Elsevier

Microelectronics Reliability

Volume 91, Part 2, December 2018, Pages 243-250
Microelectronics Reliability

Investigation of DNA sequencing droplet trajectory observation and analysis

https://doi.org/10.1016/j.microrel.2018.10.012Get rights and content

Highlights

  • DNA sequencing droplet trajectories are observed and analyzed using an ASIC circuit system and a MEMS structure jetting chip.

  • The structure is a three-dimensional, multi-channel drive system that can control droplets more precisely.

  • Droplets near the end of their trajectories are far from the nozzle hole and therefore are easily affected by air disturbance.

  • Images captured by the CCD are blurrier, which reduces the accuracy of calculations.

Abstract

In this study, DNA sequencing droplet trajectories are observed and analyzed using an application-specific integrated circuit system and a micro-electromechanical system structure jetting chip. We investigate a droplet jetting technique and apply it to biomedical test chips. This use of a sprayed chip structure can reduce sequencing time by two-thirds compared with traditional methods. The structure is a three-dimensional, multi-channel drive system that can control droplets more precisely. The circuit's input control signal was generated and placed on a chip based on the quantitative design of liquid droplets. Delay time and frequency were used to set the LED light sources. In this study, we would use frequencies of 4 kHz, 8 kHz, and 12 kHz combined with two groups of different orifices and frequencies for ink droplet outlet velocity.

Introduction

Inkjet printing can be classified as continuous or non-continuous. In turn, non-continuous printing can be divided into thermal bubble type and pressure type, depending on the ink ejection mechanism. A thermal bubble head microstructure is large, and thermal resistance can occur under the ink; within a few microseconds, the ink can be heated to 350–450 °C, vaporizing the water to produce microbubbles. Heating also leads volume expansion, causing the ink in the original space to be extruded out of the cartridge's orifice. At this point, the heating plate rapidly cools, breaking the bubbles. The force of the bubbles breaking causes the extruded ink to form droplets. When the ink droplets fly to the substrate, ink dots are formed on it. This substrate is an integrated micro-electromechanical system (MEMS) structure and has a special chip circuit architecture. Ink is continuously replenished through the flow path connecting the inkjet and ink storage areas. Every ink droplet ejected is the result of the above process [[1], [2], [3], [4], [5], [6], [7], [8], [9]]. The ink jet rate of this mechanism can reach 3000–8000 droplets per second, in some cases even 12,000 drops, meaning the cycle can occur from thousands to tens of thousands of times per second. In contrast to George's point-and-shoot paintings, inkjet printing can produce a large number of high-quality graphic prints in a short period of time.

Piezoelectric inkjet technology is exemplified by EPSON's self-developed micro-needle-point approach. The key to this technology is a crystal with piezoelectric characteristics. When the crystal is energized, it expands. EPSON facilitates stable control of the voltage applied to the crystal via a multilayered piezoelectric wave, using the crystal's own characteristics. The crystal expands to eject the ink, then pulls the ink back when the power is turned off. Because the voltage can be precisely controlled, the production rate and size of the resulting ink dots can also be precisely controlled. The factors affecting the quality of inkjet printing include ink dot size, resolution, number of colors, inkjet electronic control technology, and color conversion technology. However, the most important are ink dot size, resolution, and number of colors [[10], [11], [12], [13], [14], [15], [16]].

DNA sequencing technology has developed in three phases. The earliest e-fluorescent sequencing of a gene sequence took as long as three years and cost millions of dollars. The second stage combined microprocessing, optical detection, and automatic control technology, permitting the rapid interpretation of large numbers of DNA sequences using different sequencing principles [[17], [18], [19], [20], [21]]. System sequencing time was reduced to a few weeks, and the cost dropped to only tens of thousands of dollars. In the third stage, optical and electronic solutions were used, the instruments' readability increased dramatically, the sequencing time was reduced to several hours, and the cost was only a few thousand dollars.

