulations and automation systems. First, magnetic analysis has been conducted to show the current MMT problem and proved that static friction makes MMT control difficult. New driving methodologies that reduce the friction on the MMT effectively are introduced, and supported by finite element analysis and experimental results. The positioning accuracy improves 3–10 times and the response speeds become 10 times faster against the driving linear stage than in the conventional drive method. Stage feedback control by PI with a disturbance observer has been also investigated in order to obtain precise positioning accuracy and this was successfully improved by 16 times as compared to the conventional drive. Using this methodology, the enucleation of oocytes is demonstrated to show the effectiveness of the method. The required force to cut a swine oocyte is also estimated by the simplified model to prove that the MMT has sufficient force. Two MMT blades made of nickel were set on the microfluidic chip with a new drive methodology and successfully achieved the enucleation process with high throughput.

A new stiffness evaluation toward high speed cell sorter

Cell stiffness could be an index for evaluating its activity. Although various systems measuring cell stiffness have been proposed so far, they are slow for adaptively connecting to cell sorters capable of handling more than 1000 [cells/sec]. This paper proposes a new approach that can indirectly evaluate the cell stiffness by measuring the passing time for a narrow channel. When a cell passes through the channel, it receives a viscous force depending upon how much deformation is exerted on the cell. We show that the stiffness is a function of both the passing time and the initial diameter of cell. We also show that the stiffness is proportional to the passing time and inversely proportional to the initial diameter, under the assumption that the thickness of fluid film is inversely proportional to the normal force. The experimental validation is given together with the basic working principle.

Magnetically modified PDMS microtools for micro particle manipulation

In this paper we describe novel magnetically driven polymeric microtool for non-intrusive and no contamination experiments on a chip. The composite is formed by suspending magnetite particles (Fe3O4) in polydimethylsiloxane (PDMS). In order to obtain precise and complicated pattern of micromagnetic tools, a photolithography techniques has been applied by making good use of thick KMPR-1050 photoresist as sacrificed mould. The surface of the produced micromagnetic tools is specially coated in order to suppress stiction in the biochip. The novelties of these tools are (1) fabrication of any 2D shape, (2) softness (harmless to cells), (3) no contact actuation (no stiction), 4. mass production with low cost. Here we have demonstrated that the mass-produced versatile micromagnetic tools such as stirrer and valve. The potential impact of this technology includes sample selection and separation, cell immobilization, genetic operation, tracking, mixing and reaction techniques into portable microfluidic labs-on-a-chip, culture systems and cell loading system.

Fabrication and Application of 3-D Magnetically Driven Microtools

In this paper, we describe a novel method of fabricating polymeric 3-D magnetically driven microtools (MMTs) for performing nonintrusive and contamination-free experiments on chips. In order to obtain precise and complicated 3-D patterns from magnetically driven 3-D microtools, a grayscale photolithography technique was applied by making good use of a thick negative photoresist as a sacrifice mold. By controlling the amount of ultraviolet light with a gradation of gray-tone mask, we fabricated a smoothly curved (100-¿ m gap) object without steps, which tend to appear in the case of conventional layer-by-layer photolithography techniques. A wide range of on-chip applications of microactuators can be realized by using the softness of the polymer-based 3-D MMT. For example, a microfilter and a microloader were successfully operated by a combination of magnetic and fluidic forces. The finite element method analysis of flow showed that a rotation of the 3-D MMT produces a relatively strong downward axial flow, which prevents particles from stagnating on the surface of the MMT. The produced 3-D MMT can be applied to complex on-chip manipulations of sensitive materials such as cells.

Magnetically Modified Soft Micro Actuators for Oocyte Manipulation

We have developed novel magnetically driven polymeric microtool for non-intrusive and no contamination experiments on a chip. The composite is formed by suspending magnetite particles in polydimethylsiloxane. In order to obtain precise and complicated pattern of magnetic microtools, a photolithography techniques has been applied by making good use of thick KMPR-1050 photoresist as sacrifice-mold. The novelties of these tools are 1. fabrication of any 2D shape, 2.softness, 3. no contact actuation, 4. mass production with low cost. These versatile magnetic mirotools can be applied to various functions such as stirrer, valve, loader and sorter and so on. The potential impact of this technology includes sample selection and separation, particle loading and immobilization, genetic operation, tracking, mixing and reaction techniques into portable microfluidic labs-on-a-chip, culture systems.

Omnidirectional Actuation of Magnetically Driven Microtool for Cutting of Oocyte in a Chip

In this paper, we developed and fabricated a magnetically driven microtool (MMT) and installed it on a microfluidic chip for use in the enucleation of oocytes. The fabricated tool is much smaller than a conventional mechanical micromanipulator used for cell manipulation. We succeeded in driving this MMT in two degrees of freedom-in the X- and Y-directions. The MMT works on the principle of noncontact actuation by magnetic force; therefore, the microfluidic-chip part is fully disposable and inexpensive. The MMT consists of a polymer part with a controllable attitude and a rigid metal (Ni) part with good magnetic properties, which are useful for cutting oocytes. We analytically evaluated that the structure for easy attitude control of the polymer part is a four-leg-type configuration. Based on the novel and original design, the MMT and microfluidic chip were fabricated by photolithography. The MMT could generate a force of 3 mN, which is sufficient to cut an oocyte into half. We successfully demonstrated the cutting of an oocyte on a microfluidic chip by using the MMT.

On-chip Temperature Sensing and Control for Cell Immobilization

In this study, a temperature sensing and controlling microfluid chip has been developed for cell immobilization using a thermo-sensitive hydrogel (PNIPAAm). The PDMS-based micromagnetic stirrers make microscale fluid mixing to provide the temperature stability in the microchannel. The ITO (indium tin oxide) microheaters and thermosensors, fabricated by micromachining technology, perform in situ fluid heating and feedback temperature control. All temperature sensing and controlling devices are integrated on a chip, in which yeast cell immobilization is performed by the gelation of the PNIPAAm solution.

High speed microrobot actuation in a microfluidic chip by levitated structure with riblet surface

This paper presents the high speed microrobot actuation driven by permanent magnets in a microfluidic chip. The riblet surface, which is regularly arrayed V groove reduces the fluid friction and enables stable actuation in high speed. The comprehensive analysis of fluid force, the optimum design and its fabrication were conducted and proved the friction reduction by riblet. The Ni and Si composite fabrication was employed to form the optimum riblet shape on the microrobot surface by wet and dry etching. The evaluation experiments show the microrobot can actuate up to 90 Hs, which is 10 times higher than the original microrobot. In addition, it can be applied to cell manipulation without harm since the microrobot is covered by Si, which is bio-compatible. One of the applications of developed microrobot was demonstrated by assembling cell aggregation in high speed.