CN103502423A - 测量阵列的温度调节 - Google Patents

测量阵列的温度调节 Download PDF

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CN103502423A
CN103502423A CN201280006799.4A CN201280006799A CN103502423A CN 103502423 A CN103502423 A CN 103502423A CN 201280006799 A CN201280006799 A CN 201280006799A CN 103502423 A CN103502423 A CN 103502423A
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R·陈
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Abstract

本发明公开了一种用于调节测量阵列的温度的系统。该系统包括测量阵列，该测量阵列包括多个传感器，其中所述多个传感器被集成到集成电路管芯上。该系统包括被集成到所述集成电路管芯上的热传感器，其中所述热传感器感测与所述多个传感器相关联的温度。该系统进一步包括被耦合到所述集成电路管芯的热泵，其中所述热泵由包括所述热传感器的反馈控制电路控制。

Description

测量阵列的温度调节
对其他申请的交叉引用
本申请要求于2011年1月27日提交的、名称为“TEMPERATUREREGULATION OF BIOCHEMICAL MEASUREMENT ARRAYS”的美国临时专利申请No.61/436,948(代理人案号GENIP010+)的优先权，该临时申请出于所有目的以引用方式并入本文。
背景技术
近年来半导体产业内的微小型化中的进展已经使得生物技术专家能够开始将其传统上庞大的感测工具包装为越来越小的形状因子，包装到所谓的生物芯片上。将期望开发用于生物芯片的技术。
附图说明
在以下的详细描述和附图中公开了本发明的各种实施例。
图1是示意了在其中使用开关式(bang-bang)温度控制机制的生化测量阵列中的温度中的短时持续时间变化性的图。
图2A是示意了生化测量芯片200的顶视图的图。
图2B是示意了如图2A中所示的相同生化测量芯片的侧视图的图。
图2C是示意了如图2A和2B中所示的生化测量芯片200的温度调节系统的一实施例的图。
图3是示意了用于驱动图2C中的帕尔贴(Peltier)器件214的线性反馈控制电路300的一实施例的图。
图4是示意了温度调节系统220的热模型的图。
具体实施方式
本发明可以以多种方式来实现，包括被实现为：过程；设备；系统；物质组成；计算机可读存储介质上体现的计算机程序产品；和/或处理器，诸如被配置为执行存储在耦合至处理器的存储器上和/或由该存储器提供的指令的处理器。在该说明书中，这些实施方式或者本发明可采用的任何其他形式可以被称为技术。一般地，在本发明的范围内，所公开的过程的步骤的顺序可以被更改。除非另有声明，可以将被描述为被配置为执行任务的诸如处理器或存储器之类的部件实现为被临时配置为在给定的时间处执行该任务的一般部件或被制造为执行该任务的具体部件。如本文所使用的那样，术语“处理器”涉及被配置为处理诸如计算机程序指令之类的数据的一个或多个器件、电路和/或处理核心。
在各个实施例中，在多种系统或形式中实现本文所描述的技术。在一些实施例中，以硬件方式将技术实现为专用集成电路(ASIC)或现场可编程门阵列(FPGA)。在一些实施例中，使用处理器(例如，诸如ARM核心之类的嵌入式处理器)，其中该处理器被提供或加载有用于执行本文描述的技术的指令。在一些实施例中，将技术实现为在计算机可读存储介质中体现且包括计算机指令的计算机程序产品。
下文中，连同示意本发明原理的附图一起，提供本发明的一个或多个实施例的详细描述。与这些实施例结合描述本发明，但本发明并不限于任何实施例。本发明的范围仅由权利要求限定，且本发明包含多种替换、修改及等同物。为了提供对本发明的透彻理解，在下面的描述中阐述多个具体细节。这些细节是为了示例的目的而提供的，并且可以在没有这些具体细节中的一些或全部的情况下根据权利要求来实施本发明。为了清楚的目的，并未详细地描述本发明相关技术领域中已知的技术材料，以便不会不必要地使本发明模糊。
生化传感器是能够测量可变生化量且根据特定规则将测量变换为输出信号(例如电信号或光信号)的器件。生化传感器可以是电化学传感器或光学传感器。可以在多种应用中采用生化传感器；例如，它们可以用于核苷酸测序、医疗诊断、患者监视等等。
纳米孔阵列是将生化传感器用于生化测量的测量阵列的一个示例。用于核苷酸测序的纳米孔阵列可以包含几千或几百万个单个细胞或测量部位。每个细胞包含纳米孔，纳米孔是可被用作单分子传感器的电绝缘膜中的小孔。可以使用诸如α-溶血素或MspA之类的生物材料来形成纳米孔。可以使用诸如半导体材料之类的固态材料来形成纳米孔。当跨越纳米孔施加较小电压时，可以测量通过该纳米孔的离子电流，以提供关于经过该纳米孔的分子的结构的信息。在纳米孔阵列的单个细胞中，可以将电路用于控制跨越包含该纳米孔的脂双层施加的电刺激，并用于感测穿过该纳米孔的分子的电图案或签名。