Current DNA sequencing technology uses genetic engineering methods to place small fragments of gene sequences in order and then insert them into bacterial plasmids. The bacteria's rapid growth and reproduction enables large quantities of chromosomal fragments to be replicated and then separated. Sequencing by either a separation method or electrophoretic analysis and synthesis can then be used to interpret the DNA sequences. Sequencing technology continues to move toward lowering the cost, increasing the length of sequencing reads, and increasing the amount of sequencing per unit of time [[22], [23], [24], [25], [26]]. Reduced costs and better understanding of gene function have greatly increased the feasibility of genetic testing applications. Future DNA sequencing could become as widespread as current health examinations and help with diagnosing illnesses and developing new drugs. Conceivably, it could even be individually tailored to achieve personalized medicine.

In the DNA detection part of the sequencing process, gene microarray technology is an important factor. It can be used, for example, to compare normal cells and cancer cells. It can also determine which genes are more prevalent in cancer cells and further analyze those genes. The method for achieving this involves marking normal cells and cancer cells with different colors. The cells are then smeared on a chip, and the DNA corresponding to the nucleotide probe on the wafer remains on the board, looking like a colorful grid. Gene microarray technology is a multidisciplinary combination of technologies that can help us to better understand the genetic code. The objective of the present study was to place a defined DNA segment into droplets on a glass slide using a MEMS structure jetting chip. In the past, this was mainly done by a “sticky” method, which used a large-array adhesive force. This method imposes structural limits upon the placement of a defined DNA segment in droplets. We investigated a droplet jetting technique and applied it to biomedical test chips. We show that compared with the traditional method, this use of a sprayed chip structure can reduce sequencing time by two-thirds, and we can place the technology on the corresponding position of the slide.

The special wafer integrated circuit design has provided a multiplexed addressing technique and can reduce the sorting time by two-thirds. The technique of multiplexed addressing can be used to calculate the sequences of the liquid droplets in order. That is, a liquid crystal film system can first determine the pre-planted DNA droplets ejection with “even group” nucleobase of A, G, C, and T, the pre-planted DNA droplets ejection with “odd group” nucleobase of A, G, C, and T, the DNA droplets ejection with an addressing of two elements on the same period driving, and the DNA droplets ejection with an addressing of three elements on the same period driving. Compared to the conventional technology, it is sequentially assigned from the first orifice to the last one. In this case, it is necessary to wait for the front nozzle to complete the spray, and then it can obtain the command signal of the spray. The traditionally technology consumes much time as compared with this technology.

Section snippets

Architecture

The first important technique to investigate is the application of droplet jetting in biomedical test chips to jet DNA droplets. This involves adjusting the size of the droplets using the size of the power signal. A second technique is the use of logic multiplexing to select nozzles. This involves a supply sequence signal that is processed by bit data to obtain a spray nozzle position. In Fig. 1, tf is the falling time of the pulse, tr is the raising time of the pulse, and CLK1 is the count

Experiment and signal measurement

The multidimensional driver DNA nucleobases A, G, C, and T are ordered in the desired gene selection framework. They determine the sequence of DNA that can quantify a whole piece of DNA by placement on the wafer's input control signal. For example: “ATCG” and “AUCG” are combined corresponding to DNA and RNA sequences. DNA is a deoxyribonucleotide and a two-stranded nucleotide chain with four nitrogen-containing bases (ATCG). RNA is a ribonucleic acid and a single-stranded nucleotide chain

Results

We examined the relationship between droplet outlet speed and output signal frequency. By adjusting the LED delay time, we were able to observe changes in droplet length. LED is used as a light source and it illuminates at the same frequency as the droplet jets. Since it is synchronized with the time the droplet is produced, it can observe the trajectory produced by the droplets at the corresponding lighting frequency. CCD can capture the image of droplet outlet speed and output signal

Conclusions

In this study, we investigated DNA sequencing droplets' trajectory and techniques for forming DNA droplets. We would observe that as the DNA sequencing droplets were ejected, the investigated devices could shear liquid of DNA to decrease the disturbance of the sequencing data. We took measurements using two groups of orifices and frequencies to determine ink droplet outlet velocity. Droplets near the end of their trajectories are far from the nozzle hole and therefore are easily affected by air

Acknowledgments

This work was supported by TMU 106-AE1-B17.

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