DNA bases are separated by only 3.4 angstroms the width of a few atoms. DNA sequencing methods cannot easily resolve this dimension.
sequencing by expansion technology or SPX overcomes this limitation by creating a surrogate molecule called an "Xpandomer". this molecule is more than 50 times longer than its Target DNA and encodes the DNA sequence information in large high signal to noise reporters.
the building blocks for the Xpandomer are novel nucleotides called X-NTPs, a modified DNA replication process synthesizes the Xpandomers.
by sequentially linking the X-NTPs along a Target DNA template using a proprietary enzymatic process.
this forms a double stranded helix each of the four X-NTP types depicted as A、C、G and T, has a tether that is linked between the base and the α phosphate.
the tether supports a high signal to noise reporter that mirrors the base sequence identity.
located in the center of each reporter is the translocation control element or TCE that modulates expander movement during sequencing as the extension proceeds.
only an X-NTP that correctly complements the next base on the DNA template will be incorporated.
the sequence information of the DNA is now expressed in the reporter sequence of the X-NTP.
this process of linking X-NTPs is continued sequentially and extends along the entire length of the DNA template.
after synthesis a reagent is added, which degrades the DNA template and the cleavable bond between each of the X-NTP bases is broken, allowing the backbone to expand.
this product is called the Xpandomer. the Xpandomer is then threaded electrically through a biological nanopore in a deterministic manner.
the translocation control element holds the reporter in the nanopore, altering the electrical resistance of the pore to provide one of four signals that uniquely ident.
identifies the corresponding base in the original DNA sequence.
after measurement a short high voltage pulse is applied, and the Xpandomer is reliably Advanced to the next reporter.
this process is performed in a highly parallel manner across millions of Wells on a single CMOS based sensor module. and can provide for remarkable real-time sequencing rates of hundreds of millions of bases per second.
Roche's innovative SBX technology can flexibly scale to satisfy a broad range of applications setting a new paradigm for Next Generation sequencing technology.
DNA 碱基之间的距离仅为 3.4 埃，几个原子的宽度。DNA 测序方法无法轻松解决这一问题。
通过扩展技术或 SPX 进行测序，通过创建称为扩展器（Xpandomer）的替代分子
来克服这一限制。
该分子比其目标 DNA 长 50 多倍，并将 DNA 序列信息编码在大型高信噪比报告子中。
扩展器的构建块是称为 X-NTP 的新核苷酸，一种经过修改的 DNA 复制过程合成扩展器。
通过使用专有的酶促反应沿目标 DNA 模板顺序连接 X-NTP 过程，这形成了一个双链螺旋。
四种 X-NTP 类型中的每一种都被描述为 A、C、G 和 T，带有连接碱基和 α 磷酸盐之间的链子。链子支持高信噪比报告子，该报告子反映了碱基序列。
位于每个报告子的中心的，是“转位控制元件”，或者叫“TCE”。（TCE）在延伸过程中调节测序过程中的扩展器运动。
只有正确地与 DNA 模板上下一个碱基互补的 X-NTP 才会被结合。DNA 的序列信息现在在 X-NTP 的报告基因序列中表达。连接 X-NTP 的过程是连续的、顺序的。并沿着 DNA 模板的整个长度延伸。
（在 DNA 链的）合成完成后，加入一种试剂，降解 DNA 模板，并切断每个 X-NTP 碱基之间的可裂解键。这允许主链舒展开。
该产物称为 Xpandomer。然后，Xpandomer 以确定性方式通过电穿过生物纳米孔。
转位控制元件将报告基因保持在纳米孔中，改变纳米孔内的电阻。提供四个信号之一，唯一地识别原始 DNA 序列中的相应碱基。
测量后施加短高压脉冲，并且 Xpandomer 可以可靠地推进到下一个报告基因。
该过程以高度并行的方式，数百万个孔中执行，单个孔是基于 CMOS 的传感器模块的。
并且可以提供每秒数亿个碱基的惊人实时测序速率。
罗氏的创新 SBX 技术可以灵活扩展以满足广泛的应用，为下一代测序技术树立了新典范。