在一些应用中，生化测量阵列可以用于进行精确的生化测量；然而，它们的性能可能受到测量部位处的温度影响。典型地，生化传感器被安装在集成电路上或者是集成电路的组成部分。由于直接从可产生热量的集成电路的表面进行由生化传感器进行的测量，因此需要仔细地控制测量部位处的温度的准确性和可变性；否则将导致性能降低。
出于若干原因，生化测量阵列的温度调节富有挑战性。转导生化测量的精确点处的温度是困难的。此外，热测量点与生化测量点之间的任何温度差将转换为在调节生化测量点处的温度时的误差。
在一些温度调节方案中，采用开关式控制机制。开关式控制器是在两种状态之间突然切换的反馈控制器。例如，冷却或加热元件被完全开启或完全关闭，而不在任何中间级别处运行。该技术简化了温度调节电路，但在生化测量部位处的温度中引入了短时持续时间变化性(波纹)。
图1是示意了在其中使用开关式温度控制机制的生化测量阵列中的温度中的短时持续时间变化性的图。如图1中所示，这些波纹可以基于持续从数毫秒至数分钟的周期在超过半摄氏度的温度范围内波动。然而，为了实现生化测量部位处的温度的精确控制，在全部时间尺度上，温度波动应当比半摄氏度小得多。
图2A是示意了生化测量芯片200的顶视图的图。图2B是示意了如图2A中所示的相同生化测量芯片的侧视图的图。参照图2A和图2B，生化测量阵列202位于集成电路管芯204的顶表面的中心区中。生化测量阵列202具有生化测量部位的多个列和行。位于集成电路管芯204的外围处的多个接合焊盘是用于与生化测量阵列202连通的电接触部。贮存器208可以被安装在集成电路管芯204上，以容纳覆盖生化测量阵列202的表面的液体。覆盖生化测量阵列202的表面的液体可以通过沟道210而引入。
图2C是示意了图2A和图2B中描绘的生化测量芯片200的温度调节系统220的一实施例的图。生化测量芯片200被安装在热传导材料212上。帕尔贴器件214的第一侧面214A被安装在集成电路管芯204的底表面上。帕尔贴器件214的第二侧面214B被安装在对流散热器216上，对流散热器216包括柱鳍(pin-fin)218。帕尔贴器件(也被称作帕尔贴热泵、固态冷藏库或热电冷却器(TEC))是固态主动热泵，其在消耗能量的情况下逆温度梯度(从冷到热)将热量从器件的一侧传递到另一侧。当DC电流流过帕尔贴器件时，热量从一侧移除到另一侧。因此，帕尔贴器件可以用于加热或用于冷却，而且它也可以被用作进行加热或冷却的温度控制器。
在一些实施例中，帕尔贴器件214的第一侧面214A所具有的表面足够大以覆盖集成电路管芯204的整个底表面或整个生化测量阵列202，使得整个集成电路管芯204或整个生化测量阵列202的温度能够被维持在预定的操作温度处。在一些实施例中，预定的操作温度是可配置的，并选自多个操作温度。
图3是示意了用于驱动图2C中的帕尔贴器件214的线性反馈控制电路300的一实施例的图。如图3中所示，热测量晶体管302(例如，二极管连接的晶体管)与放大器304相耦合。放大器304的输出作为输入而被馈送至热电冷却器控制器芯片306(例如来自Linear Technology的LTC1923)，并且热电冷却器控制器芯片306的输出用于驱动帕尔贴器件214。
典型地，生化测量芯片可以包括多达一百万个生化测量部位。由于每个生化测量部位可以消耗多达3.3μW(3.3V处，1μA)，因此整个生化测量芯片可以消耗总共3.3W。在不存在高效地用泵将热量从管芯抽离的温度调节系统220时，生化测量芯片的电路所消耗的功率可能导致管芯过热。
参照图2B和图3，热测量晶体管302被集成至管芯204中。将热测量晶体管302集成至管芯204中的优势在于：从而可以进行管芯温度的直接测量。如上所述，在管芯自身内生成热量。如果热测量晶体管位于管芯外部，则管芯与热测量晶体管之间的热阻将会升高，从而使得跨越管芯与热测量晶体管之间的距离建立较大的热梯度。因此，不能进行管芯的温度的精确测量。注意，在一些实施例中，多于一个热测量晶体管302可以被集成至管芯204中。仅出于示意的目的提供具有单个热测量晶体管302的示例；相应地，本申请不仅限于该具体示例：温度传感器可以是晶体管、二极管、温度敏感型电阻器、或管芯上包括的其他温度敏感型器件。
如本申请中所描述的温度调节系统220提供了用于调节生化测量芯片200的温度的李亚普诺夫渐进稳定的(asymptotically Lyapunov stable)线性控制回路。特别地，温度调节系统220中的各种部件的机械布置确保了系统热时间常数是李亚普诺夫渐进稳定的。
图4是示意了温度调节系统220的热模型的图。在图4中，“R”表示热阻(单位为开尔文/瓦特)。例如，Rdie-ambient是管芯204与管芯周围的环境空气之间的热阻。“C”表示热容(单位为焦耳/开尔文)，并且“T”表示特定位置处的温度(单位为开尔文)。为了实现闭合回路稳定性，各种部件的热容C和热阻R满足如图4的底部处所示的一组准则。特别地，对流散热器216的热容应当是帕尔贴器件214的热容和管芯204的热容的若干倍大(例如10倍大)。管芯与管芯周围的环境空气之间的热阻Rdie-ambient应当是Rambient-sink、Rsink-peltier和Rpeltier-die的若干倍大(例如10倍大)。
虽然为了清楚理解的目的较为详细地描述了上述实施例，但是本发明并不限于所提供的细节。存在多种替换方式来实现本发明。所公开的实施例是示意性的而非限制性的。

Claims (24)

1.一种用于调节测量阵列的温度的系统，包括：
包括多个传感器的测量阵列，其中所述多个传感器被集成到集成电路管芯上；
被集成到所述集成电路管芯上的热传感器，其中所述热传感器感测与所述多个传感器相关联的温度；和
被耦合到所述集成电路管芯的热泵，其中所述热泵由包括所述热传感器的反馈控制电路控制。
2.根据权利要求1所述的系统，其中所述测量阵列包括生化测量阵列，并且其中所述多个传感器中的每一个包括生化传感器。
3.根据权利要求1所述的系统，其中所述反馈控制电路被配置为将与所述多个传感器相关联的温度维持在预定温度处，并且其中所述预定温度是可配置的。
4.根据权利要求1所述的系统，其中感测与所述多个传感器相关联的温度包括：感测与所述集成电路管芯相关联的温度。
5.根据权利要求1所述的系统，其中所述热泵包括帕尔贴热泵。
6.根据权利要求1所述的系统，其中所述热泵包括与所述集成电路管芯相接触的第一表面和与散热器相接触的第二表面，并且其中热量从一个表面传递到另一表面。
7.根据权利要求1所述的系统，其中所述反馈控制电路被配置为线性反馈控制电路。
8.根据权利要求7所述的系统，其中所述线性反馈控制电路包括放大器，并且其中所述放大器被耦合到所述热传感器。
9.根据权利要求7所述的系统，其中所述线性反馈控制电路进一步包括热电冷却器控制器芯片。
10.根据权利要求7所述的系统，其中所述系统被配置为形成李亚普诺夫渐进稳定的线性控制回路。
11.根据权利要求7所述的系统，其中所述系统由热模型表示，并且其中所述系统是至少部分地基于关联于所述热模型的两个参数之间的至少一个关系来配置的。
12.根据权利要求11所述的系统，其中所述至少一个关系包括关联于耦合至所述热泵的散热器的热容与关联于所述热泵的热容之间的关系。
13.根据权利要求12所述的系统，其中关联于耦合至所述热泵的散热器的热容基本上大于关联于所述热泵的热容。
14.根据权利要求11所述的系统，其中所述至少一个关系包括关联于耦合至所述热泵的散热器的热容与关联于所述集成电路管芯的热容之间的关系。
15.根据权利要求14所述的系统，其中关联于耦合至所述热泵的散热器的热容基本上大于关联于所述集成电路管芯的热容。
16.根据权利要求11所述的系统，其中所述至少一个关系包括第一热阻与第二热阻之间的关系，并且其中所述第一热阻包括所述集成电路管芯与所述集成电路管芯周围的环境空气之间的热阻，并且其中所述第二热阻包括耦合至所述热泵的散热器与所述散热器周围的环境空气之间的热阻。
17.根据权利要求16所述的系统，其中所述第一热阻基本上大于所述第二热阻。
18.根据权利要求11所述的系统，其中所述至少一个关系包括第一热阻与第二热阻之间的关系，并且其中所述第一热阻包括所述集成电路管芯与所述集成电路管芯周围的环境空气之间的热阻，并且其中所述第二热阻包括耦合至所述热泵的散热器与所述热泵之间的热阻。
19.根据权利要求18所述的系统，其中所述第一热阻基本上大于所述第二热阻。
20.根据权利要求11所述的系统，其中所述至少一个关系包括第一热阻与第二热阻之间的关系，并且其中所述第一热阻包括所述集成电路管芯与所述集成电路管芯周围的环境空气之间的热阻，并且其中所述第二热阻包括所述热泵与所述集成电路管芯之间的热阻。
21.根据权利要求20所述的系统，其中所述第一热阻基本上大于所述第二热阻。
22.根据权利要求1所述的系统，其中所述热传感器包括下述各项之一：热晶体管、二极管或其他芯片上温度传感器。
23.根据权利要求1所述的系统，其中所述反馈控制电路被配置为开关式控制电路。
24.一种用于调节测量阵列的温度的方法，包括：
将测量阵列集成到集成电路管芯上，其中所述测量阵列包括多个传感器；
将热传感器集成到所述集成电路管芯上；
使用所述热传感器来感测与所述多个传感器相关联的温度；以及
利用包括所述热传感器的反馈控制电路来控制热泵，其中所述热泵被耦合到所述集成电路管芯。
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